SNPMiner Trials by Shray Alag


SNPMiner Trials: SNP Report


Report for SNP rs6971

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

There are 21 clinical trials

Clinical Trials


1 Pilot Study of Positron Emission Tomography (PET) Imaging: Correlations With Advanced Magnetic Resonance Imaging in Multiple Sclerosis

Traditional Magnetic Resonance Imaging (MRI) in Multiple Sclerosis (MS) has enabled clinicians to measure disease activity but there are inherent limitations. Clinical/radiographic dissociation can be seen in some patients and the abnormalities are not specific. This pilot study is an opportunity to determine the relationship between quantitative advanced MRI measures and OCT with PET measurements of microglial activation and myelin health.

NCT02869360 Multiple Sclerosis
MeSH: Sclerosis Multiple Sclerosis

- Aged 18 to 60 - High or mixed affinity binder to rs6971 TSPO polymorphism Exclusion Criteria: - Pregnant or breastfeeding - Suffering from an unstable medical condition - Have a neurological or ocular disorder other than MS - Any contra-indications to MRI Inclusion Criteria: - Diagnosed with Multiple Sclerosis according to the 2011 McDonald criteria.

- Aged 18 to 60 - High or mixed affinity binder to rs6971 TSPO polymorphism Exclusion Criteria: - Pregnant or breastfeeding - Suffering from an unstable medical condition - Have a neurological or ocular disorder other than MS - Any contra-indications to MRI Multiple Sclerosis Sclerosis Multiple Sclerosis null

Primary Outcomes

Measure: Whole Brain PBR28 binding

Time: Baseline

Secondary Outcomes

Measure: Lesional PiB binding

Time: Baseline

Measure: Myelin Water Imaging

Time: Baseline

Measure: MR Spectroscopy (Total NAA, NAA/Cr, mI)

Time: Baseline

Measure: Optical Coherence Tomography (RNFL thickness)

Time: Baseline

2 Development of Minocycline as a Neuroimmune Therapy for Alcohol Use Disorder

The objective of this proposal is to advance medication development for alcohol use disorder by examining the efficacy and mechanisms of action of minocycline, a neuroimmune modulator, as a potential treatment. This study has important clinical implications, as the available treatments for alcohol use disorder are only modestly effective and testing novel medications is a high research priority.

NCT03244592 Alcohol Use Disorder Inflammation Neurocognitive Dysfunction Craving Alcohol Drinking Drug: Minocycline Drug: Sugar pill
MeSH: Disease Inflammation Alcohol Drinking Alcoholism Cognitive Dysfunction
HPO: Cognitive impairment Mental deterioration

15. low affinity rs6971 genotype Inclusion Criteria: 1. Ages 25 - 45 2. Meet DSM-5 diagnostic criteria for an AUD [n.b., only participants with moderate or severe AUD will be enrolled] 3. Drink ≥ 48 standard drinks in a 30-day period before enrollment Exclusion Criteria: 1. Currently in treatment for AUD, a history of treatment in the 30 days before enrollment, or currently treatment seeking 2. Current (last 12 months) DSM-V diagnosis of substance use disorder for any psychoactive substances other than alcohol and nicotine 3. Lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder 4. Positive urine screen for narcotics, amphetamines, or sedative hypnotics 5. Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised 6. Pregnancy, nursing, or refusal to use reliable method of birth control (if female) 7. A medical condition that may interfere with safe study participation (e.g., unstable cardiac, renal, or liver disease, uncontrolled hypertension or diabetes) 8. AST, ALT, or GGT ≥ 3 times upper normal limit 9. Attempted suicide in the past 3 years and/or serious suicidal intention or plan within the past year 10.

15. low affinity rs6971 genotype Alcohol Use Disorder Inflammation Neurocognitive Dysfunction Craving Alcohol Drinking Disease Inflammation Alcohol Drinking Alcoholism Cognitive Dysfunction The research objective of this project is to advance medication development for AUD by conducting a randomized, double blind, placebo-controlled, neuroimaging study to examine the effects of minocycline on neuroinflammation, alcohol cue reactivity, neurocognitive performance, and alcohol use.

Primary Outcomes

Description: Level of [11C]DAA1106 binding during PET imaging

Measure: Microglial Activation

Time: Change from baseline after 28 days of medication dosing

Description: Alcohol Urge Questionnaire (AUQ)

Measure: Cue-Induced Alcohol Craving

Time: Change from baseline after 28 days of medication dosing

Description: Total drinks consumed

Measure: Alcohol consumption

Time: Day 28 of medication dosing period

Description: Hopkins Verbal Learning Test

Measure: Verbal Learning and Memory

Time: Change from baseline after 28 days of medication dosing

Description: Wisconsin Card Sorting Test

Measure: Set-Shifting

Time: Change from baseline after 28 days of medication dosing

Description: Stop Signal Task

Measure: Response Inhibition

Time: Change from baseline after 28 days of medication dosing

Description: Grooved Pegboard Test

Measure: Manipulative Dexterity

Time: Change from baseline after 28 days of medication dosing

Description: Digit Symbol Substitution Test

Measure: Executive Function

Time: Change from baseline after 28 days of medication dosing

Description: Digit Span

Measure: Memory

Time: Change from baseline after 28 days of medication dosing

Description: WAIS Vocabulary

Measure: Vocabulary

Time: Change from baseline after 28 days of medication dosing

Description: Rey Complex Figure Copy

Measure: Executive Function

Time: Change from baseline after 28 days of medication dosing

Secondary Outcomes

Description: Serum level of cytokines and innate immune receptors

Measure: Peripheral Proinflammatory Marker levels

Time: At baseline (day zero) and after 7, 14, and 21 and 28 days of medication dosing

Description: Symptom count from the alcohol module for the Structured Clinical Interview for DSM-5

Measure: Alcohol Use Disorder Severity

Time: At baseline (day zero) and after 28 days of medication dosing

3 Pilot Study of the Effect of Ibudilast on Neuroinflammation in Methamphetamine Users

Addiction to methamphetamine is a serious health problem in the United States. Right now, there are no medications that a doctor can give someone to help them stop using methamphetamine. More research is needed to develop drugs for methamphetamine addiction. Ibudilast (the study drug) is a drug that could help people addicted to methamphetamine. The investigators are interested to know if the study drug can help some symptoms that methamphetamine can cause, specifically inflammation in the brain. Inflammation has been shown to affect decision-making. The study drug has anti-inflammatory properties, however it is not yet known whether the drug will reduce inflammation in the brain.

NCT03341078 Methamphetamine-dependence Drug: Ibudilast Drug: Placebo Oral Tablet

Pre and post differences in brain function will be assessed.. Effects of ibudilast on overall cognitive battery score.. Pre and post differences in overall cognitive battery score will be assessed.. Inclusion Criteria: - abstinent from all drugs and have a negative urine drug screen on test days - Meet diagnosis for recent Methamphetamine-Use Disorder (DSM-V) or does not meet any substance-use disorders Exclusion Criteria: - Known sensitivity to ibudilast - Left handed - MRI contraindications - Clinically significant neurological, endocrine, renal, hepatic, or systemic diseases that would compromise safe participation or confound outcomes - Any psychiatric diagnoses or primary psychotic or mood disorders (past depression diagnoses allowed) - Any drug use disorder diagnosis besides methamphetamine or tobacco - Any recreational or prescriptive use of psychotropic medications - Claustrophobia - Women who are pregnant or breast-feeding - Neurodegenerative diseases that present with neuroinflammation - More than 4 weeks abstinent from methamphetamine - rs6971 genotype that confers low translocator protein (TSPO) binding affinity to prevent unnecessary radiation exposure - Liver disease requiring medication or medical treatment and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit - Participation in any drug study in the last 3 months Inclusion Criteria: - abstinent from all drugs and have a negative urine drug screen on test days - Meet diagnosis for recent Methamphetamine-Use Disorder (DSM-V) or does not meet any substance-use disorders Exclusion Criteria: - Known sensitivity to ibudilast - Left handed - MRI contraindications - Clinically significant neurological, endocrine, renal, hepatic, or systemic diseases that would compromise safe participation or confound outcomes - Any psychiatric diagnoses or primary psychotic or mood disorders (past depression diagnoses allowed) - Any drug use disorder diagnosis besides methamphetamine or tobacco - Any recreational or prescriptive use of psychotropic medications - Claustrophobia - Women who are pregnant or breast-feeding - Neurodegenerative diseases that present with neuroinflammation - More than 4 weeks abstinent from methamphetamine - rs6971 genotype that confers low translocator protein (TSPO) binding affinity to prevent unnecessary radiation exposure - Liver disease requiring medication or medical treatment and/or aspartate or alanine aminotransferase levels greater than 3 times the upper limit - Participation in any drug study in the last 3 months Methamphetamine-dependence null

Primary Outcomes

Description: Pre and post differences in brain neuroinflammation will be assessed.

Measure: Effects of ibudilast on neuroinflammation as assessed by magnetic resonance spectroscopy (MRS)

Time: 6 weeks

Description: Pre and post differences in brain neuroinflammation will be assessed.

