SNPMiner Trials by Shray Alag


SNPMiner Trials: SNP Report


Report for SNP rs4680

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

There are 8 clinical trials

Clinical Trials


1 Effect of COMT (Catecholamine-O-methyltransferase) Genetic Polymorphisms on Response to Propranolol Therapy in Temporomandibular Disorder

Purpose: Primary: To evaluate the efficacy of extended-release (ER) propranolol compared to placebo in the reduction of a pain index in patients with temporomandibular disorder (TMD). Secondary: To determine if extended-release propranolol efficacy varies according to participants' catechol-O-methyltransferase (COMT) genetic polymorphisms and to investigate the efficacy of extended-release propranolol compared with placebo using secondary endpoints. Exploratory: To investigate whether the efficacy of extended-release propranolol in the reduction of the pain index varies according to participants' polymorphisms in 3 other genetic regions and according to various phenotypic characteristics. Participants: 200 patients with chronic TMD will be randomly assigned, in a 1:1 parallel, double-blind fashion, to receive either extended-release propranolol or placebo at one of three study sites: University of North Carolina-Chapel Hill School of Dentistry; University of Florida-Gainesville College of Dentistry; and the State University of New York at Buffalo School of Dental Medicine. Procedures (methods): Randomization will be to either propranolol or placebo. The 10-week study treatment period is divided into: 1 week of drug titration, 8 weeks of drug maintenance, and 1 week of drug tapering. The titration and tapering doses are 60 mg (capsules) once per day orally; the maintenance dose is 60 mg twice per day orally. Participants will attend 6 clinic visits over 12-15 weeks as follows: screening and baseline visit (Visit [V] 0, 7-21 days prior to V1); randomization and start of treatment (titration) (V1, study day 0); maintenance visit 2 (V2, 1 week post-randomization, study day 7+3); maintenance visit 3 (V3, 5 weeks post-randomization, study day 35 +/- 7); tapering visit (V4, 9 weeks post-randomization, study day 63 +/- 7); and tapering visit 5 (V5, 11 weeks post-randomization and 1 week after drug tapering ends, study day 77 +/- 7). Depending on the visit, procedures will include: reviews of medical history, weekly alcohol consumption, concomitant therapies and medications, adverse events, compliance, and eligibility; administration/review of questionnaires; blood draw; pregnancy test in women of childbearing potential; and dispensing of study drug.

NCT02437383 Temporomandibular Disorders Drug: Propranolol ER Drug: Placebo
MeSH: Temporomandibular Joint Disorders Temporomandibular Joint Dysfunction Syndrome

The pain index was stratified per number of catechol-O-methyltransferase (COMT) Low Pain Sensitive (LPS) haplotypes.. Change in the Weekly Mean Pain Index After 9 Weeks of Treatment Stratified Per Number of COMT Valine Alleles at rs4680.

The pain index was stratified per number of catechol-O-methyltransferase (COMT) valine alleles at single nucleotide polymorphism (SNP) rs4680.. Inclusion: - Diagnostic criteria for TMD: Group II, Masticatory Muscle Disorders, Myalgia - Facial pain for at least 3 months (and at least 10 of the last 30 days at Visit 0) - Average pain intensity rating ≥30 (0-100 numeric rating scale) over the past week or average daily pain intensity rating ≥30 on the same scale on at least 3 days over the past week - Agrees to terms for continuing/discontinuing certain prescription/over-the-counter pain medications throughout participation - Agrees to not commence new prescription medication, injection therapy, occlusal splint therapy or certain other pain management techniques throughout participation - Agrees to limit consumption of alcohol to no more than 7 drinks/week (females) and no more than 14 drinks/week (males) throughout participation - If a female of childbearing potential, agrees to use of contraception (licensed hormonal method, intrauterine device, condoms with contraceptive foam, abstinence, or partner vasectomy) throughout participation - Able to understand and comply with study procedures and provide written informed consent Exclusion: - History of congestive heart failure or certain cardiac conditions including coronary artery disease, uncontrolled hypertension, or hypotension - Bronchial asthma, nonallergic bronchospasm, renal failure or dialysis, diabetes mellitus, hyperthyroidism, fibromyalgia, or uncontrolled seizures - Currently taking a β-blocker or certain other medications including haloperidol, intravenous verapamil, or reserpine - Currently taking an opioid medication - Daily prescription medication, occlusal splint therapy, or an investigational drug or treatment for pain management within past 30 days - Injection therapy or certain other pain management techniques within last 2 weeks - Facial trauma or orofacial surgery within past 6 weeks - Active orthodontic treatment - History of major depression or other psychiatric disorder requiring hospitalization within past 6 months - Treatment for drug or alcohol abuse within the last year - Smokes 25 or more cigarettes/day - Currently receiving chemotherapy or radiation therapy - Pregnant or breastfeeding Inclusion: - Diagnostic criteria for TMD: Group II, Masticatory Muscle Disorders, Myalgia - Facial pain for at least 3 months (and at least 10 of the last 30 days at Visit 0) - Average pain intensity rating ≥30 (0-100 numeric rating scale) over the past week or average daily pain intensity rating ≥30 on the same scale on at least 3 days over the past week - Agrees to terms for continuing/discontinuing certain prescription/over-the-counter pain medications throughout participation - Agrees to not commence new prescription medication, injection therapy, occlusal splint therapy or certain other pain management techniques throughout participation - Agrees to limit consumption of alcohol to no more than 7 drinks/week (females) and no more than 14 drinks/week (males) throughout participation - If a female of childbearing potential, agrees to use of contraception (licensed hormonal method, intrauterine device, condoms with contraceptive foam, abstinence, or partner vasectomy) throughout participation - Able to understand and comply with study procedures and provide written informed consent Exclusion: - History of congestive heart failure or certain cardiac conditions including coronary artery disease, uncontrolled hypertension, or hypotension - Bronchial asthma, nonallergic bronchospasm, renal failure or dialysis, diabetes mellitus, hyperthyroidism, fibromyalgia, or uncontrolled seizures - Currently taking a β-blocker or certain other medications including haloperidol, intravenous verapamil, or reserpine - Currently taking an opioid medication - Daily prescription medication, occlusal splint therapy, or an investigational drug or treatment for pain management within past 30 days - Injection therapy or certain other pain management techniques within last 2 weeks - Facial trauma or orofacial surgery within past 6 weeks - Active orthodontic treatment - History of major depression or other psychiatric disorder requiring hospitalization within past 6 months - Treatment for drug or alcohol abuse within the last year - Smokes 25 or more cigarettes/day - Currently receiving chemotherapy or radiation therapy - Pregnant or breastfeeding Temporomandibular Disorders Temporomandibular Joint Disorders Temporomandibular Joint Dysfunction Syndrome "Temporomandibular disorder" (TMD) encompasses all musculoskeletal disorders of the masticatory system and includes myalgia, arthralgia, temporomandibular joint (TMJ) disc displacements, and TMJ degenerative joint diseases.

Primary Outcomes

Description: Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary and divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome.

Measure: Change in the Weekly Mean Pain Index After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Secondary Outcomes

Description: Weekly mean pain intensity computed as the arithmetic mean of daily pain intensity values during the week prior to randomization and prior to each study visit. Daily pain intensity is measured on 0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") as reported in the Daily Symptom Diary. A higher score means a worse outcome.

Measure: Change in the Weekly Mean Pain Intensity After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Weekly mean pain duration computed as the arithmetic mean of daily pain duration values during the week prior to randomization and prior to each study visit. Daily pain duration is measured on 0-100 percentage scale where percent = "percent of waking day you had facial pain" as reported in the Daily Symptom Diary. A higher score means a worse outcome.

Measure: Change in the Weekly Mean Pain Duration After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The SF-McGill Pain Questionnaire contains 4 affective descriptors rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe." The item scores are summed to yield a total score ranging from 0 to 12. A higher score means a worse outcome.

Measure: Change in the SF-McGill Pain Questionnaire Affective Component After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The SF-McGill Pain Questionnaire contains 11 sensory descriptors rated on a 0-3 scale where 0 = "none," 1 = "mild," 2 = "moderate," and 3 = "severe." The item scores are summed to yield a total score ranging from 0 to 33. A higher score means a worse outcome.

Measure: Change in the SF-McGill Pain Questionnaire Sensory Component After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Self-reported present intensity of facial pain at the moment of assessment scored on a descriptive scale where 1 = "no pain' and 6 = "excruciating pain." A higher score means worse outcome.

Measure: Change in the SF-McGill Pain Questionnaire Present Facial Pain Intensity After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Self-reported average facial pain intensity for the last week scored on 0-100 numerical rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable". A higher score means a worse outcome.

Measure: Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Intensity After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Self-reported average facial pain duration for the last week scored on 0-100 percentage scale where percent = "percent of waking day you had facial pain". A higher score means a worse outcome.

Measure: Change in the SF-McGill Pain Questionnaire Weekly Average Facial Pain Duration After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Self-reported average fatigue for the last week scored on 0-100 numerical rating scale where 0 = "no fatigue" and 100 = "the greatest imaginable." A higher score means a worse outcome.

Measure: Change in the SF-McGill Pain Questionnaire Weekly Fatigue After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Individuals were classified into 6 chronic pain grades: 0 = no pain; I = low pain intensity and low pain-related disability; IIa = high pain intensity and low pain-related disability; IIb = high pain intensity and high activity interference; III = moderate pain-related disability; and IV = severe pain-related disability. For analyses, this variable was dichotomized: grades 0-IIa were combined in one category and all higher grades in another. A higher grade means a worse outcome.

Measure: Number of Participants Stratified Per Graded Chronic Pain Scale (GCPS) Grade After 9 Weeks of Treatment

Time: Visit 4 (study day 63 +/-7)

Description: The JFLS contains 20 items that measure limitations across mastication, vertical jaw mobility, and verbal/emotional expression rated on a 0-10 scale where 0 = "no limitation" and 10 = "severe limitation." The Global Score is computed as the mean response for all items and ranges from 0 to 10. A higher score means a worse outcome.

Measure: Change in the Jaw Functional Limitation Scale (JFLS) Global Score After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The HIT-6 contains 6 items and assesses headache-related disability by the frequency of daily activity limitations ranging from "never" to "always." The 6 item scores are summed to yield a global score ranging from 36 to 78. A higher score means a worse outcome.

Measure: Change in the Headache Impact Test (HIT-6) Global Score After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The PSQI has 19 items grouped into 7 component scores, each weighted equally on a 0-3 scale, The 7 component scores are summed to yield a global PSQI score, which has a range of 0-21. A higher score means a worse outcome.

Measure: Change in the Pittsburgh Sleep Quality Index (PSQI) Global Score After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The PGIC scale assesses patient overall change in the severity of illness following treatment. Participants rate how they feel now compared with how they felt before receiving study drug on a 7-point scale where 0 = "No change or condition has got worse" and 6 = "A great deal better." A higher score means a better outcome. For analyses, this variable was dichotomized: scores from 0 to 3 were combined in one category of "No" (no significant improvement) and scores from 4 to 6 were combined in another category of "Yes" (significant improvement with the study treatment).

Measure: Number of Participants Stratified Per Dichotomized Score From the Patient Global Impression of Change (PGIC) Scale After 9 Weeks of Treatment

Time: Visit 4 (study day 63 +/-7)

Description: The PSS assesses the frequency of 14 sources of stress on a scale from 0 = "never" to 4 = "very often." The item scores are summed to yield a global score ranging from 0 to 56. A higher score means a worse outcome.

Measure: Change in the Perceived Stress Scale (PSS) Global Score After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression with a range from 0 to 21. A higher score means a worse outcome.

Measure: Change in the Hospital Anxiety and Depression Scale (HADS) Depression Score After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The HADS is a 14-item assessment of anxiety (7 items) and depression (7 items) using the relative frequency of symptoms over the past week, rated on a 4-point scale ranging from 0 = "not at all" to 3 = "very often indeed". Responses are summed to provide separate scores for anxiety and depression with a range from 0 to 21. A higher score means a worse outcome.

Measure: Change in the Hospital Anxiety and Depression Scale (HADS) Anxiety Score After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The SCL-90R Somatization Scale is a 12-item assessment of somatic symptom distress over the past 7 days rated from 0 = "not at all" to 4 = "extremely." The scale score is computed as the mean for all items. The score range is from 0 to 4. A higher score means a worse outcome.

Measure: Change in the Symptom Checklist 90-Revised (SCL-90R) Somatization Scale Score After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The SF-12v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). summary (MCS). The range for each component is 0-100 and a higher score means a better outcome.

Measure: Change in the SF-12 Health Survey v2 (SF-12v2) Physical Component Summary (PCS) After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: The SF-12v2 contains 7 questions assessing 8 domains of functioning and well-being rated from: "excellent" to "poor" (for general health); "yes, limited a lot" to "no, not limited at all" (for functional level); and "all of the time" to "none of the time" (for emotional state). These 8 domains can be further summarized into a physical component summary (PCS) and a mental component summary (MCS). The range for each component is 0-100 and a higher score means a better outcome.

