PMID- 17210134 OWN - NLM STAT- MEDLINE DCOM- 20071026 LR - 20151119 IS - 0006-3223 (Print) IS - 0006-3223 (Linking) VI - 62 IP - 5 DP - 2007 Sep 1 TI - Genotype and childhood sexual trauma moderate neurocognitive performance: a possible role for brain-derived neurotrophic factor and apolipoprotein E variants. PG - 391-9 AB - BACKGROUND: Limited success in the identification of genetic variants underpinning psychiatric illness has prompted attempts to elucidate gene-environment interactions and illness-associated endophenotypes. Here we measured childhood sexual abuse, a potential environmental risk factor, and verbal and visual recall and recognition memory, a possible illness-associated endophenotype in a cohort of bipolar disorder (BPD) subjects and their relatives. We predicted that memory would be affected by sexual trauma and that a number of functional polymorphisms previously implicated in BPD and cognition would moderate the effect of psychological trauma on memory. METHODS: A cohort of 350 individuals from 47 BPD families was recruited, tested with a neuropsychological battery, and given the Childhood Trauma Questionnaire (CTQ). Eleven different genetic variants previously found to be relevant to BPD or memory dysfunction were typed. RESULTS: As predicted, scores on the sexual abuse scale of the CTQ were negatively associated with memory performance. Furthermore, the low-activity Met allele of the brain-derived neurotrophic factor (BDNF) gene and the epsilon4 allele of the apolipoprotein E gene interacted with sexual abuse scores to result in reduced memory test performance. CONCLUSIONS: Apolipoprotein E and BDNF exert a neurotrophic effect in response to cellular injury. Their possible moderation of the association between sexual abuse and memory performance might indicate that there is some degree of overlap in the pathophysiological mechanisms by which psychological and physical trauma impact brain function. The finding of an environmental effect on memory performance and a gene-environment interaction on this hypothetical endophenotype of BPD illustrates the difficulty of identifying genetically and phenotypically simple intermediate traits for molecular genetic studies. FAU - Savitz, Jonathan AU - Savitz J AD - MRC/UCT Human Genetics Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa. savitzj@mail.nih.gov FAU - van der Merwe, Lize AU - van der Merwe L FAU - Stein, Dan J AU - Stein DJ FAU - Solms, Mark AU - Solms M FAU - Ramesar, Rajkumar AU - Ramesar R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070108 PL - United States TA - Biol Psychiatry JT - Biological psychiatry JID - 0213264 RN - 0 (Apolipoproteins E) RN - 0 (Brain-Derived Neurotrophic Factor) RN - AE28F7PNPL (Methionine) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Apolipoproteins E/*genetics MH - Bipolar Disorder/etiology/genetics MH - Brain-Derived Neurotrophic Factor/*genetics MH - *Child Abuse, Sexual MH - Cognition Disorders/genetics/*physiopathology MH - Cohort Studies MH - Female MH - *Genetic Variation MH - Humans MH - Male MH - Memory/*physiology MH - Methionine/genetics MH - Middle Aged MH - Models, Statistical MH - Neuropsychological Tests MH - Psychometrics/methods MH - Retrospective Studies MH - Surveys and Questionnaires EDAT- 2007/01/11 09:00 MHDA- 2007/10/30 09:00 CRDT- 2007/01/11 09:00 PHST- 2006/04/11 00:00 [received] PHST- 2006/09/30 00:00 [revised] PHST- 2006/10/05 00:00 [accepted] PHST- 2007/01/11 09:00 [pubmed] PHST- 2007/10/30 09:00 [medline] PHST- 2007/01/11 09:00 [entrez] AID - S0006-3223(06)01322-9 [pii] AID - 10.1016/j.biopsych.2006.10.017 [doi] PST - ppublish SO - Biol Psychiatry. 2007 Sep 1;62(5):391-9. doi: 10.1016/j.biopsych.2006.10.017. Epub 2007 Jan 8.