SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02931487

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Restoring Emotion Regulation Networks in Depression Vulnerability: An Experimental Study Applying an Attention Bias Modification Procedure

Selective biases in attention can be modified by a simple computerized technique: The Attention Bias Modification Task (ABM) pioneered by MacLeod et al. Cognitive biases may be one reason depression recurs, and altering these biases should reduce risk of recurrence. Recently, evidence has supported this hypothesis . The mechanisms by which ABM works are not well understood. More research is needed to explore how altering an implicit attentional bias can lead to changes in subjective mood. One possible explanation is that positive attentional biases are an important component of explicit methods of emotion regulation. The ability to effectively regulate one's emotions is a fundamental component of mental health and this ability is impaired in depression. It has also been shown that recovered depressed people spontaneously show a more dysfunctional pattern of emotion regulation as compared to never depressed controls. Supporting this, growing evidence implicates dysregulation of a medial/orbitofrontal circuit in mood disorders. This circuit includes the orbitofrontal cortex and anterior cingulate cortex, the ventral striatum, the ventral pallidum and medial thalamus. Components of this circuit are reciprocally connected with the amygdala, which is implicated in emotional processing in the healthy brain and dysregulated in depression. Negative emotion processing biases depend on both enhanced "bottom-up" responses to emotionally salient stimuli and reduces "top-down" cognitive control mechanisms, required to suppress responses to emotionally salient but task irrelevant information. Cognitive reappraisal and distancing are common strategies to down- or upregulate emotional responses. Reappraisal is an emotion regulation strategy that involves reinterpretation and changing the way one thinks about an event or stimulus with the goal of changing its affective impact. Distancing is a type of reappraisal that involves creating mental space between oneself and the emotional event in order to see things from a different, less self-focused perspective. It has been shown that distancing is a strategy that people can improve at over time compared to reinterpretation. The neural systems which support the explicit regulation of emotion have previously been characterized and include both lateral- and prefrontal cortex. This frontal activity is predicted to downregulate limbic circuitry involving the amygdala during passive viewing of emotional salient stimuli.

NCT02931487 Major Depression
MeSH: Depression Depressive Disorder Depressive Disorder, Major
HPO: Depressivity

2 Interventions

Name: Attentional Bias Modification

Description: Computerized

Type: Behavioral

Attentional Bias Modification

Name: Sham Comparator

Description: Computerized

Type: Behavioral

Sham comparator


Primary Outcomes

Description: Stronger fMRI BOLD response in prefrontal cortical regions in ABMT compared to neutral AMB placebo condition.

Measure: BOLD response in prefrontal cortical regions

Time: Two weeks after after ABM-training

Secondary Outcomes

Description: Lower ABM fMRI BOLD response within the amygdala in ABMT compared to neutral ABM placebo condition.

Measure: BOLD response within the amygdala

Time: Two weeks after ABM-training

Description: Increased neural integrity as measured by fractional anisotropy values in the uncinate fasciculi (UF) in the active AMBT compared to neutral ABM placebo condition.

Measure: DTI

Time: Two weeks after ABM-training

Description: Increased integrity within the attentional networks at rest as measured by independent component analysis (ICA) in ABMT compared to neutral ABM training.

Measure: RSFC

Time: Two weeks after ABM-training

Description: The low expressive variant will be associated with more frontal BOLD activation and lower amygdala activation after ABMT

Measure: 5-HTTLPR + A>G polymorphic variation divided by the triallelic functional "high expressive" versus "low expressive" genotype will moderate the impact from ABMT as measured by whole brain BOLD responses.

Time: Two weeks after ABM-training

Description: Brain Derived Neurotropic Factor (BDNF) val66met polymorphic variation linked to Brain Derived Neurotropic Factor (BDNF) variation will differentiate between ABMT and neutral AMB placebo as measured by fMRI whole brain BOLD responses.

Measure: BDNF

Time: Two week after ABM-training

Description: A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on fMRI BOLD signal compared to a neutral placebo condition.

Measure: Serotonergic cumulative genetic score and fMRI

Time: Two weeks after ABM-training

Description: A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on structural MRI as measured by total grey matter volume compared to a neutral placebo condition.

Measure: Serotonergic cumulative genetic score and morphompetry

Time: Two weeks after ABM-training

Description: A serotonergic cumulative Genetic score, including (5-HHTLPR, HTR1A 8rs6295) and HTR 2A (rs 6311) polymorphisms will moderate the effects of ABM on DTI MRI as measured by fractional anisotropy compared to a neutral placebo condition.

Measure: Serotonergic cumulative genetic score and fMRI and DTI

Time: Two weeks after ABM-training

Purpose: Prevention

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 V66M

Brain Derived Neurotropic Factor (BDNF) val66met polymorphic variation linked to Brain Derived Neurotropic Factor (BDNF) variation will differentiate between ABMT and neutral AMB placebo as measured by fMRI whole brain BOLD responses.. Serotonergic cumulative genetic score and fMRI. --- val66met ---



HPO Nodes


HPO:
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