Measure: Change in the SF-12 Health Survey v2 (SF-12v2) Mental Component Summary (MCS) After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli will be averaged to measure the experimental thermal pain threshold (temperature at which pain is first perceived). The range was 32-50 degrees Celsius and a higher value means a better outcome.

Measure: Change in Thermal Pain Threshold After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Temperature values, measured in degrees Celsius, from 4 examiner-applied contact heat stimuli will be averaged to measure the experimental thermal pain tolerance (temperature at which pain can no longer be tolerated). The range was 32-50 degrees Celsius and a higher value means a better outcome.

Measure: Change in Thermal Pain Tolerance After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Pressure values, measured in kilopascals (kPa), from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporalis muscle, are averaged to obtain a single pressure pain threshold value per anatomical site. The range is 0-500 kPa and a higher value means a better outcome.

Measure: Change in Pressure Pain Threshold at Temporalis Muscle After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of masseter muscle, will be averaged to obtain a single pressure pain threshold value per anatomical site.

Measure: Change in Pressure Pain Threshold at Masseter Muscle After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/- 7)

Description: Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of temporomandibular joint, will be averaged to obtain a single pressure pain threshold value per anatomical site.

Measure: Change in Pressure Pain Threshold at Temporomandibular Joint After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of trapezius muscle, will be averaged to obtain a single pressure pain threshold value per anatomical site.

Measure: Change in Pressure Pain Threshold at Trapezius Muscle After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Pressure values, measured in kilopascals, from up to 5 experimental pressure stimuli, bilaterally applied to the area of lateral epicondyle, will be averaged to obtain a single pressure pain threshold value per anatomical site.

Measure: Change in Pressure Pain Threshold at Lateral Epicondyle After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Measured at TMD exam. A higher value means a better outcome.

Measure: Change in Pain-free Jaw Opening After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Measured at TMD exam. A higher value means a better outcome.

Measure: Change in Maximum Unassisted Jaw Opening After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Measured at TMD exam. A higher value means a better outcome.

Measure: Change in Maximum Assisted Jaw Opening After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Average of 3 repeated measures taken with a 2-minute interval.

Measure: Change in Systolic Blood Pressure After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Average of 3 repeated measures taken with a 2-minute interval.

Measure: Change in Diastolic Blood Pressure After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Average of 3 repeated measures taken with a 2-minute interval.

Measure: Change in Heart Rate After 9 Weeks of Treatment

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Other Outcomes

Description: Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary, divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. The pain index was stratified per number of catechol-O-methyltransferase (COMT) Low Pain Sensitive (LPS) haplotypes.

Measure: Change in the Weekly Mean Pain Index After 9 Weeks of Treatment Stratified Per Number of COMT LPS Haplotypes

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

Description: Weekly mean pain index computed as the arithmetic mean of daily pain index values during the week prior to randomization and prior to each study visit. Daily pain index is computed as pain intensity (0-100 numeric rating scale where 0 = "no pain" and 100 = "the most intense pain imaginable") multiplied by pain duration (0-100 percentage scale where percent = "percent of waking day you had facial pain") as reported in the Daily Symptom Diary, divided by 100. The pain index range is from 0 to 100. A higher score means a worse outcome. The pain index was stratified per number of catechol-O-methyltransferase (COMT) valine alleles at single nucleotide polymorphism (SNP) rs4680.

Measure: Change in the Weekly Mean Pain Index After 9 Weeks of Treatment Stratified Per Number of COMT Valine Alleles at rs4680

Time: Visit 1 (study day 0) and Visit 4 (study day 63 +/-7)

2 The Role of Sex Steroids and Serotonin Brain Dynamics in Perinatal Mental Health

Hormonal transitions such as across pregnancy and postpartum may trigger depressive episodes in some women. It is not known why, but estrogen sensitivity may play a critical role. A preclinical human risk model showed that depressive symptoms induced by pharmacological sex-hormone manipulation is linked to increases in serotonin transporter (SERT) brain binding, which lowers serotonergic brain tone. It is currently unknown if these findings translates to women across pre- to postpartum transitions. This longitudinal project studies a group of women who will deliver by planned caesarian, thus permitting the collection of cerebrospinal fluid (csf) containing central markers of serotonergic signaling, at the latest point in pregnancy. The women are followed across late pregnancy, delivery and 6 months postpartum to illuminate relations between sex-hormones, stress-regulation, estradiol sensitivity, csf markers of neurotransmission, serotonin transporter genotype variance, and potential development of subclinical or manifest depressive symptoms. Further, markers of relevance for the infant brain development and stress-regulation will be obtained from placenta tissue and umbilical cord blood. A subgroup of 70 women will participate in a brain imaging program early postpartum (week 3-5), which includes an evaluation of brain activity and structure and in vivo molecular brain imaging serotonergic markers. Thus, serotonergic markers in csf can be combined with postpartum molecular brain imaging of key features of serotonin signaling. Women in the imaging program are selected based on variation in their level of mental distress immediately postpartum (day 2-5). The study's main hypothesis is that women with high-expressing SERT genotypes are more sensitive to peripartum hormonal transition in terms of changes in serotonergic tone and emergence of depressive symptoms and that such an association will be stronger in the presence of candidate gene transcript biomarkers of oestrogen sensitivity. A further hypothesis is that in vivo molecular brain imaging and csf based serotonergic markers will be associated with depressive symptoms both early and later postpartum. Ideally, this project will provide a rationale for future targeted prevention and/or treatment of perinatal depression in women at high risk, which holds grand potential to protect not only mother but also infant brain health long-term.

NCT03795688 Major Depressive Disorder Perinatal Depression Other: Pregnancy
MeSH: Depressive Disorder Depression Depressive Disorder, Major
HPO: Depressivity

Assessed in blood from umbilical cord blood sample from infants, total group.. COMT-genotype (rs4680) variant, i.e met/met vs other polymorphisms.

val158met (rs4680) status, binary variable, i.e. "val/val, val/met" vs "met/met" variants.

Primary Outcomes

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Total group

Measure: Depressive symptoms

Time: Week 3-6 postpartum

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Week 3-6 postpartum

Description: 116 a priori defined gene transcripts, which where differentially expressed in third trimester of women who later developed perinatal depression with postpartum onset relative to pregnant women who did not and to other depressed (reference Mehta et al, 2014, Psychological Medicine) and confirmed to be coupled to estrogen fluctuations (Mehtaet al. 2018 British Journal of Psychiatry) will be evaluated in the total group. Also DNA methylation of the genes of these transcripts will be determined and analysed in terms of their predictive value (above chance) for perinatal depression.

Measure: Gene transcript and DNA methylation markers of estrogen sensitivity

Time: Prior to caesarean section

Description: Latent variable construct of brain 5-HT4R level based on quantification of 5-HT4R binding from 11C-SB207145 positron emission tomography in primary volumes of interest; neocortex, nucleus caudatus, putamen and hippocampus. Assessed in imaging group.

Measure: Cerebral serotonin 4 receptor binding postpartum

Time: Week 3-6 postpartum

Description: Assessed in total group

Measure: CSF levels of GABA

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of serotonin metabolite (5-HIAA)

Time: On day of caesarean section

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Week 3-6 postpartum

Description: Provides an estimate of cortisol exposure up to 6 months prior to delivery, total group

Measure: Hair cortisol level mothers

Time: On day of caesarean section.

Description: Provides an estimate of fetal cortisol exposure, infants from total group

Measure: Hair cortisol level newborns

Time: Day 0-5 postpartum.

Description: Hippocampal brain volume (including hippocampus) from structural MRI, imaging group.

Measure: Hippocampal volumes

Time: Week 3-6 postpartum.

Description: fMRI (BOLD response) based assessment of brain activity in response to reward, relative to non-reward, stimuli. Assessed in imaging cohort

Measure: functional MRI response to reward

Time: Week 3-6 postpartum.

Description: rsfMRI based spontaneous co-fluctuations in low frequency BOLD signal, (functional connectivity). Assessed with rsfMRI scan in the resting state, i.e. non-goal oriented spontaneous thought and awake. Assessed in imaging group.

Measure: Resting state functional connectivity MRI

Time: Week 3-6 postpartum

Description: Change in epigenetic SERT status from late pregnancy to postpartum week 3-6.

Measure: Change in epigenetic SERT status

Time: From just before delivery to 3-6 weeks postpartum

Description: Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Concentration of inflammatory markers, i.e hsCRP and immunoactive cytokines, in peripheral blood

Time: At week 3-6

Description: fMRI (BOLD response) based assessment of brain activity to emotionally salient, relative to neutral, stimuli. Assessed in imaging cohort.

Measure: functional MRI response to emotional faces

Time: Week 3-6 postpartum.

Secondary Outcomes

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Day 3-5 postpartum

Description: Score on the Hamilton 17-item depression scale. Score range: 0-52. Higher scores indicate more depressive symptoms. Assessed in imaging group

Measure: Depressive symptoms

Time: Week 12 postpartum

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in total group

Measure: Depressive symptoms

Time: Day 3-5 postpartum

Description: Edinburgh Postnatal Depression Scale. Score range: 0-30. Higher scores indicate more symptoms of postpartum depression. Assessed in all

Measure: Depressive symptoms

Time: 6 months postpartum

Description: Assessed in total group

Measure: CSF levels of serotonin

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of dopamine metabolites

Time: On day of caesarean section

Description: Assessed in total group

Measure: CSF levels of noradrenaline metabolites

Time: On day of caesarean section

Description: Composite measure of IFN-c, IFN-alfa TNF-alfa og IL-6, in total group

Measure: CSF levels of inflammatory markers

Time: On day of caesarean section

Description: Estradiol level in peripheral blood, total group

Measure: Estradiol level

Time: Prior to caesarean section.

Description: Estradiol level peripheral blood, total group

Measure: Estradiol level

Time: At week 3-6 postpartum.

Description: Estradiol change pre- to postpartum, peripheral blood total group

Measure: Change in estradiol level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Progesterone level in peripheral blood

Measure: Progesterone level

Time: Prior to caesarean section.

Description: Progesterone level in peripheral blood

Measure: Progesterone level

Time: At week 3-6 postpartum.

Description: Progesterone change pre- to postpartum, peripheral blood total group

Measure: Change in progesterone level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Allopregnanolone level in peripheral blood

Measure: Allopregnanolone level

Time: Prior to caesarean section.

Description: Allopregnanolone level in peripheral blood

Measure: Allopregnanolone level

Time: At week 3-6 postpartum.

Description: Change in allopregnanolone level in peripheral blood

Measure: Change in allopregnanolone level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Cortisol change pre- to postpartum, peripheral blood total group

Measure: Change in cortisol level

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Week 12 postpartum

Description: Cortisol awakening response, area under the curve with respect to baseline from 0 to 60 minutes from awakening.

Measure: Cortisol awakening response

Time: Prior to caesarean section

Description: Change in cortisol awakening response, from caesarean section to 3-6 weeks postpartum.

Measure: Change in cortisol awakening response

Time: ´From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the SERT gene, total group

Measure: DNA methylation of the SERT gene

Time: Prior to caesarean section

Description: DNA Methylation status for the SERT gene, total group

Measure: DNA methylation of the SERT gene

Time: Week 3-6 postpartum

Description: Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group

Measure: DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: Prior to caesarean section.

Description: Methylation status for the FK506-binding protein 51 (FKBP5) gene, total group

Measure: DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the FK506-binding protein 51 (FKBP5) gene from late pregnancy to postpartum week 3-6.

Measure: Change in DNA methylation of the FK506-binding protein 51 (FKBP5) gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the glucocorticoid receptor gene, total group

Measure: DNA methylation of the glucocorticoid receptor gene

Time: Prior to caesarean section.

Description: Methylation status for the glucocorticoid receptor gene, total group

Measure: DNA methylation of the glucocorticoid receptor gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the glucocorticoid receptor gene from late pregnancy to postpartum week 3-6.

Measure: Change in DNA methylation of the glucocorticoid receptor gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the COMT gene, total group

Measure: DNA methylation of the COMT gene

Time: Prior to caesarean section.

Description: Methylation status for the COMT gene, total group

Measure: DNA methylation of the COMT gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the COMT gene from just before delivery to 3-6 weeks postpartum

Measure: Change in DNA methylation of the COMT gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the MAO-A gene, total group

Measure: DNA methylation of the MAO-A gene

Time: Prior to caesarean section.

Description: Change in methylation status for the MAO-A gene, total group

Measure: Change in DNA methylation of the MAO-A gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the MAO-A gene, total group

Measure: DNA methylation of the MAO-A gene

Time: Week 3-6 postpartum

Description: Methylation status for the oxytocin receptor gene, total group

Measure: DNA methylation of the oxytocin receptor gene

Time: Prior to caesarean section.

Description: Methylation status for the oxytocin receptor gene, total group

Measure: DNA methylation of the oxytocin receptor gene

Time: Week 3-6 postpartum

Description: Change in methylation status for the oxytocin receptor gene, total group

Measure: Change in DNA methylation of the oxytocin receptor gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Methylation status for the oxytocin gene, total group

Measure: DNA methylation of the oxytocin gene

Time: Prior to caesarean section.

