Gagan Joshi

Does ADHD Predict Substance-Use Disorders? A 10-Year Follow-up Study of Young Adults With ADHD

OBJECTIVE High rates of substance-use disorders (SUD) have been found in samples of adolescents and adults with attention-deficit/hyperactivity disorder (ADHD). Predictors of SUD in children with ADHD who are at risk for the development of SUDs remain understudied. The main aims of this study were to identify clinically meaningful characteristics of children that predicted the future development of SUDs and to see whether the role of these characteristics varied by sex. METHOD Subjects were children and adolescents with (n = 268; mean age ± standard deviation = 10.9 ± 3.2 years) and without (n = 229; mean age 11.9 ± 3.3 years) DSM-III-R ADHD followed prospectively and blindly over a 10-year follow-up period onto young adult years. Subjects were assessed with structured diagnostic interviews for psychopathology and SUDs. RESULTS Over the 10-year follow-up period, ADHD was found to be a significant predictor of any SUD (hazards ratio 1.47; 95% confidence interval 1.07-2.02; p = .01) and cigarette smoking (2.38; 1.61-3.53; p < .01). Within ADHD, comorbid conduct disorder (2.74; 1.66-4.52; p < .01) and oppositional defiant disorder (2.21; 1.40-3.51; p < .01) at baseline were also found to be significant predictors of SUDs. Similar results were found for cigarette-, alcohol-, and drug-use disorders. There were few meaningful sex interaction effects. No clinically significant associations were found for any social or family environment factors or for cognitive functioning factors (p > .05 for all comparisons). CONCLUSIONS These results indicate that ADHD is a significant risk factor for the development of SUDs and cigarette smoking in both sexes.

An open-label trial of aripiprazole monotherapy in children and adolescents with bipolar disorder.

INTRODUCTION Aripiprazole is a novel second-generation antipsychotic approved for the treatment of bipolar disorder in adults but there is no systematic data available in pediatric bipolar disorder. METHODS This was an 8-week, open-label, prospective study of aripiprazole 9.4+/-4.2 mg/day monotherapy to assess the efficacy and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale, Clinical Global Impressions-Improvement scale, and Brief Psychiatric Rating Scale. Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. RESULTS Fifteen of the 19 bipolar youth (79%) completed the study. Aripiprazole treatment was associated with clinically and statistically significant improvement in mean Young Mania Rating Scale scores (-18.0+/-6.9, P<.0001). With the important exception of two cases of extrapyramidal symptoms that precipitated dropout, aripiprazole was well tolerated with no statistically significant increase in body weight (1.8+/-1.7 kg, P=.2). CONCLUSION Open-label aripiprazole treatment was beneficial in the treatment of mania in youth with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Autistic Traits in Children With and Without ADHD

OBJECTIVE: To assess the implications of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD) without a diagnosis of autism. METHODS: Participants were youth with (n = 242) and without (n = 227) ADHD and controls without ADHD in whom a diagnosis of autism was exclusionary. Assessment included measures of psychiatric, psychosocial, educational, and cognitive functioning. ATs were operationalized by using the withdrawn + social + thought problems T scores from the Child Behavior Checklist. RESULTS: A positive AT profile was significantly overrepresented among ADHD children versus controls (18% vs 0.87%; P < .001). ADHD children with the AT profile were significantly more impaired than control subjects in psychopathology, interpersonal, school, family, and cognitive domains. CONCLUSIONS: A substantial minority of ADHD children manifests ATs, and those exhibiting ATs have greater severity of illness and dysfunction.

Treatment of Pediatric Obsessive-Compulsive Disorder: A Review

Recently, research in pediatric obsessive-compulsive disorder (OCD) has expanded to include large family genetic studies, elaboration of phenotypic dimensions, description of co-morbid disorders and their moderating effects on treatment response and outcome, research on immune-based neuropsychiatric causes, randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs), randomized controlled trials of cognitive behavioral therapy (CBT), comparative treatment trials; new approaches in behavior therapy, and increased awareness of newer approaches to treatment. The purpose of this article is to review assessment and treatment strategies to include current advances in research.

