Study Report

Reference	Schumacher, J.,2005 PMID: 16005437
Citation	Schumacher, J., R. A. Jamra, et al. (2005). Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. Biol Psychiatry 58(4): 307-314.
Disease Type	Bipolar Disorder & Schizophrenia & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	465 MDD, 281 BPAD, 533 schizophrenia, and 1,097 control subjects
SNP/Region/Marker Size	3 polymorphisms
Predominant Ethnicity	Caucasian
Population	German
Gender	The Bonn sample:65% women in MDD patients, 45% women in BPAD patients,56% women in schizophrenic patients and 50% women in controls;the Munich sample:68% women in MDD patients and 67% women in controls
Age Group	Adults : Mean age(SD)(year):the Bonn sample:47.35(13.70) in MDD patients, 42.82(13.23) in BPAD patients,36.84(11.54) in schizophrenic patients and 44.57(15.85) in controls;the Munich sample:52.16(13.43) in MDD patients and 50.45(12.83) in controls

Sample Diagnosis	DSM
Sample Status	In total, we investigated 1,591 patients and 1,541 control subjects.The study was approved by the ethical review board of the Medical Faculty at the University of Bonn. For the Bonn sample, patients were systematically recruited from the inpatient and outpatient sections of the Department of Psychiatry at the University of Bonn.The sample consisted of 465 patients with MDD, 281 BPAD patients , 533 schizophrenic patients, and 1,097 ethnically matched control individuals. 351 MDD patients suffered from unipolar recurrent disorder (UPR), and 114 from unipolar single episode disorder (UPS).For the Munich sample, inpatients were recruited from the departments of the Max-Planck-Institute of Psychiatry in Munich and the psychiatric hospitals in Augsburg and Ingolstadt, and outpatients were recruited from community's practices in the Munich area. The Munich sample comprised 312 MDD patients ; all patients hadbeen diagnosed with UPR; and 444 ethnically matched control subjects .
Technique	genotyping
Statistical Method	Departure from Hardy-Weinberg equilibrium (HWE) for the two biallelic SNP markers was tested using a chi-square test (1 df ). For the multiallelic dinucleotide repeat (GT)n-marker,departure from HWE was assessed with a Fisher Exact Test as implemented in option 11 of the MENDEL software package(version 5.5, http://www.genetics.ucla.edu/software/mendel5;Lange et al 2001). Single-marker association analysis was performed using the Cochrane-Armitage Trend Test (Armitage 1955), which in the case of HWE is equivalent to the standard chi-square test for allele frequencies. Haplotype frequencies were compared between case and control subjects with the FAMHAP program that is able to calculate both family-based and case- control data (Becker and Knapp 2004).
Result Summary	RESULTS: Single-marker analysis did not provide strong evidence for association. Haplotype analysis of marker combination rs988748-(GT)n-rs6265 produced nominally significant associations for all investigated phenotypes (global p values: MDD p = .00006, BPAD p = .0057, schizophrenia p = .016). Association with MDD was the most robust finding and could be replicated in a second German sample of MDD patients and control subjects (p = .0092, uncorrected). Stratification of our schizophrenia sample according to the presence or absence of a lifetime history of depressive symptoms showed that our finding in schizophrenia might be attributable mainly to the presence of depressive symptoms. CONCLUSIONS: Association studies of genetic variants of the BDNF gene with various psychiatric disorders have been published with reports of associations and nonreplications. Our findings suggest that BDNF may be a susceptibility gene for MDD and schizophrenia-in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.