Description: Methylation status for the oxytocin gene, total group

Measure: DNA methylation of the oxytocin gene

Time: Week 3-6 postpartum

Description: Change methylation status for the oxytocin gene, total group

Measure: Change in DNA methylation of the oxytocin gene

Time: From baseline (caesarean section to week 3-6 postpartum)

Description: Composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Systemic inflammation peripheral blood hsCRP and immunoactive cytokines

Time: Prior to caesarean section.

Description: Change in composite measure of hsCRP, TNF-α, IL-6, IL-18 and IL-10 levels, total group

Measure: Change in systemic inflammation peripheral blood hsCRP and immunoactive cytokines

Time: From baseline (caesarean section to week 3-6 postpartum

Description: Family History Assessment Module (OS-FHAM). Number of first degree relatives with a history of depressive episodes or bipolar disorder. Total group.

Measure: Self reported family history of mood disorders

Time: Day 3-5 postpartum or before

Description: Barratt Impulsiveness Scale (BIS-11), self-reported. Range: 30-120. Total group.

Measure: Self reported impulsiveness score

Time: Day 3-5 postpartum or before

Description: NEO-PI-R - Revised NEO Personality Inventory, self-reported. Participants may score 20-80 for each of the personality traits: openness, conscientiousness, extraversion, agreeableness, and neuroticism. The higher the score, the more prominent is the personality trait. Total group.

Measure: Self reported Neuroticism score from NEO personality questionnaire

Time: Day 3-5 postpartum or before

Description: Parental bonding instrument (PBI), both parents, self-reported. Total group.

Measure: Self reported parental bonding quality

Time: Day 3-5 postpartum or before

Description: Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Self-reported perceived stress

Time: Day 3-5 postpartum

Description: Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Self-reported perceived stress

Time: Week 3-6 postpartum

Description: Change in Perceived Stress Scale (PSS), range 0-40, a score of 0 indicates no perceived stress. Total group.

Measure: Change in self-reported perceived stress

Time: Change from day 3-5 to week 3-6 postpartum

Description: Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Self-reported anhedonia

Time: Day 3-5 postpartum

Description: Snaith-Hamilton Pleasure Scale (SHAPS), range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Self-reported anhedonia

Time: Week 3-6 postpartum

Description: Change in Snaith-Hamilton Pleasure Scale (SHAPS) score, range 0-14, a score of 0 indicates no self-reported anhedonia. Total group.

Measure: Change in self-reported anhedonia

Time: Change from day 3-5 to week 3-6 postpartum

Description: Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Self-reported rumination

Time: Day 3-5 postpartum

Description: Rumination Response Scale (RRS), range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Self-reported rumination

Time: Week 3-6 postpartum

Description: Change in Rumination Response Scale (RRS) score, range 22-88, a score of 22 indicates no ruminative symptoms. Total group.

Measure: Change in elf-reported rumination

Time: Change from day 3-5 to week 3-6 postpartum

Description: Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Self-reported mood

Time: Day 3-5 postpartum

Description: Profile of Mood States (POMS), range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Self-reported mood

Time: Week 3-6 postpartum

Description: Change in Profile of Mood States (POMS) score, range 0-260, a score of 0 indicates no mood disturbance. Total group.

Measure: Change in self-reported mood

Time: Change from day 3-5 to week 3-6 postpartum

Description: Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Self-reported sleep quality

Time: Day 3-5 postpartum

Description: Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Self-reported sleep quality

Time: Week 3-6 postpartum

Description: Change in Pittsburgh Sleep Quality Index (PSQI), range 0-21, a score of 0 indicates a healthy sleep quality. Total group.

Measure: Change in self-reported sleep quality

Time: Change from day 3-5 to week 3-6 postpartum

Description: Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Self-reported psychiatric symptoms

Time: Day 3-5 postpartum

Description: Brief symptom Inventory-53 item (BSI-53), range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Self-reported psychiatric symptoms

Time: Week 3-6 postpartum

Description: Change in Brief symptom Inventory-53 item (BSI-53) score, range 0-212, increasing score means worsening of symptoms.Total group.

Measure: Change in self-reported psychiatric symptoms

Time: Change from day 3-5 to week 3-6 postpartum

Description: WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Self-reported well-being

Time: Day 3-5 postpartum

Description: WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Self-reported well-being

Time: Week 3-6 postpartum

Description: Change in WHO-5 well-being index, range 0-100, low score means less well-being. Total group.

Measure: Change in self-reported well-being

Time: Change from day 3-5 to week 3-6 postpartum

Description: State Trait Anxiety Inventory (STAI-AD-D), state and trait subscales each have a range of 20-80, 20 means no anxiety. Total group.

Measure: Self-reported anxiety

Time: Day 3-5 postpartum

Description: State Trait Anxiety Inventory (STAI-AD-D), state subscale range 20-80, 20 means no anxiety. Total group.

Measure: Self-reported anxiety

Time: Week 3-6 postpartum

Description: Change in State Trait Anxiety Inventory (STAI-AD-D) score, state subscale range 20-80, 20 means no anxiety. Total group.

Measure: Change in self-reported anxiety

Time: Change from day 3-5 to week 3-6 postpartum

Description: Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Self-reported obsessive and compulsive symptoms

Time: Day 3-5

Description: Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Self-reported obsessive and compulsive symptoms

Time: Week 3-6 postpartum

Description: Change in Obsessive-Compulsive Inventory (OCI) score, self-reported, range 0-72, higher scores indicate more symptoms. Total group.

Measure: Change in self-reported obsessive and compulsive symptoms

Time: Change from day 3-5 to week 3-6 postpartum

Description: Performance on Simple Reaction Time, in imaging cohort.

Measure: Performance on Simple Reaction Time

Time: Week 3-6 postpartum

Description: Gray matter brain volume prefrontal cortex and anterior cingulate cortex

Measure: Gray matter brain volume prefrontal cortex and anterior cingulate cortex

Time: At week 3-6 postpartum

Description: Composite measure of serotonin, tryptophan og tryptofan hydroxylase levels relative to 5-HIAA, in placenta sample. Infants from total group

Measure: Serotonergic turnover in placenta

Time: At delivery.

Description: 11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta. Infants from total group

Measure: 11-beta-hydroxysteroid dehydrogenase type 2 activity in placenta

Time: At delivery

Description: Composite measure of methylation status for the FKBP5, glucocorticoid receptor, 11-beta hydroxysteroid dehydrogenase type 2 genes. Infants from total group

Measure: Methylation status of genes relevant for stress-hormone regulation in placenta

Time: At delivery

Description: Composite measure of the methylation status for monoamine oxidase, serotonin receptor and serotonin transporter genes. Infants from total group

Measure: Methylation status of genes related to serotonergic signaling in placenta

Time: At delivery

Description: Composite measure of methylation status and gene transcript profiles of Glucocorticoid receptor, FKBP5, oxytocin and oxytocin receptors, Brain-derived neurotrophic factor (BDNF) genes. Assessed in blood from umbilical cord blood sample from infants, total group.

Measure: Methylation status and gene transcript profiles of relevance for early brain development and stress regulation in newborn infants

Time: At delivery.

Other Outcomes

Description: val158met (rs4680) status, binary variable, i.e. "val/val, val/met" vs "met/met" variants

Measure: COMT-genotype (rs4680) variant, i.e met/met vs other polymorphisms

Time: Prior to caesarean section.

Description: BDNF val66met (rs6265) status, binary variable, i.e. "val/val" versus "met-carrier" status

Measure: BDNF genotype (rs6265) status, i.e. val/val versus met-carrier variants

Time: Prior to caesarean section.

Description: 5-HTTLPR genotype status (binary), i.e. high-expressing LALA vs low-expressing (S or LG) variants, based on SLC6A4, i.e. L or S variants, and further subtyping on rs25531 haplotype L(A)L(A) vs LGLA, LGLG or variants containing as S as specified above.

Measure: 5-HTT genotype status, i.e LALA vs low-expressing (S or LG) variants

Time: Prior to caesarean section.

Description: In house interview based on Kennerley Maternity Blues Questionnaire, range: 0-28, higher score indicates more severe postpartum blues symptoms. High blues score is associated with greater risk for perinatal depression at week 3-6.

Measure: Postpartum blues symptoms

Time: Day 3-5 postpartum.

Description: In house interview based on Stein's Maternity Blues Scale, range 0-26. High blues score is associated with greater risk for perinatal depression at week 3-6.

Measure: Postpartum blues symptoms

Time: Day 3-5 postpartum.

3 The Impact of Supplementation With Multi-vitamins/Minerals, With and Without Fatty Acids, on Impulsivity and Aggression

There is a series of well designed studies that have reported, in those with a history of anti-social behavior, that supplementation with vitamins / minerals, omega-3 fatty acids (n-3 FA), or both, reduces the incidence of aggressive behavior. Although there is evidence that all these nutrients have a role, to date the relative contribution of fatty acids and vitamins / minerals has not been considered: for example the possibility of a synergistic interaction has not yet been examined. In addition the topic has to date been studied under real-life condition, such as a prison, making the topic difficult to study. The major aim of the present study was to develop a paradigm that would allow the study of the topic in a sample from the general population without a history of anti-social behavior. Subjects received either a vitamin/mineral supplement, a fatty acid supplement, both or neither for three months, Measures of impulsivity and aggression were assessed before and after supplementation. Although in the past measures of actual behaviour have proved to be sensitive to supplementation, questionnaire measures have not. The second major objective was therefore to consider whether such phenomena can be studied in a sample without a history of anti-social behavior, using standardized, sensitive laboratory based measures and to compare these with questionnaire measures. POLYMORPHISMS AND THE RESPONSE TO MICRO-NUTRIENT SUPPLLMENTATION The data set were subsequently used to test an a priori hypothesis not related to the initial hypothesis. A meta-analysis found a consistent pattern that micro-nutrient supplementation improved mood (Long SJ, Benton D. Effects of vitamin and mineral supplementation on stress, mild psychiatric symptoms, and mood in nonclinical samples: a meta-analysis. Psychosom Med 2013; 75: 144-153). To produce evidence of possible mechanisms the extent was determined, to which the impact of micro-nutrient supplementation was influenced by a range of polymorphisms associated with neurotransmitter systems known to modulate mood. The primary outcome measure was the General Health Questionnaire, a 30-item self-report questionnaire that was developed to detect, in a community sample, those who would benefit from seeing a psychiatrist. Given the literature that relates polymorphisms to mood disorders, and the known pharmacology of anti-depressant drugs, a range of polymorphisms were chosen associated with serotonin and catecholamines. Dopamine The SNPs associated with the metabolism and functioning of dopamine were: Dopamine beta hydroxylase (DBH, rs16111115); Dopamine transporter (DAT1, rs2550946); Catechol-O-methyltransferase (COMT, rs4680, rs6269). Dopamine receptor D1 (DRD1, rs4532); Dopamine receptor D2 (DRD2, rs1079598, rs1800497); Dopamine receptor D3 (DRD3, rs6280); Dopamine receptor D4 (DRD4, rs1800955). Serotonin Ten SNPs associated with different aspects of serotonin metabolism were also considered. Rs1843809 is a SNP of the TPH2 gene that encodes Tryptophan hydroxylase. Rs1050565 is a SNP in the BLMH gene that influences the activity of 5HTT (SLC6A4), the serotonin transporter. SNPs associated with various serotonin receptors were also examined: genetic variations of the HTR1A gene (5-HT1A receptor, rs6295); HTR1B gene (5-HT1B receptor, rs6296); HTR2A gene (5-HT2A receptor, rs6311); HTR2B gene (5-HT2B receptor, rs1549339); HTR2C gene (5-hydroxytryptamine receptor 2C, rs518147); HTR3A gene (5-hydroxytryptamine receptor 3A, rs1150226); HTR3B (5-HT3B receptor, rs1672717); HTR4 gene (5-HT4 receptor, rs2278392). Adrenergic mechanisms Finally six SNPs associated with adrenergic receptors were considered: ADRA2A (adrenoceptor alpha 2A, rs553668); ADRB1 (adrenoceptor alpha B1, rs1801253); ADRB2 (adrenoceptor alpha B2, rs1042713; ADRB3 (adrenoceptor alpha B3, rs4994); SLC6AC (noradrenaline transporter, rs5569 and rs2242447). Analysis The data will be analyzed using analysis of variance with a change in GHQ from before to after supplementation as the dependent variable: Micronutrient/placebo X Polymorphism.

NCT01558193 Aggression Dietary Supplement: Placebo Dietary Supplement: Multi-vitamin/mineral Dietary Supplement: Docosahexaenoic acid Dietary Supplement: DHA plus vitamins/minerals
MeSH: Aggression Impulsive Behavior
HPO: Aggressive behavior Impulsivity

Dopamine The SNPs associated with the metabolism and functioning of dopamine were: Dopamine beta hydroxylase (DBH, rs16111115); Dopamine transporter (DAT1, rs2550946); Catechol-O-methyltransferase (COMT, rs4680, rs6269).