Comorbidity in Pediatric Bipolar Disorder

The growing literature shows the pervasiveness and importance of comorbidity in youth with bipolar disorder (BPD). For instance, up to 90% of youth with BPD have been described to manifest comorbidity with attention-deficit hyperactivity disorder. Multiple anxiety, substance use, and disruptive behavior disorders are the other most commonly reported comorbidities with BPD. Moreover, important recent data highlight the importance of obsessive-compulsive and pervasive developmental illness in the context of BPD. Data suggest that not only special developmental relationships are operant in the context of comorbidity but also that the presence of comorbid disorders with BPD results in a more severe clinical condition. Moreover, the presence of comorbidity has therapeutic implications for the treatment response for both BPD and the associated comorbid disorder. Future longitudinal studies to address the relationship and the impact of comorbid disorders on course and therapeutic response over time are required in youth with BPD.

Child Behavior Checklist Clinical Scales Discriminate Referred Youth With Autism Spectrum Disorder: A Preliminary Study

Objective: To evaluate the properties of clinical scales of the Child Behavior Checklist in discriminating referred children with autism spectrum disorders (ASDs) (autistic disorder, Aspergers disorder, and pervasive developmental disorder not otherwise specified) from psychiatrically referred children without ASDs. Method: Comparisons were made between children with ASDs (n = 65) with intelligence quotient >70 and children without ASDs (N = 83) on the clinical scales of the Child Behavior Checklist. Stepwise logistic regression was used to identify those scales that best predicted ASDs when compared with the non-ASD comparison group. Receiver operating characteristic curves examined the ability of the significant predictor T-scores to identify ASDs versus the non-ASD subjects. Results: Withdrawn, Social Problems, and Thought Problems T-scores were the best independent predictors of ASD status. The Withdrawn + Social + Thought Problems T-scores yielded an area under the curve of 0.86, indicating an 86% chance that a randomly selected sample of ASD subject will have abnormal scores on these scales than a randomly selected sample of non-ASD subjects. Conclusion: These findings suggest that a new Child Behavior Checklist-ASD profile consisting of the Child Behavior Checklist-Withdrawn, Social, and Thought Problems scales could serve as a rapid and cost-effective screening instrument to help identify cases likely to meet clinical criteria for ASDs in the clinical setting.

A prospective open-label trial of lamotrigine monotherapy in children and adolescents with bipolar disorder.

Aim: To evaluate the safety and efficacy of lamotrigine monotherapy as an acute treatment of bipolar mood elevation in children with bipolar spectrum disorders. Method: This was a 12‐week, open‐label, prospective trial of lamotrigine monotherapy to assess the effectiveness and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions‐Improvement scale (CGI‐I), Childrens Depression Rating Scale (CDRS), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self‐reports, vital signs weight monitoring, and laboratory analysis. Results: Thirty‐nine children with bipolar disorder (YMRS at entry: 31.6 ± 5.5) were enrolled in the study and 22 (56%) completed the 12‐week trial. Lamotrigine was slowly titrated to an average endpoint dose of 160.7 ± 128.3 in subjects <12 years of age (N = 22) and 219.1 ± 172.2 mg/day in children 12–17 years of age (N = 17). Treatment with lamotrigine was associated with statistically significant levels of improvement in mean YMRS scores (−14.9 ± 9.7, P < 0.001) at endpoint. Lamotrigine treatment also resulted in significant improvement in the severity of depressive, attention‐deficit/hyperactivity disorder (ADHD), and psychotic symptoms. Lamotrigine was generally well tolerated with marginal increase in body weight (47.0 ± 18.0 kg vs. 47.2 ± 17.9 kg, P= 0.6) and was not associated with abnormal changes in laboratory parameters. Several participants were discontinued due to skin rash; in all cases, the rash resolved shortly after discontinuation of treatment. No patient developed Steven Johnson syndrome. Conclusions: Open‐label lamotrigine treatment appears to be beneficial in the treatment of bipolar disorder and associated conditions in children. Future placebo‐controlled, double‐blind studies are warranted to confirm these findings.

Clinical characteristics of comorbid obsessive-compulsive disorder and bipolar disorder in children and adolescents