Measure: Effects of ibudilast on neuroinflammation as assessed by positron emission tomography (PET)

Time: 6 weeks

Description: Pre and post differences in brain function will be assessed.

Measure: Effects of ibudilast on brain function as assessed by magnetic resonance imaging (MRI)

Time: 6 weeks

Secondary Outcomes

Description: Pre and post differences in overall cognitive battery score will be assessed.

Measure: Effects of ibudilast on overall cognitive battery score.

Time: 6 weeks

4 Imaging and BioFluid Biomarkers in Amyotrophic Lateral Sclerosis

This is a multicenter, 18-month study, which aims to identify imaging and biofluid biomarkers in people with ALS to expand the understanding of ALS pathology, treatment targets, disease progression, and anatomical differences between different disease phenotypes. This pilot project is tailored to produce imaging tools that will allow researchers to conduct future ALS clinical trials more efficiently which may in turn impact the pace for ALS drug discovery.

NCT02559869 Amyotrophic Lateral Sclerosis (ALS) Drug: [18F] GE-180
MeSH: Sclerosis Motor Neuron Disease Amyotrophic Lateral Sclerosis
HPO: Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis

The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to SI judgment 7. Pregnant women or women currently breastfeeding 8. Anything that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study In addition, any subject meeting any of the following criteria during screening evaluations will be excluded from entry into the PET portion of the study: 1. Radiation exposure that exceeds the site's current guidelines 2. Low affinity TSPO binders determined by having a Thr/Thr polymorphism in the TSPO gene (rs6971) at the Screening Visit Women of Childbearing Potential (WOCBP) For the purposes of this study, women of child bearing potential are defined as all women who are capable of becoming pregnant, unless they meet one of the following criteria: - 12-months post-menopausal - Post-hysterectomy - Surgically sterile Inclusion Criteria Study subjects meeting all of the following criteria will be allowed to enroll in the study: 1.

The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to SI judgment 7. Pregnant women or women currently breastfeeding 8. Anything that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study In addition, any subject meeting any of the following criteria during screening evaluations will be excluded from entry into the PET portion of the study: 1. Radiation exposure that exceeds the site's current guidelines 2. Low affinity TSPO binders determined by having a Thr/Thr polymorphism in the TSPO gene (rs6971) at the Screening Visit Women of Childbearing Potential (WOCBP) For the purposes of this study, women of child bearing potential are defined as all women who are capable of becoming pregnant, unless they meet one of the following criteria: - 12-months post-menopausal - Post-hysterectomy - Surgically sterile Amyotrophic Lateral Sclerosis (ALS) Sclerosis Motor Neuron Disease Amyotrophic Lateral Sclerosis In this trial, approximately 200 subjects will participate in this study from 2 Northeast ALS Consortium (NEALS) centers in the United States.

Primary Outcomes

Description: Aim 1 will be accomplished by obtaining [18F] GE-180 PET imaging from 25 people with ALS compared to 25 age, gender, and binding affinity matched healthy volunteers.

Measure: Measure & localize brain inflammation in people with ALS via [18F] GE-180 PET imaging.

Time: 12 months

Description: Aim 1 will be accomplished by obtaining state of-the-art MRI acquisition sequences from 50 people with ALS compared to 50 MRI age- and gender-matched healthy volunteers.

Measure: Define anatomical, structural, and functional changes in the brain via MRI of ALS Subjects vs. Healthy Controls at Baseline

Time: 12 months

Description: Blood from 100 subjects will be studied to quantitate circulating pro- and anti-inflammatory monocyte/macrophage and T cells, with results to be correlated with neuroimaging and evaluated as potential biomarkers of disease progression.

Measure: Determine systemic inflammatory factors that may modify the progression or other clinical or imaging correlates of ALS.

Time: 12 months

Secondary Outcomes

Description: Clinical and [18F] GE-180 PET imaging data will be collected every 6 months from the 25 people with ALS for at least 12 months.

Measure: Determine the longitudinal changes in brain inflammation in people with ALS in correlation with ALS severity and rate of progression.

Time: 12 months

Description: Clinical and MRI data will be collected every 3 months from 50 people with ALS for at least 12 months.

Measure: Determine the longitudinal changes in the anatomical, structural, and functional measures in people with ALS, and build ALS prediction models using the clinical and MRI data.

Time: 12 months

5 PET Evaluation of Brain Peripheral Benzodiazepine Receptors Using [(11)C]PBR28 in Patients With Multiple Sclerosis (MS)

This study will use positron emission tomography (PET) to measure a brain protein called peripheral benzodiazepine receptor (PBR) in patients with multiple sclerosis. PBR is created during the inflammation process, and brain inflammation is a key feature of multiple sclerosis (MS). PBR usually affects one type of brain cell, but it can also cause damage to surrounding areas of the brain in patients with MS. PET studies of PBRs and brain inflammation may help elucidate the role of these brain cells in patients with MS. Healthy normal volunteers and patients with MS between 18 and 70 years of age may be eligible for this study. Patients with MS must have had onset of disease between 18 and 40 years of age. Patients with MS undergo the following procedures: Visit 1: Medical history, physical examination, blood tests and magnetic resonance imaging (MRI). Visit 2: Blood tests and PET scan. Visits 3 and 4: MRI and physical examination. Visit 5: PET scan and blood tests. Visit 6: MRI and physical examination. Healthy volunteers undergo the following: Visit 1: Medical history, physical examination, blood tests. Visits 2 and 3: PET and blood tests. Magnetic Resonance Imaging MRI uses a magnetic field and radio waves to produce images of body tissues and organs. For this procedure, the subject lies on a table that can slide in and out of the scanner (a metal cylinder), wearing earplugs to muffle loud knocking noises that occur during the scanning process. The procedure lasts about 90 minutes; the patient is asked to lie still for up to 25 minutes at a time. The subject can communicate with the MRI staff at all times during the scan. During part of the scan a contrast agent is administered through a catheter (plastic tube) placed in an arm vein to enhance the images. Positron Emission Tomography (PET) The PET scan gives information on brain and body chemistry and function. The subject lies on a bed that slides in and out of the doughnut-shaped scanner. A catheter is placed in a vein in the arm and another is placed in an artery in the wrist or elbow area. The catheter in the arm is used for injecting a radioactive material that the scanner detects, and the other is used to collect blood samples. A custom-molded plastic mask is used to support the head and prevent it from moving during the procedure. The subject may be asked to perform various tasks during the PET scan or to lie quietly. The scan lasts about 2.5 hours.

NCT00432900 Multiple Sclerosis Radiation: [(11)C]PBR28
MeSH: Sclerosis Multiple Sclerosis

- Homozyous for the low- affinity binding form of TSPO by TSPO genotype analysis ( Ala147Thr polymorphism in rs6971 SNP in exon 4 of the TSPO gene).

HEALTHY VOLUNTEERS - EXCLUSION CRITERIA: Homozyous for the low- affinity binding form of TSPO by TSPO genotype analysis ( Ala147Thr polymorphism in rs6971 SNP in exon 4 of the TSPO gene).

Primary Outcomes

Measure: Correspondence between increased PBR expression measured by [11C]PBR28 PET and gadolinium-enhancing lesions on MRI.

Time: At time of dosing

Measure: Correspondence between increased PBR expression and previously and/or persistently gadolinium-enhancing lesions on MRI.

Time: At time of dosing

Secondary Outcomes

Measure: Correspondence between PBR expression and other MRI defined pathology including T2-weighted hyperintense and T1-weighted hypointense lesions.

Time: Follow-up (~Month 4)

Measure: Correspondence between PBR expression and normal appearing white and gray matter on MRI.

Time: Follow-up (~Month 4)

6 Brain Microglial Activation in the Early Stage of the Parkinson's Disease: a Predictive Biomarker of the Evolution?

Phase II, Open-labeled, Prospective, Multi-center study of assessing the link between microglial activation and dopaminergic denervation kinetics in the early stage of Parkinson disease, by using the imaging of [18F]DPA-714 a new ligand of Translocator Protein-18 kDa (TSPO) by Positron Emission Tomography (PET).

NCT03230526 Parkinson Disease Drug: [18F]DPA-714 PET scan
MeSH: Parkinson Disease

Exclusion Criteria: - Pregnant woman - Minor - Adult protected by the law - Contraindication to PET-scan - Contraindication to brain MRI - History of inflammatory or dysimmune chronic disease - History of psychiatric disease or drug addiction - History of cognitive disorders (MMS<26) - Hypersensibility to iodine derivates or one of these components - Long-term Treatments which can interfere in neuroinflammation process - Treatments / substances susceptible to interfere with the 18F-DPA-714 - TSPO gene Polymorphisms rs6971 corresponding to groups of affinity of low affinity (LAB=Low Affinity Binder) or moderated MAB = Mixed Affinity Binder) - Modification of diagnosis of Parkinson disease during follow-up, in particular towards an atypical parkinson-like syndrome Inclusion Criteria: - Patients having a Parkinson's disease diagnosed according to the criteria UKPDSBB.