Primary Outcomes

Description: The GoStop Impulsivity Paradigm measures the ability to inhibit an already initiated response. A number of five digits are presented on a computer screen for 500ms followed by a 500ms blackout. A second number then appears for 500ms followed by a 500ms blackout. If the numbers are identical the mouse button has to be pressed before the second number disappeared. However, the response has to be with-held if a "Stop" signal appeared; that is the second number was identical but changed from black to red. If the two numbers were different then no response was required.

Measure: Go Stop Impulsivity Paradigm

Time: Change from before to after supplementation for three months

Description: This is test of the tendency to respond in an aggressive manner. A series of cartoons are presented that present an intentionally frustrating situation. The participant reports what he or she would say in that situation. Blind the responses are assessed in terms of the extent to which the responses are aggressive in matter Note that the use of two primary outcomes reflects the aim of the study to contrast performance and questionnaire measures

Measure: Rosenzweig Picture Frustration Test

Time: Change from before to after supplementation for three months

Secondary Outcomes

Description: The Buss-Perry Aggression Questionnaire assesses four aspects of aggressive behavior: physical aggression, verbal aggression, anger and hostility. Participants rank statements about their temperament using a 7-point Likert scale ranging from 1 (extremely uncharacteristic of me) to 7 (extremely characteristic of me).

Measure: Buss Perry Aggression Scale

Time: Change from before to after supplementation for three months

Description: The Perceived Stress Scale assesses the extent to which stressful thoughts and feeling had been experienced during the last month. For example: "In the last month, how often have you been upset because of something that happened unexpectedly?" The participant responded on a scale ranging from 0 = Never to 4 = Very Often. An overall score is calculated.

Measure: Perceived Stress Scale

Time: Change from before to after supplementation for three months

Description: A measure of the subjects ability to forgo initial reward for a later larger reward. The subject can choose to wait for a reward and get more points or alternatively respond more quickly and get fewer points sooner. The longer a subject waits the higher the reward; that the more points are earned. A mouse click began the task and a second resulted in a reward. Two counters display the most recent and cumulative reward over a 20 minute session. Subject are able to infer that responses at a faster rate earn smaller rewards.

Measure: Single Key Impulsivity Paradigm

Time: Change from before to after supplementation for three months

Description: Polymorphisms associated with the metabolism and receptors of dopamine and serotonin will be related to the response to micro-nutrient supplementation

Measure: General Health Questionnaire

Time: Further analysis of existing data - considers changes from baseline to three months

4 A Longitudinal Study on the Trainability of Socio-affective and Cognitive Functions and Abilities.

The purpose of the study is to look at the long term effects of a complex socio-affective mental training program on a neuroscientific-, hormonal-, behavioral-, biological, and subjective measures-level. The training protocol consists of a variety of meditation and other mental health techniques, which are trained over the period of 3-9 months (13 weeks per Module; 1-3 Modules)

NCT01833104 Healthy Subjects Behavioral: Presence - Perspective - Affect Behavioral: Presence - Affect - Perspective. Behavioral: Affect

Polym., RS1 and RS3 oxytocin-receptor gene; rs53576 catechol-O-methyltransferase gene, rs4680 serotonin-transporter 5HTTPLR gene (SCL6A4, S/L Allele and rs25531) monoamine-oxidase A gene (rs6323) mu-opioid-receptor gene (rs6323) neuropeptide Y (NPY); rs5573, rs5574, rs16139, rs16147 tryptophan hydroxylase-2 gene (rs4570625) Gene for a-subunit of L-type calcium channel Cav1.2;

Primary Outcomes

Description: Each structural MRI session has ca. 27-30 min of scan time. Investigation of long-lasting changes in cortical and sub-cortical networks after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in several structural MRI measures (MRI-based cortical thickness, mprage; T1-mapping, mp2rage; automatic amygdala volumetry; tensor-based morphometry, Diffusion Tensor Imaging; Flair)

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: The measure is part of the MRI session and lasts for ca. 15-25 min. Goal is the Investigation of dynamic changes of functional MRI signals during affective and cognitive tasks in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects. All cohorts: after T0 only "Generation" part of paradigm. TC1, TC2 and RCC1: not assessed at T1.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Regulation and Generation of Emotions (RAGE)

Time: TC1, TC2, RCC1: Changes from T0 to T2 (T0 + 26 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months);

Description: The measure is part of the MRI session and lasts for ca. 7 min. Goal is the Investigation of dynamic changes of functional MRI signals during resting state in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Resting State measurement

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: The measure is part of the MRI session and lasts ca. 15 min. Goal is the Investigation of dynamic changes of functional MRI signals during affective tasks in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Emotional Anticipation (EmoAnt)

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: The measure is part of the session and lasts ca. 20 min. Goal is the Investigation of dynamic changes of functional MRI signals during a pain perception task in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Modulation of pain perception

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: The measure is part of the MRI session and lasts 15 min. Goal is the Investigation of dynamic changes of functional MRI signals during an attention and orienting task in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: Cued flanker task (CueFla), an attention and orienting task

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: The measure is part of the MRI session and lasts ca. 35-40 min. Goal is the Investigation of dynamic changes of functional MRI signals during a theory of mind and social cognition task in order to test the correlation of functional and structural network changes after training. How do psychological traits and certain brain structures predict individual differences in training effects.

Measure: Changes in functional magnetic resonance imaging (fMRI) measure: a Theory of Mind and Social Cognition task (the EmpaToM)

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: ] Examination of the diurnal cortisol profile (awakening, day timeline): on two weekdays, subjects collect saliva samples during the day (7 timepoints, each ca. 3 min). This will be coordinated with the experience sampling via the smartphones.

Measure: Changes in stress physiology: "diurnal cortisol profile"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: People sit quietly and no specific task given. We will use "Biopac MP150 Bionomadix" for measurement of autonomic activity (inferred from heart rate variability) by measuring a 3-point ECG in the chest area, as well as electrodermal activity (on the fingertips of the left index and middle finger), and breathing.

Measure: Changes in autonomic nervous system functions: Physiological Resting Baseline (electrocardiogram (ECG), electrodermal activity (EDA), and breathing)

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Part of the Virtual Reality Session (ca. 40 min): In a virtual world, we will look at attention and change detection in an unknown environment with emotional stimuli. It will happen on the same day as the MRI measurements and will be measured by counting the amount of changes of the virtual environment that could be detected. Behavioral measures will be combined with physiological data assessment during the test.

Measure: Changes in a Virtual Reality Setting: The Panopticon --> attention and change detection

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Part of the Virtual Reality Session (ca. 40 min): In a virtual world, we will look at changes in social distance. It will happen on the same day as the MRT measurements and will be measured by detecting the preferred proximity to avatars within the virtual worlds. Behavioral measures will be combined with physiological data assessment during the test.

Measure: Changes in a Virtual Reality Setting: The Crowded Room --> changes in social distance to avatars

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Part of the Virtual Reality Session (ca. 40 min): In a virtual world, we will look at changes in approach and avoidance behavior in terms of affective preferences of available affective stimuli. It will happen on the same day as the MRT measurements and will be measured by detecting the amount of exploratory behavior (approaching, examining objects with neutral or emotional content). Behavioral measures will be combined with physiological data assessment during the test.

Measure: Changes in a Virtual Reality Setting: The Affect Gallery --> changes in affective preferences

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Part of the Virtual Reality Session (ca. 40 min): In a virtual world, we will look at changes in acute stress reactions to aversive affective stimuli (e.g., ground shaking, bugs, sudden loud noise, angry avatars). It will happen on the same day as the MRT measurements. Behavioral measures will be combined with physiological data assessment during the test.

Measure: Changes in a Virtual Reality Setting: Room 101 --> acute stress reactions

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: In this task, two stimuli are presented consecutively (e.g., a pattern with horizontal lines). The two stimuli differ slightly and the participants are asked to identify the differences (e.g., length or direction of the lines). The difference between the two stimuli gradually decreases with each round. The point, at which the participants cannot distinguish between the two stimuli is called the perceptional sensitivity. After each round, the participants are asked to assess their level of certainty regarding their answers. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the Inhibition and Alerting task (Stop-Signal-Reaction Time task).

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: The participants are presented with 4, 6 or 8 letters, which they have to remember over a short period of time (about 2 seconds). Then they are presented with another letter and are asked to state whether or not that letter was part of the set of letters presented beforehand. After each round, the participants are asked to assess their level of certainty regarding their answers. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in Working Memory Performance

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: The cognitive and affective flexibility is measured in this task. Participants are asked to complete comparable cognitive and affective task-switching tasks respectively. We use a task-cueing paradigm in which participants have to judge different stimuli. These stimuli are cognitive or affective in nature. The dependent variable is reaction time and accuracy in so-called "shift" or "no-shift" rounds, i.e. rounds which either have the same task as the round before ("no-shift") or rounds, which consist of a new task ("shift"). All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the Task Emotional Switching Paradigm

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Participants are asked to judge the similarity of a number of adjectives which describe emotional states. Using network analysis and multi-dimensional scaling, the data regarding the proximity of the adjectives are transformed in a depiction of the emotional-concept networks of the participant. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the Emotional Granularity task

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Participants watch a number of short clips (max. 15 sec) of news programs or documentaries. These clips have either neutral or have emotional (negative) content. After watching a clip participants report on their emotional state and on how much compassion they feel. Additionally, we will use physiological data assessment of the following parameters during the task: respiration frequency (belt in the chest / abdominal area) heart rate (3-point ECG in the chest area) EDA

Measure: Changes in autonomic nervous system functions and computer experiment: Changes in the Socio-affective Video Task (SoVT)

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: In this computer-based task, participants see a person standing in a room, in which oval-shaped objects can be seen on the walls. The participants are asked to report on how many of these objects can be seen from their own perspective and how many objects the person in the room is able to see. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Visual Spatial Perspective Taking Task" by Samson

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: In this task, a number of visual stimuli are presented consecutively for short periods of time (about 100ms). The relevant stimuli are embedded in a number of distractor-stimuli. The participants are asked to report on the number of perceived relevant stimuli. They are also supposed to identify them. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Emotional Attentional Blink" paradigm

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: In this computer-based game, participants have to find their way through a labyrinth and solve little tasks on their way. They are under the impression, that there is another participant playing with them. The participant's readiness to share resources, necessary to complete the game, is measured. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Trust Game"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: There are two parts to this game: 2nd person punishing and 3rd person punishing. In the 2nd person punishing game, there are two players. One Player (player A) has a larger amount of money at her disposal, than the other player (player B). The player with the larger amount of money can decide how she wants to split the money between herself and the other player. Then player B can decide whether he wants to punish player A by taking money from player A while using his own money (for each unit of money she spends three three units are taken from the other player). After two rounds, the tasks of the players are reversed. In the 3rd person punishing game, the participants watch the interaction of anonymous players A and B. After each round, the participant can decide whether or not to punish the player, who split the money. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Punishing Game"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: In this game, participants can decide how they split a set amount of money between themselves and an anonymous player. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Dictator Game"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: In a first step, participants are asked to cluster 30 positive or negative personality traits around their depicted self in such a way, that the spatial closeness or distance reflects, how much they identify with the trait. In a second step, they are asked to choose selected items and pile them. The height of the stack then is thought to reflect the complexity of the self. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Self-complexity Task"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: In the first part of this task, participants are asked to judge adjectives regarding a) whether they apply to themselves, b) whether they apply to a famous person (e.g., Angela Merkel), or c) whether they meet linguistic criteria (e.g., whether they are written in capital letters). In the second part, participants are asked to identify the adjectives, which had been presented in the first part. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: "Self-reference Task"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Aim of this measure is to access the amount and content of spontaneously generated cognition. Main focus is "day dreaming" or "mind wandering" that occurs, when our minds drift off, while working on a task. In this measure, subjects are asked to work on two little, rather boring PC-based exercises (1. choice reaction time task (CRT); 2. working memory (WM) task). During selective queries, they are then asked for the content and valence of their thoughts ("thought probe"). All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in the "Mind-wandering task"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: This economic game assesses the participant's willingness to donate to selected charity groups. In this game, they receive a certain amount of money and can decide, if and how much they would like to contribute. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: Changes in "Donation Task"; willingness to make donations in the economic computer experiment.

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Participants divide money between themselves and close friends, strangers, or enemies. All computer tasks are divided into 6 blocks and participants completed one block per week (1 hour each).

Measure: Computer-based experiment: "Social Discounting" Task

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Subjects are asked to silently count their heart beats in five intervals [15, 25, 35, 45, 55], presented in a random order, and note the counted number.

Measure: Changes in interoception: Heart Beat Perception Task

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Local Power (LP), as short term estimate of high frequency heart rate variability is reported to the subjects. They observe a ball on a computer screen, which ascends in accordance with their LP. Goal is to make the ball rise. We will use the "Biopac MP150 Bionomadix" for measurement of respiration frequency (belt in the chest / abdominal area) as well as ECG and electrodermal activity.

