The "younger-sibling-at-risk design": a pilot study of adolescents with ADHD and an older sibling with substance use disorder.

INTRODUCTION: This article introduces a ?younger at-risk sibling? design to study progression from other psychopathologies to their substance use disorder (SUD) complications. The design selects not-yet-SUD adolescents with high-risk-for-SUD psychopathology only if an older sibling has SUD. This "proof of concept' pilot study examines the design?s feasibility if the younger sibling has attention deficit hyperactivity disorder (ADHD). METHOD: Subjects were recruited from families at substance abuse treatment centers that had a non-SUD younger child with ADHD, from families at behavior disorder clinics that had a younger child with ADHD and SUD older child, and through general advertisements. Subjects were seen weekly for at least 3 months and monthly thereafter for 3 months. All were treated with open-label lisdexamfetamine dimesylate 30-70 mg per day. Outcomes explored were recruitment, compliance, diversion, ADHD improvement, and substance use interest. RESULTS: 25 families were screened, 13 evaluated, and 8 began medication. ADHD Rating Scale-IV scores obtained by parent?adolescent consensus improved as expected with a stimulant. Rating forms could quantify substance use interest in subjects with some drug culture exposure but encountered a floor effect in those without. The design's complexity and implicit commentary on family dynamics complicated recruitment but may have facilitated retention. CONCLUSION: Sibling pairs in which the older sibling has substance use and the younger sibling has ADHD exist. Such younger siblings can be recruited into a treatment study. The design may shed light on the pathogenesis and prevention of SUD complications from ADHD and theoretically other SUD comorbidities.

Verbal abilities as predictors of retention among adolescents in a therapeutic community.

The relationship between verbal skills and retention among adolescents in substance abuse treatment is understudied. In order to assess verbal predictors of retention, twenty-eight 16-19 year old adolescents in a therapeutic community for substance abuse were evaluated between 30 and 90 days after admission. These adolescents were then followed prospectively for 1 year. Verbal and non-verbal cognitive screens, audio taped narrative responses, and self-reports of socio-emotional function and psychiatric symptoms were completed. Verbal scores were associated with self-restraint and counselor reports of therapeutic engagement and comprehension. General verbal scores predicted attrition, while therapeutic expressiveness (verbal expressiveness in a therapeutic context) predicted retention. Remediation of verbal communication skills may be an overlooked aspect of the therapeutic process in treating adolescent substance abusers.

"Outer-directed irritability": a distinct mood syndrome in explosive youth with a disruptive behavior disorder?

OBJECTIVE: To examine whether "outer-directed irritability," a mood construct from the adult literature, characterizes a subgroup of disruptive behavior disordered children and adolescents previously shown to improve on divalproex, a mood stabilizer. METHOD: A sample (N = 20) of disruptive youth (aged 10-18 years) entering a divalproex treatment study of temper and irritable mood swings was compared to normal controls (N = 18) on measures of aggression/irritability directed against others (externalizing symptoms) and on aggression/ irritability against self, anxiety, and depression (internalizing symptoms). All patients met DSM-IV criteria for a disruptive behavior disorder (oppositional defiant disorder of conduct disorder) in addition to research criteria. RESULTS: "Outer-directed irritability" most clearly distinguished patients from controls (effect size 4.1) and did not correlate with other mood measures. Patients and controls showed no to minimal differences on internalizing symptoms. CONCLUSION: Disruptive behavior disordered children and adolescents characterized by outer-directed irritability exist, can be identified, and should be further investigated, especially since they are potentially treatable.

Increased glucocorticoid receptor expression in human skeletal muscle cells may contribute to the pathogenesis of the metabolic syndrome.

Altered glucocorticoid hormone action may contribute to the etiology of the metabolic syndrome, but the molecular mechanisms are poorly defined. Tissue sensitivity to glucocorticoid is regulated by expression of the glucocorticoid receptor (GR)-alpha and 11beta-hydroxysteroid dehydrogenase type I (11beta-HSD1)-mediated intracellular synthesis of active cortisol from inactive cortisone. We have analyzed GRalpha and 11beta-HSD1 expression in skeletal myoblasts from men (n = 14) with contrasting levels of insulin sensitivity (euglycemic clamp measurements of insulin-dependent glucose disposal rate), blood pressure, and adiposity. Positive associations were evident between myoblast expression of GRalpha under basal conditions and levels of insulin resistance (r(2) = 0.34, P < 0.05), BMI (r(2) = 0.49, P < 0.01), percent body fat (r(2) = 0.34, P < 0.02), and blood pressure (r(2) = 0.86, P < 0.001). Similar associations were evident when myoblasts were incubated with physiological levels of cortisol (P < 0.01 for all). Importantly, GRalpha expression was unaffected by variations in in vivo concentrations of insulin, IGF-1, or glucose concentrations. In common with the GR, 11beta-HSD1 expression in myoblasts incubated with physiological concentrations of cortisol in vitro was positively associated with levels of insulin resistance (r(2) = 0.68, P < 0.001), BMI (r(2) = 0.63, P < 0.005), and blood pressure (r(2) = 0.27, P < 0.05). Regulation of GRalpha and 11beta-HSD1 by cortisol was abolished by the GR antagonist RU38486. In summary, our data suggest that raised skeletal muscle cell expression of GRalpha and 11beta -HSD1-mediated regulation of intracellular cortisol may play a fundamental role in mechanisms contributing to the pathogenesis of the metabolic syndrome.