Predictive utility of autistic traits in youth with ADHD: a controlled 10-year longitudinal follow-up study.

The objective of this study was to investigate the stability and predictive utility of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD). Participants were referred youth with and without ADHD, without a diagnosis of autism spectrum disorder, and their siblings, derived from identically designed longitudinal case-control family studies of boys and girls with ADHD. Subjects were assessed with structured diagnostic interviews and measures of social, cognitive, and educational functioning. The presence of ATs at baseline was operationalized using a unique profile of the Child Behavior Checklist (CBCL) consisting of an aggregate T score of ≥ 195 on the Withdrawn, Social, and Thought Problems subscales (CBCL-AT profile). At the follow-up, 83% of the ADHD youth with a positive AT profile at baseline continued to have a positive CBCL-AT profile. The presence of a positive CBCL-AT profile at baseline in youth with ADHD heralded a more compromised course characterized by a greater burden of psychopathology that emerged at an earlier age, along with poorer interpersonal, educational, and neurocognitive outcomes. Findings indicate a high level of persisting ATs in ADHD youth over time, as indexed through the CBCL-AT profile, and the presence of this profile prognosticates a compromised course in adult life in multiple domains of functioning.

A prospective open-label trial of long-acting liquid methylphenidate for the treatment of attention deficit/hyperactivity disorder in intellectually capable adults with autism spectrum disorder.

Objectives: This treatment trial is aimed at assessing the short-term tolerability and efficacy of liquid-formulation extended-release methylphenidate (MPH-ER) for the treatment of attention deficit/hyperactivity disorder (ADHD) in adults with high-functioning autism spectrum disorder (HF-ASD).Methods: A 6-week open-label trial (ClinicalTrials.gov: NCT02096952) was conducted in 15 HF-ASD adults (mean age 24.9 ± 4.6; male, 12 (80%)) suffering from moderate-severe ADHD. MPH-ER was administered based on a flexible titration schedule. Efficacy was assessed on clinician- and self-rated measures. Tolerability was assessed by documenting treatment-emergent adverse events (AEs) and other safety measures.Results: Short-term MPH-ER treatment was associated with significant improvement in ADHD severity (Adult ADHD Investigator Symptom Report Scale (AISRS) mean change (MC), -22.8 ± 8.8, P < 0.001; Adult ADHD Self-Report Scale (ASRS) MC, -8.2 ± 15.3, P < 0.001). Twelve (80%) participants were deemed responders, based on ≥30% reduction in AISRS score and an ADHD Clinical Global Impression-Improvement score ≤2. MPH-ER was well-tolerated (treatment-limiting AEs, 1/15; severe AEs, 1/15) at mean dose of 48.7 ± 15 mg/day. AEs were transient and experienced by 13/15 (87%) participants at mild to moderate severity. Frequently reported AEs were as typically expected (headache (53%), insomnia (33%), anxiety (33%), decreased appetite (27%)).Conclusions: Our findings suggest that MPH-ER is effective and well-tolerated in the treatment of ADHD in HF-ASD adults.

A Retrospective Chart Review of Buspirone for the Treatment of Anxiety in Psychiatrically Referred Youth with High-Functioning Autism Spectrum Disorder.

OBJECTIVES: Anxiety disorders (ADs) are commonly associated with high-functioning Autism Spectrum Disorder (HF-ASD) and often worsen with age. Buspirone is a commonly prescribed anxiolytic drug with a favorable tolerability profile that may offer potential benefits in anxiety management for patients with HF-ASD. This study examines inadequately explored tolerability and effectiveness of buspirone in treating ADs comorbid with high-functioning ASD. METHODS: A retrospective chart review of a 1-year period was conducted in psychiatrically referred population of HF-ASD youth with AD (age 8-17 years) who were treated with buspirone (N = 31). Information on the demographics and treatment history was recorded. Effectiveness was assessed through the Clinical Global Impressions Scale (CGI) severity (CGI-S) and improvement (CGI-I) scores noted by the treating clinician. RESULTS: A total of 31 patients were prescribed buspirone during the determined period, at a mean dose of 41.61 ± 24.10 mg for an average duration of 272 ± 125 days. Change in the CGI-S mean scores with treatment suggests an overall improvement in the severity of anxiety symptoms (MT1 = 4.9 ± 0.7; MT2 = 2.8 ± 0.87; p < 0.001). Significant improvement in anxiety symptoms (CGI-I ≤ 2) was observed in 58% and mild improvement (CGI-I = 3) in 29% of the HF-ASD patients who received buspirone treatment. Buspirone was well tolerated with no adverse events reported by the majority of participants, with the exception of two subjects who developed treatment emergent adverse events (activation and mood lability). CONCLUSIONS: Findings from this retrospective chart review suggest a promising role of buspirone in managing anxiety among youth with HF-ASD. Further research with prospective and randomized-controlled trials is necessary.