Measure: Changes in autonomic nervous system functions: Local Power Biofeedback and Heart Rate Biofeedback

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: TSST: a standardized stress test, that induces stress in the laboratory. Here, cortisol and alpha-amylase are analyzed from saliva (Department of Biological and Clinical Psychology, Trier University), oxytocin (Max-Planck-Institute for Psychiatry, Munich) as well as the inflammatory markers Interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and C-reactive protein (CRP) are analysed from blood (Aghia Sophia Children's Hospital, Department of Clinical Biochemistry) and heart rate and heart rate variability (HRV) are assessed as adjunct measurement. Stress-related questionnaires will be filled out during the TSST as well.

Measure: Stress Physiology: "Trier Social Stress Test" (TSST)

Time: Because it includes elements of deception, the TSST is only done once: Participants will either do the TSST at T0, T1, or T2

Description: Heart rate, body movement,respiratory frequency and heart rate variability are being measured during two meditation sessions in each training block (week 3 and 13). We use the non-invasive "Zephyr BioHarness 3 multi-sensor-device", which comes with a chest belt. After the meditation session, subjects are asked to answer a 5-item questionnaire.

Measure: Changes in autonomic nervous system functions: "Physiological Signature of Meditation states"

Time: Only in TC1, TC2, TC3: Changes from T1, to T2, to T3; week 3 and 13 of each module.

Description: During each measurement time point, blood samples will be collected from each subject and stored at -80 degrees Celsius. The aim is to test if the training leads to reduced shortening of the telomeres, the probes are sent to the Blackburn lab of UCLA in San Francisco, USA. Additionally, a complete blood count is drawn. Not aiming in diagnostic directions, the goal is to assess the status of neutrophils, lymphocytes, and monocytes in the probes. These are thought to be general markers of immune activity and are inspected in relation to telomere length. Blood counts will be assessed by a lab in Leipzig, Germany.

Measure: Changes telomere length (+ number of neutrophils, lymphocytes, and monocytes)

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Once during the training for each subject, before and directly after a 2h "Perspective" or "Affect" training session, a blood sample will be drawn and stored at -80 degrees celsius. To analyze blood levels of oxytocin, probes are sent to the Max-Planck-Institut für Psychiatrie, Munich, Germany (Department of Prof. Rainer Landgraf). The same procedure was done pre and post the TSST session.

Measure: Training induced short-term changes in oxytocin blood level (pre/post Meditation)

Time: Changes pre/post a "Perspective" or "Affect" training session during T1, T2, or T3; Week 12 of Training (i.e. for arm one: between 11/21/13 - 12/23/13 or 3/3/14 - 4/5/14; for arm two: between 1/20/14 - 2/20/14 or 5/2/14 - 5/24/14). Pre/Post TSST

Description: 10 ml blood samples will be drawn. Plasma levels of interleukin-6, brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP) will be assessed. They are sent to the "First Dept of Pediatrics, Director, Division of Endocrinology, Metabolism and Diabetes, University of Athens Medical School, Aghia Sophia Children's Hospital, Athens, Greece" for analysis.

Measure: Changes in amount of plasma levels (blood samples) of interleukin-6, brain-derived neurotrophic factor, C-reactive protein.

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months); Pre/Post TSST

Description: All cohorts: • weekly questions via online platform, concerning: actual affective condition, actual activity, actual thoughts, social closeness, quality of sleep (administered once a week via short questions online, duration 2-4 min.). TC1, TC2, TC3: • questions via online platform before and after all core training exercise participants perform at home; duration is ca. 2-4 min, concerning: actual effects and experiences after daily mental training practice. All cohorts: • experience- sampling via smartphones, concerning: valance and arousal of current emotional state using "single item affect grid" method. Current activity and situation. Current thoughts. Amount of significant or stressful events since last sampling and how positive or negative or stressful was this event. How did you cope with this event. (7-10 times for 2 consecutive days for each cohort at T0-T4).

Measure: Changes in "subjective experience sampling by smartphones or by means of an internet platform"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Secondary Outcomes

Description: above: w=weeks, m=months. Administration of the questionnaire via an online platform. It assesses effortful control, extraversion, frustration, inhibitory control, negative affect, sadness, sociability, etc. TC1 and TC2 participants will not fill out the questionnaire at time point T2.

Measure: Questionnaire: Changes in "Adult temperament questionnaire (ATQ)"

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m).

Description: Administration of the German questionnaire via an online platform. It assesses symptoms of attentional deficits, attention deficit hyperactivity disorder (ADHD), hyperactivity.

Measure: Questionnaire: Change in "ADHS-Selbstbeurteilungsfragebogen (ADHS-SB)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses non-judgmental acceptance of experience, awareness of experience, and mindfulness.

Measure: Questionnaire: Change in "FFA Freiburger Fragebogen zur Achtsamkeit".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses awareness, describing, non-judging of experiences, non-reactivity, observing, mindfulness. This questionnaire is also filled out by the observers of participants.

Measure: Questionnaire: Change in questionnaire "Five Facets Mindfulness Questionnaire (FFMQ)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses different facets of interoceptive awareness.

Measure: Questionnaire: Change in "Multidimensional Assessment of Interoceptive Awareness (MAIA)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses self-compassion, self-kindness, self-judgment, over-identification, mindfulness, isolation, and common humanity.

Measure: Questionnaire: Change in "Self-Compassion Scale" by Kristin Neff (SCS).

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses serenity, i.e. low arousal positive affect. TC1 and TC2 participants will not fill out the questionnaire at time point T2 and T3.

Measure: Questionnaire: Change in "The Short Affect intensity scale (only serenity subscale) (SAIS)".

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m). w=weeks; m=months

Description: Administration of the questionnaire via an online platform. It assesses compassion for others, common humanity, disengagement, indifference towards others, kindness towards others, mindfulness, separation.

Measure: Questionnaire: Change in "Compassion scale - How I typically act towards others (COSN)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses empathic concern, empathic distress and ability to take other's perspective. This questionnaire is also filled out by observers of the participants.

Measure: Questionnaire Participants and Observer: Change in "Interpersonal Reactivity Index (IRI)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses active, reactive and safe/warm positive affect.

Measure: Questionnaire: Change in "Types of Positive Affect (TTPAS)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses fear of compassion from others or for self.

Measure: Questionnaire: Change in "Fears of Compassion Scales (FOCS)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: above: w=weeks, m=months Administration of the questionnaire via an online platform. It assesses impulsivity, affective instability, relationships, abandonment, quasi-psychotic states, self image, emptiness, anger, suicide, borderline personality traits. TC1 and TC2 participants will not fill out the questionnaire at time point T2.

Measure: Questionnaire: Change in "Borderline Personality Questionnaire (BPQ)".

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m).

Description: above: w=weeks, m=months Administration of the questionnaire via an online platform. It assesses narcissism, exhibitionism, entitlement, authority, superiority, exploitativeness, self-sufficiency, vanity. TC1 and TC2 participants will not fill out the questionnaire at time point T2.

Measure: Questionnaire: Change in "Narcissistic Personality Inventory (NPI)".

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m).

Description: Administration of the questionnaire via an online platform. It assesses regulation via catastrophizing, positive refocusing, or blaming others strategy (self-blame, acceptance, rumination, positive refocus, planning refocus, planning refocus, positive reappraisal, perspective, catastrophizing, other blame)

Measure: Questionnaire: Change in "Cognitive Emotion Regulation Questionnaire (CERQ)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: above: w=weeks, m=months, T2 (T1+ 13 weeks), T3 (T2 + 13 weeks) Administration of the questionnaire via an online platform. It assesses several coping strategies. TC1 and TC2 participants will fill out a shorter version at time point T2 and T3. This questionnaires is also filled out by observers of participants.

Measure: Questionnaire Participants and Observers: Change in "Brief COPE" inventory.

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w) and at T4 (T3 + 4.5 or 10 m). Short version at T2 and T3; RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2, to T3, to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 o

Description: Administration of the questionnaire via an online platform. It assesses expressivity of negative and positive emotions, and strength of expression impulse. TC1 and TC2 participants will not fill out the questionnaire at time point T2 and T3.

Measure: Questionnaire: Change in "Berkeley Expressivity Questionnaire (BEQ)".

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m). w=weeks; m=months

Description: Administration of the questionnaire via an online platform. It assesses range of experience emotions, and differentiation of experienced emotions.

Measure: Questionnaire: Change in "Range and Differentiation of Emotion Scale (RDEES)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses tendency to choose decisions that maximize other's output.

Measure: Questionnaire: Change in "An Instrument to Measure Social Value Orientation (SVO) " by van Lange et al.

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses internally focussed emotion regulation of positive and negative affect. TC1 and TC2 participants will not fill out the questionnaire at time point T2 and T3.

Measure: Questionnaire: Change in "Emotion Regulation of Others and Self (EROS)".

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m). w=weeks; m=months

Description: Administration of the questionnaire via an online platform. It assesses compassionate and self-image goals.

Measure: Questionnaire: Change in "Friendship, Compassionate and Self-Image Goals Scale".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses the degree to which people's self-concepts center on moral traits.

Measure: Questionnaire: Change in "Self Importance of Moral Identity Scale".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses global awareness and understanding of others and attempts and endeavours to understand the perspective ot others.

Measure: Questionnaire: Change in "Self Dyadic Perspective-Taking Scale and Other Dyadic Perspective Taking Scale (SDPT /ODPT )".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses the tendency to perceive oneself as interdependent with others or as an independent person.

Measure: Questionnaire: Change in "Self Construal Scale".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses the tendency to behave in a prosocial way (help and support others). This questionnaire is also filled out by observers of participants.

Measure: Questionnaire Participants and Observers: Change in "Prosocialness Scale" by Capara.

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses self reported self attitudes using an open-ended response format beginning with: "Who am I...".

Measure: Questionnaire: Change in "Twenty Statement Test (TST)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses tendency to value own advantage over moral principles.

Measure: Questionnaire: Change in "The Machiavellianism Scale".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses personality traits such as neuroticism, extraversion, openness, agreeableness, conscientiousness, aesthetic interests, negative affect, sociability, etc.

Measure: Questionnaire: Change in "NEO Fünf Faktoren Inventar (NEO FFI)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses rumination, magnification and helplessness regarding pain.

Measure: Questionnaire: Change in "Pain Catastrophizing Questionnaire (PCS)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses uncertainty intolerance, paralysis by uncertainty, negative affect by uncertainty and increased vigilance by uncertainty.

Measure: Questionnaire: Change in "Unsicherheitstoleranz-Skala (Uncertainty Intolerance, UI-18)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses work dissatisfaction, excessive demands at work, lack of social recognition, social isolation, chronic concern, chronic stress, and social tensions etc.

Measure: Questionnaire: Change in "Trier Inventory for Chronic Stress (TICS)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses the degree to which situations in one's life are appraised as stressful.

Measure: Questionnaire: Change in "Perceived Stress Scale (PSS-10)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses paternal and maternal care and overprotection.

Measure: Questionnaire: Change in "Parental Bonding Inventory (PBI)".

Time: TC1, TC2, RCC1, RCC2, TC3: T0 only

Description: Administration of the German questionnaire via an online platform. It assesses general well-being, tiredness, emotional reactivity, sensory problems, gastrointestinal problems, nose/throat irritation, tension, pain, and cardiovascular problems.

Measure: Questionnaire: Change in "Freiburger Beschwerdeliste (FBL)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses sleep habits and sleep quality.

Measure: Questionnaire: Change in "Pittsburgh Sleep Inventory (PSQI)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses hope for success and control, fear of rejection and failure or losing control, and hope for affiliation.

Measure: Questionnaire: Change in "Multi Motive Grid (MMG)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses overall psychological well-being, emotional and social well-being, etc.

Measure: Questionnaire: Change in "Mental Health Continuum short form (MHC-SF)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses satisfaction with one's life. This questionnaire is also filled out by observers of participants.

Measure: Questionnaire Participants and Observers: Change in "Satisfaction with Life Scale (SWLS)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses severity of depression, affective and somatic symptoms of depression.

Measure: Questionnaire: Change in "Becks Depression Inventory (BDI-2)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses ego-resiliency.

Measure: Questionnaire: Change in "Ego Resiliency Scale (ER-89)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses anxiety and avoidance. TC1 and TC2 will not fill out this questionnaire at time point T2 and T3.

Measure: Questionnaire: Change in "Experiences in Close Relationships - revised (ECR-RD)".

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m). w=weeks; m=months

Description: Administration of the questionnaire via an online platform. It assesses lonliness.

Measure: Questionnaire: Change in "UCLA Lonliness Scale".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses positive and negative affect in the last weeks.

Measure: Questionnaire: Change in "Positive Affect Negative Affect Schedule (PANAS)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses positive and negative emotions. This questionnaire was assessed on a weekly basis.

Measure: Questionnaire: Change in "modified Differential Emotions Scale (mDES)".

Time: Weekly; TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses difficulties in identifying and describing emotions, as well as an externally oriented thinking style.

Measure: Questionnaire: Change in "Toronto Alexithymia Scale (TAS-20)"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of a paper & pencil version of the POMS mood scale, for each subject on that day, when they do the TSST stress test. It assesses mood states.

Measure: Questionnaire: Change in "Profile of Mood States - 2nd Edition (POMS-2)".

