BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses

Abstract

Objective: Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood abuse, cognitive function, and brain abnormalities in psychoses.

Method: 249 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited to the TOP research study (mean±age: 30.7±10.9; gender: 49% males). History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Cognitive function was assessed through a standardized neuropsychological test battery. BDNF val66met was genotyped using standardized procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder (mean±age: 32.67±10.85; 49% males) had data on sMRI.

Results: Carriers of the Methionine (met) allele exposed to high level of childhood abuse demonstrated significantly poorer cognitive functioning compared to homozygotic Valine (val/val) carriers. Taking in consideration multiple testing, using a more conservative p value, this was still shown for physical abuse and emotional abuse, as well as a trend level for sexual abuse. Further, met carriers exposed to high level of childhood sexual abuse showed reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively). Our findings were independent of age, gender, diagnosis and intracranial volume.

Conclusion: Our data demonstrate that in patients with psychoses, met carriers of the BDNF val66met with high level of childhood abuse have more cognitive and brain abnormalities than all other groups.

Keywords: BDNF; BDNF val66met; Bipolar NOS; Bipolar Not Otherwise Specified; Brain derived neurotrophic factor; CTQ; Childhood Trauma Questionnaire; Cognition; D-KEFS; DNA; DSM-IV; Delis–Kaplan Executive Function Scale; Deoxyribonucleic acid; Diagnostic and Statistical Manual of Mental Disorders, fourth edition; EA; EN; Early trauma; GR; Gene×environmental interaction; IQ; PA; PANSS; PASW; PN; Positive and Negative Syndrome Scale; Precursor of brain-derived neurotrophic factor; Predictive Analytic software; Psychoses; Psychosis NOS; Psychosis Not Otherwise specified; RNA; Ribonucleic acid; SA; SCID; SNP; Structured Clinical Interview for DSM Disorders; TOP study; Thematically Organized Psychosis research study; WASI; Wechsler Abbreviated Scale of Intelligence; emotional abuse; emotional neglect; glucocorticoid receptor; intelligence quotient; met; methionine; physical abuse; physical neglect; proBDNF; sMRI; sexual abuse; single-nucleotide polymorphism; structural magnetic resonance imaging; val; valine.