High Risk for Severe Emotional Dysregulation in Psychiatrically Referred Youth with Autism Spectrum Disorder: A Controlled Study.

To assess prevalence and severity of emotional dysregulation (ED) in psychiatrically referred youth with autism spectrum disorder (ASD). ASD youth (N = 123) were compared to youth with attention-deficit/hyperactivity disorder (ADHD) and controls. The majority of psychiatrically referred youth with ASD had positive Child Behavior Checklist-ED (CBCL-ED) profile that was significantly higher than in youth with ADHD (82 vs. 53%; p < 0.001). The severe emotional dysregulation (SED) profile was significantly greater in ASD youth than ADHD (44 vs. 15%; p < 0.001). In the presence of SED profile ASD youth suffered from greater severity of autism, associated psychopathology, and psychosocial dysfunction. Greater than expected prevalence of SED in psychiatrically referred youth with ASD that identifies distinct clinical correlates associated with severe morbidity and dysfunction.

Symptom Profile of ADHD in Youth With High-Functioning Autism Spectrum Disorder: A Comparative Study in Psychiatrically Referred Populations.

OBJECTIVE: To compare the clinical presentation of ADHD between youth with autism spectrum disorder (ASD) and ADHD and a sample of youth with ADHD only. METHOD: A psychiatrically referred sample of autism spectrum disorder (ASD) youth with ADHD attending a specialized ambulatory program for ASD ( n = 107) and a sample of youth with ADHD attending a general child psychiatry ambulatory clinic ( n = 74) were compared. RESULTS: Seventy-six percent of youth with ASD met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria for ADHD. The clinical presentation of ADHD in youth with ASD was predominantly similar to its typical presentation including age at onset (3.5 ± 1.7 vs. 4.0 ± 1.9; p = .12), distribution of diagnostic subtypes, the qualitative and quantitative symptom profile, and symptom severity. Combined subtype was the most frequent presentation of ADHD in ASD youth. CONCLUSION: Despite the robust presentation of ADHD, a significant majority of ASD youth with ADHD failed to receive appropriate ADHD treatment (41% vs. 24%; p = .02). A high rate of comorbidity with ADHD was observed in psychiatrically referred youth with ASD, with a clinical presentation typical of the disorder.

A study of the neuropsychological correlates in adults with high functioning autism spectrum disorders.

OBJECTIVE: To examine the unique neuropsychological presentation in adults with high functioning autism spectrum disorders (HF-ASD) by comparison with adults with attention deficit hyperactivity disorder (ADHD). METHODS: Adults with ASD referred to a specialty clinic (n=26) were compared to two non-ASD groups with (n=52) and without (n=52) ADHD of similar age and sex. RESULTS: No differences in IQ were found. Subjects with HF-ASD were significantly more impaired than both comparison groups in processing speed, cognitive flexibility and sight words. Subjects with HF-ASD were more impaired than controls in working memory, but not the ADHD group. CONCLUSION: These findings suggest that there may be specific neuropsychological correlates of HF-ASD differing from ADHD that could have significant implications for identifying individuals at risk for ASD.

Examining the clinical correlates of autism spectrum disorder in youth by ascertainment source.

To examine whether presentation of autism spectrum disorder (ASD) and associated patterns of psychiatric comorbidity and dysfunction vary by referral source. ASD youth referred to a specialized ambulatory program for ASD (N = 143) were compared to ASD youth referred to a general child psychiatry clinic (N = 217). More ASD clinic youth met criteria for a more robust form of ASD (autistic disorder); more youth referred to the psychiatry clinic met criteria for broader spectrum ASD (pervasive developmental disorder not otherwise specified). General psychiatry clinic youth with ASD suffered from a greater burden of psychopathologies and higher levels of dysfunction. The presentation of ASD in psychiatrically referred youth differs between general and ASD-specialized clinics, though both referral populations have high levels of comorbidity and dysfunction.

