Background: Pediatric bipolar disorder (BP) is frequently comorbid with conduct disorder (CD) and... more Background: Pediatric bipolar disorder (BP) is frequently comorbid with conduct disorder (CD) and its presence adds to the morbidity of BP. While there are no known pharmacological treatments for CD, pediatric BP is responsive to treatment with medications initially indicated for the treatment of psychosis, several of which have Food and Drug Administration (FDA) approval for the treatment of pediatric mania. Aims: The main aim of this secondary analysis was to examine whether pediatric BP comorbid with CD responds similarly to treatment with such selected medications. Considering the well-documented morbidity of CD, this finding could have important clinical and public health significance. Methods: We conducted a secondary analysis of six prospective 8-week open-label trials of selected medications (risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) using identical methodology in youth with BP with and without comorbid CD. Results: Of 165 youths with BP, 54% ( N = ...
Journal of Developmental & Behavioral Pediatrics, 2010
To evaluate the properties of clinical scales of the Child Behavior Checklist in discriminating r... more To evaluate the properties of clinical scales of the Child Behavior Checklist in discriminating referred children with autism spectrum disorders (ASDs) (autistic disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified) from psychiatrically referred children without ASDs. 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. Withdrawn, Social Problems, and Thought Problems T-scores were the best independent predictors of ASD status. The Withdrawn + Social + Thought Problems T-scores yielded an area under the curve of 0.86, indicating an 86% chance that a randomly selected sample of ASD subject will have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. 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.
Although mood dysregulation is frequently associated with autism spectrum disorders (ASD) and aut... more 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. 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. 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. 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.
Journal of Autism and Developmental Disorders, 2010
The objective of the study was to systematically examine patterns of psychiatric comorbidity in r... more The objective of the study was to systematically examine patterns of psychiatric comorbidity in referred youth with autism spectrum disorders (ASD) including autistic disorder and pervasive developmental disorder not otherwise specified. Consecutively referred children and adolescents to a pediatric psychopharmacology program were assessed with structured diagnostic interview and measures of psychosocial functioning. Comparisons were made between those youth satisfying diagnostic criteria for ASD and age and sex matched youth without ASD referred to the same clinical program. 9.3% (217/2323) of the referred youth (age range: 3-17 years) met DSM-III-R criteria for ASD. ASD youth suffered from significantly higher number of comorbid disorders than comparisons (6.4 ± 2.7 vs. 5.2 ± 2.9; p < 0.001). Ninety-five percent of the youth with ASD had three or more comorbid psychiatric disorders and 74% had five or more comorbid disorders. ASD youth were also more functionally impaired and required extra-assistance in school and therapeutic interventions at higher rates than age and sex matched non-ASD referred youth. Youth with ASD have high levels of psychiatric comorbidity and dysfunction comparable to the referred population of youth without ASD. These findings emphasize the heavy burden of psychiatric comorbidity afflicting youth with ASD and may be important targets for intervention.
To compare antimanic response to olanzapine therapy in youth with bipolar disorder (BPD) based on... more To compare antimanic response to olanzapine therapy in youth with bipolar disorder (BPD) based on the status of comorbidity with obsessive-compulsive disorder (OCD). Secondary analysis of identically designed 8-week open-label trials of olanzapine therapy in youth with BPD. Severity of mania assessed with the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI) scales. Of the 52 BPD subjects (mean age 8.4 +/- 3.1 years) enrolled in the olanzapine trials (mean dose 8.5 +/- 4.3 mg/day), 39% (n = 20) met criteria for comorbid OCD. Antimanic response in BPD subjects was significantly worse in the presence of comorbid OCD (YMRS mean reduction: -5.9 +/- 13.1 versus -13.7 +/- 18.8, p = 0.04; > or = 30% reduction: 25% versus 63%, p = 0.008; CGI-Improvement score < or = 2: 25% versus 68%, p = 0.003). There was no difference in the rate of dropouts (50% versus 29%, p = 0.2) or adverse effects in BPD subjects with or without comorbid OCD. Less than expected antimanic response to olanzapine therapy in the presence of comorbidity with OCD suggests that OCD is an important functionally impairing psychiatric comorbidity that may impact the efficacy of antimanic agents in youth with BPD. This study is limited by its design of secondary analysis of data from trials of an uncontrolled nature. Further prospective controlled trials are warranted.
