Childhood Urbanicity and BDNF Val/Met Interaction alters activation in bilateral parahippocampal gyrus

Authors

• TG Vargas Lopez
• J Ihne
• K Berman
• D Weinberger
• A Mattay
• S Marenco
• JH Callicott

Abstract

Background: Growing up in an urban area predicts increased risk for mental illness, and recently, neuronal activation in task-related fMRI. We found a COMT-by-urbanicity interaction whereby carriers of the risk allele, Val/Val showed more parahippocampal gyrus activation during an encoding task when raised exclusively in an urban environment. We hypothesized that urbanicity would also interact with the brain derived neurotrophic factor (BDNF) gene during an encoding memory paradigm. Methods: 134 healthy subjects participated in BOLD fMRI, neutral and aversive stimuli encoding and retrieval tasks. As in previous experiments rural subjects were raised where the population was less than 10,000, town between 10,000 and 100,000, and urban greater than 100,000. We tested for the BDNF-by-urbanicity interaction and main effect of urbanicity. Results: Main effects of BDNF and urbanicity, as well as an interaction, were observed in the parahippocampal gyrus during encoding. We found that urban upbringing and BDNF genotype interacted to alter activation in areas in the bilateral parahippocampal gyrus, whereby urban Met/Met carriers activated the least. Discussion: As was seen with the COMT gene, the BDNF-by-Urbanicity interaction yielded greatest activation in bilateral parahippocampal gyrus for carriers of the risk allele. Performance was controlled for, suggesting that this difference in activation is not due to differences in memory retrieval. Our results suggest that childhood urbanicity may have effects beyond prefrontal regions and in genes tied to hippocampal area neuronal function.

Scientific Focus Area: Neuroscience

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