Neuroticism, social network, stressful life events: association with mood disorders, depressive symptoms and suicidal ideation in a community sample of women.

According to the stress-diathesis hypothesis, depression and suicidal behavior may be precipitated by psychosocial stressors in vulnerable individuals. However, risk factors for mental health are often gender-specific. In the present study, we evaluated common risk factors for female depression in association with depressive symptoms and suicidal ideation in a community sample of women. The sample was composed by 415 women evaluated for mood disorders (MDs), depressive symptoms and suicidal ideation by structured interviews and the Beck depression inventory II (BDI II). All women also filled in the Eysenck personality questionnaire to evaluate neuroticism and were interviewed for social contact frequency and stressful life events (SLEs). In the whole sample, 19% of the women satisfied criteria for MD and suicidal ideation was reported by 12% of the women. Though stressful life events, especially personal and interpersonal problems, and poor social network were associated with all the outcome variables (mood disorder, depressive symptomatology and suicidal ideation), neuroticism survived to all multivariate analyses. Social network, together with neuroticism, also showed strong association with depressive severity, independently from current depressive state. Though we were unable to compare women and men, data obtained from the present study suggest that in women neurotic traits are strongly related to depression and suicidal ideation, and potentially mediate reporting of stressful life events and impaired social network. Independently from a current diagnosis of depression, impaired social network increases depressive symptoms in the women.

Potential role of membrane-bound COMT gene polymorphisms in female depression vulnerability.

BACKGROUND: Several polymorphic variants within the catechol-O-methyltransferase (COMT) gene locus have been associated with a number of diverse psychiatric phenotypes including affective disorders. COMT enzyme participates in metabolic pathways involving brain catecholamines, as well as steroid hormones such as estrogens. Given the suggested mood enhancing role of estrogens and the higher prevalence of depression in women, we set out to investigate the potential impact of functional COMT genetic variants on depression and anxiety symptoms in a homogeneous female community sample. METHODS: We genotyped three common polymorphisms within the COMT gene in a rural female population isolate (n=391) interviewed for the presence of lifetime major depression episodes and generalized anxiety disorder. Furthermore, well validated self-rated questionnaires were administered evaluating state depressive symptoms and neuroticism personality trait. Single-marker and haplotype association analyses were performed. RESULTS: Two highly correlated markers located in the membrane-bound (MB) COMT promoter region (rs2020917, rs737865) were significantly associated with both self-rated and clinician-rated depressive symptomatology. We did not detect any robust association with generalized anxiety disorder or neuroticism. Exploratory haplotype analysis examining the two promoter markers in combination with the extensively studied val 158met polymorphism (rs4680) did not provide any further support for the contribution of this variant in depressive mood. LIMITATIONS: The relative small sample size should be considered a limitation of this study. CONCLUSIONS: Our results provide promising evidence that MB-COMT specific genetic variation may represent an as yet unrecognized genetic factor that influences predisposition to depression amongst females.

The role of serotonergic genes and environmental stress on the development of depressive symptoms and neuroticism.

BACKGROUND: Depression is considered to be the result of a complicated synergy between genetic and environmental factors. Several genes of the serotonergic neurotransmission have been related to depression phenotypes, however results are inconsistent, possibly due to the oversight of the role of environmental stress. METHODS: We examined gene-environment (GxE) interactions with serotonergic genes on depressive symptoms and neuroticism in a homogeneous population-based sample of 415 females. We chose several genetic variants within candidate genes (SLC6A4, TPH2, HTR1A) that have been previously found to provide some evidence of association with depression outcomes. RESULTS: Single marker analyses showed a significant GxE interaction with several TPH2 variants, including rs4570625, on depressive symptoms. Significant GxE interactions were also observed with TPH2 haplotypes. No reliable associations were observed with SLC6A4 and HTR1A genes. We did not find any robust evidence of a direct impact of serotonergic genes on depressive symptoms or neuroticism. LIMITATIONS: Due to the high number of analyses conducted, results must be interpreted with caution. CONCLUSIONS: The present study indicates an association between TPH2 and depressive symptoms that is conditional on prior experience of stressful life events. Further evidence is provided about the role of the environment in genetic vulnerability to depression.

The 3111T/C polymorphism interacts with stressful life events to influence patterns of sleep in females.

Genetic variations in clock-relevant genes have been investigated in relation to sleep abnormalities, both in healthy populations and in mood-disorder patients with inconsistent results. Environmental influences may moderate associations between genes and phenotype. The authors examined the CLOCK 3111T/C polymorphism and several variants within the PER3 gene and their possible interaction with stressful life events in a group of female volunteers (n = 415). Gene-environment (G × E) interactions and gene main effects were investigated on depressive symptoms using the Beck Depression Inventory and on change of sleep patterns (Item 16). Results showed a G × E interaction on alteration of sleeping pattern: the 3111C homozygous genotype reported greater disruption in sleep pattern after the experience of stressful life events. Within the PER3 gene, one G × E interaction was observed with rs228642 on sleep change. These findings show that the 3111T/C polymorphism is not associated with depressive symptoms, but only with symptoms of sleep change in the case of prior stressful life experiences. The combination of a sensitive genotype (3111C/C) and environmental stress increases vulnerability to circadian rhythm disruption in females.