Response to second generation antipsychotics in youth with comorbid bipolar disorder and autism spectrum disorder.

OBJECTIVE: To assess the impact of comorbid autism spectrum disorders (ASD) on the response to second-generation antipsychotics (SGA) in pediatric bipolar disorder (BPD). METHODS: Secondary analysis of identically designed 8-week open-label trials of SGA monotherapy (risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole) in youth with BPD. RESULTS: Of the 151 BPD subjects 15% (n= 23) met criteria for comorbid ASD. There were no differences in the rate of antimanic response (YMRS change ≥30% or CGI-Improvement ≤2: 65% vs. 69%; P= 0.7) in the presence of comorbid ASD. CONCLUSION: No difference observed in the rate of antimanic response or tolerability to SGA monotherapy in the presence of ASD comorbidity.

Discriminant and concurrent validity of a simplified DSM-based structured diagnostic instrument for the assessment of autism spectrum disorders in youth and young adults.

BACKGROUND: To evaluate the concurrent and discriminant validity of a brief DSM-based structured diagnostic interview for referred individuals with autism spectrum disorders (ASDs). METHODS: To test concurrent validity, we assessed the structured interview's agreement in 123 youth with the expert clinician assessment and the Social Responsiveness Scale (SRS). Discriminant validity was examined using 1563 clinic-referred youth. RESULTS: The structured diagnostic interview and SRS were highly sensitive indicators of the expert clinician assessment. Equally strong was the agreement between the structured interview and SRS. We found evidence for high specificity for the structured interview. CONCLUSIONS: A simplified DSM-based ASD structured diagnostic interview could serve as a useful diagnostic aid in the assessment of subjects with ASDs in clinical and research settings.

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, Asperger's 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.

The heavy burden of psychiatric comorbidity in youth with autism spectrum disorders: a large comparative study of a psychiatrically referred population.

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.

Can a subtype of conduct disorder linked to bipolar disorder be identified? Integration of findings from the Massachusetts General Hospital Pediatric Psychopharmacology Research Program.

Our intent was to investigate systematically the overlap between conduct disorder (CD) and bipolar disorder (BPD). We hypothesized that neither CD nor manic symptoms were secondary to the other disorder and that children with the two disorders would have correlates of both. Results from a series of programmatic studies examining phenotypic features of bipolar and conduct disorder alone or combined in probands and relatives were evaluated within and without the context of ADHD. Examination of the clinical features, patterns of psychiatric comorbidity, functioning in multiple domains, and familiality showed that children with CD and BPD had similar features of each disorder irrespective of the comorbidity with the other disorder. Our data suggest that when BPD and CD co-occur in children, both are correctly diagnosed. In these comorbid cases, CD symptoms should not be viewed as secondary to BPD, and manic symptoms should not be viewed as secondary to CD.

Patterns of comorbidity and dysfunction in clinically referred preschool and school-age children with bipolar disorder.

OBJECTIVE: Despite its common onset in preschool years, few studies have examined the characteristics of bipolar disorder (BPD) in preschoolers. This study reports on the clinical characteristics, psychiatric comorbidity, and functioning of preschoolers identified with BPD who were referred to a pediatric psychiatric clinic. METHODS: Structured psychiatric interviews assessing lifetime psychopathology by Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) criteria were completed with parents about their children and confirmed by clinical interview of the child. Family, social, and overall functioning were also assessed at intake. Findings from preschoolers ages 4 to 6 years were compared with a group of children ages 7 to 9 years (school age). RESULTS: We identified 44 preschoolers and 29 consecutively ascertained school-age youth with BPD. Preschoolers had similar rates of comorbid psychopathology compared to school-age youth with BPD. Preschoolers and school-age children with BPD typically manifest symptoms of mania and major depression simultaneously (mixed states). Both preschoolers and school-age children had substantial impairment in school, social, and overall functioning. CONCLUSIONS: These results suggest that clinically referred preschoolers with BPD share with school-age children with BPD high rates of comorbid psychopathology and impaired functioning. Follow-up of these clinically referred preschoolers with BPD evaluating the stability of their diagnoses, treatment response, and their long-term outcome is necessary.