Time: Only once per participant during the TSST

Description: Administration of a paper & pencil version, for each subject on that day, when they do the TSST stress test. It assesses state anxiety.

Measure: Questionnaire: Change in "STAI -X1 State, State Trait Anxiety Inventory".

Time: Only once per participant during the TSST

Description: Administration of a paper & pencil version of a measure for the visualisation of body sensations following Fox et al. (2012). The measure will be administered at the start and the end of the first training block, the "presence block". The start of the presence block for arm one will be: Aug. 19th 2013 till Sept. 19th 2013. The start of the presence block for arm two will be: Okt. 7th 2013 till Okt. 30th 2013.

Measure: Questionnaire: Change in "Subjective Sensory Sensitivity questionnaire" following Fox et al. (2012)".

Time: Changes during the Presence Module (beginning and end of Module).

Description: above: w=weeks, m=months; Administration of the questionnaire via an online platform. It assesses the noticing of body sensations. TC1 and TC2 will not fill out this questionnaire at time point T2

Measure: Questionnaire: Change in "Private Body Consciousness subscale of the Body Consciousness Questionnaire (PBCS)".

Time: TC1, TC2: Changes from T0 to T1 (T0 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). RCC1, RCC2: from T0 to T1 (T0 + 13 w), to T2 (T1 + 13 w), to T3 (T2 + 13 w), to T4 (T3 + 4.5 or 10 m). TC3: from T0 to T1 (T0 + 13 w), to T2 (T1 + 4.5 or 10 m).

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses responsiveness to partner's disclosure of positive events.

Measure: Questionnaire - Observer only: Change in "Perceived Responsiveness Scale (12 items)" filled out by observers.

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months)

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses positive reactions of partner by several subscales.

Measure: Questionnaire - Observer only: Change in "Capitalization" by Gable et al., 2004 filled out by observers

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months)

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses degrees to which respondent agrees with partner, do activities together, or satisfaction with partner.

Measure: Questionnaire - Observer only: Change in "Dyadic Adjustment Scale (DAS)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months)

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses personality traits such as emotional stability, openness, conscientiousness, agreeableness, extraversion. This questionnaire has also been used for matching the cohorts into their respective groups.

Measure: Questionnaire - Observer: Change in "Ten Item Personality Scale (TIPI-10)"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months)

Description: Administration of questionnaire via online platform. The scale is answered by observers of participants only. It assesses the feelings of closeness to others

Measure: Questionnaire - Observer only: Change in "Inclusion of Other in the Self Scale (IOS)"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months)

Description: During each measurement time point, the subjects are asked for small hair samples from the back of their head. It will be sent to a cooperating lab in Dresden to assess long-term stress by analyzing the the amount of cortisol in hair samples.

Measure: Stress physiology: Changes in "Long-term cortisol levels from hair samples"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Analyze the connection between gene variants, personality traits, training effects, behavior, brain activation. Arginine-vasopressin-receptor gene; microsat. Polym., RS1 and RS3 oxytocin-receptor gene; rs53576 catechol-O-methyltransferase gene, rs4680 serotonin-transporter 5HTTPLR gene (SCL6A4, S/L Allele and rs25531) monoamine-oxidase A gene (rs6323) mu-opioid-receptor gene (rs6323) neuropeptide Y (NPY); rs5573, rs5574, rs16139, rs16147 tryptophan hydroxylase-2 gene (rs4570625) Gene for a-subunit of L-type calcium channel Cav1.2; CACNA1C gene (rs1006737) Gene for a-subunit of nico. acetylch. receptor channel, CHRNA4 gene (rs1044396) Deletion mutation of a-2-beta adrenoreceptor gene Cannabinoid-receptor 1 gene (CNR1); rs6454674, rs806380, rs806377, rs1049353 Dopamine D4 Receptor gene (DRD4); rs1800955, VNTR Exon 3 repeat allele Dicarboxylate/amino acid cation sodium transporter (DAT1); rs27072, VNTR repeat allele

Measure: Assessment of gene variants / polymorphisms

Time: Blood samples are taken once during T0

Description: Administration of the questionnaire via an online platform. It assesses affiliation tendency and rejection sensitivity.

Measure: Questionnaire: Change in "Affiliation Tendency and Rejection Sensitivity Scales"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses self-reported fidgeting and mind-wandering behavior.

Measure: Questionnaire: Change in "Spontaneous Activity Questionnaire (SAQ)"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses self-reported deliberate and spontaneous mind wandering behavior.

Measure: Questionnaire: Change in "Spontaneous and Deliberate Mind Wandering Scales (MDD, MDS)"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses subscales of personality traits such as warmth, gregariousness, assertiveness, activity, seeking excitement, positive emotions, and extraversion.

Measure: Questionnaire: Change in "Subscales from the NEO Persönlichkeitsinventar nach Costa and McCrae - revised version (NEO-PI-R)"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses the tendency to respond in a socially desirable way.

Measure: Questionnaire: Change in "Soziale Erwünschtheits-Skala-17 (SES-17)"

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Description: Administration of the questionnaire via an online platform. It assesses trait anxiety. It was used of screening possible participants for the study.

Measure: Questionnaire: Change in "State-Trait Anxiety Inventory (STAI-X2; STAI-Trait)".

Time: TC1, TC2, RCC1, RCC2: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 13 weeks), to T3 (T2 + 13 weeks), to T4 (T3 + 4.5 months or 10 months). TC3: Changes from T0 to T1 (T0 + 13 weeks), to T2 (T1 + 4.5 months or 10 months)

Other Outcomes

Description: German Paper/Pencil questionnaire that assesses psychopathological occurences in family members.

Measure: Questionnaire: "Psychopathologie der Familie / Psychopathology in family members".

Time: Only once per participants at time point T0

Description: The d2 Test is a timed test of selective attention/concentration. In response to the discrimination of similar visual stimuli, the test measures processing speed, rule compliance, and quality of performance, allowing estimation of individual attention and concentration performance. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching: Score of "Test d2 - Revision (d2R)" attention task.

Time: 2 months before T0 and during initial proband screening phase of the project, each subject takes the d2 test in paper & pencil version..

Description: The TIPI is designed to assess the constellation of traits defined by the Five Factor Theory of Personality. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching: Score of "Ten Item Personality Inventory (TIPI-10)" personality test.

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: Administration of the questionnaire via an online platform. It assesses overall psychological well-being, emotional and social well-being, etc. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching: Score of "Mental Health Continuum short form (MHC-SF)".

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: Administration of the questionnaire via an online platform. It assesses compassion for others, common humanity, disengagement, indifference towards others, kindness towards others, mindfulness, separation. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching: Score of "Compassion scale - How I typically act towards others (COSN)".

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: Administration of the questionnaire via an online platform. It assesses the degree to which situations in one's life are appraised as stressful. It was used of matching participants into cohorts. This questionnaire is also filled out by observers of participants.

Measure: Questionnaire - Matching/Observers: Score of "Perceived Stress Scale (PSS-10)".

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: Administration of the questionnaire via an online platform. It assesses awareness, describing, non-judging of experiences, non-reactivity, observing, mindfulness. This questionnaire is also filled out by the observers of participants. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching/Observer: Score of "Five Facets of Mindfulness Questionnaire (FFMQ)".

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: German Paper/Pencil Questionnaire that assesses Non-verbal Intelligence.

Measure: Questionnaire: Score of "Grundlagenintelligenztest Skala 2- Revision without WS/ZF-R" (Intelligence Test)

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: On a voluntary basis and with written consent, conducted qualitative interviews with some of the participants, where they are able to describe the subjective experience of the whole training. The interviews will be video-taped with the consent of the participants. We will be using depth-interview techniques that assess not only what the subjects experience but also how they process it. Interviews will be done by a interview specialist with a degree in Psychology and Philosophy. The data will be treated in accordance with data protection laws. In further publications, all statements of the subjects will be anonymized, the tapes will be erased after transcription. In case they agreed to be video-taped, the material will potentially be used for a video documentation of the whole ReSource Project.

Measure: Qualitative Elicitation Interviews and Interviews about subjective Experience during the study (1-2 hours)

Time: only TC1, TC2, or TC3: Voluntarily, possible during each Training Module

Description: Administration of the questionnaire via an online platform. It assesses self-compassion, self-kindness, self-judgment, over-identification, mindfulness, isolation, and common humanity. It was used of matching participants into cohorts.

Measure: Questionnaire - Matching: Score in "Self-Compassion Scale" by Kristin Neff (SCS).

Time: 2 months before T0 and during initial proband screening phase of the project, each subject fills out this questionnaire at the online recruiting webpage via secure connection.

Description: Administration of the questionnaire via an online platform. It assesses mild to severe depression. It was used of screening possible participants for the study

Measure: Questionnaire - Screening/Matching: "Major Depression Inventory (ICD-10, MDI)"

Time: Screening procedure of each participant before matching into cohorts

Description: Administration of the questionnaire via an online platform. It assesses difficulties in describing emotions, tendency to focus attention externally, alexithymia, identification of emotions. It was used of screening possible participants for the study.

Measure: Questionnaire - Screening/Matching: "Toronto Alexithymia Scale (TAS-20)".

Time: Screening procedure of each participant before matching into cohorts

Description: Administration of the questionnaire via an online platform. It assesses trait anxiety. It was used of screening possible participants for the study.

Measure: Questionnaire - Screening/Matching: "State-Trait Anxiety Inventory (STAI-X2; STAI-Trait)"

Time: Screening procedure of each participant before matching into cohorts

Description: Administration of the questionnaire via an online platform. It assesses psychological health and drug abuse. It was used of screening possible participants for the study.

Measure: Questionnaire- Screening: "Patient Health Questionnaire - D (PHQ-D)

Time: Screening procedure of each participant before matching into cohorts

Description: Interview with possible participants. It assesses psychological disorders. It was used of screening possible participants for the study.

Measure: Screening - Interview: DIA-X for Axis II psychiatric disorders of DSM-IV and clinical interviews for personality disorders (SCID-II)

Time: Screening procedure of each participant before matching into cohorts

Description: Interview with possible participants. It assesses psychological disorders. It was used of screening possible participants for the study.

Measure: Screening - Interview: DIA-X for Axis I psychiatric disorders of DSM-IV

Time: Screening procedure of each participant before matching into cohorts

5 Dexamethasone for the Treatment of Established Postoperative Nausea and Vomiting - a Randomised, Placebo-controlled, Dose-finding Study

Postoperative nausea and vomiting (PONV) are frequent after surgery and anaesthesia. Dexamethasone is widely used as antiemetic for the prevention of PONV. Little is known about the efficacy of antiemetic drugs for the treatment of established PONV symptoms. No single randomised trial has been published so far that tests the efficacy of dexamethasone for the treatment of established PONV symptoms. In this trial the investigators want to test the antiemetic efficacy of three different doses of intravenous dexamethasone for the treatment of established PONV symptoms. In adjunct protocols of this study the investigators aim to establish a novel method to quantify the anti-nausea efficacy of an antiemetic drug, to study pharmacogenetics of PONV, and to further our understanding on the smoking status as a predictive factor of PONV.

NCT01975727 Postoperative Nausea and Vomiting Vomiting Drug: Placebo Drug: Dexamethasone 3 mg Drug: Dexamethasone 6 mg Drug: Dexamethasone 12 mg
MeSH: Nausea Vomiting Postoperative Nausea and Vomiting
HPO: Nausea Vomiting

The SNP rs4680 (c.472G > A) is a missense mutation leading to a four-fold reduction of the COMT enzyme.

The COMT Val158Met polymorphism (rs4680) will be genotyped using a commercially available TaqMan® SNP genotyping assay (C_25746809_50, Applied Biosystems, Warrington, UK).

Primary Outcomes

Description: Complete absence of any nausea and/or vomiting (including retching) in a previously nauseated or vomiting patient within 24 hours after administration of the study treatment.

Measure: Treatment efficacy of Dexamethasone for established PONV

Time: 24 hour follow up

Secondary Outcomes

Description: Free from PONV during the first 6 hours

Measure: Short term efficacity

Time: 6 hours

Description: Number of patients staying PONV free after rescue antiemetic during the first 24 postoperative hours

Measure: PONV free after rescue antiemtic

Time: 24 hour follow up

Description: quality of sleep during the first postoperative night (numerical rating scale ranging from 0 = no sleep at all to 10 = excellent sleep)

Measure: Quality of sleep

Time: 24 hour follow up

Description: any minor or major adverse effects during 24h.

