BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Basic Info

Reference	Chepenik, L. G.,2009 PMID: 18704093
Citation	Chepenik, L. G., C. Fredericks, et al. (2009). Effects of the brain-derived neurotrophic growth factor val66met variation on hippocampus morphology in bipolar disorder. Neuropsychopharmacology 34(4): 944-951.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	20 individuals with BD and 18 healthy comparison (HC) subjects
SNP/Region/Marker Size	1 variant
Predominant Ethnicity	Caucasian
Population	American
Gender	Male/female:9/11 in BD patients and 6/12 in HC participants
Age Group	Adults : age 21-56 years in BD patients and 18-58 years in healthy controls

Detail Info

Sample Diagnosis	DSM
Sample Status	Subjects included 20 adults with BD (11 female patients: age 21-56 years; race: 18 European Americans; 2 other) and 18 HC participants (12 female patients: age 18-58 years; race:13 European Americans; 3 African Americans; 2 other).Subjects with BD included 12 val/val homozygotes and 8'met carriers' (seven individuals heterozygous for the met allele and one met/met homozygote). In the HC group, 12 subjects were homozygous for the val allele and 6 subjects were met carriers (all heterozygous for the met allele). Study participants were recruited through the Veterans Affairs Connecticut Health Care System, West Haven; the Yale School of Medicine, New Haven, CT; and practitioners in the community or from advertisement in local newspapers.Presence or absence of DSM-IV Axis I disorders was confirmed using the Structured Clinical Interview for DSMIV Axis I Disorders, version 2.0 (First et al, 1995). None of the participants had a significant medical or neurologic illness, history of loss of consciousness greater than 5 min, or active drug or alcohol dependence. HC subjects also lacked a personal history of an Axis I disorder. Mean age of BD onset was 21 years (SD=8 years, range=11-35 years). Mean length of BD illness duration was 18 years (SD=10 years; range= 2-40 years). Five (25%) of the BD subjects had experienced past psychotic symptoms that occurred within the context of a manic episode. None of the subjects were psychotic at the time of scan. Two (10%) of the BD subjects had a history of panic disorder and 14 (70%) had a history of substance abuse or dependence (including alcohol). All were in remission for at least 1 year (range=1-27 years), with the exception of one subject who was in remission for 5 months. Average length of time in remission was 11 years. Five (25%) of these subjects had a history of alcohol dependence and had additional comorbid substance dependence(1 cocaine and 1 polysubstance dependence). One subject had a history of cannabis dependence. An additional 8 (40%) BD subjects had a history of substance abuse (4 alcohol and cannabis, 2 alcohol only, 1 cannabis only and 1 abused multiple substances). Eight (40%) of the BD subjects met past criteria for rapid cycling. Six (30%) of the subjects were euthymic at the time of scan, 8 (40%) were depressed, and 5(25%) were manic or hypomanic. Six (30%) of the BD subjects were unmedicated at the time of scan. Of the remaining 13 subjects, 5 (25%) were prescribed lithium salts, 8 (40%) an anticonvulsant, 6 (30%) an atypical antipsychotic,6 (30%) an antidepressant, and 1 (5%) levothyroxine.
Technique	genotyping and Magnetic resonance imaging (MRI) scans
Statistical Method	Statistical analyses for region of interest (ROI)-based hippocampus tracings were performed using SAS software, version 9.1(SAS Institute Inc., Cary, NC).Three-dimensional mapping methods were used to localize effects of BDNF genotypes within BD by performing two sample t-tests comparing BD val/val homozygotes with BD met carriers at all hippocampus voxels. These analyses were performed using the Yale BioImage Suite software package(www.bioimagesuite.org) with morphometric Jacobian values as the dependent variables.
Result Summary	We found that hippocampus volumes were significantly smaller in BD compared to HC subjects, and presence of the BDNF met allele was associated with smaller hippocampus volume in both diagnostic groups. The BD subgroup who carried the BDNF met allele had the smallest hippocampus volumes, and three-dimensional mapping identified these decreases as most prominent in left anterior hippocampus. These results support effects of BD diagnosis and BDNF genotype on hippocampus structure and suggest a genetic subgroup within BD who may be most vulnerable to deficits in hippocampus and may most benefit from interventions that influence BDNF-mediated signaling.

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
BDNF Val66Met	BDNF	point mutation	Val66Met		The ROI analyses:1.genotype:P-value < 0.001, Carriers of the BDNF met alleleï¼šLSmean-met=2433, SE-met=115; LSmean-val=2950, SE-val=86.BD met carriers: LSmean-HCval=3166, SE=134; LSmean-HCmet=2683, SE=178; LSmean-BDval=2734, SE=125; LSmean-BDmet=2181, SE=149 2.group:P-value < 0.01, Case-control:LSmean-BD=2458, SE-BD=100;LSmean-HC=2925, SE-HC=100.	We found that hippocampus volumes were significantly smaller...... We found that hippocampus volumes were significantly smaller in BD compared to HC subjects, and presence of the BDNF met allele was associated with smaller hippocampus volume in both diagnostic groups. The BD subgroup who carried the BDNF met allele had the smallest hippocampus volumes, and three-dimensional mapping identified these decreases as most prominent in left anterior hippocampus. More...	Positive

Genes reported by this study for BD (count: 1)