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Report for Clinical Trial NCT02931487

Developed by Shray Alag, 2020.
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
HPO:Depressivity

2 Interventions

Name: Attentional Bias Modification

Description: Computerized
Type: Behavioral
Group Labels: 1

Attentional Bias Modification

Name: Sham Comparator

Description: Computerized
Type: Behavioral
Group Labels: 1

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:
HP:0000716: Depressivity
Genes 381
TRNF ARSG FUS ANG PDE11A GLE1 SARS1 PLA2G6 NEK1 SLC18A2 HLA-DRB1 FMN2 TRNS2 XK SMPD1 HTT CHD7 ATXN10 SNCAIP TCF4 ATP1A3 GPR101 DRD2 PDGFB OPTN TWNK RRM2B GBA KCNT1 BCR JPH3 NOTCH3 PDCD1 PAH PIGC HTR2A PRKN DNMT1 TRNL1 ZC3H14 ST3GAL3 USH1G LMNB1 LIMK1 SNCA ADH1C ATRX OCRL PRKACA TBL2 FMR1 PRNP CPOX USP8 PPARGC1A UCHL1 VPS13C GLUD2 KCNJ2 TBK1 MST1 TWNK MSTO1 MAPT B3GALNT2 PPP2R2B PROKR2 PRNP XPR1 RPS20 POLG SQSTM1 ARMC5 NDST1 TRNN TARDBP USH2A TRNL2 GNAS DCPS STX16 TTC19 ATXN10 SLC20A2 TBX1 CSF1R GSN ND1 ATP7B CDH23 TAC3 MYO7A WFS1 TWNK PDGFRB HS6ST1 PRKCG ESPN COX2 HIRA GNAS CLCN4 CASR ARSA GABRA1 GCH1 DNA2 MAPT UBQLN2 GDAP2 FGF8 TOR1A SEMA4A TK2 UFD1 FUS DGUOK EPM2A HARS1 C9ORF72 POLG UNC13A PODXL TBK1 LRRK2 CLIP2 HTRA2 DCTN1 TRAPPC9 C19ORF12 PLA2G6 MATR3 C12ORF4 GRIK2 SLC6A4 PRNP MECP2 CP HLA-DQB1 CFAP410 CACNA1G MED23 AARS2 VCP TRNQ PRNP JMJD1C SRPX2 VAPB MYO7A SGCE CC2D1A VPS35 ABCA7 CCNF EHMT1 C9ORF72 SNCA MLH1 PANK2 DUSP6 CEP78 GABRB3 FIG4 NR4A2 BMPR1A PTPN22 PARK7 MECP2 DNMT1 WASHC4 TRNS1 CACNA1G AMACR VCP ALMS1 IDUA CHMP2B PMS1 GIGYF2 KISS1R TSC1 RPS6KA3 COQ2 ERBB4 KDM5B POLG2 SEC24C SLC2A1 COQ2 DNAJC13 MSTO1 MSH6 FBXO31 RRM2B CHMP2B HTT POLG EDC3 PGAP1 NSMF SLC25A4 ATXN2 PIK3CA THOC2 PER2 GLA CACNA1H TBC1D7 PAH SQSTM1 POLG GNAS PRNP AIMP1 ARMC5 CIB2 LINS1 GABRG2 FGFR1 C9ORF72 CDH23 METTL23 TACR3 EPCAM TRNS1 PPOX KRAS ANOS1 SLC45A1 WARS2 POLG FA2H COASY HLA-DQB1 GNAS TRNL1 PRSS12 CLN6 GBA PMS2 C9ORF72 CLCN4 HBB TSC2 PDGFB AIP PRKAR1A COMT MAPT DNAJC5 CRADD ATXN8 ATXN2 ATP13A2 ARVCF GTF2I WHRN GBA TRNW COX3 KISS1 TREM2 TGFBR2 PDZD7 AFG3L2 PDGFRB BCS1L MAN1B1 SNCA VCP NEFH TRNH COX1 ATP1A3 DAO CPOX PINK1 LRRK2 HMBS CRBN DCTN1 CTSF GPR35 CLIP1 TBX1 ND5 TAF15 ND4 PTS PON3 MED25 DNAJC6 TRNS2 NSUN2 FMO3 SPAST HMBS FGF17 ELN PON1 CBS CYP27A1 FGF14 PSAP FMR1 TMEM106B KCTD17 RREB1 CHCHD10 TWNK TBP AP2S1 ATXN8OS FRRS1L ATXN8OS BAZ1B HNMT FAN1 ADGRV1 PINK1 HNRNPA1 PRPH TUSC3 MBOAT7 PRNP PANK2 FGF14 GABRG2 KCTD17 PDGFRB TECR LMAN2L EIF4G1 GNAS CLRN1 EPHA4 GP1BB JRK IQSEC1 TREM2 MSH2 PSEN1 RFC2 PON2 MAPK1 SGCE PER3 PROK2 GRIN2A TNIK PFN1 MLH3 GRN ND6 CRKL ANXA11 C9ORF72 GNRHR EZR VCP USH1C GNRH1 TOR1A WFS1 POLG NHLRC1 CISD2 CHCHD10 WDR11 SPRY4 PPT1 PCDH15 TBP GTF2IRD1 SOD1 RSRC1 GLT8D1 DCTN1 GNA11 TARDBP