Measure: Minor or major adverse effects

Time: 24 hour follow up

6 Efficacy of Transcranial Direct Current Stimulation for Severe Refractory Primary Dysmenorrhea: Translational and Genetic Neuroimaging Studies

Primary Dysmenorrhea (PDM), defined as menstrual pain without discernable organic causes, is inexorably common in adolescent women, about 40-90% of women may suffer from it, and 20% of them can be severe in the context of being refractory to medication, daily function impairment, and having pain of severe degree. Novel therapeutic method is in need for pain alleviation for this particular phenotype. We have previously reported that PDM females may engage motor-cortex based descending pain modulation system in our resting-state functional Magnetic Resonance Imaging (rs-fMRI) and thermal pain-activation fMRI studies. Based on the reported analgesic efficacy of transcranial Direct Current Stimulation (tDCS) on the motor cortex for various experimental painful conditions and clinical pain disorders, we reason that tDCS can be effective for the severe and medication-refractory PDM patients. This study aim to investigate the analgesic efficacy of tDCS in severe PDMs and to elucidate the dynamic brain neuroplasticity in the context of functional connectivity (FC) of pain matrix after tDCS intervention. We will recruit 30 severe PDMs and randomly allocate them to either real or sham group in a triple-blind manner. rs-fMRI for functional connectivity analysis will be performed before and after the tDCS intervention. The imaging data will be correlated with behavioral and psychological measurements. This is the first study in the literature investigating the tDCS efficacy for severe PDM. The result can promise a new possibility for clinical application.

NCT03594916 Primary Dysmenorrhea Device: Active tDCS Device: Sham tDCS
MeSH: Dysmenorrhea
HPO: Dysmenorrhea

To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen.

Primary Outcomes

Description: pain scale; from 0 to 10; score 0: no pain, score 10: unbearable pain

Measure: Visual Analog Scale (VAS)

Time: change from baseline (1st menstrual phase, before tDCS) at one month (2nd menstrual phase, with tDCS), change from baseline (1st menstrual phase, before tDCS) at two months (3rd menstrual phase)

Description: Resting-state functional magnetic resonance imaging (rs-fMRI) is a well established method of functional magnetic resonance imaging (fMRI) that is used to evaluate regional interactions in the brain that occur in a resting (task-negative) state, when a subject is not performing an explicit task. Functional connectivity is the connectivity between brain regions that share functional properties, it can be defined as the correlation between spatially remote neurophysiological events, expressed as the neural networks of brain.

Measure: Functional connectivity of rs-fMRI Imaging

Time: change from baseline (before tDCS, before 2nd menstrual phase) at one week (after tDCS completion), change from baseline (before tDCS, before 2nd menstrual phase) at four weeks (before the 3rd menstrual phase)

Secondary Outcomes

Description: To assess the threshold of thermal sensation (cold, cold-pain, heat, heat-pain; from 0 to 50 centigrade temperature), according to the established protocol of an ascending limit approach for heat pain and a descending limit approach for cold pain.

Measure: Quantitative sensory testing (QST)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 20 to 80; score 20: not anxious, score 80: extremely anxious

Measure: Spielberger State-Trait Anxiety Inventory (STAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 0 to 63; score 0: not anxious, score 63: extremely anxious

Measure: Beck Anxiety Inventory (BAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess depressive symptoms; from 0 to 63; score 0: not depressed, score 63: extremely depressed

Measure: Beck Depression Inventory (BDI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain-maladaptive psychological status; from 0 to 52; score 0: not pain Catastrophizing , score 52: extremely pain Catastrophizing

Measure: Pain Catastrophizing Scale (PCS)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain status; from 0 to 78; score 0: not painful, score 78: extremely painful

Measure: Long-form McGill Pain Questionnaire (MPQ)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess quality of life; he SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. From 0 to 100; score 0: equivalent to maximum disability, score 100: no disability.

Measure: Short-Form Health Survey (SF-36)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess testosterone, progesterone, estrogen

Measure: Blood Hormones Measurement

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase)

Description: To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen

Measure: Genotyping

Time: baseline

Description: To assure blinding efficacy; Patients do self-assessment about whether they receive real tDCS or sham tDCS. Assessment questionnaire:1 or 0. 1: real tDCS; 0: sham tDCS.

Measure: Efficacy of tDCS blinding

Time: At 1 months after tDCS intervention

7 Neuromodulation Effect of Transcranial Direct Current Stimulation in Severe Refractory Primary Dysmenorrhea: BDNF and MEG Study

Primary Dysmenorrhea (PDM), defined as menstrual pain without discernable organic causes, is inexorably common in adolescent women, about 40-90% of women may suffer from it, and 20% of them can be severe in the context of being refractory to medication, daily function impairment, and having pain of severe degree. Novel therapeutic method is in need for pain alleviation for this particular phenotype. It has been reported that PDM females may engage motor-cortex based descending pain modulation system in our resting-state functional Magnetic Resonance Imaging (rs-fMRI) and thermal pain-activation fMRI studies. Based on the reported analgesic efficacy of transcranial Direct Current Stimulation (tDCS) on the motor cortex for various experimental painful conditions and clinical pain disorders, it is plausible that tDCS can be effective for the severe and medication-refractory PDM patients. This study aim to investigate the analgesic efficacy of tDCS in severe PDMs and to elucidate the dynamic brain neuroplasticity in the context of experimental pain after tDCS intervention. Thirty severe PDMs will be recruited and randomly allocated to either real or sham group in a triple-blind manner. Experimental pain electrical stimulation will be performed before and after the tDCS intervention. The experimental pain-evoked magnetoencephamographic (MEG) data will be correlated with behavioral and psychological measurements. This is the first study in the literature investigating the tDCS efficacy for acute pain in severe PDM. The result can promise a new possibility for clinical application.

NCT03608215 Primary Dysmenorrhea Device: Active tDCS Device: Sham tDCS
MeSH: Dysmenorrhea
HPO: Dysmenorrhea

To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen.

Primary Outcomes

Description: pain scale; from 0 to 10; score 0: no pain, score 10: unbearable pain

Measure: Visual Analog Scale (VAS)

Time: change from baseline (1st menstrual phase, before tDCS) at one month (2nd menstrual phase, with tDCS), change from baseline (1st menstrual phase, before tDCS) at two months (3rd menstrual phase)

Description: Somatosensory evoked magnetic fields (SEFs) is a well established magnetoencephalographic (MEG) cortical response evoked by electric stimulation. SEFs to experimental pain stimulation using electrical stimulator applied on the skin over the trajectory of median nerve will be used to evaluate pain-evoked cortical response.

Measure: Somatosensory evoked magnetic fields to experimental pain

Time: change from baseline (before tDCS, before 2nd menstrual phase) at one week (after tDCS completion), change from baseline (before tDCS, before 2nd menstrual phase) at four weeks (before the 3rd menstrual phase)

Secondary Outcomes

Description: To assess the threshold of thermal sensation (cold, cold-pain, heat, heat-pain; from 0 to 50 centigrade temperature), according to the established protocol of an ascending limit approach for heat pain and a descending limit approach for cold pain.

Measure: Quantitative sensory testing (QST)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 20 to 80; score 20: not anxious, score 80: extremely anxious

Measure: Spielberger State-Trait Anxiety Inventory (STAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess anxious symptoms; from 0 to 63; score 0: not anxious, score 63: extremely anxious

Measure: Beck Anxiety Inventory (BAI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess depressive symptoms; from 0 to 63; score 0: not depressed, score 63: extremely depressed

Measure: Beck Depression Inventory (BDI)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain-maladaptive psychological status; from 0 to 52; score 0: not pain Catastrophizing , score 52: extremely pain Catastrophizing

Measure: Pain Catastrophizing Scale (PCS)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess pain status; from 0 to 78; score 0: not painful, score 78: extremely painful

Measure: Long-form McGill Pain Questionnaire (MPQ)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess quality of life; he SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. From 0 to 100; score 0: equivalent to maximum disability, score 100: no disability.

Measure: Short-Form Health Survey (SF-36)

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at five weeks (after the 3rd menstrual phase)

Description: To assess testosterone, progesterone, estrogen

Measure: Blood Hormones Measurement

Time: change from baseline (before tDCS) at one week (after tDCS completion), change from baseline (before tDCS) at four weeks (before the 3rd menstrual phase)

Description: To genotype the single nucleotide polymorphism genotyping (i.e., BDNF Val66Met polymorphism (rs6265), COMT Val158Met polymorphism (rs4680), OPRM1 (rs1799971), 5HTR2A (rs6313), SLC6A4 (rs25531)) from blood specimen

Measure: Genotyping

Time: baseline

Description: To assure blinding efficacy; Patients do self-assessment about whether they receive real tDCS or sham tDCS. Assessment questionnaire:1 or 0. 1: real tDCS; 0: sham tDCS.

Measure: Efficacy of tDCS blinding

Time: At 1 months after tDCS intervention

8 Pharmacologic Augmentation of Neurocognition and Cognitive Training in Psychosis

This application seeks renewed support for MH59803, "Dopaminergic substrates of startle gating across species," to extend a clear path of "bench-to-bedside" progress towards a critical paradigm shift in therapeutic models for schizophrenia (SZ) and schizoaffective disorder, depressed type (SZA): the use of Pharmacologic Augmentation of Cognitive Therapies (PACTs). This novel therapeutic strategy for SZ/SZA directly addresses the need for more effective treatments for this devastating disorder. MH59803 has investigated the neural regulation of laboratory-based measures of deficient information processing in SZ/SZA patients, using rodents and healthy human subjects (HS) to explicate the biology of these deficits, and to establish a rational basis for developing novel therapies for SZ/SZA. In its first 9 years, MH59803 studies of the neural regulation of prepulse inhibition (PPI) of startle in rats focused on basic neurobiological and molecular mechanisms. Over the past 2 years of support, MH59803 studies moved "from bench-to-bedside," focusing on dopamine (DA) agonist effects on PPI and neurocognition in HS, and their regulation by genes identified in cross-species studies. These studies detected biological markers that predict PPI-enhancing and pro-cognitive effects of the DA releaser, amphetamine (AMPH) in humans, leading to specific predictions of AMPH effects on PPI, neurocognition and Targeted Cognitive Training in SZ/SZA patients. If confirmed in the present application, these predictions could help transform therapeutic approaches to SZ/SZA. This renewal application of MH59803 thus reflects a logical progression of studies at systems and molecular levels, translated first to HS, and now to potentially transformative therapeutic models in SZ/SZA patients.

NCT02634684 Schizophrenia Drug: Dextroamphetamine Drug: Placebo
MeSH: Schizophrenia
HPO: Schizophrenia

Analytic software yields the dependent measures: subjects' across-session improvement score, processing speed percentile and total number of levels completed.. Inclusion Criteria: - 18-55 years old: - Drug Free (No recreational/street drugs) - Diagnosis of Schizophrenia or Schizoaffective Disorder, Depressed Type - Must be stable on antipsychotic medication for at least 1 month - Any medications other than antipsychotic medications need to be stable for at least 1 week Exclusion Criteria: - Dominant hand injury - Hearing impairment at 40 dB - Irregular menstrual cycle or cycle is no within in 25-35 days (menopausal is eligible) - EKG, conduction abnormalities confirmed by cardiologist - Reading component of Wide Range Achievement Test 4 (WRAT4) Score less than 70 - Any serious illness, including: Insulin-dependent diabetes, HIV, AIDS, cancer, stroke, heart attack, uncontrolled hypothyroidism - Sleep apnea - A diagnosis of epilepsy or history of seizures with loss of consciousness - Open/closed head injury with loss of consciousness greater than 1 minute at any time in the lifetime - Blood pressure: Systolic Blood Pressure < 90 or > 160, Diastolic Blood Pressure < 45 or > 95 - Heart Rate < 55 or > 110 - Current use of Dexatrim or drugs containing phenylephrine (eligible if not used for at least 72 hours prior to participation) - Current use of St. John's Wort, Milk Thistle (eligible if for at least 1 month) - Self report of any illicit drug use within the last 30 days - Positive urine toxicology - Self-report of any use of ecstasy, lysergic acid diethylamide (LSD), mushrooms, gamma hydroxybutyrate (GHB), ketamine, phencyclidine (PCP), heroin or any intravenous-drugs within past year - If there is a history of substance abuse/addiction, participant must be in remission for at least 6 months - Within 1 month of recent psychiatric hospitalization - Current mania - Dementia/Alzheimer's diagnosis - Mania episode meeting criteria outlined in the MINI-International Neuropsychiatric Interview Plus 6.0 (M.I.N.I. plus 6.0) anytime in the lifetime (hypomania/Bipolar II eligible) Inclusion Criteria: - 18-55 years old: - Drug Free (No recreational/street drugs) - Diagnosis of Schizophrenia or Schizoaffective Disorder, Depressed Type - Must be stable on antipsychotic medication for at least 1 month - Any medications other than antipsychotic medications need to be stable for at least 1 week Exclusion Criteria: - Dominant hand injury - Hearing impairment at 40 dB - Irregular menstrual cycle or cycle is no within in 25-35 days (menopausal is eligible) - EKG, conduction abnormalities confirmed by cardiologist - Reading component of Wide Range Achievement Test 4 (WRAT4) Score less than 70 - Any serious illness, including: Insulin-dependent diabetes, HIV, AIDS, cancer, stroke, heart attack, uncontrolled hypothyroidism - Sleep apnea - A diagnosis of epilepsy or history of seizures with loss of consciousness - Open/closed head injury with loss of consciousness greater than 1 minute at any time in the lifetime - Blood pressure: Systolic Blood Pressure < 90 or > 160, Diastolic Blood Pressure < 45 or > 95 - Heart Rate < 55 or > 110 - Current use of Dexatrim or drugs containing phenylephrine (eligible if not used for at least 72 hours prior to participation) - Current use of St. John's Wort, Milk Thistle (eligible if for at least 1 month) - Self report of any illicit drug use within the last 30 days - Positive urine toxicology - Self-report of any use of ecstasy, lysergic acid diethylamide (LSD), mushrooms, gamma hydroxybutyrate (GHB), ketamine, phencyclidine (PCP), heroin or any intravenous-drugs within past year - If there is a history of substance abuse/addiction, participant must be in remission for at least 6 months - Within 1 month of recent psychiatric hospitalization - Current mania - Dementia/Alzheimer's diagnosis - Mania episode meeting criteria outlined in the MINI-International Neuropsychiatric Interview Plus 6.0 (M.I.N.I. plus 6.0) anytime in the lifetime (hypomania/Bipolar II eligible) Schizophrenia Schizophrenia MH59803 demonstrated that AMPH (20 mg p.o.) significantly increased PPI and neurocognitive performance (MATRICS Consensus Cognitive Battery; MCCB) in HS characterized by specific performance-based or genetic biomarkers, including the val/val genotype for the rs4680 polymorphism of catechol-O-methyltransferase (COMT).

