Polygenic risk for major depression is associated with lifetime suicide attempt in US soldiers independent of personal and parental history of major depression

We carried out two studies to test the hypothesis that altered central serotonergic function, as assessed by lower prolactin (PRL) response to fenfluramine (D-FEN), is more closely associated with suicidal behavior than a particular psychiatric diagnosis. A D-FEN test was performed in 85 major depressed inpatients, 33 schizophrenic inpatients, and 18 healthy controls. We showed that PRL response to D-FEN is a marker of suicidality, regardless of psychiatric disorder. We then examined the association en the serotonin (5-hydroxytryptamine) receptor 5-HT(2A) gene polymorphism (T102C) and suicide in a sample of Brazilian psychiatric inpatients (95 with schizophrenia, 78 with major depression) and 52 healthy controls. No differences were found in genotypic frequencies across patients and controls. Overall, no differences were found between patients with (n=66) and without (n=107) a history of suicide attempt. We also compared patients with a history of severe suicide attempts (lethality>3; n=32) and patients without such a history (n=107), but they did not exhibit different genotypic frequencies either. These results show thai the 5-HT(2A) gene polymorphism (T102C) may not be involved in the genetic susceptibility to suicidal behavior.

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GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores

American Journal of Psychiatry ◽

10.1176/appi.ajp.2019.18080957 ◽

2019 ◽

Vol 176 (8) ◽

pp. 651-660 ◽

Cited By ~ 49

Author(s):

Niamh Mullins ◽

Tim B. Bigdeli ◽

Anders D. Børglum ◽

Jonathan R.I. Coleman ◽

Ditte Demontis ◽

...

Keyword(s):

Major Depression ◽

Suicide Attempt ◽

Psychiatric Disorders ◽

Risk Scores ◽

Polygenic Risk

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50 ABSOLUTE RISK OF MAJOR DEPRESSION ASSOCIATED WITH THE POLYGENIC RISK SCORE FOR DEPRESSION, PARENTAL SOCIO-ECONOMIC STATUS AND HISTORY OF MENTAL DISORDERS: A DANISH POPULATION-BASED STUDY

European Neuropsychopharmacology ◽

10.1016/j.euroneuro.2019.07.191 ◽

2019 ◽

Vol 29 ◽

pp. S87-S88

Author(s):

Esben Agerbo ◽

Betina Trabjerg ◽

Andrew Schork ◽

Bjarni Vilhjálmsson ◽

Clara Albiñana Climent ◽

...

Keyword(s):

Major Depression ◽

Absolute Risk ◽

Economic Status ◽

Population Based ◽

Polygenic Risk Score ◽

Danish Population ◽

Population Based Study ◽

Polygenic Risk ◽

Socio Economic Status ◽

History Of

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Vulnerability and resiliency to suicidal behaviours in young people

Psychological Medicine ◽

10.1017/s0033291702006748 ◽

2002 ◽

Vol 33 (1) ◽

pp. 61-73 ◽

Cited By ~ 189

Author(s):

D. M. FERGUSSON ◽

A. L. BEAUTRAIS ◽

L. J. HORWOOD

Keyword(s):

Sexual Abuse ◽

Family History ◽

Suicidal Ideation ◽

Major Depression ◽

Childhood Sexual Abuse ◽

Young People ◽

Suicide Attempt ◽

Personality Factors ◽

History Of ◽

Peer Affiliations

Background. We aimed to examine factors that influence vulnerability/resiliency of depressed young people to suicidal ideation and suicide attempt.Method. Data were gathered during a 21-year longitudinal study of a birth cohort of 1265 New Zealand young people. Measures included: suicide attempt; suicidal ideation; major depression; childhood, family, individual and peer factors.Results. Young people who developed major depression had increased rates of suicidal ideation (OR=5·4; 95% CI 4·5–6·6) and suicide attempt (OR=12·1; 95% CI 7·9–18·5). However, the majority of depressed young people did not develop suicidal ideation or make suicide attempts, suggesting that additional factors influence vulnerability or resiliency to suicidal responses. Factors influencing resiliency/vulnerability to suicidal responses included: family history of suicide; childhood sexual abuse; neuroticism; novelty seeking; self-esteem; peer affiliations; and school achievement. These factors operated in the same way to influence vulnerability/resiliency among those depressed and those not depressed.Conclusions. Vulnerability/resiliency to suicidal responses among those depressed (and those not depressed) is influenced by an accumulation of factors including: family history of suicide, childhood sexual abuse, personality factors, peer affiliations and school success. Positive configurations of these factors confer increased resiliency, whereas negative configurations increase vulnerability.

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Genome-wide association study of suicide attempt in psychiatric disorders identifies association with major depression polygenic risk scores

10.1101/416008 ◽

2018 ◽

Cited By ~ 2

Author(s):

Niamh Mullins ◽

Tim B. Bigdeli ◽

Anders D Børglum ◽

Jonathan R I Coleman ◽

Ditte Demontis ◽

...

