The BDNF Val66Met polymorphism is an independent risk factor for high lethality in suicide attempts of depressed patients

BackgroundThe role of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of affective disorders such as depression has been controversial. Mounting evidence comes from structural imaging, that the functional BDNF Val66Met polymorphism influences the hippocampal volume with carriers of the 66Met allele (Val/Met and Met/Met group) having smaller hippocampi. Given that stress-induced atrophy of the hippocampus is associated with the pathogenesis of affective disorders, the functional BDNF Val66Met polymorphism could be an incremental risk factor.MethodEighty-seven healthy Caucasian participants underwent structural imaging and were genotyped for the BDNF Val66Met polymorphism. Data were analysed by means of voxel-based morphometry (VBM).ResultsRegion of interest (ROI) analyses revealed an association between the 66Met allele and smaller parahippocampal volumes and a smaller right amygdala. In addition, the whole-brain analysis showed that the thalamus, fusiformus gyrus and several parts of the frontal gyrus were smaller in 66Met allele carriers.ConclusionsThis study demonstrates that the impact of the BDNF Val66Met polymorphism is not confined to the hippocampus but also extends to the parahippocampal gyrus and the amygdala.

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The BDNF Val66Met polymorphism is associated with escitalopram response in depressed patients

Psychopharmacology ◽

10.1007/s00213-014-3694-z ◽

2014 ◽

Vol 232 (3) ◽

pp. 575-581 ◽

Cited By ~ 15

Author(s):

Wissam El-Hage ◽

Patrick Vourc’h ◽

Philippe Gaillard ◽

Julie Léger ◽

Catherine Belzung ◽

...

Keyword(s):

Val66met Polymorphism ◽

Depressed Patients ◽

Bdnf Val66met Polymorphism

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Brain derived neurotrophic factor (BDNF) Val66Met polymorphism is not risk factor for bipolar disorder

10.1101/19010280 ◽

2019 ◽

Author(s):

Vandana Rai ◽

Farhin Jamal ◽

Pradeep Kumar

Keyword(s):

Bipolar Disorder ◽

Risk Factor ◽

Meta Analysis ◽

Pooled Analysis ◽

Caucasian Population ◽

Psychiatric Disease ◽

Bdnf Gene ◽

Genetic Studies ◽

Val66met Polymorphism ◽

Bdnf Val66met Polymorphism

AbstractBipolar disorder (BPD) is a psychiatric disease, characterized by the cycles of mania and depression. Several genetic studies investigated BDNF gene Val66Met polymorphism as risk factor for BPD, but results were inconclusive. Therefore, present meta-analysis was performed to reevaluate the BDNF Val66Met polymorphism and BPD association. Four databases (Pubmed, Springer Link, Science Direct and Google Scholar) were searched for eligible studies up to March 31,2018. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated to estimate the strength of the association. All statistical analyses were done by MetaAnalyst and Mix program. Forty studies with a total of 28,787 subjects (10,085 cases and 18,702 controls) were included in this meta-analysis. Overall, pooled analysis indicated that there was no significant association between BDNF Val66Met polymorphism and BPD risk under all five genetic models (ORA vs.G =0.99, 95%CI= 0.94-1.03, p=0.49; ORAG vs. GG= 0.1.02, 95%CI= 0.95-1.07, p= 0.57; ORAA vs. GG = 0.98, 95%CI=0.89-1.08, p=0.75; ORAA+AG vs. GG= 1.0, 95%CI= 0.94-1.06, p= 0.89;ORAA vs. AG+GG= 0.96, 95%CI= 0.89-1.05, p= 0.47). Similarly, no significant association was observed in ethnicity based subgroup analysis in both Asian and Caucasian population. However, significant association was found in subtype analysis between BDNF Val66Met and BPDII (ORAA+AG vs. GG= 1.21, 95%CI= 1.06-1.37, p= 0.003) but not with BPDI. These findings suggested that the BDNF Val66Met polymorphism confer no genetic susceptibility to BPD I but risk for BPDII.

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HOMA-IR increase after antidepressant treatment in depressed patients with the Met allele of the Val66Met BDNF genetic polymorphism

Psychological Medicine ◽

10.1017/s0033291718003240 ◽

2018 ◽

Vol 49 (14) ◽

pp. 2364-2369

Author(s):

Séverine Martin ◽

Romain Colle ◽

Khalil El Asmar ◽

Adrien Rigal ◽

Albane Vievard ◽

...