Prediction: In a within-subject, placebo-controlled, randomized design, AMPH (10 and/or 20 mg po) will increase PPI and enhance MCCB and TCT performance in medicated SZ/SZA patients, particularly among those characterized by low basal performance levels and/or the val/val rs4680 COMT polymorphism.

Prediction: In a within-subject, placebo-controlled, randomized design, AMPH (10 and/or 20 mg po) will increase PPI and enhance MCCB and TCT performance in medicated SZ/SZA patients, particularly among those characterized by low basal performance levels and/or the val/val rs4680 COMT polymorphism.

Primary Outcomes

Description: Startle and PPI are assessed using 42 trials of 6 types: a 118 decibels (dB) (A) 40 ms noise alone, and the same "pulse" preceded 10, 20, 30, 60, or 120 ms by a prepulse 16 dB over a 70 dB(A) background. Startle amplitude, habituation, latency and latency facilitation are tested, and are used to interpret drug and subgroup effects on %PPI. Primary dependent measure: AMPH effects on %PPI.

Measure: Prepulse inhibition (PPI)

Time: 5 years

Secondary Outcomes

Description: The MCCB includes 10 tests assessing 7 cognitive domains". In "low baseline" HS, AMPH primarily increased speed of processing (SP) and attention/ vigilance (A/V), but some gains were evident in all domains except visual learning (30). Total test time is 1-1.5h. The primary dependent measures will be AMPH effects on SP and A/V T-scores; secondary and exploratory measures will include T-scores for both spatial (Wechsler Spatial Span) and verbal (Letter-Number Span) working memory, as well as T-scores for the other cognitive domains.

Measure: MATRICS Consensus Cognitive Battery Performance (MCCB)

Time: 5 years

Description: Sensory discrimination learning module: Sound "Sweeps" of adaptive auditory processing exercises: 1) parameters (e.g. inter-stimulus interval, stimulus duration) are established for subjects to maintain 80% correct responses in each stimulus set, and 2) task difficulty increases systematically and parametrically as performance improves. On screen and test days, subjects complete 1h of TCT. Analytic software yields the dependent measures: subjects' across-session improvement score, processing speed percentile and total number of levels completed.

Measure: Targeted Cognitive Training (TCT): PositScience, Inc.

Time: 5 years


HPO Nodes


Dysmenorrhea
Genes 13
LMNA INHBA ANTXR1 FOS CYP17A1 CAVIN1 BSCL2 CYB5A AIP CAV1 AGPAT2 PPARG GPR101
Vomiting
Genes 181
PIGY CFH CACNA1A MPV17 FLNA RANBP2 HNF1A PDSS2 GALC GALE RARS GALT ACADL ACADM ATRX TCN2 ACADVL ACAT1 AVP AIMP1 INHBA AVPR2 PPM1D CYP11A1 CYP11B1 CYP11B2 RRM2B POLG ACP2 CYP24A1 ETFA ETFB ETFDH MC2R APC CD55 HLCS ELP1 ACTG2 FARSB CDH23 HMBS ALG11 GCDH BCKDHA BCKDHB RELA HMGCL CD46 DBH HMGCS2 MCCC2 AIP MCCC1 CPOX TXNRD2 SSR4 CPS1 DBT ACY1 SLC7A7 CPT2 TYMP CFI COQ2 HNF4A AQP2 BOLA3 SLC1A3 ZEB2 COA8 SHANK3 NDUFS1 F12 STAR PHGDH NDUFV1 NAGS NDUFS4 KRIT1 MLYCD PPOX HELLPAR MEN1 ARG1 IVD MMAA GHSR SLC6A8 TRMU MRPS7 MET NBAS STK11 SAA1 OTC CCM2 LIPA GK FBP1 OXCT1 ATP6 GLA SLC12A1 TRNC SLC12A3 COX1 BRAF COX2 COX3 EGFR ST3GAL5 SUGCT CYTB MTHFD1 BTD KCNJ1 ABCC8 ASL HPRT1 DGUOK DHCR7 SLC25A15 MRAP KCNJ11 ND1 UCP2 SAR1B ND2 SLC22A5 ATP6V0A4 ND3 ND4 NAXD ND5 ASS1 ND6 SCNN1A SCNN1B SCNN1G SERPING1 ALDH18A1 ACSF3 DLD ALG8 TRNF C11ORF95 PNPLA8 SMPD1 ALAD NR3C2 CLMP ALG3 HSD3B2 TRNK TRNL1 CTNS HADH CTNNB1 TRNQ TNFRSF1A TRNS1 TRNS2 TRNV TRNW PDCD10 ALDOB MMAB PCCA PCCB NNT D2HGDH NEUROG3 MMUT DGAT1 MVK ALPL OPLAH PMM2 FOXP3 MPI
Schizophrenia
Genes 50
WHRN FLI1 GJA5 GJA8 DNAJC13 CIB2 ARSA PSAP COMT SEC24C CEP78 ARVCF MYO7A ZDHHC9 WFS1 USH1G KRT81 DISC2 KRT83 KRT86 VPS35 UFD1 EIF4G1 LRRK2 PCDH15 GBA CDH23 GIGYF2 TRNE PDZD7 DSG4 UPF3B ADGRV1 HARS SNCA TRNS2 RREB1 USH1C USH2A ATP2A2 CLRN1 JMJD1C MED12 MSTO1 CHRNA7 TBX1 ARSG PRODH HIRA GP1BB
Aggressive behavior
Genes 157
MYT1L PIGY CUL4B GABRB3 GABRD SOX5 DPAGT1 DGCR2 NDST1 TCF4 DPYD C12ORF4 CACNB4 SATB2 AMT ZMYND11 CUX2 DGCR6 ZBTB20 DEAF1 ADAT3 SPAST ESS2 ATP7B IMPA1 FRMPD4 AFF2 MANBA PSEN1 ANK3 MAOA TRIO MAPT SPR RBBP8 USP9X INPP5E KDM5C SMC1A SLC6A17 TTI2 NAGLU CPLX1 NAA10 ICK NFASC GRIA3 UQCC2 GRN CHD2 NDP SIN3A PSMD12 UROC1 OCRL GCSH PRRT2 BCOR ECM1 TRIP12 ATP13A2 MECP2 SLITRK1 SHANK3 WARS2 LEPR SLC2A1 SH2B1 NAGS HNRNPH2 DDX3X TTC19 TBC1D24 CHMP2B WAC RUSC2 EEF1A2 NSDHL SLC52A3 SLC6A1 SLC6A8 TMEM106B TYROBP BPTF PACS1 LINS1 WDR45 SETD2 ARID1B BCAP31 EFHC1 MGAT2 UBE2A CLCN2 SARS ADSL CLCN4 LINGO1 PIGH FIG4 GLDC NFIB SQSTM1 EIF2S3 SCN1A JRK DHCR7 PCDH19 ENTPD1 RLIM PAH VPS13A CNTNAP2 TIMM50 TREM2 SMARCA2 EHMT1 SYN1 PAK3 SASS6 AP1S2 KMT2A SMARCC2 KCNQ3 PLA2G6 FOXP1 ELP2 FGF14 CEP152 HSD17B10 ATXN10 DGCR8 HERC2 SLC52A2 CAMTA1 TMEM231 DNM1 C9ORF72 MBD5 MAPK10 NONO ALDH5A1 KCNT1 PHIP MED12 TBX1 MAN1B1 PUS7 PRNP WDR62 VCP TMEM240 KIF11 PRODH GABRA1 KNL1 TBP
Impulsivity
Genes 65
GABRB2 SLC6A1 CACNA1A UBA5 ATP6V1A AARS AMT DNAJC13 MAGEL2 PANK2 HIVEP2 KCNA2 PPP3CA STXBP1 WWOX AFF2 KANSL1 MAOA KCNB1 ARV1 SYNJ1 SZT2 MAPT GLDC VANGL1 HCN1 NTRK2 C19ORF12 PCDH19 NUS1 SCN3A AP3B2 VPS35 CLTC EIF4G1 LRRK2 SCN8A GBA FUZ GIGYF2 DHDDS SLC13A5 PLA2G6 FGF12 CHD2 CNKSR2 CEP152 GRIN2D GCSH SNCA DNM1 SLC1A2 CREBBP YWHAG PHIP EP300 CYFIP2 WDR62 TMEM240 NECAP1 DNMT1 TRAK1 KNL1 EEF1A2 SYNGAP1
Depressivity
Genes 240
VAPB NHLRC1 GABRB3 GABRG2 CTSF ERBB4 CHCHD10 SPAST ATP7B PSAP PSEN1 ATRX PDGFB MYO7A PDGFRB MAPT AMACR RPS6KA3 MATR3 TBC1D7 CYP27A1 LRRK2 GBA CDH23 HMBS DAO PTPN22 RPS20 PDZD7 GCH1 ADGRV1 GPR101 RREB1 PFN1 COQ2 BCR DCTN1 BCS1L ATXN8 HNRNPA1 MECP2 FGF17 TTC19 HIRA NEFH PPARGC1A NEK1 BMPR1A ANOS1 AP2S1 PANK2 KISS1R GLA PER3 CLCN4 PER2 ALMS1 AARS2 CEP78 PROKR2 ATXN2 FIG4 PIK3CA ATXN8OS GLE1 PTS SQSTM1 USH1G KCNJ2 HS6ST1 DGUOK C19ORF12 UFD1 AFG3L2 PCDH15 MLH1 CLN6 FGF8 PLA2G6 SGCE GNA11 CACNA1H CACNA1G TAC3 FGF14 FGFR1 ATXN10 TACR3 GNAS SEMA4A DNA2 KISS1 USH2A CLRN1 GNRH1 KCNT1 GNRHR CFAP410 TBX1 NOTCH3 VCP DNMT1 PDE11A GP1BB TBP PMS1 PROK2 WHRN KRAS TCF4 PMS2 DRD2 DNAJC13 EPM2A CIB2 FMO3 UBQLN2 ANG FMR1 COMT SLC25A4 CLIP2 CISD2 WFS1 GPR35 FA2H RRM2B POLG ANXA11 DUSP6 NR4A2 PON1 TOR1A PON2 PON3 BAZ1B CP TWNK CASR GRN XK MSH2 CHD7 OCRL AIP CPOX RFC2 GTF2IRD1 IDUA USH1C ATP13A2 CBS JMJD1C SLC2A1 MSTO1 ARSG CRKL KCTD17 CHMP2B PPOX FAN1 CCNF MST1 TMEM106B TGFBR2 TARDBP MSH6 USP8 LIMK1 PPP2R2B OPTN MLH3 GTF2I ARSA SNCAIP NSMF CSF1R SEC24C COX1 LMNB1 COX2 COX3 PPT1 ARVCF WDR11 SLC18A2 TK2 SLC20A2 JRK TBK1 ND1 ARMC5 VPS35 SPRY4 ND4 ND5 EIF4G1 ND6 PAH PRKACA TREM2 EHMT1 PRKAR1A GIGYF2 DNAJC5 TRNF PRKCG TRNH TAF15 ELN TRNL1 TRNL2 FUS TRNN MAPK1 COASY HARS TRNQ ATP1A3 TRNS1 SNCA TRNS2 C9ORF72 POLG2 TRNW STX16 HBB EPCAM TNXB TBL2 UNC13A PRNP SOD1 HTT GABRA1 PINK1 JPH3 EPHA4 XPR1 PRPH
Nausea
Genes 39
CFH APC VHL SERPING1 CACNA1D HMBS SAA1 CD46 KCNA1 RET GLA FH MDH2 SLC7A7 TYMP CFI ALDOB SDHAF2 TMEM127 INHBA SLC1A3 CYP11B1 CYP11B2 KCNJ5 NAGS RRM2B POLG MAX SDHA SDHB SDHC KIF1B SDHD MGME1 HELLPAR ETFA FSHR ETFB ETFDH