Subsyndromal Manifestations of Depression in Children Predict the Development of Major Depression.

OBJECTIVE: To evaluate the utility of assessing subsyndromal symptoms of major depressive disorder in childhood, indexed through the Child Behavior Checklist (CBCL) anxiety/depression scale, in predicting risk of developing major depressive disorder in adolescent and young adult years. STUDY DESIGN: The sample consisted of 537 children, 6-17 years of age, originally ascertained for a longitudinal family genetic study of youth with and without attention-deficit hyperactivity disorder and their first-degree relatives who were followed prospectively and blindly for 10 years from childhood into young adult years. Children with full diagnosis major depressive disorder at baseline were excluded. For analysis, the sample was stratified into 4 groups based on the presence or absence of parental mood disorders and by the presence or absence of subsyndromal scores on the CBCL anxiety/depression scale at baseline assessment in childhood. RESULTS: Children of parents with mood disorders plus subsyndromal scores on the CBCL anxiety/depression scale at baseline (n = 22) had the highest risk for developing major depressive disorder and anxiety disorders at the 10-year follow-up when compared with the other groups. Children with either subsyndromal scores on the CBCL anxiety/depression scale at baseline alone (n = 22) or parental mood disorders alone (n = 172) had intermediate outcomes. CONCLUSION: The CBCL anxiety/depression scale was useful in identifying children at high risk for the development of major depressive disorder and anxiety disorders at the 10-year prospective follow-up. Furthermore, our results emphasized the importance of familial psychiatric history in youth with subthreshold symptoms of depression. Parental mood disorder and subthreshold anxiety/depressive symptoms were predictive of developing depression.

Do stimulants reduce the risk for cigarette smoking in youth with attention-deficit hyperactivity disorder? A prospective, long-term, open-label study of extended-release methylphenidate.

OBJECTIVE: Although attention-deficit hyperactivity disorder (ADHD) is a well-known risk factor for cigarette smoking, prospective studies aimed at reducing smoking risk in this population are critically needed. STUDY DESIGN: This was a 2-year, prospective, open-label clinical trial of extended-release methylphenidate for smoking prevention in adolescents with ADHD (n = 154). Smoking outcomes were assessed with the Fagerstrom Tolerance Questionnaire. Comparisons were made using data from a historical, naturalistic sample of ADHD (n = 103) and non-ADHD comparators (n = 188) of similar age and sex assessed with the same assessment battery as that used in subjects participating in the clinical trial. RESULTS: The smoking rate at endpoint (mean, 10 months of methylphenidate treatment) was low in the clinical trial subjects and not significantly different from that in the non-ADHD comparators or the ADHD comparators receiving stimulants naturalistically (7.1% vs 8.0% vs 10.9%; P > .20). In contrast, the smoking rate was significantly lower in the clinical trial subjects than in the naturalistic sample of ADHD comparators who were not receiving stimulant treatment (7.1% vs 19.6%; P = .009 [not significant], adjusting for comorbid conduct disorder and alcohol and drug abuse). CONCLUSION: Although considered preliminary until replicated in future randomized clinical trials, the findings from this single-site, open-label study suggest that stimulant treatment may contribute to a decreased risk for smoking in adolescents with ADHD. If confirmed, this finding would have significant clinical and public health impacts.

A naturalistic 10-year prospective study of height and weight in children with attention-deficit hyperactivity disorder grown up: sex and treatment effects.

OBJECTIVE: To assess the effect of attention-deficit/hyperactivity disorder (ADHD) and its treatment on growth outcomes in children followed into adulthood. STUDY DESIGN: Two identically designed, longitudinal, case-control studies of males and females with and without ADHD were combined; 124 and 137 control and subjects with ADHD, respectively, provided growth information at the 10- to 11-year follow-up. We used linear growth curve models to estimate the effect of time on change in height and whether this effect differed by sex and ADHD status. We also examined the effect of stimulant treatment on growth outcomes. RESULTS: We found no evidence that ADHD was associated with trajectories of height over time or differences at follow-up in any growth outcomes. Similarly, we found no evidence that stimulant treatment was associated with differences in growth. However, among subjects with ADHD, major depression was associated with significantly larger weight in females and smaller height in males. CONCLUSIONS: Our results do not support an association between deficits in growth outcomes and either ADHD or psychostimulant treatment for ADHD. These findings extend the literature on this topic into young adulthood and should assist clinicians and parents in formulating treatment plans for children with ADHD.

Cardiovascular effects of longer-term, high-dose OROS methylphenidate in adolescents with attention deficit hyperactivity disorder.

