Dataset Information

Influence of CRHR1 Polymorphisms and Childhood Abuse on Suicide Attempts in Affective Disorders: A GxE Approach.

ABSTRACT: Background: Previous studies have shown that the hypothalamus-pituitary-adrenal-axis (HPA-axis) is closely involved in the development of affective disorders. Given that early life events are also linked to dysregulation of the same system, there might be an association between childhood adversities and suicidal behavior in affective disorders, moderated by HPA-axis genes. We aimed to investigate a potential association between childhood trauma and previous suicide attempts in affective disorder patients, moderated by variants of the corticotropin-releasing hormone receptor 1 (CRHR1) gene. Methods: The current pilot study is part of an ongoing study on suicidal behavior in affective disorders (VieSAD). Two hundred fifty eight Caucasian affective disorder patients were assessed at the Department of Psychiatry and Psychotherapy of the Medical University Vienna and the Karl Landsteiner University for Health and Science. An assemblage of psychiatric interviews was performed (e.g., SCAN, HAMD, SBQ-R, CTQ) and DNA samples of peripheral blood cells were genotyped with TaqMan® SNP Genotyping Assays (rs7209436, rs4792887, rs110402, rs242924, and rs242939). Results: Neither genetic, nor haplotypic associations between CRHR1 polymorphisms and previous suicide attempts could be established for the present sample. Using a binary logistic regression model, significant gene-environment-interactions were found for the single nucleotide polymorphisms (SNPs) rs7209436 and rs110402, reflecting the impact of childhood trauma and CRHR1 polymorphisms on previous suicide attempts. Limitations: A larger sample size will be required to ultimately elucidate the link between childhood trauma and the HPA axis in suicidal behavior. Conclusion: This pilot study presents promising gene-environment-interaction findings in affective disorder patients with a history of suicide attempts.

SUBMITTER: Ludwig B

PROVIDER: S-EPMC5933260 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Influence of CRHR1 Polymorphisms and Childhood Abuse on Suicide Attempts in Affective Disorders: A GxE Approach.

Ludwig Birgit B Kienesberger Klemens K Carlberg Laura L Swoboda Patrick P Bernegger Alexandra A Koller Romina R Wang Qingzhong Q Inaner Michelle M Zotter Melanie M Kapusta Nestor D ND Haslacher Helmuth H Aigner Martin M Kasper Siegfried S Schosser Alexandra A

Frontiers in psychiatry 20180426

<b>Background:</b> Previous studies have shown that the hypothalamus-pituitary-adrenal-axis (HPA-axis) is closely involved in the development of affective disorders. Given that early life events are also linked to dysregulation of the same system, there might be an association between childhood adversities and suicidal behavior in affective disorders, moderated by HPA-axis genes. We aimed to investigate a potential association between childhood trauma and previous suicide attempts in affective d ...[more]

PMID: 29755375

Similar Datasets

Project description:Background: Childhood sexual abuse (CSA) is a well-established risk factor for non-suicidal self-injury (NSSI) and suicide attempts (SA); still few studies have examined predictors of individual differences in NSSI/SA amongst CSA survivors. Objective: To examine predictors of NSSI and SA among adult CSA-survivors. Methods: In a sample of 516, primarily female adult CSA-survivors recruited from support centres for sexual abuse survivors in Norway, we examined the role of abuse/perpetrator characteristics, and the degree/severity of exposure to other types of childhood maltreatment (cumulative childhood maltreatment; CCM), as predictors of lifetime NSSI and SA. In a subsample of 138 individuals responding to follow-up waves two- and four years later, these same distal factors, as well as previous NSSI and proximal factors in the form of symptoms of mental health disorders (posttraumatic stress, anxiety, depression, sleep disturbances, and eating disorders), relational problems, and perceived social support, were examined as predictors of persistent NSSI. Finally, those attempting new SA during the follow-up period were compared to those who did not on these variables. Results: Higher CCM scores and having had an unknown perpetrator positively predicted lifetime NSSI scores. Higher CCM scores, violent abuse, and having had an unknown perpetrator predicted lifetime SA. Higher CCM scores, previous NSSI, having had a known perpetrator, as well as higher depression-, anxiety- and eating disorder scores, positively predicted persistent NSSI during the four-year follow-up period. Compared to those with no new SA, those reporting new SA during the follow-up period had higher CCM, lifetime NSSI, mental health symptoms and relational problem scores, lower perceived social support scores, and were more likely to have done a past SA and to have experienced abuse involving physical violence. Conclusions: A broad range of both distal and proximal factors should be assessed as potential predictors of NSSI and SA among adult CSA-survivors.