Exclusion Criteria: - Pregnant woman - Minor - Adult protected by the law - Contraindication to PET-scan - Contraindication to brain MRI - History of inflammatory or dysimmune chronic disease - History of psychiatric disease or drug addiction - History of cognitive disorders (MMS<26) - Hypersensibility to iodine derivates or one of these components - Long-term Treatments which can interfere in neuroinflammation process - Treatments / substances susceptible to interfere with the 18F-DPA-714 - TSPO gene Polymorphisms rs6971 corresponding to groups of affinity of low affinity (LAB=Low Affinity Binder) or moderated MAB = Mixed Affinity Binder) - Modification of diagnosis of Parkinson disease during follow-up, in particular towards an atypical parkinson-like syndrome Parkinson Disease Parkinson Disease The Parkinson's disease ( MP) is a frequent but heterogeneous neurodegenerative disease in term of clinical presentation(display) and evolutionary profile.

Primary Outcomes

Description: Coefficient of correlation between the striatal microglial activation level measured by PET imaging [binding potential (BP) of 18F-DPA-714 in the striatum] and dopaminergic denervation kinetics obtained from two 123I-FP-CIT (DaTscan) scans

Measure: Coefficient of correlation between level of microglial striatal activation and the And the dopaminergic denervation kinetics

Time: 36 months

Secondary Outcomes

Description: Will be estimated by imaging PET with [18F]DPA-714

Measure: Analyze the relationship between the level of microglial activation in the black substance at the early stage of MP and the dopaminergic denervation kinetics

Time: 36 months

Description: The equivalent dose of cumulative L-Dopa

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: baseline

Description: The equivalent dose of cumulative L-Dopa

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 18 months

Description: The equivalent dose of cumulative L-Dopa

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 36 months

Description: MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: Baseline

Description: MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 18 Months

Description: MDS-UPDRS scale (part III "OFF" - Part III "ON" and part II)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 36 Months

Description: MDS-UPDRS scale (part IV)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: baseline

Description: MDS-UPDRS scale (part IV)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 18 months

Description: MDS-UPDRS scale (part IV)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Time: 36 months

Description: QUIP RS

Measure: Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Time: baseline

Description: QUIP RS

Measure: Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Time: 18 months

Description: QUIP RS

Measure: Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Time: 36 months

Description: MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: baseline

Description: MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: 18 months

Description: MDS-UPDRS scale (part III ON : 3.1 ; 3.2 ; 3.9 to 3.13)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: 36 months

Description: MDS-UPDRS scale (part II : 2.13 and part III : 3.11)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: baseline

Description: MDS-UPDRS scale (part II : 2.13 and part III : 3.11)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: 18 months

Description: MDS-UPDRS scale (part II : 2.13 and part III : 3.11)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Time: 36 months

Description: MDS-UPDRS scale (part I)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: MDS-UPDRS scale (part I)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: MDS-UPDRS scale (part I)

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: NMS SCALE

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: baseline

Description: NMS SCALE

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: NMS SCALE

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Scopa-Aut Score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: baseline

Description: Scopa-Aut Score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Scopa-Aut Score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Evaluation of constipation according to Rome III criteria

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Evaluation of constipation according to Rome III criteria

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Evaluation of constipation according to Rome III criteria

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Detection of hypotension

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Detection of hypotension

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Detection of hypotension

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 months

Description: Epworth's Sleepiness Scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Epworth's Sleepiness Scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 Months

Description: Epworth's Sleepiness Scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: UPSIT test

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: baseline

Description: UPSIT test

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: MoCA score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: MoCA score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 Months

Description: MoCA score

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: MATTIS scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: MATTIS scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 Months

Description: MATTIS scale

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: Anxiety symptoms assessed using Beck's anxiety inventory

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Anxiety symptoms assessed using Beck's anxiety inventory

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 months

Description: Anxiety symptoms assessed using Beck's anxiety inventory

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: Symptoms of depression assessed using the Beck Depression

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: Baseline

Description: Symptoms of depression assessed using the Beck Depression

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 18 Months

Description: Symptoms of depression assessed using the Beck Depression

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Time: 36 Months

Description: Dopaminergic denervation at inclusion will be measured by the binding potential (BP) of ioflupane (123I-FP-CIT) by regions of interest in the caudate and putamen of the striatum

Measure: Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic denervation at baseline (DaTscan initial)

Time: Baseline

Description: MDS-UPDRS scale

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: QUIP questionnaire

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: NMS questionnaire

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: Scopa-Aut Score

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: Rome III criteria

Measure: Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Time: 36 Months

Description: The level of cortical microglial activation measured by fixation of the radioligand 18F-DPA-714, on some volumes of interest in the brain

Measure: Evaluate the link between the level of striatal microglial activation and the level of activation in other brain regions (black substance, bridge and cortex)

Time: 36 months

Description: Neurologic Evaluation

Measure: Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Time: baseline

Description: Neurologic Evaluation

Measure: Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Time: 18 months

Description: Neurologic Evaluation

Measure: Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Time: 36 months

Description: The serum levels of 13 cytokines will be analyzed

Measure: Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation

Time: Baseline

Description: The serum levels of 13 cytokines will be analyzed

Measure: Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation Evaluate the relationship between the level of nigrostriatal microglial activation

Time: 18 months

Description: The serum levels of 13 cytokines will be analyzed

Measure: Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation

Time: 36 months

Description: Measurement of serum uric acid

Measure: Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Time: Baseline

Description: Measurement of serum uric acid

Measure: Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Time: 18 months

Description: Measurement of serum uric acid

Measure: Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Time: 36 months

7 UAB Neuroinflammation in Parkinson's Disease - TSPO-PET Substudy

The primary objective of this substudy is to measure the concentration and the regional brain distribution of activated brain microglia/macrophages using the PET ligand [18F]DPA-714 in participants enrolled in the UAB Neuroinflammation in PD study. The PET tracer [18F]DPA-714 binds to the 18 kDa translocator protein (TSPO, also known as the peripheral benzodiazepine receptor) in the mitochondria of activated microglia/macrophages and provides a non-invasive measure of neuroinflammation. The amount and distribution of [18F]DPA-714 in the brain will be correlated to clinical data acquired through the separate ongoing Neuroinflammation in PD study. The primary objective of this study is to determine if patients with PD have higher levels of neuroinflammation than healthy controls as measured with [18F]DPA-714-PET/MRI.

NCT03457493 Parkinson Disease Drug: DPA-714-PET/MRI
MeSH: Parkinson Disease

3. High or mixed affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971.

4. Low affinity binder for TSPO ligands based on genotyping for SNP rs6971.

Primary Outcomes

Description: Estimates of brain TSPO concentrations measured with PET will serve as a marker for neuroinflammation. TSPO-PET measures will be compared between PD patients and healthy controls. We expect the PD patients to have higher measures of neuroinflammation than healthy controls.

Measure: Comparison of TSPO-PET measures of neuroinflammation between PD patients and healthy controls.

Time: 2 years

Description: The estimates of neuroinflammation measured with TSPO-PET will be correlated with clinical assessments of PD severity and biospecimens collected through the UAB Neuroinflammation in PD study.

Measure: Correlation of DPA-714-PET/MRI with demographics, clinical and biospecimen assessments from Neuroinflammation in PD study

Time: 2 years

8 Positron Emission Tomography (PET) Imaging Study in Relapsing-Remitting and Primary-Progressive Multiple Sclerosis (MS): Correlations With Advanced MRI in MS

While both conventional and advanced MRI techniques offer important insights into MS pathophysiology, important aspects of this inflammatory disorder are undetectable with existing MRI technology. In Multiple Sclerosis (MS), there is growing interest in PET as an imaging modality that can increase the investigator's understanding of the disease processes and may add to an understanding of MS phenotype, particularly when combined with advanced MRI techniques such as myelin water imaging.

NCT03787446 Multiple Sclerosis
MeSH: Sclerosis Multiple Sclerosis Multiple Sclerosis, Chronic Progressive

- Mixed affinity binder according to rs6971 TSPO polymorphism1.

Exclusion Criteria: - Low and high affinity binders according to rs6971 TSPO polymorphism - Subject pregnant or breastfeeding.

A separate pre-screening consent form will be issued for the TSPO rs6971 polymorphism and eGFR blood samples, a separate pre-screening step.

Eligible participants, according to their TSPO rs6971 polymorphism will be presented a separate study consent form to continue into the clinical trial.

Primary Outcomes

Description: To show an increase in 11C-PBR28 binding in all sub-types of MS compared to healthy controls.

Measure: Whole Brain PBR28 binding

Time: January 2020

Secondary Outcomes

Description: To quantitatively measure the brain levels of water located within myelin

Measure: Myelin Water Imaging by MRI

Time: January 2020

Description: To correlate brain levels of inflammation measured by 11C-PBR28 with Retinal Nerve Fiber Layer (RNFL) thickness on Optical Coherence Tomography (OCT).

Measure: Optical Coherence Tomography

Time: January 2020

Description: To correlate brain levels of inflammation and myelin measured by PET with cognitive dysfunction in MS patients.

