Faculty Bibliography

Although the etiology of Attention Deficit/Hyperactivity Disorder (ADHD) is not well understood, evidence from the family and twin studies suggest that ADHD is familial and highly heritable. The aim of the study was to test whether dopamine transporter gene (DAT1) and dopamine receptor D4 gene (DRD4) polymorphisms are in linkage disequilibrium with ADHD in Korean children, using a family-based association study. One hundred and twenty-six trios were studied and 87% of probands were boys (mean age=8.2 years, mean IQ=104). ADHD not otherwise specified (NOS) was the most common subtype and comorbidity rates were low. Descriptive analysis and the TDT test were the primary analyses. In exploratory analyses, logistic regression and QTDT were performed. The 10-repeat allele and 4-repeat allele were the most frequent for DAT1 and DRD4. TDT test for DAT1 and DRD4 did not show preferential transmission. Based on logistic regression and QTDT, the 5-repeat allele of DRD4 may confer protection for hyperactive-impulsivity symptom severity compared to the 4-repeat allele. The negative TDT finding between DAT1 and DRD4 VNTR polymorphisms and ADHD should be interpreted with caution; partly due to lack of power caused by low heterozygosity in the study population. Future studies are necessary to test the hypothesis generated in this study that the 5-repeat allele of DRD4 is protective for hyperactive-impulsivity symptom severity compared to the 4-repeat allele

OBJECTIVE: To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid tic disorders. METHODS: Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks. RESULTS: Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures. CONCLUSIONS: Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated

BACKGROUND: Smell identification deficits (SID) are common in adult schizophrenia, where they are associated with negative symptoms and lower intelligence. However, smell identification has not been examined in adolescents with early onset psychosis, wherein diagnosis is often obscure, and there are few prognostic predictors. METHOD: We examined smell identification, diagnosis, neuropsychological performance and symptoms in 26 well characterized adolescents with early onset psychosis, age 11-17 years. RESULTS: SID existed in the sample and were more common in patients with schizophrenia and psychotic depression than in patients with psychosis NOS and bipolar disorder. As in adults, SID were significantly associated with greater negative symptoms and lower verbal IQ. However, the associations of verbal IQ (and other verbal tasks) to smell identification in this pediatric sample were explained by the relation of both of these types of variables to negative symptoms. CONCLUSIONS: SID existed across this sample of youths with psychotic disorder, and were specifically related to typical characteristics of schizophrenia, such as negative symptoms and lower intelligence, but not to features of bipolar disorder, such as grandiosity. SID is a characteristic of early onset psychosis that may be useful for prognostic purposes

There are large differences between nations in the diagnosis and management of children with marked impulsiveness and inattention. The differences extend to the names and definitions of disorder and the extent to which medication should be used. This paper uses data from a large randomized clinical trial of pharmacological and psychosocial treatments, conducted in North America, to clarify its implications for other parts of the world. A diagnostic algorithm was applied to 579 children, diagnosed with ADHD-Combined Type in the MTA trial, to generate the ICD-10 diagnosis of 'hyperkinetic disorder' (HD); only a quarter met these more stringent criteria. HD was a moderator of treatment response. The superiority of medication to behavioral treatment was greater for children with HD. Children with ADHD but not HD also showed some improvement with medication. The results provide evidence for the validity of HD as a subgroup of those presenting ADHD; and suggest that treatment with stimulants is a high priority in children with HD. Results also suggest that some children with other forms of ADHD will respond better to medication than to psychosocial intervention, and therefore that European guidelines should extend their indications.

Social anxiety disorder, whose onset peaks in adolescence, is associated with significant impairment. Despite the availability of effective treatments, few affected youth receive services. Transporting interventions into schools may circumvent barriers to treatment. The efficacy of a school-based intervention for social anxiety disorder was examined in a randomized wait-list control trial of 35 adolescents (26 females). Independent evaluators, blind to treatment condition, evaluated participants at preintervention, postintervention, and 9 months later. Adolescents in the intervention group demonstrated significantly greater reductions than controls in social anxiety and avoidance, as well as significantly improved overall functioning. In addition, 67% of treated subjects, compared to 6% of wait-list participants, no longer met criteria for social phobia following treatment. Findings support the possible efficacy of school-based intervention for facilitating access to treatment for socially anxious adolescents.

This study investigated the utility of several scales of the Child Behavior Checklist (CBCL) when diagnosing anxiety disorders in youth. Participants were the mothers and fathers of 130 children (ages 7 to 14; M = 9.61 years, SD = 1.74; 69 boys, 61 girls) who were evaluated at a specialty mental health clinic (100 were referred for treatment; 30 were nonanxious volunteers). For both mothers' and fathers' reports, the highest correlations were found between the Anxious/Depressed subscale and the severity of generalized anxiety disorder (GAD); the second highest relations were between the Withdrawn subscale and the severity of social phobia (SP). Using either mothers' reports or fathers' reports, receiver operating characteristics (ROC) analyses identified cutoff scores that were useful in ruling in the presence of an anxiety disorder in general but did not identify cutoff scores to rule in the presence of principal GAD or principal SP. For mothers' reports only, receiver operating characteristics analyses identified a useful cutoff score to rule out the presence of an anxiety disorder, as well as a cutoff score to rule out the presence of principal GAD. Finally, discriminant function analyses determined the most useful subscales for ruling in and ruling out an anxiety disorder in general, as well as principal GAD and principal SP. Findings are discussed with regard to diagnosis of child anxiety and the clinical utility of the CBCL with anxious youth

Sensation seeking (SS) has traditionally been viewed as a phenomenon of the appetitive motivational system. The limited SS research exploring contributions from the aversive motivational system reveals greater anxious reactivity to dangerous activities among low sensation seekers. The present study extends this line of work by comparing levels of fear and anxiety during anticipation of predictable and unpredictable aversive stimuli across high- and low-SS groups. Low sensation seekers displayed greater fear-potentiated startle (FPS) to predictable aversive stimuli, and only those low on SS showed FPS and skin conductance response effects during experimental contexts in which aversive stimuli were delivered unpredictably. Findings implicate enhanced apprehensive anticipation among those low on SS as a potential deterrent for their participation in intense and threatening stimulus events.