Keyword(s):

Major Depression ◽

Suicide Attempt ◽

Psychiatric Disorders ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Risk Scores ◽

Genetic Associations ◽

Suicide Attempters ◽

Polygenic Risk ◽

Genome Wide

AbstractObjectiveOver 90% of suicide attempters have a psychiatric diagnosis, however twin and family studies suggest that the genetic etiology of suicide attempt (SA) is partially distinct from that of the psychiatric disorders themselves. Here, we present the largest genome-wide association study (GWAS) on suicide attempt using major depressive disorder (MDD), bipolar disorder (BIP) and schizophrenia (SCZ) cohorts from the Psychiatric Genomics Consortium.MethodSamples comprise 1622 suicide attempters and 8786 non-attempters with MDD, 3264 attempters and 5500 non-attempters with BIP and 1683 attempters and 2946 non-attempters with SCZ. SA GWAS were performed comparing attempters to non-attempters in each disorder followed by meta-analysis across disorders. Polygenic risk scoring investigated the genetic relationship between SA and the psychiatric disorders.ResultsThree genome-wide significant loci for SA were found: one associated with SA in MDD, one in BIP, and one in the meta-analysis of SA in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. Polygenic risk scores for major depression were significantly associated with SA in MDD (P=0.0002), BIP (P=0.0006) and SCZ (P=0.0006).ConclusionsThis study provides new information on genetic associations and the genetic etiology of SA across psychiatric disorders. The finding that polygenic risk scores for major depression predict suicide attempt across disorders provides a possible starting point for predictive modelling and preventative strategies. Further collaborative efforts to increase sample size hold potential to robustly identify genetic associations and gain biological insights into the etiology of suicide attempt.

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Childhood sexual abuse and the risk for recurrent major depression in Chinese women

Psychological Medicine ◽

10.1017/s0033291711001462 ◽

2011 ◽

Vol 42 (2) ◽

pp. 409-417 ◽

Cited By ~ 16

Author(s):

E. Cong ◽

Y. Li ◽

C. Shao ◽

J. Chen ◽

W. Wu ◽

...

Keyword(s):

Sexual Abuse ◽

Major Depression ◽

Childhood Sexual Abuse ◽

Age Of Onset ◽

Chinese Women ◽

Parental History ◽

Western Countries ◽

Increased Risk ◽

History Of ◽

Depressive Episodes

BackgroundStudies in Western countries have repeatedly shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in China?MethodThree levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 1970 clinically ascertained with recurrent MD and 2597 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression and regression coefficients by linear or Poisson regression.ResultsAny form of CSA was significantly associated with recurrent MD [OR 3.26, 95% confidence interval (CI) 1.95–5.45]. This association strengthened with increasing CSA severity: non-genital (OR 2.47, 95% CI 1.17–5.23), genital (OR 2.77, 95% CI 1.32–5.83) and intercourse (OR 13.35, 95% CI 1.83–97.42). The association between any form of CSA and MD remained significant after accounting for parental history of depression, childhood emotional neglect (CEN), childhood physical abuse (CPA) and parent–child relationship. Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes and an increased risk for generalized anxiety disorder (GAD; OR 1.92, 95% CI 1.39–2.66) and dysthymia (OR 2.16, 95% CI 1.52–3.09).ConclusionsIn Chinese women CSA is strongly associated with MD and this association increases with greater severity of CSA. Depressed women with CSA have an earlier age of onset, longer depressive episodes and increased co-morbidity with GAD and dysthymia. Although reporting biases cannot be ruled out, our results are consistent with the hypothesis that, as in Western countries, CSA substantially increases the risk for MD in China.

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Adolescent residential mobility, genetic liability and risk of schizophrenia, bipolar disorder and major depression

The British Journal of Psychiatry ◽

10.1192/bjp.2020.8 ◽

2020 ◽

Vol 217 (1) ◽

pp. 390-396 ◽

Cited By ~ 2

Author(s):

Diana Paksarian ◽

Betina B. Trabjerg ◽

Kathleen R. Merikangas ◽

Ole Mors ◽

Anders D. Børglum ◽

...

Keyword(s):

Bipolar Disorder ◽

Major Depression ◽

Mental Disorder ◽

Residential Mobility ◽

Odds Ratio ◽

Population Sample ◽

Risk Scores ◽

Parental History ◽

Genetic Liability ◽

History Of

BackgroundResidential mobility during upbringing, and especially adolescence, is associated with multiple negative mental health outcomes. However, whether associations are confounded by unmeasured familial factors, including genetic liability, is unclear.AimsWe used a population-based case–cohort study to assess whether polygenic risk scores (PRSs) for schizophrenia, bipolar disorder and major depression were associated with mobility from ages 10–14 years, and whether PRS and parental history of mental disorder together explained associations between mobility and each disorder.MethodInformation on cases (n = 4207 schizophrenia, n = 1402 bipolar disorder, n = 18 215 major depression) and a random population sample (n = 17 582), born 1981–1997, was linked between Danish civil and psychiatric registries. Genome-wide data were obtained from the Danish Neonatal Screening Biobank and PRSs were calculated based on results of separate, large meta-analyses.ResultsPRSs for schizophrenia and major depression were weakly associated with moving once (odds ratio 1.07, 95% CI 1.00–1.16; and odds ratio 1.10, 95% CI 1.04–1.17, respectively), but not twice or three or more times. Mobility was positively associated with each disorder, with more moves associated with greater risk. Adjustment for PRS produced slight reductions in the magnitude of associations. Adjustment for PRS and parental history of mental disorder together reduced estimates by 5–11%. In fully adjusted models mobility was associated with all three disorders; hazard ratios ranged from 1.33 (95% CI 1.08–1.62; one move and bipolar disorder) to 3.05 (95% CI 1.92–4.86; three or more moves and bipolar disorder).ConclusionsAssociations of mobility with schizophrenia, bipolar disorder and depression do not appear to be attributable to genetic liability as measured here. Potential familial confounding of mobility associations may be predominantly environmental in nature.

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