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The Role of Gene Encoding Variation of DRD4 in the Relationship between Inattention and Seasonal Daylight

By M.A. Vollebregt, Barbara Franke, Jan K. Buitelaar, L. Eugene Arnold, Stephen V Faraone, E.H. Grevet, Andreas Reif, T. Zayats, Janita Bralten, C.H.D. Bau, J. Haavik, Jonna Kuntsi, R.B. Cupertino, S.K. Loo, Astri J. Lundervold, M. Ribasés, C. Sánchez-Mora, J.A. Ramos-Quiroga, Philip Asherson, J.M. Swanson, M. Arns

Posted 31 Oct 2019
bioRxiv DOI: 10.1101/825083

Daylight is the strongest synchronizer of human circadian rhythms. The circadian pathway hypothesis posits that synchrony between daylight and the circadian system relates to (in)attention. The dopamine neurotransmitter system is implicated in regulating the circadian system as well as in (attention)-deficit hyperactivity disorder [ADHD]. We studied the role of functional genetic variation in the gene encoding of dopamine-receptor-D4 (DRD4) in the relationship between inattention and seasonal daylight (changes). Gene-by-environment (GxE) mega-analyses were performed across eight studies including 3757 adult participants (with and without ADHD). We tested 1) the Spring-focus hypothesis, in which attention in 7R-carriers normalizes with increasing daylight levels preceding measurement, 2) the Summer-born ADHD hypothesis, in which 7R-carriers report more inattention when born in spring/summer than in autumn/winter, 3) the Winter-born ADHD hypothesis, opposing the second hypothesis. The Spring-focus hypothesis was upheld (1386 ADHD, 760 controls; d=- 0.16 between periods); 7R-carriers reported even less inattention than 7R-non-carriers after winter solstice (d=0.27 between genotype-groups). Results were diagnosis-independent. Sensitivity analyses at individual study level confirmed the circannual patterns for 7R- carriers. Incorporating geographic changes into the independent measure, we also calculated changes in sunlight levels. This approach likewise showed that inattention correlated negatively with increasing light levels in 7R-carriers (r=-.135). Results emphasize peripheral effects of dopamine and the effects of (seasonal) daylight changes on cognition.

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