An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit͞hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD. Dopamine plays an important role in normal attention (1) and disorders of attention (2, 3). Recently, this role of dopamine has stimulated molecular genetic studies (4) of attention deficit͞ hyperactivity disorder (ADHD), the most prevalent psychiatric disorder of childhood recognized in the United States. The dopamine receptor genes (5) have been investigated in other psychiatric disorders (e.g., schizophrenia; see refs. 6 and 7), and the background from this work set the stage for our molecular genetic investigations of ADHD.In our program of research, we adopted a candidate gene approach, focusing on the dopamine receptor D4 (DRD4) gene on chromosome 11p15.5. This gene has a polymorphism in a coding region-a variable number of tandem repeats of a 48-base pair sequence in exon 3 (8) that codes for variation in the third intracellular loop of the D4 receptor, which may have functional significance. In vitro studies suggest that the receptor encoded by the DRD4 7-repeat allele may be subsensitive to endogenous dopamine compared with the receptor encoded by the 2-repeat allele (9), although this apparently is not due merely to the length of the third intracellular loop (10). Initially, in our clinical studies we used population-based (11) and family-based (12) association designs, which suggested that the DRD4 7-repeat allele is associated with ADHD, but with a small relative risk (about 1.5). A review of the recent literature (4) revealed that two independent groups have confirmed this association in children (13,14), but one group did not (15). The pattern of replication has held up in several other case studies not yet published.The presence of the DRD4, 7-repeat allele is not a necessary condition (about half of the ADHD cases did not have a 7-repeat allele) (11, 12) or a sufficient condition (about 20% of ethnically matched control subjects d...

Surveys and electronic diaries were used to examine depressive and extemalizing dispositions as they relate to smoking and moods in 170 early adolescents. Negative moods were prevalent, with anger and anxiety reported on 26%-60% and sadness on 16%-40% of occasions. The risk of smoking, urges to smoke, and alcohol intake were elevated in teens with aggressive and depressive dispositions, as were diary reports of feeling hassled, angry, and sad. Girls high in depression and aggression also reported more anxiety, stress, and fatigue and less happiness and well-being than did their peers. For boys, depression seemed to dampen the elevated smoking risks associated with externalizing behaviors. Discussion focuses on gender differences in personality-smoking linkages, adolescent negative affectivity, the unique contributions of survey and diary methods, and the promise of targeted preventive interventions such as affect regulation training.

Individuals with attentional and emotional dysfunctions are most at risk for smoking initiation and subsequent nicotine addiction. This article presents converging findings from human behavioral research, brain imaging, and basic neuroscience on smoking as self-medication for attentional and emotional dysfunctions. Nicotine and other tobacco constituents have significant effects on neural circuitry underlying the regulation of attention and affect. Age, sex, early environment, and exposure to other drugs have been identified as important factors that moderate both the effects of nicotine on brain circuitry and behavior and the risk for smoking initiation. Findings also suggest that the effects of smoking differ depending on whether smoking is used to regulate attention or affect. Individual differences in the reinforcement processes underlying tobacco use have implications for the development of tailored smoking cessation programs and prevention strategies that include early treatment of attentional and emotional dysfunctions.

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e.EMA showed that the social and physical contexts of adolescent exercise and walking vary as a function of gender, grade in school, day of the week, and season. Understanding the contexts of physical activity during the high school years can be helpful in designing interventions during adolescence.