Measure: MS Spectroscopy

Time: January 2020

9 An Experimental Medicine Study to Validate the 18 kiloDalton Translocator Protein (TSPO) as a Novel Neuroimmunodulatory Target in Multiple Sclerosis

In multiple sclerosis (MS) cells of the immune system attack the brain causing tissue damage. In secondary progressive MS (SPMS) these repeated immune attacks have stopped but despite this new damage continues to appear. TSPO is a protein found in the brain and cells of the immune system, whose levels increase during MS. The investigators would like to know whether drugs that bind TSPO could dampen the immune responses in patients with SPMS. The investigators will be testing two drugs that affect TSPO; etifoxine and XBD173. Subjects with SPMS will be recruited from neurology clinics at hospitals associated with Imperial College Healthcare NHS Trust. Healthy volunteers will also be recruited in order to provide a comparison to these patients. The volunteers recruited will be invited to the clinical research facility (CRF) at Hammersmith Hospital. The volunteers will take one of the two drugs every day for 7 days. The researchers will perform blood tests before the first dose and after the last dose to investigate the effects of the drugs, including the expression of genes and immune cell activity. This will allow the researchers to explore which of the two drugs produces the greatest changes in the amount of TSPO in the blood in MS patients relative to healthy controls.

NCT03850301 Multiple Sclerosis Drug: XBD173 Drug: Etifoxine
MeSH: Sclerosis Multiple Sclerosis

b To explore the potential dependence of these pharmacodynamic responses on variation at rs6971 (a common polymorphism influencing ligand binding affinities in the TSPO protein) in the TSPO gene.

Primary Outcomes

Description: Plasma cytokine concentrations

Measure: Monocyte phenotye - Tissue necrosis factor-α

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotye - Interferon-γ

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotype - Interleukins- 1β

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotype - Interleukins- 16

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotype - Interleukins- 17

Time: 7 days

Description: Plasma cytokine concentrations

Measure: Monocyte phenotype - Interleukins- 23

Time: 7 days

Description: Transforming growth factor-β

Measure: Immunomodulatory factor -Transforming growth factor-β

Time: 7 days

Description: Interleukins -4

Measure: Immunomodulatory factor - Interleukins -4

Time: 7 days

Description: Interleukins - 10

Measure: Immunomodulatory factor - Interleukins - 10

Time: 7 days

Description: Flow

Measure: Relative proportions of WBC subsets

Time: 7 days

Secondary Outcomes

Description: Genome, proteome, metabolome

Measure: Monocyte phenotype - 'omic analyses

Time: 7 days

Description: Plasma levels of neurofilament

Measure: Neurofilament

Time: 7 days

10 Imaging the Neuroimmune Effects of Acute Opioid Administration

In this study, a novel human laboratory model will be evaluated. Acute opioid-induced neuroimmune responses will be quantified among healthy volunteers (Specific Aim). To measure the neuroimmune system, we will use [11C]PBR28 positron emission tomography (PET) imaging to quantify 18kDa translocator protein (TSPO) levels. TSPO is an imaging marker of the neuroimmune system thought to reflect microglia levels. Up to twenty healthy volunteers will complete two 120-minute [11C]PBR28 PET scans. One scan will take place prior to a single morphine administration (0.07 mg/kg i.m.) and the second scan will be will start approximately 2-hours post-injection. Specific Aim: To determine whether an acute morphine injection increases TSPO availability in healthy volunteers. Hypothesis: Relative to baseline, morphine will significantly increase whole-brain TSPO availability, consistent with a neuroimmune response.

NCT03801629 Microgliosis Drug Effect Drug: Intramuscular Morphine

Exclusion Criteria: - 1) Any Axis 1 DSM-5 diagnosis (SCID-5), including substance dependence for any drug of abuse; - 2) Psychotropic medication use; - 3) Recent (past 6 months) medical opioid use; - 4) Prior medical use of opioids for >5 consecutive days; - 5) Prior non-medical, i.e. recreational, opioid use; - 6) Positive urine drug screen (UDS) result (excluding marijuana); - 7) Current/past chronic pain (>6 months of continuous pain); - 8) 'Low affinity binding' individuals based on rs6971 polymorphism (<10% population) who exhibit negligible [11C]PBR28 binding; - 9) For females, pregnancy (urine or blood test); - 10) Current use of non-steroidal anti-inflammatory medications or statins; - 11) CYP2D6 genotype indicative of 'poor' or 'ultra-rapid' morphine metabolizer which is associated with greater side effect risk; - 12) First-degree relative with history of opioid- or alcohol-use disorder; - 13) MRI contraindications; - 14) Subjects who would exceed annual radiation dose limits (5 rem/12 months) if he/she participated in this study; - 15) Allergy to morphine; - 16) Medical contraindication to receive up to 0.1 mg/kg intramuscular morphine administration (as determined by Study Physician) or medical conditions that, in the opinion of the Study Physician, would increase the risk of side effects from morphine administration, such as asthma, will be excluded.

Primary Outcomes

Description: The percentage change in 18kDa translocator protein (TSPO) availability will be measured via 2 PET [11C]PBR28 scans

Measure: Morphine-induced Change in TSPO availability

Time: One 120-minute PET [11C]PBR28 scan before and the other ~2 hours after morphine challenge

Secondary Outcomes

Description: The percentage change in Cogstate memory performance will be calculated

Measure: Morphine-induced Change in Memory Proficiency

Time: The Cogstate Battery will be administered twice: once before and once ~4 hours after the morphine challenge

11 Brain Inflammation and Function in Alcoholism

Background: - Brain inflammation due to high alcohol intake may affect thinking, memory, and concentration. Researchers want to measure this using positron emission tomography (PET). Objective: - To study how excessive alcohol consumption affects brain function. Eligibility: - Adults 30-75 years old who are moderate or severe alcohol drinkers. - Healthy volunteers. Design: - Participants will be screened with medical history, physical exam, interview, and blood and urine tests. Their breath will be tested for alcohol and recent smoking. - Phase 1: - Participants will stay in the hospital 3 days. They will have blood and heart tests and daily urine tests. - A small plastic tube will be inserted by needle in each arm. One will go in a vein, the other in an artery. - Participants will have 2 PET scans with 2 different radioactive compounds. Participants will lie on a bed that slides in and out of the scanner with a cap on their head. - Participants will have magnetic resonance imaging (MRI) scans. Participants will lie in the scanner either resting with their eyes open or while performing an attention task. - Participants will have tests of memory, attention, concentration, and thinking. They may answer questions, take tests, and perform simple actions. - Phase 2 of the study will only be done if Phase 1 results show brain inflammation. - Phase 2 will repeat Phase 1. - For healthy volunteers, Phase 2 will begin 3 weeks after Phase 1. - Other volunteers must not have alcohol for at least 3 weeks and stay in a hospital up to 4-6 weeks between Phase 1 and Phase 2. After Phase 2, they will have 5 follow-up calls over 3 months.

NCT02233868 Alcoholism Device: MRI Drug: C-11PBR28 Drug: F-18FDG
MeSH: Inflammation Alcoholism Encephalitis
HPO: Encephalitis

Homozygosity for the rs6971 polymorphism on TSPO that results in LB (Owen et al 2011) (genotyping results).

Primary Outcomes

Measure: To assess if there is inflammation in the brain of alcoholics as measured with [11C]PBR28 and to determine if it recovers with 3 weeks of detoxification.

Time: 2020

Secondary Outcomes

Measure: To assess the impact of neuroinflammation on brain function (assessed with PET and 18FDG and with MRI for fMRI with task activation and for functional connectivity).

Time: 2020

Measure: To determine if the NP variables correlate with neuroinflammation.

Time: 2020

Measure: To determine if the measure of neuroinflammation predicts relapse in AD participants in the 3 month follow-up period.

Time: 2020

12 Biomarkers of Neuroinflammation and Anti-Inflammatory Treatments in Major Depressive Disorder

The purpose of this study is to determine if translocator protein total distribution volume (TSPO VT) is elevated in major depressive disorder that is not responding to medication and if adding minocycline can affect TSPO VT. Many remain treatment resistant with common antidepressant treatments and the investigators think it may be due to poor targeting of brain pathologies.

NCT02362529 Major Depressive Disorder Drug: Minocycline Drug: Placebo Drug: Celecoxib
MeSH: Disease Depressive Disorder Depression Depressive Disorder, Major
HPO: Depressivity

The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA.

Primary Outcomes

Description: TSPO VT will be measured using [18F]FEPPA positron emission tomography brain scans. Eligible MDE participants will be randomized to either minocycline or placebo. Following 8 weeks of either minocycline or placebo treatment, MDE participants will have a second PET scan .

Measure: Translocator total distribution volume (TSPO VT): Treatment Effect of Minocycline in MDE Subjects

Time: Pre- and post-minocycline or placebo treatment= 8 weeks total between pretreatment and posttreatment scans

Description: Compare baseline TSPO VT prior to treatment between MDE group and healthy group

Measure: Translocator total distribution volume (TSPO VT): Difference between MDE and healthy subjects

Time: Pre-treatment scan will take place up to 8 weeks from initial assessment

Secondary Outcomes

Description: Change in HDRS score following minocycline vs. placebo treatment. Change in HDRS score following celecoxib treatment.

Measure: Change in Hamilton Depression Rating Scale Score

Time: Pre- and post-minocycline treatment (8 weeks total between pre- and post-treatment). Pre- and post-celecoxib treatment (8 weeks total between pre- and post-treatment).