OBJECTIVE: To examine the effects of high doses of extended-release methylphenidate (OROS MPH) on cardiovascular variables in adolescents with attention deficit hyperactivity disorder (ADHD). STUDY DESIGN: ECG indices plus systolic blood pressure (SBP), diastolic BP (DBP) and heart rate (HR) were assessed during an open-label study of OROS MPH in 114 adolescents with ADHD (doses up to 1.5 mg/kg/d). Cardiovascular parameters were assessed at 6 weeks and 6 months. RESULTS: Small but statistically significant changes in DBP and HR were observed at 6 weeks, without further increases up to 6 months' follow-up. A small but statistically significant increase in SBP was observed over time. Twenty-nine percent of patients had isolated elevations in BP readings prior to study entry, and 14% had >3 consecutive visits at which elevated BP were observed during OROS MPH treatment. No clinically significant changes in ECG parameters were observed. No serious cardiovascular adverse events occurred. CONCLUSIONS: Treatment with relatively high doses of OROS MPH was associated with small but statistically significant mean increases in BP and HR, primarily during the first 6 weeks of treatment, without clinically meaningful changes in ECG. These observations are consistent with previous reports using lower doses.

Cigarette smoking associated with attention deficit hyperactivity disorder.

OBJECTIVE: To evaluate the association between attention deficit hyperactivity disorder (ADHD) and severity of physical dependence on nicotine in a controlled study of adolescents and young adults with ADHD. STUDY DESIGN: In controlled longitudinal family studies of ADHD, we examined self-reports on the modified Fagerström Tolerance Questionnaire (mFTQ) for degrees of physical dependence on nicotine. RESULTS: We obtained mFTQ data from 80 ADHD probands and 86 control probands (mean age, 19.2 years). The smokers with ADHD had significantly higher scores on the mFTQ, indicative of more severe physical dependence on nicotine. Similarly, in current smokers, a positive linear relationship was found between mFTQ score and both inattentive and hyperactive ADHD symptoms. Environmental factors, such as current parental smoking, peer smoking, and living with a smoker, all increased the risk for smoking in those with ADHD compared with controls. CONCLUSION: Male and female smokers with ADHD manifest more severe physical dependence on smoking compared with controls. Important environmental factors appear to add to the risk of smoking associated with ADHD.

Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents.

OBJECTIVE: This secondary analysis evaluated the efficacy of modafinil in children and adolescents by subtype of attention-deficit/hyperactivity disorder (ADHD) using pooled data from 3 double-blind, placebo-controlled studies. STUDY DESIGN: The patients were boys and girls age 6 to 17 years. ADHD subtype diagnoses (ie, inattentive, hyperactive-impulsive, combined) were based on criteria published in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Patients received modafinil (170 to 425 mg) or placebo once daily for 7 to 9 weeks. Efficacy assessment used the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) School and Home Versions, Clinical Global Impression of Improvement scale (CGI-I), and Conners' Parent Rating Scale-Revised: Short Form (CPRS-R:S). RESULTS: A total of 638 patients received modafinil (n = 423) or placebo (n = 215). The inattentive, hyperactive-impulsive, and combined subtypes included 187 (30%), 27 (4%), and 403 (65%) patients, respectively. Modafinil (vs placebo) significantly improved mean total scores for the ADHD-RS-IV School and Home Versions for the inattentive (change from baseline: School, modafinil, -15.7, placebo, -7.1; Home, modafinil, -13.8, placebo, -5.9) and combined subtypes (School, -16.5 vs -8.8; Home, -15.7 vs -7.6). Modafinil was associated with greater improvements on the CGI-I and improved CPRS-R:S subscale scores in inattentive and combined subtypes. CONCLUSIONS: Modafinil improved ADHD symptoms and behaviors in patients with the inattentive and combined subtypes as determined by teachers, investigators, and parents.

Short- and long-term cardiovascular effects of mixed amphetamine salts extended release in children.

OBJECTIVE: To assess the short- and long-term cardiovascular effects of once-daily treatment with a mixed amphetamine salts extended-release formulation (MAS XR; Adderall XR(R)) in children age 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD). STUDY DESIGN: Short-term cardiovascular effects were assessed during a 4-week, double-blind, randomized, placebo-controlled, forced-dose-titration study of once-daily 10, 20, and 30 mg MAS XR (n = 580). Long-term cardiovascular effects were assessed in 568 subjects during a 2-year, open-label extension study of MAS XR (10 to 30 mg/day). Resting sitting blood pressure and pulse were measured at baseline and weekly during the short-term study, then monthly during long-term treatment. RESULTS: Changes in blood pressure, pulse, and QT interval corrected by Bazett's formula (QTcB) in children receiving MAS XR were not statistically significantly different than those changes seen in children receiving placebo during short-term treatment. Mean increases in blood pressure after 2 years of MAS XR treatment (systolic, 3.5 mm Hg; diastolic, 2.6 mm Hg) and pulse (3.4 bpm) were clinically insignificant, and there was no apparent dose-response relationship. CONCLUSIONS: Cardiovascular effects of short- and long-term MAS XR were minimal during short- and long-term MAS XR treatment at doses of

Dopamine transporter gene, response to methylphenidate and cerebral blood flow in attention-deficit/hyperactivity disorder: a pilot study.

The homozygosity of the 10-repeat allele at dopamine transporter gene (DAT1) seems to be associated with a poor response to methylphenidate (MPH) in children with attention-deficit/hyperactivity disorder (ADHD). This pilot study aimed to simultaneously assess polymorphisms at DAT1, response to MPH, and neuroimaging. Only ADHD children with at least a moderate response to MPH were included. Significantly higher regional cerebral blood flows assessed by single photon emission computerized tomography (SPECT) were detected in medial frontal and left basal ganglia areas in children with homozygosity for the 10-repeat allele at DAT1 gene (n = 4) than in children without this genotype (n = 4) (P < 0.05). These findings provide a preliminary connection between pharmacogenetics and neurobiological investigations on stimulant treatment of ADHD.

Estimated mental retardation and school dropout in a sample of students from state public schools in Porto Alegre, Brazil

OBJECTIVES: To assess the association between estimated Mental Retardation (MR) and school dropout in a sample of students of the third and fourth grades at state schools in Porto Alegre, the capital of the southernmost state of Brazil. METHOD: In this case - control study, students that dropped out from schools (n=44) and a control group who continued attending schools (n=44) had their intelligence quotient (IQ) determined by the vocabulary and cubes subtests of the Wescheler Intelligence Scale ¾ third edition (WISC¾III). Students with IQ lower than 70 were considered as potential cases of MR. Other prevalent mental disorders in this age range were assessed in both groups using the Schedule for Affective Disorders and Schizophrenia for School¾ Age Children, Epidemiological Version (K-SADS-E). RESULTS: The prevalence of potential MR was significantly higher in the dropped out group than in the control group (p<0.001). Odds ratio for school dropout was significantly higher in the presence of MR even after controlling for potentially confounding factors (age, conduct disorder, grade repetition, family structure and income) (p<0.01). CONCLUSION: Children with IQ lower than 70 (potential MR) were at higher risk for school dropout. These children need to be identified at school and specific educational strategies should be implemented to assure their inclusion in the learning process

Dopamine transporter gene and response to methylphenidate in attention-deficit/hyperactivity disorder.

This study aims to evaluate whether a previously reported association between homozygosity for the 10-repeat allele of the dopamine transporter gene (10/10) and poor response to methylphenidate (MPH) would be replicated in a sample of Brazilian attention deficit/hyperactivity disorder (ADHD) boys. In a blind naturalistic study, 50 male ADHD youths were treated with MPH. Efficacy of the medication was measured by means of the 10-item Conners Abbreviated Rating Scale (ABRS), and the Children's Global Assessment Scale (CGAS). While 75% (15/20) of the youths without 10/10 genotype demonstrated an improvement higher than 50% in the ABRS scores with MPH, only 47% (14/30) of the subjects with 10/10 genotype achieved the same level of improvement with medication (one-tailed P = 0.04). In addition, the group without this genotype had significantly higher increase in the CGAS scores than the other group (one-tailed P < 0.01). Our findings support an association between homozygosity for the 10-repeat allele at dopamine transporter gene locus and poor response to MPH.

Exploring DSM-IV ADHD number of symptoms criterion: preliminary findings in adolescents

Objective: To explore DSM-IV number of symptoms criterion for the diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) in a non-referred sample of young Brazilian adolescents. Methods: 170 students aged 12 to 14 year-old were evaluated using DSM-IV ADHD criteria, measures of ADHD symptoms, global and school impairment. Results: ADHD adolescents (n=30) had significantly higher scores on Attention Problems scale of Child Behavior Checklist (CBCL) and higher rates of school repetition than both non-ADHD adolescents (n=128) and adolescents who had a subthreshold number of inattentive or hyperactive/impulse symptoms (5 symptoms), but fulfilled all other DSM-IV ADHD criteria (n=12). The two last groups did not differe significantly in any measure assessed. Conclusion: These preliminary results support the appropriateness of DSM-IV number of symptoms criterion for the diagnoses of ADHD in young adolescents.