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

TY - JOUR

T1 - BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses

AU - Aas, Monica

AU - Haukvik, Unn K.

AU - Djurovic, Srdjan

AU - Bergmann, Ørjan

AU - Athanasiu, Lavinia

AU - Tesli, Martin S.

AU - Hellvin, Tone

AU - Steen, Nils Eiel

AU - Agartz, Ingrid

AU - Lorentzen, Steinar

AU - Sundet, Kjetil

AU - Andreassen, Ole A.

AU - Melle, Ingrid

N1 - Funding Information: We thank the patients who took part in the study and the TOP study researchers who contributed to the data collection. This study was funded by grants from the University of Oslo, South-Eastern Norway Health Authority (# 2004123 , # 2006258 ) and the Research Council of Norway (# 167153/V50 , # 163070/V50 , # 190311/V50 ). The authors declare that they have no conflict of interest concerning this manuscript.

PY - 2013/10/1

Y1 - 2013/10/1

N2 - 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 (r2=0.43; p=0.008), and larger right and left lateral ventricles (r2=0.37; p=0.002, and r2=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.

AB - 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 (r2=0.43; p=0.008), and larger right and left lateral ventricles (r2=0.37; p=0.002, and r2=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.

KW - BDNF val66met

KW - Cognition

KW - Early trauma

KW - Gene×environmental interaction

KW - Psychoses

KW - SMRI

UR - http://www.scopus.com/inward/record.url?scp=84882780371&partnerID=8YFLogxK

U2 - 10.1016/j.pnpbp.2013.07.008

DO - 10.1016/j.pnpbp.2013.07.008

M3 - Article

C2 - 23876786

AN - SCOPUS:84882780371

SN - 0278-5846

VL - 46

SP - 181

EP - 188

JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry

ER -