OBJECTIVE To explore bidirectional comorbidity between bipolar disorder (BPD) and obsessive-compulsive disorder (OCD) in youth and to examine the symptom profile and clinical correlates of both disorders in the context of reciprocal comorbidity and ascertainment status. METHODS Two samples of consecutively referred youth (ages 6-17 years) ascertained contemporaneously for respective studies of BPD and OCD were compared using clinical and scalar assessment and structured diagnostic interviews. RESULTS A total of 21% (17/82) of the BPD subjects and 15% (19/125) of the OCD subjects met DSM-III-R diagnostic criteria for both disorders. In the presence of BPD, youth with OCD more frequently experienced hoarding/saving obsessions and compulsions along with a clinical profile of greater comorbidity, poorer global functioning, and higher rate of hospitalization that is characteristic of BPD. Multiple anxiety disorders (> or = 3), especially generalized anxiety disorder and social phobia, were present at a higher frequency when OCD and BPD were comorbid than otherwise. In subjects with comorbid OCD and BPD, the primary disorder of ascertainment was associated with an earlier onset and more severe impairment. CONCLUSIONS An unexpectedly high rate of comorbidity between BPD and OCD was observed in youth irrespective of primary ascertainment diagnosis. In youth with comorbid OCD and BPD, the clinical characteristics of each disorder run true and are analogues to their clinical presentation in youth without reciprocal comorbidity, with the exception of increased risk for obsessions and compulsions of hoarding/saving and comorbidity with other anxiety disorders.

Examining the comorbidity of bipolar disorder and autism spectrum disorders: a large controlled analysis of phenotypic and familial correlates in a referred population of youth with bipolar I disorder with and without autism spectrum disorders.

OBJECTIVE Although mood dysregulation is frequently associated with autism spectrum disorders (ASD) and autistic traits are common in youth with bipolar disorder, uncertainties remain regarding the comorbid occurrence of bipolar disorder and ASD. This study examines the clinical and familial correlates of bipolar disorder when it occurs with and without ASD comorbidity in a well-characterized, research-referred population of youth with bipolar disorder. We hypothesized that in youth with bipolar disorder, the clinical and familial correlates of bipolar disorder will be comparable irrespective of the comorbidity with ASD. METHOD Clinical correlates and familial risk were assessed by secondary analysis of the data from a large family study of youth with bipolar I disorder (diagnosis based on DSM-IV criteria; probands n = 157, relatives n = 487; study period: November 1997-September 2002). Findings in bipolar I youth were compared with those in youth with attention-deficit/hyperactivity disorder (diagnosis based on DSM-III-R criteria) without bipolar I disorder (probands n = 162, relatives n = 511) and age- and sex-matched controls without bipolar I disorder or attention-deficit/hyperactivity disorder (probands n = 136, relatives n = 411). All subjects were comprehensively assessed using structured diagnostic interviews and a wide range of nonoverlapping measures assessing multiple dimensions of functioning. RESULTS Thirty percent (47/155) of the bipolar I probands met criteria for ASD (diagnosis based on DSM-III-R criteria). The mean ± SD age at onset of bipolar I disorder was significantly earlier in the presence of ASD comorbidity (4.7 ± 2.9 vs 6.3 ± 3.7 years; P = .01). The phenotypic and familial correlates of bipolar disorder were similar in youth with and without ASD comorbidity. CONCLUSIONS A clinically significant minority of youth with bipolar I disorder suffers from comorbid ASD. Phenotypic and familial correlates of bipolar disorder were typical of the disorder in the presence of ASD comorbidity. Bipolar I disorder comorbidity with ASD represents a very severe psychopathologic state in youth.

A prospective open-label trial of extended-release carbamazepine monotherapy in children with bipolar disorder.

OBJECTIVE The aim of this study was to evaluate the safety and efficacy of extended release carbamazepine (CBZ-ER) monotherapy in the treatment of pediatric bipolar disorder (BD). METHOD This was an 8-week, open-label, prospective trial of CBZ-ER monotherapy (788 +/- 252 mg/day) to assess the effectiveness and tolerability of this compound in treating pediatric bipolar spectrum disorders. Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impressions-Improvement scale, Childrens Depression Rating Scale, and Brief Psychiatric Rating Scale. Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis. RESULTS Of the 27 participating children with BD, 16 (59.%) completed the study. CBZ-ER treatment was associated with statistically significant, but modest, levels of improvement in mean YMRS scores (-10.1 +/- 10.2, p < 0.001) with end-point mean YMRS score (21.8 +/- 12.2) suggesting a lack of complete resolution of mania. CBZ-ER treatment also resulted in significant improvement in the severity of depressive, attention-deficit/hyperactivity disorder, and psychotic symptoms. With the exception of 2 participants who discontinued due to skin rash, CBZ-ER was well tolerated with marginal increase in body weight (0.8 +/- 2.5 kg, p = 0.04) and was not associated with any abnormal changes in laboratory parameters. CONCLUSIONS Open-label CBZ-ER treatment was beneficial for the treatment of BD in children. Future controlled trials are warranted.