Dataset Information

Family-based study of AVPR1B association and interaction with stressful life events on depression and anxiety in suicide attempts.

ABSTRACT: The cortisol response to psychosocial stress may become dysregulated in stress-related disorders. It is potentiated by pituitary secretion of adrenocorticotropic hormone (ACTH), which is, in part, regulated by arginine vasopressin receptor-1B (AVPR1B). AVPR1B variants were previously reported to associate with mood and anxiety disorders. This study aims, for the first time, to investigate association of AVPR1B genetic variants with mood and anxiety outcomes in suicidal behavior.Using a family-based study design of 660 complete nuclear family trios with offspring who have made a suicide attempt (SA), we tested the direct association and linkage of AVPR1B single nucleotide polymorphisms (SNPs) with SA, as well as with depression and anxiety in SA. Main findings were the association and linkage of AVPR1B exon 1 SNP rs33990840 and a major 6-SNP haplotype representative of all common AVPR1B-SNPs, on the outcome of high Beck Depression Inventory scores in SA. By contrast, genetic associations with lifetime diagnoses of depression and anxiety in SA or gene-environment interactions between AVPR1B variants and stressful life events (SLEs) were not significant. An exploratory screen of interactions between AVPR1B and CRHR1 (corticotropin-releasing hormone receptor-1), the principal pituitary regulator of ACTH secretion, showed no support for gene-gene interactions on the studied outcomes. The results suggest that AVPR1B genetic variation, eg, non-synonymous SNP rs33990840 mediating putative consequences on ligand binding, has a role in SA etiology characterized by elevated depression symptoms, without involving AVPR1B-moderation of SLEs.

SUBMITTER: Ben-Efraim YJ

PROVIDER: S-EPMC3682145 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Family-based study of AVPR1B association and interaction with stressful life events on depression and anxiety in suicide attempts.

Ben-Efraim Yair J YJ Wasserman Danuta D Wasserman Jerzy J Sokolowski Marcus M

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20130219 8

The cortisol response to psychosocial stress may become dysregulated in stress-related disorders. It is potentiated by pituitary secretion of adrenocorticotropic hormone (ACTH), which is, in part, regulated by arginine vasopressin receptor-1B (AVPR1B). AVPR1B variants were previously reported to associate with mood and anxiety disorders. This study aims, for the first time, to investigate association of AVPR1B genetic variants with mood and anxiety outcomes in suicidal behavior.Using a family-ba ...[more]

PMID: 23422793

Similar Datasets

Project description:Background: The association between stressful life events (SLEs) and adolescent anxiety symptoms has been extensively studied, but the specific impacts of different SLEs domains remain inconclusive. Moreover, limited research has examined the role of family functioning in these associations.Objective: This study aimed to investigate the associations between various recent SLEs and adolescent anxiety symptoms and explore the role of family functioning.Methods: Data were obtained from the second phase of the Longitudinal Study of Adolescents' Mental and Behavioral Well-being Research in Guangzhou, China. A total of 10,985 students (51.9% boys; mean [SD] age, 15.3 [1.5] years) from forty middle schools participated in the study in 2022 and completed a self-report questionnaire assessing anxiety symptoms, SLEs, and family functioning using the Generalized Anxiety Disorder-7 (GAD-7), Adolescent Self-rating Life Events Checklist (ASLEC; including five subscales: interpersonal stress, academic stress, punishment-related stress, loss-related stress, and adaptation-related stress), and the adapted Chinese version of the Family Assessment Device (FAD), respectively. Linear mixed-effects models were performed and the moderation role of family functioning was also examined.Results: The fully adjusted model revealed that a 1-SD increase in the overall ASLEC score was associated with higher levels of anxiety symptoms (β = 2.23, 95%CI: 2.15-2.32). Among various SLEs domains, the academic domain shows the most significant association (β = 2.25, 95%CI: 2.17-2.33). Family functioning exerted an independent protective influence on anxiety symptoms, with each 1-SD increase in FAD scores negatively associated with anxiety symptoms (β = -2.11, 95%CI: - 2.29 to - 1.93) in the adjusted model. Moreover, family functioning significantly buffered the impacts of overall SLEs and each domain, except for adaptation-related SLEs, on anxiety symptoms.Conclusion: Higher recent SLEs levels were associated with increased anxiety symptoms among adolescents, with academic SLEs showing the greatest association. Positive family functioning had both direct and buffering influences on anxiety symptoms.

Project description:ContextSubstantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) and stressful life events on an increased risk of major depression.ObjectiveTo conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data.Data sourcesSearch of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis.Study selectionCriteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, > or = 3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data.Data extractionLogistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR, the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14,250 participants, 1769 were classified as having depression; 12,481 as not having depression.ResultsIn the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data.ConclusionThis meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.

Project description:BackgroundBoth genetic and environmental factors play crucial roles in the development of major depressive disorder (MDD) and suicide attempts (SA). However, the interaction between both items remains unknown. This study aims to explore the interactions between the genetic variants of the serotonin 2 A receptor (HTR2A) and the nitric oxide synthase 1 (NOS1) and environmental factors in patients who experience MDD and SA.MethodsA total of 334 patients with MDD and a history of SA (MDD-SA) were recruited alongside 518 patients with MDD with no history of SA (MDD-NSA), and 716 healthy controls (HC). The demographic data and clinical characteristics were collected. Sequenom mass spectrometry was used to detect eight tag-single nucleotide polymorphisms (tagSNPs) in HTR2A (rs1328683, rs17068986, and rs3125) and NOS1 (rs1123425, rs2682826, rs3741476, rs527590, and rs7959232). Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-environment interactions.ResultsFour tagSNPs (rs17068986, rs3125, rs527590, and rs7959232) exhibited significant differences between the three groups. However, these differences were not significant between the MDD-SA and MDD-NSA groups after Bonferroni correction. A logistic regression analysis revealed that negative life events (OR = 1.495, 95%CI: 1.071-2.087, P = 0.018), self-guilt (OR = 2.263, 95%CI: 1.515-3.379, P < 0.001), and negative cognition (OR = 2.252, 95%CI: 1.264-4.013, P = 0.006) were all independently associated with SA in patients with MDD. Furthermore, GMDR analysis indicated a significant interaction between HTR2A rs3125 and negative life events. Negative life events in conjunction with the HTR2A rs3125 CG + GG genotype were associated with a higher SA risk in patients with MDD when compared to the absence of negative life events in conjunction with the CC genotype (OR = 2.547, 95% CI: 1.264-5.131, P = 0.009).ConclusionSeveral risk factors and a potential interaction between HTR2A rs3125 and negative life events were identified in patients with SA and MDD. The observed interaction likely modulates the risk of MDD and SA, shedding light on the pathogenesis of SA in patients with MDD.

Dataset Information

Family-based study of AVPR1B association and interaction with stressful life events on depression and anxiety in suicide attempts.

Publications

Family-based study of AVPR1B association and interaction with stressful life events on depression and anxiety in suicide attempts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets