TOMM40 rs2075650 may represent a new candidate gene for vulnerability to major depressive disorder.

Evidence suggests that depression is a risk factor for dementia; however, the relationship between the two conditions is not fully understood. A novel gene (TOMM40) has been consistently associated with Alzheimer's disease (AD), but has received no attention in depression. We conducted a three-level cross-sectional study to investigate the association of the TOMM40 rs2075650 SNP with depression.

Genetic variants in the catechol-o-methyltransferase gene are associated with impulsivity and executive function: relevance for major depression.

The catechol-o-methyltransferase (COMT) gene has been extensively investigated in depression with somewhat contradictory results but the role of impulsivity, as a possible intermediate phenotype in this disorder, has not been considered yet. In our study, four tagging SNPs in the COMT gene (rs933271, rs740603, rs4680, rs4646316) were genotyped in two independent population cohorts: Manchester (n = 1267) and Budapest (n = 942). First, we investigated the association between COMT genotypes, impulsivity, neuroticism and depression using haplotype trend regression, and constructed a model using structural equation modeling to investigate the interaction between these factors.

State-dependent alteration in face emotion recognition in depression.

Background: Negative biases in emotional processing are well recognised in people who are currently depressed but are less well described in those with a history of depression, where such biases may contribute to vulnerability to relapse.

Aims: To compare accuracy, discrimination and bias in face emotion recognition in those with current and remitted depression.

Method: The sample comprised a control group (n = 101), a currently depressed group (n = 30) and a remitted depression group (n = 99).

The CREB1-BDNF-NTRK2 pathway in depression: multiple gene-cognition-environment interactions.

Background: The neuroplastic pathway, which includes cyclic adenosine monophosphate response element-binding protein 1 (CREB1), brain-derived neurotrophic factor (BDNF), and its receptor (neurotrophic tyrosine kinase receptor, type 2 [NTRK2]), plays a crucial role in the adaptation of brain to stress, and thus variations of these genes are plausible risk factors for depression.

Methods: A population-based sample was recruited, subsets of which were interviewed and underwent functional magnetic resonance imaging. We investigated the association of nine polymorphisms throughout the CREB1-BDNF-NTRK2 pathway with lifetime depression, rumination, current depression severity, negative life events, and sad face emotion processing in a three-level design.

The HTR1A and HTR1B receptor genes influence stress-related information processing.

The serotonergic system has been widely implicated in stress related psychiatric disorders such as depression and anxiety. We investigated the possible association between depression and anxiety scores and SNPs within the HTR1A and HTR1B genes in a population sample (n=1387). There was no direct SNP-phenotype association, but in interaction with recent stressful life events rs6295 G, rs878567 T alleles and rs6296 C alleles were associated with significantly higher symptom scores.

Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders.

Decision making, choosing the best option from the possible outcomes, is impaired in many psychiatric conditions including affective disorders. We tested the hypothesis that variations in serotonergic genes (TPH2, TPH1, SLC6A4, HTR1A), which influence serotonin availability, affect choice behavior in a probabilistic gambling task. A population cohort (N=1035) completed a paper-and-pencil gambling task, filled out personality and symptom questionnaires and gave consent for the use of their DNA in a genetic association study.

Variations in the cannabinoid receptor 1 gene predispose to migraine.

In animal models endogenous cannabinoids have an inhibitory effect on trigeminovascular activation through the cannabinoid receptor 1 (CB1), although there is no evidence of the potential role of CB1 in human migraine. In this study we applied single marker association and haplotypic trend regression analysis to investigate the relationship between the CB1 gene (CNR1) and headache with migraine symptoms (nausea, photophobia and disability, measured by the ID-migraine questionnaire). We identified our controls (CO=684) as those who have not reported ID-migraine symptoms at all and defined migraine headache sufferers (M=195) as those who reported all three symptoms.

CNR1 gene is associated with high neuroticism and low agreeableness and interacts with recent negative life events to predict current depressive symptoms.

Cannabinoid receptor 1 (CB1) gene (CNR1) knockout mice are prone to develop anhedonic and helpless behavior after chronic mild stress. In humans, the CB1 antagonist rimonabant increases the risk of depressed mood disorders and anxiety. These studies suggest the hypothesis that genetic variation in CB1 receptor function influences the risk of depression in humans in response to stressful life events.