Attention deficit hyperactivity disorder (ADHD) is a common, multifactorial disorder with significant genetic contribution. Multiple candidate genes have been studied in ADHD, including the norepinephrine transporter (NET1) and dopamine D1 receptor (DRD1). NET1 is implicated in ADHD because of the efficacy of atomoxetine, a selective noradrenergic reuptake inhibitor, in the treatment of ADHD. DRD1 is primarily implicated through mouse models of ADHD. DNA from 163 ADHD probands, 192 parents, and 129 healthy controls was used to investigate possible associations between ADHD and polymorphisms in 12 previously studied candidate genes (5-HT1B, 5-HT2A, 5-HT2C, ADRA2A, CHRNA4, COMT, DAT1, DRD1, DRD4, DRD5, NET1, and SNAP-25). Analyses included case-control and family-based methods, and dimensional measures of behavior, cognition, and anatomic brain magnetic resonance imaging (MRI). Of the 12 genes examined, two showed a significant association with ADHD. Transmission disequilibrium test (TDT) analysis revealed significant association of two NET1 single nucleotide polymorphisms (SNPs) with ADHD (P < or = 0.009); case-control analysis revealed significant association of two DRD1 SNPs with ADHD (P < or = 0.008). No behavioral, cognitive, or brain MRI volume measurement significantly differed across NET1 or DRD1 genotypes at an alpha of 0.01. This study provides support for an association between ADHD and polymorphisms in both NET1 and DRD1; polymorphisms in ten other candidate genes were not associated with ADHD. Because family-based and case-control methods gave divergent results, both should be used in genetic studies of ADHD.
Relations among hormone levels, emotional dispositions, and aggressive attributes were examined in 56 boys and 52 girls, age 9 to 14 years. The adolescents represented all 5 stages of pubertal development. Serum levels of gonadotropins, gonadal steroids, adrenal androgens, and testosterone-estradiol binding globulin were assessed. Levels of these hormones were related to stage of pubertal development and were assumed to represent relatively stable biological characteristics. The emotional dispositions assessed were adolescent self-reported anger, nervousness, sadness, and impulse control. The aggressive attributes assessed were mother-reported acting out and aggressive behavior problems and rebellious and nasty characteristics. Hormone levels were related to emotional dispositions and aggressive attributes for boys but not for girls. For example, higher levels of androstenedione in boys were related to higher levels of acting-out behavior problems. Level of testosterone-estradiol binding globulin was negatively related to sad affect and acting out behavior.
This study was designed (a) to examine relations among ratings of pubertal stage by adolescents, parents, and health care personnel, and (b) to determine if accuracy of adolescent and parent ratings varied with stage of puberty. Ss were 90 healthy adolescents: 46 boys, ages 10-15, and 44 girls, ages 9-15, and their parents. Ss were shown photos of the 5 stages of puberty (Tanner criteria). Ss rated the adolescents' pubertal stage, and a nurse practitioner completed an examination to rate the adolescents' stage. Correlations between adolescent and examiner ratings ranged from r = .77 to r = .91 (p < .001, K = .33 to .50), and between parent and examiner from r = .75 to r = .87 (p <, .001, K = . 13 to .55). When inaccurate, Ss ratings were lower than examiner ratings and less accurate at later stages of puberty. Use of adolescent and parent ratings is limited if precise ratings of stage are necessary to answer a research question.
The study examined the relation between timing of physical maturation and problems of adjustment and peer relations. The participants were 9-14-year-old boys (N=56) and girls (N=52). Assessments of physical maturation consisted of pubertal staging according to Tanner criteria and serum determinations of luteinizing hormone, follicle stimulating hormone, testosterone, estradiol, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione. There was approximately an equal number of boys and girls in each pubertal stage. The psychological measures were the Psychopathology and Emotional Tone subscales from the Offer Self-Image Questionnaire for Adolescents and interview questions to assess interactions with peers. Psychopathology and emotional tone (sad effect) scores were higher for boys with high-for-age adrenal androgens and lower for boys with high-for-age sex steroids. Behavioral manifestations of sexuality, interest in dating, was higher for boys with high-for-age adrenal androgens. Dating and spending time with friends were higher for boys with high-for-age gonadotropins. Psychopathology and emotional tone were higher for girls with high-for-age gonadotropins. The results indicate that high-for-age hormone level or early timing of puberty generally was related to adverse psychological consequences for boys and girls, with relations being stronger for boys than for girls.
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