Project description:BackgroundClinical symptoms of affective disorders, their response to light treatment, and sensitivity to other circadian interventions indicate that the circadian system has a role in mood disorders. Possibly the mechanisms involve circadian seasonal and photoperiodic mechanisms. Since genetic susceptibilities contribute a strong component to affective disorders, we explored whether circadian gene polymorphisms were associated with affective disorders in four complementary studies.MethodsFour groups of subjects were recruited from several sources: 1) bipolar proband-parent trios or sib-pair-parent nuclear families, 2) unrelated bipolar participants who had completed the BALM morningness-eveningness questionnaire, 3) sib pairs from the GenRed Project having at least one sib with early-onset recurrent unipolar depression, and 4) a sleep clinic patient group who frequently suffered from depression. Working mainly with the SNPlex assay system, from 2 to 198 polymorphisms in genes related to circadian function were genotyped in the participant groups. Associations with affective disorders were examined with TDT statistics for within-family comparisons. Quantitative trait associations were examined within the unrelated samples.ResultsIn NR1D1, rs2314339 was associated with bipolar disorder (P = 0.0005). Among the unrelated bipolar participants, 3 SNPs in PER3 and CSNK1E were associated with the BALM score. A PPARGC1B coding SNP, rs7732671, was associated with affective disorder with nominal significance in bipolar family groups and independently in unipolar sib pairs. In TEF, rs738499 was associated with unipolar depression; in a replication study, rs738499 was also associated with the QIDS-SR depression scale in the sleep clinic patient sample.ConclusionAlong with anti-manic effects of lithium and the antidepressant effects of bright light, these findings suggest that perturbations of the circadian gene network at several levels may influence mood disorders, perhaps ultimately through regulation of MAOA and its modulation of dopamine transmission. Twenty-three associations of circadian polymorphisms with affective symptoms met nominal significance criteria (P < 0.05), whereas 15 would be expected by chance, indicating that many represented false discoveries (Type II errors). Some evidence of replication has been gathered, but more studies are needed to ascertain if circadian gene polymorphisms contribute to susceptibility to affective disorders.

Project description:BackgroundRates of suicide are increasing in the US. Although psychiatric disorders are associated with suicide risk, there is a dearth of epidemiological research on the relationship between suicide attempts (SAs) and eating disorders (EDs). The study therefore aimed to examine prevalence and correlates of SAs in DSM-5 EDs-anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED)-in a nationally representative sample of US adults. In addition, prevalence and correlates of SAs were examined in the two subtypes of AN-restricting (AN-R) and binge/purge (AN-BP) types.MethodsThe study included 36,171 respondents in the Third National Epidemiological Survey on Alcohol and Related Conditions (NESARC-III) who completed structured diagnostic interviews (AUDADIS-5) and answered questions regarding SA histories and psychosocial impairment associated with EDs. We evaluated lifetime prevalence of SA, psychosocial impairment, clinical profiles, and psychiatric comorbidity in adults with EDs with and without SA histories, and temporal relationships between age onset of SA and EDs.ResultsPrevalence estimates of suicide attempts were 24.9% (for AN), 15.7% (for AN-R), 44.1% (for AN-BP), 31.4% (for BN), and 22.9% (for BED). Relative to respondents without specific EDs, adjusted odds ratios (AORs) of SAs were significantly greater in all EDs: AN = 5.40 (95% confidence intervals [CIs] = 3.80-7.67), AN-R = 3.16 (95% CIs = 1.82-5.42), AN-BP = 12.09 (95% CIs = 6.29-23.24), BN = 6.33 (95% CIs = 3.39-11.81), and BED = 4.83 (95% CIs = 3.54-6.60). Among those with SA history, mean age at first SA and number of SAs were not significantly different across the specific EDs. SA was associated with significantly earlier ED onset in BN and BED, longer duration of AN but shorter duration of BN, greater psychosocial impairment in AN and BN, and with significantly increased risk for psychiatric disorder comorbidity across EDs. Onset of BED was significantly more likely to precede SA (71.2%) but onsets of AN (50.4%) and BN (47.6%) were not.ConclusionsUS adults with lifetime DSM-5 EDs have significantly elevated risk of SA history. Even after adjusting for sociodemographic factors, those with lifetime EDs had a roughly 5-to-6-fold risk of SAs relative to those without specific EDs; the AN binge/purge type had an especially elevated risk of SAs. SA history was associated with distinctively different clinical profiles including greater risk for psychosocial impairment and psychiatric comorbidity. These findings highlight the importance of improving screening for EDs and for suicide histories.

