Highly penetrant alterations of a critical region including BDNF in human psychopathology and obesity.
Carl ErnstChristian R MarshallYiping ShenKay MetcalfeJill RosenfeldJennelle C HodgeAlcy TorresIan BlumenthalColby ChiangVamsee PillalamarriLiam CrapperAlpha B DialloDouglas RuderferShahrin PereiraPamela SklarShaun PurcellRobert S WildinAnne C SpencerBradley F QuadeDavid J HarrisEmanuelle LemyreBai-Lin WuDimitri J StavropoulosMichael T GeraghtyLisa G ShafferCynthia C MortonStephen W SchererJames F GusellaMichael E TalkowskiPublished in: Archives of general psychiatry (2013)
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.
Keyphrases
- copy number
- mitochondrial dna
- stress induced
- endothelial cells
- genome wide
- cognitive impairment
- mental health
- end stage renal disease
- dna methylation
- type diabetes
- pluripotent stem cells
- anorexia nervosa
- bipolar disorder
- insulin resistance
- case report
- prognostic factors
- big data
- weight gain
- machine learning
- adipose tissue
- depressive symptoms
- bioinformatics analysis