Background: Pediatric bipolar disorder (BP) is frequently comorbid with conduct disorder (CD) and... more Background: Pediatric bipolar disorder (BP) is frequently comorbid with conduct disorder (CD) and its presence adds to the morbidity of BP. While there are no known pharmacological treatments for CD, pediatric BP is responsive to treatment with medications initially indicated for the treatment of psychosis, several of which have Food and Drug Administration (FDA) approval for the treatment of pediatric mania. Aims: The main aim of this secondary analysis was to examine whether pediatric BP comorbid with CD responds similarly to treatment with such selected medications. Considering the well-documented morbidity of CD, this finding could have important clinical and public health significance. Methods: We conducted a secondary analysis of six prospective 8-week open-label trials of selected medications (risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole) using identical methodology in youth with BP with and without comorbid CD. Results: Of 165 youths with BP, 54% ( N = ...
Journal of Developmental & Behavioral Pediatrics, 2010
To evaluate the properties of clinical scales of the Child Behavior Checklist in discriminating r... more To evaluate the properties of clinical scales of the Child Behavior Checklist in discriminating referred children with autism spectrum disorders (ASDs) (autistic disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified) from psychiatrically referred children without ASDs. 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. 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. 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.
Although mood dysregulation is frequently associated with autism spectrum disorders (ASD) and aut... more 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. 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. 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. 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.
Journal of Autism and Developmental Disorders, 2010
The objective of the study was to systematically examine patterns of psychiatric comorbidity in r... more The objective of the study was to systematically examine patterns of psychiatric comorbidity in referred youth with autism spectrum disorders (ASD) including autistic disorder and pervasive developmental disorder not otherwise specified. Consecutively referred children and adolescents to a pediatric psychopharmacology program were assessed with structured diagnostic interview and measures of psychosocial functioning. Comparisons were made between those youth satisfying diagnostic criteria for ASD and age and sex matched youth without ASD referred to the same clinical program. 9.3% (217/2323) of the referred youth (age range: 3-17 years) met DSM-III-R criteria for ASD. ASD youth suffered from significantly higher number of comorbid disorders than comparisons (6.4 ± 2.7 vs. 5.2 ± 2.9; p < 0.001). Ninety-five percent of the youth with ASD had three or more comorbid psychiatric disorders and 74% had five or more comorbid disorders. ASD youth were also more functionally impaired and required extra-assistance in school and therapeutic interventions at higher rates than age and sex matched non-ASD referred youth. Youth with ASD have high levels of psychiatric comorbidity and dysfunction comparable to the referred population of youth without ASD. These findings emphasize the heavy burden of psychiatric comorbidity afflicting youth with ASD and may be important targets for intervention.
To compare antimanic response to olanzapine therapy in youth with bipolar disorder (BPD) based on... more To compare antimanic response to olanzapine therapy in youth with bipolar disorder (BPD) based on the status of comorbidity with obsessive-compulsive disorder (OCD). Secondary analysis of identically designed 8-week open-label trials of olanzapine therapy in youth with BPD. Severity of mania assessed with the Young Mania Rating Scale (YMRS) and Clinical Global Impression (CGI) scales. Of the 52 BPD subjects (mean age 8.4 +/- 3.1 years) enrolled in the olanzapine trials (mean dose 8.5 +/- 4.3 mg/day), 39% (n = 20) met criteria for comorbid OCD. Antimanic response in BPD subjects was significantly worse in the presence of comorbid OCD (YMRS mean reduction: -5.9 +/- 13.1 versus -13.7 +/- 18.8, p = 0.04; > or = 30% reduction: 25% versus 63%, p = 0.008; CGI-Improvement score < or = 2: 25% versus 68%, p = 0.003). There was no difference in the rate of dropouts (50% versus 29%, p = 0.2) or adverse effects in BPD subjects with or without comorbid OCD. Less than expected antimanic response to olanzapine therapy in the presence of comorbidity with OCD suggests that OCD is an important functionally impairing psychiatric comorbidity that may impact the efficacy of antimanic agents in youth with BPD. This study is limited by its design of secondary analysis of data from trials of an uncontrolled nature. Further prospective controlled trials are warranted.
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