Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity

Context: Brain-derived neurotrophic factor (BDNF) is suspected of being a causative factor in psychiatric disorders based on case reports or studies involving large structural anomalies. Objective: To determine the involvement of BDNF in human psychopathology. Design: Case-control study. Setting: Microarray-based comparative genomic hybridization data from 7 molecular diagnostic centers including 38 550 affected subjects and 28 705 unaffected subjects. Patients: Subjects referred to diagnostic screening centers for microarray-based comparative genomic hybridization for physical or cognitive impairment. Main Outcome Measures: Genomic copy number gains and losses. Results: We report 5 individuals with psychopathology and genomic deletion of a critical region including BDNF. The defined critical region was never disrupted in control subjects or diagnostic cases without developmental abnormalities. Conclusion: Hemizygosity of the BDNF region contributes to variable psychiatric phenotypes including anxiety, behavioral, and mood disorders.