BDNF gene variants and brain morphology in schizophrenia

Abstract

The objective was to investigate putative associations between brain-derived neurotrophic factor gene (BDNF) polymorphisms and brain morphology in patients with schizophrenia and healthy control subjects. Four BDNF polymorphisms were genotyped and analyzed versus 39 brain volume measures in 96 patients with schizophrenia or schizoaffective disorder and 104 healthy subjects. In all subjects, quantitative data on segmented gray, white, and cerebrospinal fluid (CSF) tissue class volumes of total brain and major cerebral lobes including ventricular CSF were obtained using magnetic resonance imaging (MRI). In a randomly selected subset of this population (n = 101-122), MR volumes from cerebellar tonsil, hemispheres, and vermis subregions, striatal structures, hippocampus, and corpus callosum were also measured. The BDNF 11757 G/C polymorphism was highly significantly associated with frontal gray matter volume variation in patients alone and in patients and control subjects combined. In patients only, the 270 C/T polymorphism was associated with total caudate volume. Significant associations were demonstrated between the BDNF 11757 G/C and Val66Met polymorphisms and a global haplotype estimate of four BDNF polymorphisms and the posterior superior cerebellar vermis volume in the controls as well as in the combined group, but not in the patients. The 11757 G/C polymorphism was associated with cerebellar hemisphere white and gray matter volumes in the combined group. The BDNF -633 T/A polymorphism was associated with gray matter of the putamen in the controls. Trends for associations between several polymorphisms/haplotype estimates and MRI volumes were found. BDNF gene variation may influence brain morphology. The effects may be different in patients with schizophrenia and healthy subjects.

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

“…Out of 126 studies initially found by the systematic search, 14 studies measured hippocampal volumes in healthy subjects genotyped for BDNF gene Val66Met polymorphism (Szeszko et al 2005;Agartz et al 2006;Bueller et al 2006;Frodl et al 2007;Takahashi et al 2008b;Chepenik et al 2009;Dutt et al 2009;Jessen et al 2009;Joffe et al 2009;Koolschijn et al 2010;Benjamin et al 2010;Gonul et al 2011;Haukvik et al 2010;Karnik et al 2010). The study by (Haukvik et al 2010) overlapped with the (Agartz et al 2006) study, thus yielding 13 non-overlaping datasets.…”

“…The study by (Haukvik et al 2010) overlapped with the (Agartz et al 2006) study, thus yielding 13 non-overlaping datasets. The studies by Joffe et al (2009) and Karnik et al (2010) did not use manual tracing, but rather automated segmentation and registration based procedures for hippocampal volumetry, thus failing inclusion criterion 3.…”

“…There was no association between hippocampal volume and Val-66Met BDNF polymorphism in either of these studies. Two other volumetric studies measured the whole hippocampal volume only, without providing separate results for the left and the right hippocampus (Agartz et al 2006;Chepenik et al 2009). Only one of these studies provided sufficient details for calculation of effect sizes (Chepenik et al 2009), thus not allowing for a separate meta-analysis.…”

“…This study showed increased total hippocampal volume in Val-BDNF homozygotes relative to Met-BDNF carriers. The remaining study showed no association between Val66Met BDNF polymorphism and hippocampal volume but did not provide sufficient details to extract the direction and extent of the effect sizes (Agartz et al 2006). Two additional volumetric studies provided data only on a mixture of healthy controls and patients without separating the results (Szeszko et al 2005;Benjamin et al 2010).…”

Investigação de genes candidatos para psicoses funcionais: estudo caso-controle com mães e crianças (população de alto risco)

“…Estudos de imagem sugerem que a variações dos polimorfismos do gene BDNF podem ter diferentes conseqüências na morfologia cerebral e podem ser diferentes entre indivíduos saudáveis e com esquizofrenia (Agartz I et al, 2006).…”