Jennifer Covino, Matthew Albaugh, Robert Althoff, Gareth Davies & James Hudziak

1. VCCYF Vermont Center for Children Youth & Families ASSOCIATION BETWEEN BDNF VAL166MET GENOTYPE AND MATERNAL RATINGS OF OBSESSIVE-COMPULSIVE BEHAVIOR* Jennifer Covino, Matthew Albaugh, Robert Althoff, Gareth Davies & James Hudziak Vermont Center for Children, Youth, and Families, University of Vermont College of Medicine Avera Institute for Human Behavioral Genetics, Avera Behavioral Health Center * This research was sponsored by NIMH, grant number R56MH058799 Measures Results Introduction Child Behavior Checklist (CBCL):The CBCL (Achenbach, 1991), one of the most extensively used instruments for assessing child psychopathology and competence worldwide, asks parents to report on specific behaviors exhibited by their child within the past 6 months. In the present study, mothers’ ratings of their children on the CBCL Obsessive-Compulsive Scale (OCS) scale were used. Items included on the OCS are (as numbered by the CBCL): 9. Can’t get his/her mind off certain thoughts; obsessions 31. Feels he/she might think or do something bad 32. Feels he/she has to be perfect 52. Feels too guilty 66. Repeats certain acts over and over; compulsions 84. Strange behavior 85. Strange ideas 112. Worries The Val166Met polymorphism within the BDNF gene—the gene that encodes for brain-derived neurotrophic factor—has been associated with amygdalar morphology and function, as well as anxiety-like behaviors. In a recent study, the combination of early life stress and Val/Val genotype was found to predict increased amygdalar and medial prefrontal volumes in humans which in turn predicted startle-elicited heart-rate variability and greater anxiety symptomatology (Gatt et al., 2009). Given models of the neural circuits believed to mediate obsessive-compulsive behavior (Baxter et al., 1996), and the hypothesized role of the amygdala in OCD symptomatology, we predicted that the BDNF Val166Met polymorphism would be associated with measures of obsessive-compulsive behavior in youth. Figure 1: Bar graph comparing Met-carrying and Val-homozygous youth on CBCL OCS raw score. Youth Val166Met genotype and mothers’ ratings on the CBCL OCS scale were significantly associated such that mothers of Val homozygotes rated their children higher on the CBCL OCS relative to mothers of Met-carrying children after linearly controlling for child age and gender, b = .15, t(353) = 2.88, p = .004. Sample Ratings on these 8 items were summed in order to compute the CBCL OCS raw score which served as our outcome variable. Isolation of DNA and Genotyping: All DNA extractions and genotyping were performed at the Avera Institute for Human Behavioral Genetics. DNA was extracted from saliva saturated cotton spit wads using a column purification method (Ehli et al., 2008). Carriers of the Met allele were coded as “0” and Val homozygotes were coded as “1”. Participants in the present study were from the Vermont Family Study which aimed to examine genetic and environmental factors influencing aggression and attention problems (Hudziak et al., 2003). The study was approved by an institutional review board, and all consent requirements were fulfilled. Families participating in the study were recruited through the use of newspaper advertisements and posters, as well as by local pediatricians and psychiatrists practicing in a university-based outpatient clinic. Three demographic inclusion criteria were applied during the initial screening of families: (1) proband was between 6 and 18 years of age; (2) proband was living with at least one biological parent; and (3) proband had at least one sibling between 6 and 18 years of age. A total of 206 families participated in the study, and data were obtained for 205 probands (126 boys, 79 girls; mean age 10.99 years; SD, 3.66 years) as well as 287 siblings (157 boys, 130 girls; mean age 10.84 years; SD, 3.25 years). In the present study, all probands and siblings with complete data on the outcome variable and the main predictor of interest, BDNF Val166Met genotype, were used in testing the aforementioned hypothesis (N = 357). Conclusions These findings lend support to a putative association between BDNF Val166Met genotype and obsessive-compulsive behavior in youth. The next steps here will be to conduct more rigorous pedigree-based association tests (PBATs) in order further probe the association between obsessive-compulsive behavior and BDNF genotype. These analyses will utilize genotypic and phenotypic data from probands and siblings, as well as from parents. Analyses A standard multiple linear regression was employed in order to test the association between child BDNF Val166Met genotype and mothers’ ratings on the CBCL OCS while statistically controlling for child age and gender. References Achenbach TM. Manual for the Child Behavior Checklist 4–18 and 1991 profile. Burlington VT: University of Vermont, Department of Psychiatry; 1991. Baxter LR, Jr., Saxena S, Brody AL, Ackermann RF, Colgan M, Schwartz JM, Allen-Martinez Z, Fuster JM, Phelps ME. Brain mediation of obsessive-compulsive disorder symptoms: Evidence from functional brain imaging studies in the human and nonhuman primate. Seminars in Clinical Neuropsychiatry. 1996:32-47. Ehli EA, Lengyel-Nelson T, Hudziak JJ, Davies GE. Using a commercially available DNA extraction kit to obtain high quality human genomic DNA suitable for PCR and genotyping from 11-year-old saliva saturated cotton spit wads. BMC Res Notes. 2008:1:133. 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