Project description:ImportanceClarification of the joint influence of familial patterns of suicide attempts and comorbid mental disorders can enhance the understanding and prevention of suicide attempts.ObjectiveTo investigate the familial patterns of suicide attempts and comorbid mental disorders and their associations in a 2-site family study of mood and anxiety disorders.Design, setting, and participantsData were obtained from 2 parallel community-based family studies conducted in the United States (National Institute of Mental Health [NIMH] study) and in Lausanne, Switzerland (PsyCoLaus study), on the comorbidity of mood and anxiety disorders. The study sample comprised 1119 adult probands and 5355 first-degree relatives. Data were collected and analyzed from October 2004 to December 2016.Main outcomes and measuresLifetime suicide attempt and mental disorders in first-degree relatives, obtained through direct interviews or family history reports.ResultsThe study included 1119 adult probands (675 female [60.3%] and a mean [SD] age of 50 [12.0] years) and 5355 first-degree relatives (2752 female [51.4%] and a mean [SD] age of 52 [1.5] years). Of these participants, 90 (8.0%) of 1119 probands and 199 (3.7%) of 5355 relatives had a lifetime history of suicide attempt. Those with such a history had higher rates of all mental disorders, a greater number of disorders, and statistically significantly poorer current and lifetime global functioning. After adjustment for age and sex, a statistically significant association between suicide attempts in probands and in relatives was found at the NIMH site (OR, 2.6; 95% CI, 1.5-4.7), at the Lausanne site (OR, 3.1; 95% CI, 1.6-6.0), and in the combined data (OR, 2.9; 95% CI, 1.9-4.5). All mood disorder subtypes and substance use disorders were statistically significantly associated with suicide attempts. The familial association between lifetime suicide attempts in probands and relatives was not statistically significant for the combined sample (OR, 1.6; 95% CI, 1.0-2.7) after adjustment for comorbid conditions in probands and relatives. Social anxiety disorder in probands was associated with suicide attempts in relatives (OR, 2.4; 95% CI, 1.7-3.5) after controlling for comorbid mood, anxiety, and substance use disorders.Conclusions and relevanceFamiliality of suicide attempts appears to be explained by a history of mental disorders among those with suicide attempts; the novel finding of a common familial diathesis for suicide attempts and social anxiety, particularly in combination with mood disorders, has heuristic value for future research and may be a risk marker that can inform prevention efforts.