Keyword(s):

Insulin Resistance ◽

Antidepressant Treatment ◽

Time Effect ◽

Val66met Polymorphism ◽

Significant Time ◽

Depressed Patients ◽

Significant Time Effect ◽

Time Interaction ◽

Bdnf Val66met Polymorphism ◽

Fasting Glycaemia

AbstractBackgroundThe brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with response to antidepressant drugs in depressed patients and with metabolic side effects after antipsychotic treatment. This study aims to assess the association between this polymorphism and insulin resistance after antidepressant treatment in depressed patients.MethodsOne hundred forty-eight Caucasian patients with a current unipolar major depressive episode (DSM IV-TR) were genotyped for the BDNF Val66Met polymorphism and assessed at baseline and after 3 and 6 months of antidepressant treatment for the ‘Homoeostasis model assessment of insulin resistance’ (HOMA-IR) index, a valid measure of insulin resistance based on fasting plasma insulinaemia and glycaemia. Because validity assumptions were fulfilled, data were analysed using analysis of variance for repeated measures.ResultsThe 52 (35%) Met carriers and 96 (65%) Val/Val patients were not different at baseline for clinical characteristics and HOMA-IR. A significant Val66Met × time interaction (p= 0.02), a significant time effect (p= 0.03) and a significant Val66Met effect (p= 0.0497) were shown for HOMA-IR. A significant Val66Met × time interaction (p= 0.01) and a significant time effect (p= 0.003) were shown for fasting glycaemia. HOMA-IR and fasting glycaemia changes after antidepressant treatment were significantly higher in Met carrier than in Val/Val patients (HOMA-IR changes: Met: 0.71 ± 3.29v.Val/Val: −0.16 ± 1.34,t= 2.3, df = 146,p= 0.02, glycaemia changes: Met: 0.09 ± 0.30v.Val/Val: 0.02 ± 0.16,t= −2.0, df = 146,p= 0.045).ConclusionsThe Met allele of the Val66Met BDNF polymorphism confers to depressed patients a higher risk of insulin-resistance after antidepressant treatment. These patients could benefit from specific monitoring of metabolism and preventive measures.

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Cognition in Recent Suicide Attempts: Altered Executive Function

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.701140 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jessica Fernández-Sevillano ◽

Susana Alberich ◽

Iñaki Zorrilla ◽

Itxaso González-Ortega ◽

María Purificación López ◽

...

Keyword(s):

Decision Making ◽

Risk Factor ◽

Executive Function ◽

Neuropsychological Assessment ◽

Processing Speed ◽

Suicide Attempts ◽

Healthy Controls ◽

Cognitive Domains ◽

Depressed Patients ◽

Patient Groups

Background: Neuropsychological alterations can lead to inaccurate perception, interpretation, and response to environmental information, which could be a risk factor for suicide.Methods: Ninety-six subjects were recruited from the Psychiatry Department of the Araba University Hospital—Santiago, including 20 patients with a recent attempt and diagnosis of major depressive disorder (MDD) according to DSM-V, 33 MDD patients with history of attempted suicide, 23 non-attempter MDD patients, and 20 healthy controls. All participants underwent a clinical interview and neuropsychological assessment on the following cognitive domains: working memory, processing speed, decision-making, executive function, and attention. Backward multiple regressions were performed adjusting for significant confounding variables. For group comparisons, ANOVA and Bonferroni post-hoc tests were performed with a p < 0.05 significance level.Results: The patient groups did not differ regarding severity of depression and stressful events in the last 6 months. In comparison to healthy controls, depressed patients with lifetime suicide attempts had more general trauma (p = 0.003), emotional abuse (p = 0.003), emotional negligence (p = 0.006), and physical negligence (p = 0.009), and depressed patients with recent suicide attempts had experienced more child sexual abuse (p = 0.038). Regarding neuropsychological assessment, all patient groups performed significantly worse than did healthy controls in processing speed, decision-making, and attention. Comparisons between patient groups indicated that recent suicide attempters had poorer performance on executive function in comparison to both depressed lifetime attempters and depressed non-attempters (B = 0.296, p = 0.019, and B = 0.301, p = 0.028, respectively). Besides, women with recent attempts had slightly better scores on executive function than males. Regarding the rest of the cognitive domains, there were no significant differences between groups.Conclusion: Executive function performance is altered in recent suicide attempts. As impaired executive function can be risk factor for suicide, preventive interventions on suicide should focus on its assessment and rehabilitation.

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