Other Outcomes

Description: To assess verbal memory we will administer the Hopkins Verbal Learning Test-Revised to MDE participants before and after treatment.

Measure: Hopkins Verbal Learning Test-Revised

Time: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)

Description: To assess visuospatial memory we will administer the Brief Visuospatial Memory Test-Revised to MDE participants before and after treatment.

Measure: Brief Visuospatial Memory Test-Revised

Time: Pre- and post-minocycline or placebo treatment (8 weeks between pre- and post-treatment measure)

Description: To assess psychomotor speed and attention we will administer the Comprehensive Trails Making Test to MDE participants before and after treatment.

Measure: Comprehensive Trails Making Test

Time: Pre- and post-minocycline or placebo treatment.

Description: The priority of the genetic sample is to analyze the alleles of polymorphism rs6971 which has an association with the affinity of most second generation TSPO ligands including [18F]FEPPA. The genetic sample will also be used to study sequences of genes that are believed to affect TSPO expression, inflammation, mood and conditions that may predispose to mood disorders.

Measure: Genetic sample

Time: Phase 1-single sample

Description: Analyses will include complete blood cell count (CBC), ESR, hepatic and renal function. Peripheral marker analyses will include proteins related to TSPO expression and inflammation. Plasma minocycline and celecoxib levels will be analyzed.

Measure: Blood samples (serum and plasma)

Time: Pre- and post-minocycline or placebo treatment (8 weeks between measures). Pre- and post-celecoxib treatment (8 weeks between measures).

13 Reproducibility of the 11C-PBR28 PET Signal

The Translocator Protein (TSPO) is a protein which reaches very high levels when there is inflammation in the brain. Recently, radioligands have been developed which attach to the TSPO (a radioligand is a drug which has been tagged with radioactivity). Using positron emission tomography (PET) imaging, the radioligand can be detected following injection into a patient. However, it is difficult to accurately measure the amount of TSPO using PET at the moment. This is because the brain does not have a "reference region" for TSPO (ie an area in the brain with no TSPO at all). "Reference regions" are very useful to help work out how much of a PET signal represents "specific binding" (of the radioligand to the target of interest), and how much represents "non specific binding" (of the radioligand to many other structures which are not of interest). In the absence of a reference region, non specific binding can be estimated by giving a drug which binds to the TSPO. The drug prevents the radioligand binding the TSPO and (in a manner of speaking) "creates" a temporary reference region so non specific binding can be measured. To do this, we will use XBD173 (Emapunil is an anxiolytic drug which acts as a selective agonist at the peripheral benzodiazepine receptor) to bind TSPO and block binding of the PET ligand ([11C]PBR28), a TSPO ligand from the phenoxyarlyacetamide class. Most TSPO PET studies (and in one of our previous studies approved by West London REC) quantify the signal using a ratio of specific binding in the brain to radioactivity in the blood. This requires arterial line insertion which is burdensome for subjects, and increases variability. In this study we aim to determine the ratio of specific binding in the brain to nonspecific binding in the brain by using the temporary reference region. For more accuracy the participants will repeat the scanning procedure so determine test-retest variability of the amount of TSPO.

NCT02086240 Neurodegenerative Disorders Drug: XBD173
MeSH: Neurodegenerative Diseases
HPO: Neurodegeneration

Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.. To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients.. Determination of test re-test variability of both BPND and VT for 11CPBR28 in healthy volunteers and MS patients.

Primary Outcomes

Description: Participants will be screened to determine TSPO genotype at the rs6971 polymorphism from a venous blood sample.

Measure: TSPO Binding Status

Time: Baseline/Screening visit

Other Outcomes

Description: Determination of test re-test variability of both BPND and VT for 11CPBR28 in healthy volunteers and MS patients. Subjects will receive a baseline 11C-PBR28 scan, and then a repeat scan following an oral dose of 90mg XBD173 (Emapunil). Both VT and BPND will be determined. Subjects will then return approximately 10 days later for a repeat of these procedures.

Measure: To determine test re-test variability of both BPND and VT for [11C]PBR28 in healthy volunteers and MS patients.

Time: 1st and 2nd Study Visit (approximately 10 days after the 1st study visit)

14 Effect of Modulating Gamma Oscillations by Transcranial Alternating Current Stimulation on Brain Structure and Function in Humans

This study aims to implement an intervention based on multiple, individualized multifocal tACS stimulation sessions based on individual PET and MRI information in patients with amyloid-positive PET with the hope that this leads to microglia activation and decrease in cerebral amyloid and tau depositions in human patients with AD.

NCT03412604 Alzheimer Disease Device: Transcranial Alternating Current Stimulation (tACS)
MeSH: Alzheimer Disease
HPO: Alzheimer disease

- Contraindication for undergoing MRI or receiving TMS or tACS, - >50 mSv of radiation exposure for research within the past year (PET imaging exclusion) - Presence of the Thr/Thr polymorphism in the TSPO gene (rs6971) due to low affinity binding for the PBR 28 (microlgia) PET scan - History of fainting spells of unknown or undetermined etiology that might constitute seizures.

Primary Outcomes

Description: Adverse Events as a result of tACS stimulation will be reported

Measure: Incidence of Treatment-Emergent Adverse Events

Time: Up to 12 weeks

Description: Changes in the amyloid load observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions

Measure: PET amyloid burden

Time: up to 12 weeks

Description: Changes in the tau deposition observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions

Measure: PET tau deposition

Time: up to 12 weeks

Secondary Outcomes

Description: Changes in the microglia activation observed via PET imaging will be evaluated by comparing PET data acquired before and after the 20 tACS sessions

Measure: PET Microglia activation

Time: up to 12 weeks

Other Outcomes

Description: Change in Adas-Cog score will be reported, to document a potential clinical benefit of tACS. The scale ranges from a total score of 0-70 with higher score indicating greater cognitive impairment.

Measure: Alzheimer's Disease Assessment Scale -Cog Score

Time: up to 12 weeks

15 Neuroinflammation After Myocardial Infarction - Imaging Substudy

The purpose of the study is to see if positron emission tomography and magnetic resonance imaging (PET/MRI) with an investigational drug called [18F]DPA-714 will show inflammation in the brain after a heart attack. This study may help physicians and researchers better understand the role of brain inflammation in heart disease and develop new treatments to protect the brain.

NCT03968445 Myocardial Infarction Diagnostic Test: [18F]DPA-714-PET/MRI
MeSH: Infarction Myocardial Infarction
HPO: Myocardial infarction

English speaking with at least 8th grade education 4. High or mixed affinity binder for TSPO ligands based on genotyping for single nucleotide polymorphism (SNP) rs6971.

Diagnosis of dementia 12. Low affinity binder for TSPO ligands based on genotyping for SNP rs6971.

Primary Outcomes

Description: The regional brain concentrations of [F-18]DPA-714, a PET imaging marker of neuroinflammation, will be compared between study participants who have recently been hospitalized for acute myocardial infarction (AMI) and a control group undergoing elective percutaneous coronary interventions (PCI).

Measure: TPSO-PET measurement of neuroinflammation after acute myocardial infarction

Time: 2 years

16 The Relationship Between Neuropsychological Testing and MRI, PET and Blood Biomarkers in Neurodegenerative Disease (COBRE - Project 1): AIM 2

The complex pathological cascades leading to both Alzheimer's disease (AD) and Parkinson's disease (PD) involve, at various points, inflammation. Since inflammation is a treatable symptom, understanding how and when it impacts the brain, and where specifically in the brain, would offer important guidance in the development of new treatments, sorely needed in both diseases. Microglia play an important anti-inflammatory role, and produce a substance, mitochondrial translocator protein (TSPO), whose presence can be used as a marker of regional inflammation. GE180 is a newly developed PET ligand which binds to TSPO and hence can be used in imaging studies to analyze regional inflammation in living patients. In prior studies it has shown regional specificity in multiple sclerosis and brain injury. In the current study, the investigators will be using GE180 to analyze regional and global inflammation in the brains of patients with AD and PD at two time points. The results of the current study will provide enriched understanding of inflammation in these conditions, and potentially provide preliminary data to inform design of future interventional trials.

NCT03702816 Alzheimer Disease Parkinson Disease Inflammation Diagnostic Test: GE180 PET Scan
MeSH: Parkinson Disease Inflammation Alzheimer Disease Neurodegenerative Diseases
HPO: Alzheimer disease Neurodegeneration

For MCI patients, fit criteria based in Movement Disorders Task Force or NIA Exclusion Criteria: 1. Significant neurological disorders other than AD or PD; 2. Unstable medical conditions 3. History of major psychiatric diseases 4. MRI evidence of infarction or other focal lesion or multiple lacunes 5. Clinically significant abnormalities in B12 or TSH 6. Identified as having a common polymorphism (rs6971) in the TSPO gene which has been shown to reduce binding affinity of tracers similar to GE180.

Primary Outcomes

Description: We will use a linear regression model to assess whether regional microglial activation is predictive of cognitive performance in domains of memory, visuospatial function, language, and executive functioning. These differing units of measurement collected through neuropsychological evaluation will be aggregated into one model in order to assess the correlations between regional activation and cognitive performance in any different domains.

Measure: Linear Regression Model Assessing Cognitive Performance and Regional Microglial Activation

Time: Baseline

Description: We will use repeated measures analyses to asses whether there is a significant change in microglial activation between year 1 scan and year 2 scan. We will then assess if this change in microglial activation over this time period relates to changes in cognitive measures.

Measure: Repeated Measures Analyses to Asses Change in Microglial Activation Over Time

Time: Baseline (Year 1) compared to Year 2

Description: We will use a linear regression model to assess whether global microglial activation is predictive of overall cognitive performance (as assessed with scores on the Dementia Rating Scale (DRS) and Montreal Cognitive Assessment (MoCA)).

Measure: Linear Regression Model Assessing Cognitive Performance and Global Microglial Activation

Time: Baseline

17 Non-Invasive Characterization in Cardiac Sarcoidosis

In a study of Cardiac sarcoidosis, a serious heart condition, a radiotracer is being used to examine inflammation.

NCT02017522 Cardiac Sarcoidosis Device: 11C-PBR PET
MeSH: Sarcoidosis

If you have two copies of a genetic variation called rs6971 which will prevent this tracer from generating high-quality images you may not participate.

Primary Outcomes

Description: The primary outcome of this study will be the ratio of 11C-PBR28 PET activity in myocardial regions with inflammation indicated by FDG PET and/or edema indicated by increased T2 signal with cardiac MRI compared to the 11C-PBR28 PET activity in myocardial segments which appear normal on FDG PET and cardiac MRI. The primary outcome is thus the intensity of uptake in abnormal regions as a percentage of the intensity of uptake in normal segments.

Measure: Ratio of 11C-PBR28 in the Myocardium

Time: 1 hour scan

Secondary Outcomes

Description: As a secondary outcome of this study we will evaluate the ratio of 11C-PBR28 PET activity in regions with fibrosis indicated by decreased myocardial perfusion on 82Rb PET and/or late gadolinium enhancement on cardiac MRI without imaging signs of active inflammation compared to 11C-PBR28 PET activity in myocardial segments which appear normal on 82Rb PET, FDG PET and cardiac MRI. This outcome will thus be expressed by 11C-PBR28 PET uptake in fibrotic regions as a percentage of uptake in normal segments We will also evaluate the concordance between extracardiac activity seen in 11C-PBR28 and FDG PET, and when available, histopathology of contemporaneous biopsy specimens.

Measure: The Ratio of 11C-PBR28 PET Activity in Cardiac Regions With Fibrosis

Time: 1 hour scan

18 Phase 0 Clinical Protocol: A Longitudinal and Multimodal Exploratory Study to Evaluate a Neuroinflammatory Hypothesis in Patients With Schizophrenia Compared to Young Healthy Subjects

Previous research has suggested central nervous system inflammatory activity to be critically involved in disease development and progression in schizophrenia, with a complex interplay of inflammatory mechanisms leading to the development of brain abnormalities and medical symptoms related to schizophrenia. However, the mutual interactions of different inflammatory pathways and their relation to disease course have not been sufficiently studied. This study therefore aims to explore the interaction of neuroinflammatory mechanisms in patients with schizophrenia and to assess whether the inflammatory activity in schizophrenia is state-dependent and occurs mainly during psychotic episodes.

NCT02009826 Schizophrenia Psychosis Radiation: [18F]-PBR111 Positron Emission Tomography (PET) Behavioral: Cognitive and psychomotor tasks Biological: Blood sampling
MeSH: Schizophrenia Psychotic Disorders Mental Disorders
HPO: Psychosis Schizophrenia

- Low affinity binder of the TSPO, as determined by rs6971 polymorphism genotyping at Screening - Use of benzodiazepines for 3x the half-life prior to PET-scan - Presence of irremovable magnetic materials in or on the body - Has a medical history of organic brain disease - Has a medical history of traumatic brain injury - Has a medical history of allergic reaction to any of the substances in the tracer fluid.

Primary Outcomes

Description: Regional distribution volume in tissue (VT) of 2-(6-chloro-2-(4-(3-fluoropropoxy)phenyl)imidazo(1,2-a)pyridin-3-yl)-N,N-diethylacetamide (PBR111) labelled with fluorine-18 (18F) in schizophrenia patients and age- , gender-, and translocator protein (TSPO) binding profile- matched healthy controls

Measure: Regional VT of [18F]PBR111

Time: 2 years

Secondary Outcomes

Description: Levels and ratios of inflammatory and neurotoxicity markers in blood samples of schizophrenia patients compared to healthy age- and gender-matched healthy controls.

Measure: Peripheral markers

Time: 2 years

19 Assessment of [11C]ER-176 to Image Translocator Protein in Brain and Whole-Body of Healthy Subjects

Background: - A protein called translocator protein may play a role in brain inflammation. Sometimes it is present at higher levels in the lungs than in the brain. Researchers want to see if a drug called [11C]ER176 can provide an image of this protein in the brain. Objective: - To test the ability of a drug to image a protein, and test how it is distributed in the body. Eligibility: - Healthy adults over age 18. Design: - Participants will be screened with medical history, physical exam, and blood and urine tests. - Participants will have a PET scan of the brain using [11C]ER176. It will be injected through an intravenous tube into 1-2 arm veins. A tube may also be put into an artery at the wrist or elbow. Some participants will also have a lung scan. - For the PET, participants will lie on a bed that slides in and out of a doughnut-shaped scanner. A plastic mask will be molded to their face and head. They may be wrapped with restraining sheets. The scan will last about 120 minutes. Blood may be taken during the scan. - Blood and urine will be taken before and after the scan. - During another visit, participants will have an MRI scan of the brain. Participants will lie on a table that slides in and out of a metal cylinder. A strong magnetic field and radio waves will take pictures of the brain. The scanner makes loud knocking noises. Participants will be given earplugs. - Some participants will have only a whole-body PET scan using [11C]ER176.

NCT02147392 Pharmacokinetics Adult Drug: [11C]ER-176

Although [(11)C]PBR28 has high in vivo specific signal, it is very sensitive to the high and low affinity states of TSPO, which are caused by the rs6971 single nucleotide polymorphism (SNP) in the fourth exon of the TSPO gene resulting in a nonconservative alanine-to-threonine substitution in position 147 of the encoded TSPO protein.

Primary Outcomes

Measure: The identifiability and time stability of distribution volume calculated with compartmental modeling and evaluate the genotype sensitivity of [11C]ER-176

Time: 1 year

Secondary Outcomes

Measure: Whole-body biodistribution and dosimetry of [11C]ER-176.

Time: 1 year

20 Targeting Microglial Activation for Treatment of Autism Spectrum Disorder (ASD): A Proof-of-Concept, Target-Engagement Study

Autism spectrum disorders (ASD) are highly disabling, persistent neurodevelopmental disorders. There are no available treatments for core symptoms of ASD or biologically-based clinical biomarkers. Emerging evidence indicates that levels of brain inflammation are increased in ASD. In particular, recent work implicates hyperactivity of microglial cells, the resident immune cells of the brain. However, the functional consequences of microglial activation remain unknown. This study will measure microglial activation in ASD using positron emission tomography (PET) brain imaging. Adult males with ASD (n=15) and healthy controls (n=15) will be recruited for this study and undergo comprehensive clinical and behavioral baseline assessment. All subjects will then undergo baseline PET imaging using a radiotracer that labels activated microglia. Subjects with ASD will then undergo 12-week open label treatment with minocycline, an FDA-approved antibiotic thought to block microglial activation. PET imaging will be repeated at 12 weeks to confirm target engagement. A subset of control subjects will also undergo repeat PET imaging to determine test-retest reliability. During minocycline treatment, ASD subjects will be evaluated every 2 weeks for safety, clinical impression, behavioral functioning, and measures of cognition. Results will provide important information regarding the relationship between levels of brain inflammation, cognitive and behavioral function in ASD.

NCT03117530 Autism Spectrum Disorder Drug: Minocycline
MeSH: Autistic Disorder Autism Spectrum Disorder Child Development Disorders, Pervasive Encephalitis
HPO: Autism Autistic behavior Encephalitis

hepatic, neurologic, renal disease) to increase risk to the subject 3. Presence of severe behavioral disturbance likely to require initiation of treatment during the course of the protocol 4. Clinical judgment of the study physician of inability to perform the requirements of the study 5. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, or benzodiazepines 6. Homozygous genotype for minor allele of rs6971 7. History of recent febrile illness in past 30 days 8. History of allergic reactions to tetracycline antibiotics 9. Concomitant medication treatment not stable for the 4 weeks prior to study entry or anticipated to change 10.

hepatic, neurologic, renal disease) to increase risk to the subject 4. Presence of current or lifetime severe psychopathology potentially confounding assessment of TSPO binding (psychosis, severe depression, bipolar disorder, Obsessive-Compulsive Disorder) 5. Current prescribed medication likely to confound assessment of TSPO binding 6. Clinical judgment of the study physician of inability to perform the requirements of the study 7. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, benzodiazepines, or psychotropic medications likely to confound assessment of TSPO binding 8. Homozygous genotype for minor allele of rs6971 9. SRS-2 T-score score of >59 10.

Primary Outcomes

Measure: Evaluate differences in CNS microglial activation in adults with ASD versus healthy volunteers via in vivo CNS binding of [11C]-DAA1106

Time: Data will be collected at PET scan #1, which will take place during screening (Days -28 to 0) for the study

Measure: Evaluate the effect of 12-weeks of minocycline exposure on CNS microglial activation in adults with ASD by measuring change in [11C]-DAA1106 binding pre- and post- treatment

Time: Data will be collected at PET scan #1 (between days -28 and 0 before intervention) and at PET scan #2 during Week 12 of intervention

Secondary Outcomes

Measure: Effect of minocycline exposure on cognition across seven cognitive domains before and after low dose intervention and regular dose intervention as measured by MCCB (MATRICS Consensus Cognitive Battery) subdomain scores

Time: Data will be collected at baseline and during Weeks 6 and 12 of intervention

Measure: Effect of minocycline exposure on self-rated anxiety and emotion regulation as measured by ADAMS (Anxiety and Depression Mood Scale)

Time: Data will be collected at baseline and during Weeks 6 and 12 of intervention

Measure: Effect of minocycline exposure on peripheral inflammatory cytokine profiles as measured by DNA and RNA expression in blood samples

Time: Data will be collected PET #1 (week 0) and at PET scan #2 (Week 12)

Other Outcomes

Measure: Change in clinician-rated global improvement as measured by CGI

Time: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention

Measure: Change in self-reported symptoms of ASD with minocycline treatment as measured by SRS-2

Time: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention

Measure: Change in informant-reported symptoms of ASD with minocycline treatment as measured by ABC-CV

Time: Data will be collected at Screening Visit #1 (between days -28 and 0 before intervention) and at visits during Weeks 6 and 12 of intervention

21 A [C-11]-PBR28 Positron Emission Tomography Study to Evaluate the Effect of ABT-555 on Central Nervous System Inflammation in Subjects With Relapsing Forms of Multiple Sclerosis

This open-label positron emission tomography (PET) study is designed to determine the effect of ABT-555 on translocator protein expression level in participants with relapsing forms of multiple sclerosis.

NCT02606630 Multiple Sclerosis Drug: ABT-555
MeSH: Sclerosis Multiple Sclerosis

Inclusion Criteria: Diagnosis of relapsing-remitting MS (RRMS) or relapsing secondary progressive MS (SPMS) Neurologically stable at Screening, in the investigator's judgment and not actively experiencing or recovering from a recent relapse in the 30 days preceding the Screening Visit A Kurtzke Expanded Disability Status Scale (EDSS) score of 1.0 to 6.0, inclusive at the Screening Visit High or mixed affinity binder of the TSPO, as determined by rs6971 polymorphism genotyping at screening Exclusion Criteria: Diagnosis of primary progressive or non-relapsing secondary progressive MS Smoking more than 10 cigarettes per day or use of a nicotine patch Known history of, or positive screening test result for hepatitis C virus or hepatitis B virus Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before Screening Any type of live virus vaccine from 4 weeks before randomization History of abnormal laboratory results Inclusion Criteria: Diagnosis of relapsing-remitting MS (RRMS) or relapsing secondary progressive MS (SPMS) Neurologically stable at Screening, in the investigator's judgment and not actively experiencing or recovering from a recent relapse in the 30 days preceding the Screening Visit A Kurtzke Expanded Disability Status Scale (EDSS) score of 1.0 to 6.0, inclusive at the Screening Visit High or mixed affinity binder of the TSPO, as determined by rs6971 polymorphism genotyping at screening Exclusion Criteria: Diagnosis of primary progressive or non-relapsing secondary progressive MS Smoking more than 10 cigarettes per day or use of a nicotine patch Known history of, or positive screening test result for hepatitis C virus or hepatitis B virus Varicella or herpes zoster virus infection or any severe viral infection within 6 weeks before Screening Any type of live virus vaccine from 4 weeks before randomization History of abnormal laboratory results Multiple Sclerosis Sclerosis Multiple Sclerosis null

Primary Outcomes

Description: Compare 2 dynamic positron emission tomography scans to examine the effect of a single administration of ABT-555 on translocator protein expression