Project description:ImportanceRacial/ethnic and sex disparities in suicide ideation and attempts are well established, with higher risk of suicide ideation and attempt among US racial/ethnic minority school-aged youths (than their White peers) and girls and women (than boys and men). The suicide-related risk of racial/ethnic minority young adults, especially young women, may be strongly influenced by adverse childhood experiences, known early determinants of suicide ideation and attempts.ObjectivesTo assess lifetime and past-year prevalence estimates of suicide ideation and suicide attempt and to examine sex differences in the role of adverse childhood experiences as a prospective risk factor for Puerto Rican young adults from 2 sociocultural contexts.Design, setting, and participantsData in this longitudinal cohort study are from 4 waves of the Boricua Youth Study, a population-based cohort study of Puerto Rican children from San Juan and Caguas, Puerto Rico, and the South Bronx, New York, 5 to 17 years of age (N = 2491; waves 1-3: 2000-2004) and 15 to 29 years of age (wave 4: 2013-2017). Data analysis was performed from February 26, 2019, to October 16, 2020.ExposuresAdverse childhood experiences were assessed by interview in childhood and early adolescence (waves 1-3) and included child maltreatment (physical, sexual, and emotional abuse and neglect), exposure to violence, parental loss (separation, divorce, and death), and parental maladjustment (mental health problems, substance or alcohol abuse, intimate partner violence, and incarceration).Main outcomes and measuresLifetime and past-year suicide ideation and attempt were assessed in young adulthood (wave 4) using the World Health Organization Composite International Diagnostic Interview.ResultsAmong 2004 Puerto Rican young adults (80.4% of the original cohort; mean [SD] age, 22.9 [2.8] years; 1019 [50.8%] male), young women compared with young men had a higher prevalence of lifetime suicide attempt (9.5% vs 3.6%) and lifetime suicide ideation (16.4% vs 11.5%), whereas past-year suicide ideation (4.4% vs 2.4%) was not statistically different. Logistic regression models, adjusting for demographics and lifetime psychiatric disorders, found that young women but not young men with more adverse childhood experiences had higher odds of suicide ideation (lifetime; odds ratio [OR], 2.44; 95% CI, 1.54-3.87; past year: OR, 2.56; 95% CI, 1.18-5.55). More adverse childhood experiences were also prospectively associated with lifetime suicide attempt (OR, 1.16; 95% CI, 1.04-1.29), irrespective of sex.Conclusions and relevanceThe findings of this cohort study suggest that, among Puerto Rican young adults from 2 different sociocultural contexts, adverse childhood experiences were relevant to understanding suicide attempt and suicide ideation, the latter specifically among young women. The prevention of cumulative adverse childhood experiences could reduce later risk of suicide attempts and, among young women, for suicide ideation.

Project description:Background: Suicide is moderately heritable and also more common in those who report childhood abuse. Previously, it was found that allele A of GABRG2 (GABA A receptor subunit gamma2) polymorphism rs211034 was protective in a suicide attempt (SA). Hence, it was proposed that rs211034 may interact with childhood trauma to influence cognitive deficits related to SA or depression risk. Genetic variants may predict the benefits of certain cognitive treatments. Methods: A total of 52 individuals who had attempted suicide, 59 individuals with major depressive disorder (MDD) or bipolar depression who had not previously attempted suicide, and 90 healthy volunteers were subjected to the modified Suicide Stroop task and were clinically assessed using the Childhood Trauma Questionnaire (CTQ) and Hamilton Depression Scale-24 items (HAMD-24). rs211034 was genotyped using Sanger sequencing. Results: After correcting for covariates, depressed participants displayed longer reaction times for all emotional conditions, including suicide-related words, compared with healthy controls. Depressed suicide attempters displayed longer reaction times for negative words than depressed non-attempters. Depressed non-attempters displayed higher interference scores for negative words compared with healthy controls. There was an interaction between rs211034 risk allele and the effects of reported childhood sexual abuse (CSA) on reaction time for all emotional words and suicide-related words. Carriers of the rs211034 risk allele A exhibited shorter reaction times, but the protective effects of this allele were eliminated in those exposed to reported CSA. Conclusion: Only limited results were found regarding effects of a past suicide attempt on response times to emotional and suicide-related words, but there was an overall effect of major depression on slower response time. Protective genetic effects of the rs211034 A allele on this slowing were eliminated in those with a history of sexual abuse during childhood. Further research is needed to better characterize the mechanisms underlying the effects of childhood trauma on these genetic effects.

Dataset Information

Influence of CRHR1 Polymorphisms and Childhood Abuse on Suicide Attempts in Affective Disorders: A GxE Approach.

Publications

Influence of CRHR1 Polymorphisms and Childhood Abuse on Suicide Attempts in Affective Disorders: A GxE Approach.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets