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residual symptoms into late adolescence and adulthood. 1 While in children disruptive behavior is often the presenting complaint, in adolescents and adults it is deficits in mood regulation, arousal, and organization that often come to the forefront. 2 As the pressure to conform to work schedules increases over time, an inability to adapt daily activity schedules to occupational demands contributes to truancy and poor performance. This inability is often related to difficulty falling asleep, awakening on time, and maintaining arousal when performance demands are maximal. 3 In chronobiological terms, these difficulties are consistent with a phase delay in circadian activity rhythms. In clinical settings, one way to estimate circadian phase is to administer the Horne-Ostberg Morningness-Eveningness questionnaire (MEQ), 4 which asks about the timing of sleep/wake cycles and other activities. The MEQ correlates highly with objectively measured circadian rhythms 5,6 and has been used as a proxy for these rhythms in prior research. 7 Our recent pretreatment study 8 of adults with ADHD taking part in the current protocol found that over 40% reported an evening circadian preference (designated "evening types") based on the MEQ. This finding is highly discrepant with a large European study of the general population, which found only 10.8% of evening types. 9 Of great clinical relevance, in these

We have recently described an association between the hypofunctional 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F ¼ 4.42, df ¼ 8, 173, po0.0001) with season-of-birth predicting maximal lifetime BMI both on its own and in its interaction with the 7R allele. The latter finding was attributable to 7-repeat carriers born in the spring (N ¼ 17), who had a mean maximal lifetime BMI of 33.7 kg/m 2 (SD 8.6), compared to 26.7 kg/m 2 (SD 5.4) for all other probands combined (N ¼ 165) (F ¼ 20.01, df ¼ 1, 179, po0.0001). The lifetime rate of obesity (maximal BMI 430 kg/m 2 ) was also significantly higher in the 7R/spring birth group (9/17 ¼ 52.9% vs 32/ 165 ¼ 19.4%; w 2 ¼ 9.94, df ¼ 1, p ¼ 0.002; odds ratio ¼ 4.68, 95% CI ¼ 1.67-13.07). These data may reflect a novel gene-environment interaction, during early brain development, which establishes an increased risk for obesity in women with SAD. Although the mechanism for season-of-birth effects in psychiatric disorders is unknown, a characteristic pattern of melatonin exposure during the second and third trimesters may be of particular relevance in this study population. We speculate that these data may reflect the vestigial expression of a seasonal thrifty phenotype that contributed to the positive selection of the 7R allele over the past 40 000 years.