Measure: Change in translocator protein expression

Time: Day 0 and 109 days


HPO Nodes


Encephalitis
Genes 30
IL10 IKBKG IL12A L2HGDH XIAP CCR1 UBAC2 C4A BCL10 LBR ATRX HLA-B FAS SH2D1A CIITA ERAP1 RFX5 RFXAP IL12A-AS1 KLRC4 PRF1 RFXANK MEFV IL23R STAT1 BTK STAT4 TMEM70 TLR4 SLC6A19
Neurodegeneration
Genes 72
VAPB CCNF RNASEH2B IFIH1 NEFH PPARGC1A TARDBP TREX1 NEK1 WDR45 ERBB4 CHCHD10 OPTN GALC PANK2 ZBTB20 UBQLN2 ANG AARS2 RNASEH2A ATXN2 FIG4 FOLR1 GLE1 PDE8B SQSTM1 GUSB UBTF FA2H UCHL1 C19ORF12 MATR3 TBK1 ANXA11 RNASEH2C NAXD ATXN3 TREM2 PON1 PON2 PON3 GM2A DAO NBN PLA2G6 FTL SAMHD1 MFSD8 TAF15 ABCD1 FUS COASY TANGO2 IDS C9ORF72 PFN1 IDUA TXN2 ADAR DCTN1 LYST HNRNPA1 UNC13A NARS2 CFAP410 TTC19 PCNA SOD1 VCP CHMP2B EPHA4 PRPH
Alzheimer disease
Genes 6
PSEN2 CACNA1G APOE APP GATA1 PSEN1
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
Autistic behavior
Genes 282
GABRB2 SOX2 MKRN3 GABRB3 SOX3 GPHN GABRD SNORD115-1 UBA5 ATP6V1A RAB11B AARS CNNM2 PDE4D DYM ZBTB20 HIVEP2 PIGP WWOX FRMPD4 HDAC4 PSEN1 MAOA ACADL ATRX MICOS13 TMEM237 MAPT SLC35C1 NEXMIF KDM5C ZNF423 SMC1A ACOX1 BCKDK IQSEC2 TMEM216 NAGA HDAC8 ASH1L NAA10 GATM IPW PWRN1 DHDDS FTSJ1 SRY TSC1 CHD1 TSC2 CHD2 NDN RPS23 NDP PLXND1 RREB1 PTEN BCOR MECP2 MEF2C CHRNA7 SNORD116-1 HESX1 HNRNPH2 MEIS2 NDUFS4 DDX3X TBC1D24 HIRA SYNGAP1 CDKL5 KMT2C TUBB3 GJA5 GJA8 ARID1B KCNA2 NEUROD2 STXBP1 NLGN4X ADSL CLCN4 ALMS1 KCNB1 SYNJ1 NALCN PROKR2 ST3GAL5 UBE3A PIK3CA NFIB SQSTM1 HECW2 SCN1A DHCR7 PCDH19 SCN3A UFD1 ARNT2 CLTC SCN8A NPAP1 SYN1 SMG9 ALDH18A1 CC2D2A AP1S2 KMT2A PACS2 NHS AKT1 FGF12 FGFR1 GNAQ TAF1 PWAR1 HERC2 CAMTA1 TMEM231 DNM1 CLP1 ALDH5A1 NIPBL KCNT1 SLC9A6 MED12 FOXG1 SEC23B TBX1 SDHB SDHC AGTPBP1 VCP SDHD GP1BB RAD21 TBX2 TLK2 CACNA1A CACNA1C TCF4 DPYD C12ORF4 PIGL HNF1B SATB2 CUX2 MAGEL2 DEAF1 NAA15 TCF12 FMR1 RARS AFF2 COMT ARV1 CLIP2 MBOAT7 SZT2 WFS1 PUF60 PPM1D HCN1 NTRK2 CEP290 NDUFAF3 RNF135 KCNAB2 DYRK1A ARFGEF2 TMEM138 BAZ1B GRIA3 TWNK GRN CNKSR2 CHD7 SIN3A GRIN1 ST3GAL3 SPECC1L POMT1 GRIN2D REV3L SIM1 MED13L RFC2 GTF2IRD1 SKI ADNP SLC1A2 CREBBP YWHAG JMJD1C SHANK3 SH2B1 MSTO1 RSPRY1 ZFPM2 CYFIP2 OPHN1 NECAP1 CHMP2B TRAK1 MKRN3-AS1 EEF1A2 SLC6A1 IL1RAPL1 NDUFA13 LHX1 SLC6A8 TMEM106B PPP2CA SNX14 LIMK1 SETD2 SLC35A3 KLLN NDUFAF4 OTX2 GTF2I PPP3CA SLC25A12 STS EGF SEC24C COX1 COX2 COX3 ARVCF SMC3 KMT5B CTCF SETD5 SLC25A1 OTUD6B NUS1 ND1 AP3B2 ND4 ND5 CXORF56 ND6 PAH CNTNAP2 TREM2 ANKRD11 EHMT1 AUTS2 PRKAR1A FLCN SLC13A5 TRNF RORA DEPDC5 TRNH ELN TRNL1 RERE TBR1 TRNQ TBC1D23 ATP1A3 TRNS1 TRNS2 C9ORF72 TRNW MAPK10 GFM1 MCTP2 PRDM16 SNRPN STAG2 TBL2 EP300 CDH15 RAI1 SMAD4 PRODH SEMA3E SON ALG13
Abnormal anterior horn cell morphology
Genes 12
CPLANE1 VRK1 IGHMBP2 UBA1 TFG SOD1 SETX CEP126 ASAH1 GLE1 SMN1 ATXN3
Psychosis
Genes 94
NPC1 NHLRC1 MKRN3 SNORD115-1 CACNA1A SLC12A6 CLN8 TMEM106B USP8 PRDM8 EPM2A MAGEL2 PANK2 PSEN1 COX1 COX2 COX3 ACADS PDGFB PDGFRB MAPT ZDHHC9 ATXN7 WFS1 SOBP SQSTM1 SLC20A2 CLN3 PARK7 RPS6KA3 PCDH19 ND1 TBC1D7 ND4 ND5 SLC6A19 ND6 PAH VPS13A NPAP1 TREM2 DCAF17 IPW PRKAR1A PWRN1 PAK3 SPART ALDH18A1 CDH23 HMBS TWNK TRNF ZFYVE26 GRN NPC2 ALAD TRNH NDN NDP UPF3B ABCD1 TRNL1 AIP GNAS PWAR1 HERC2 TRNQ TRNS1 TRNS2 C9ORF72 SLC7A7 TRNW ITM2B ATP13A2 CBS ALDH5A1 MECP2 LMBRD1 KCNT1 SNRPN MED12 SH2B1 SNORD116-1 NAGS PRNP MYORG TTC19 VCP GSS CHMP2B DNMT1 PPOX PDE11A MKRN3-AS1
Autism
Genes 168
GABRB2 SOX2 MKRN3 SOX3 GABRD SNORD115-1 CACNA1A UBA5 CACNA1C ATP6V1A DPYD PIGL AARS HNF1B SATB2 MAGEL2 PDE4D DYM ZBTB20 TCF12 FMR1 WWOX HDAC4 COMT MAOA ARV1 ATRX CLIP2 SZT2 WFS1 SLC35C1 HCN1 KDM5C SMC1A NTRK2 BCKDK IQSEC2 NAGA HDAC8 KCNAB2 DYRK1A GATM IPW PWRN1 BAZ1B DHDDS GRIA3 FTSJ1 TSC1 TSC2 CNKSR2 NDN CHD7 NDP SIN3A PLXND1 GRIN2D REV3L SIM1 MED13L RFC2 RREB1 PTEN GTF2IRD1 SKI SLC1A2 CREBBP MECP2 YWHAG JMJD1C SHANK3 SH2B1 CHRNA7 SNORD116-1 HESX1 MEIS2 CYFIP2 OPHN1 NECAP1 TRAK1 HIRA MKRN3-AS1 EEF1A2 SYNGAP1 IL1RAPL1 LHX1 GJA5 GJA8 LIMK1 KLLN OTX2 GTF2I KCNA2 PPP3CA STS STXBP1 NLGN4X ADSL SEC24C COX1 ALMS1 KCNB1 COX2 COX3 SYNJ1 PROKR2 ARVCF SMC3 SETD5 UBE3A PIK3CA NFIB DHCR7 NUS1 ND1 SCN3A AP3B2 UFD1 ND4 ARNT2 ND5 CLTC ND6 PAH SCN8A NPAP1 ANKRD11 EHMT1 AUTS2 PRKAR1A FLCN KMT2A NHS SLC13A5 TRNF AKT1 FGF12 FGFR1 TRNH ELN TRNL1 RERE PWAR1 HERC2 TRNQ TRNS1 DNM1 TRNS2 TRNW PRDM16 ALDH5A1 NIPBL SNRPN SLC9A6 MED12 TBL2 EP300 SEC23B TBX1 SDHB RAI1 SDHC SDHD SMAD4 SEMA3E GP1BB RAD21 ALG13
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
Amyotrophic lateral sclerosis
Genes 44
VAPB TREM2 CCNF PON1 PON2 PON3 NEFH DAO PPARGC1A TARDBP NEK1 ALS2 SPG11 ERBB4 CHCHD10 TAF15 OPTN SETX FUS UBQLN2 ANG PSEN1 C9ORF72 PFN1 DCTN1 ATXN2 FIG4 SIGMAR1 MAPT HNRNPA1 GLE1 HNRNPA2B1 TUBA4A SQSTM1 UNC13A CFAP410 MATR3 TBK1 ANXA11 SOD1 VCP CHMP2B EPHA4 PRPH
Myocardial infarction
Genes 67
MPL IL10 JAK2 TET2 RAF1 SLC2A10 LDLRAP1 IL12A HGD IL12B LIMK1 ABCA1 MYH9 PTPN11 GTF2I GLA PIGA LMNA BRAF MLX HLA-B SH2B3 CLIP2 ERAP1 CALR IL12A-AS1 ENPP1 FOS LPL CFTR CYP27A1 AGPAT2 TLR4 DYRK1B WRN SCNN1A SCNN1B SCNN1G BAZ1B CCR1 UBAC2 APOA1 C4A IKZF1 APOB CAVIN1 BSCL2 ELN CAV1 CTNNB1 PPARG RFC2 GTF2IRD1 FAS CBS LDLR KLRC4 ABCC6 TBL2 ABCG5 ABCG8 MEFV IL23R TP53 STAT4 PCSK9 CEP19
Mental deterioration
Genes 266
NHLRC1 GABRB2 HEXA GABRB3 HEXB UBA5 CLN8 SDHAF1 ATP6V1A TREX1 AARS ATP6V1E1 CTSF CHCHD10 ERCC2 GALC HTRA1 ERCC4 ERCC6 SPAST ATP7B PSAP WWOX PSEN1 PSEN2 PDGFB PDGFRB MAPT DISC2 VPS13C SMC1A MATR3 APTX CYP27A1 ACTB NAGLU LRRK2 CPLX1 GBA GBE1 DHDDS NBN IRF6 CHD2 GCH1 NDP NDUFA6 PDE10A TIMMDC1 HNF4A DCTN1 ADA2 HNRNPA1 NDUFB8 TTPA ABCA7 MECP2 TTR HNRNPA2B1 TUBA4A NDUFS2 MYORG SNORD118 TBC1D24 SPG21 SYNGAP1 ERCC8 TYROBP HEPACAM TIMM8A TUBB4A PRDM8 PANK2 KCNA2 SERPINI1 PNPLA6 STXBP1 MBTPS2 GLB1 AARS2 KCNB1 KCNC1 SYNJ1 TINF2 ATXN2 ATXN7 PTS SQSTM1 SGPL1 UBTF CLN3 ABCC8 SURF1 CLN5 AP5Z1 SCN1A DGUOK C19ORF12 SUMF1 KCNJ11 UCP2 SCN3A CLTC SCN8A VPS13A ATXN3 FBXO7 DCAF17 CLN6 MFN2 GM2A ALDH18A1 KMT2A RNF216 PLA2G6 FGF12 TOMM40 ATXN10 ABCD1 GNAS RAB39B DNM1 QDPR ITM2B PLP1 RAB27A SDHA NOTCH3 SDHB VCP SDHD DNMT1 PDE11A TBP NPC1 KCTD7 CACNA1A SCO2 HNF1A CUX2 DNAJC13 EPM2A ROGDI UBQLN2 FMR1 AMN NRAS ATN1 ARV1 PLEKHG4 SZT2 CISD2 PRICKLE1 CTC1 WFS1 HCN1 FA2H NTRK2 RRM2B POLG NDUFAF3 HGSNAT NR4A2 DNM1L CP TWNK GRN NPC2 SPG11 CNKSR2 XPA GRIN2D RBM28 APOE CUBN APP IDUA TYMP GBA2 ATP13A2 MCOLN1 SLC1A2 YWHAG OPA1 SLC2A3 MMACHC CYFIP2 NECAP1 CHMP2B TRAK1 EEF1A2 SLC6A1 TMEM106B TARDBP COL18A1 WDR45 PPP2R2B ARSA PPP3CA SNCAIP CSF1R ATP6 TRNC COX1 LMNB1 COX2 COX3 PPT1 CYTB ASAH1 TK2 SLC20A2 SCARB2 TBK1 NUS1 ND1 AP3B2 VPS35 ND5 PRDX1 EIF4G1 ND6 PAH CST3 CNTNAP2 TREM2 CSTB PRKAR1A PRKAR1B GIGYF2 DNAJC5 SLC13A5 TRNE TRNF PRKCG ZFYVE26 FTL BSCL2 MFSD8 HSD17B10 TRNK TRNL1 CTNS FUS COASY CERS1 TRNQ SNCB ATP1A2 ATP1A3 TRNS1 SNCA TRNS2 C9ORF72 RNASEH1 TRNV TRNW MAPK10 CTSD PRNP HTT ATP6V0A2 PINK1 JPH3 XPR1 SORL1