Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders.

OBJECTIVES: Suicide is a serious public health concern, and it is partly genetic. The brain-derived neurotrophic factor (BDNF) gene has been a strong candidate in genetic studies of suicide (Dwivedi et al., Arch Gen Psychiatry 2010;60:804-815; Zai et al., Prog Neuropsychopharmacol Biol Psychiatry 2012;34:1412-1418) and BDNF regulates the expression of the dopamine D3 receptor. OBJECTIVE: We examined the role of the BDNF and DRD3 genes in suicide. METHODS: We analysed four tag single-nucleotide polymorphisms (SNPs) in BDNF and 15 SNPs in the D3 receptor gene DRD3 for possible association with suicide attempt history in our Canadian sample of Schizophrenia (SCZ) patients of European ancestry (N = 188). RESULTS: In this sample, we found a possible interaction between the BDNF Val66Met and DRD3 Ser9Gly SNPs in increasing the risk of suicide attempt(s) in our SCZ sample. Specifically, a larger proportion of SCZ patients who were carrying at least one copy of the minor allele at each of the Val66Met and Ser9Gly functional markers have attempted suicides compared to patients with other genotypes (Bonferroni P < 0.05). However, we could not replicate this finding in samples from other psychiatric populations. CONCLUSIONS: Taken together, the results from the present study suggest that an interaction between BDNF and DRD3 may not play a major role in the risk for suicide attempt, though further studies, especially in SCZ, are required.

Risk factors related to lifetime suicide attempts in acutely admitted bipolar disorder inpatients.

OBJECTIVE: The main aim of this study was to assess possible clinical characteristics of acutely admitted bipolar I disorder (BD-I) and bipolar II disorder (BD-II) inpatients at high risk of suicide by comparing patients who had made one or several serious suicide attempts with patients who had not. METHODS: A total of 206 consecutive patients (mean age 42 ± 15 years; 54.9% women) with DSM-IV diagnosed BD-I (n = 140) and BD-II (n= 66) acutely admitted to a single psychiatric hospital department from November 2002 through June 2009 were included. Using a detailed retrospective questionnaire, patients with a history of a serious suicide attempt were compared to those with no history of a suicide attempt. RESULTS: Ninety-three patients (45.1%) had a history of one or more serious suicide attempts. These constituted 60 (42.9%) of the BD-I patients and 33 (50%) of the BD-II patients (no significant difference). Lifetime suicide attempt was associated with a higher number of hospitalizations due to depression (p < 0.0001), antidepressant (AD)-induced hypomania/mania (p = 0.033), AD- and/or alcohol-induced affective episodes (p = 0.009), alcohol and/or substance use (p = 0.002), and a family history of alcohol abuse and/or affective disorder (p = 0.01). Suicide attempt was negatively associated with a higher Positive and Negative Syndrome Scale for Schizophrenia (PANSS) Positive Subscale score (p = 0.022) and more hospitalizations due to mania (p = 0.006). CONCLUSIONS: The lifetime suicide attempt rate in BD inpatients is high. Risk factors of suicide attempts were: (i) a predominant depressive course of illness, (ii) comorbid alcohol and substance use disorders, and (iii) a history of AD- and/or alcohol-induced affective episodes. Risk-reducing factors were a preponderant manic or psychotic course of the illness. These risk factors may be signs of a clinical subgroup at risk of suicidal behaviour, and seem to be important for suicide risk assessment in acutely admitted BD patients.