Effects of risperidone and parent training on adaptive functioning in children with pervasive developmental disorders and serious behavioral problems.
J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):136-46
Authors: Scahill L, McDougle CJ, Aman MG, Johnson C, Handen B, Bearss K, Dziura J, Butter E, Swiezy NG, Arnold LE, Stigler KA, Sukhodolsky DD, Lecavalier L, Pozdol SL, Nikolov R, Hollway JA, Korzekwa P, Gavaletz A, Kohn AE, Koenig K, Grinnon S, Mulick JA, Yu S, Vitiello B,
Abstract
OBJECTIVE: Children with Pervasive Developmental Disorders (PDDs) have social interaction deficits, delayed communication, and repetitive behaviors as well as impairments in adaptive functioning. Many children actually show a decline in adaptive skills compared with age mates over time.
METHOD: This 24-week, three-site, controlled clinical trial randomized 124 children (4 through 13 years of age) with PDDs and serious behavioral problems to medication alone (MED; n = 49; risperidone 0.5 to 3.5 mg/day; if ineffective, switch to aripiprazole was permitted) or a combination of medication plus parent training (PT) (COMB; n = 75). Parents of children in COMB received an average of 11.4 PT sessions. Standard scores and Age-Equivalent scores on Vineland Adaptive Behavior Scales were the outcome measures of primary interest.
RESULTS: Seventeen subjects did not have a post-randomization Vineland assessment. Thus, we used a mixed model with outcome conditioned on the baseline Vineland scores. Both groups showed improvement over the 24-week trial on all Vineland domains. Compared with MED, Vineland Socialization and Adaptive Composite Standard scores showed greater improvement in the COMB group (p = .01 and .05, and effect sizes = 0.35 and 0.22, respectively). On Age Equivalent scores, Socialization and Communication domains showed greater improvement in COMB versus MED (p = .03 and 0.05, and effect sizes = 0.33 and 0.14, respectively). Using logistic regression, children in the COMB group were twice as likely to make at least 6 months’ gain (equal to the passage of time) in the Vineland Communication Age Equivalent score compared with MED (p = .02). After controlling for IQ, this difference was no longer significant.
CONCLUSION: Reduction of serious maladaptive behavior promotes improvement in adaptive behavior. Medication plus PT shows modest additional benefit over medication alone. Clinical trial registration information-RUPP PI PDD: Drug and Behavioral Therapy for Children With Pervasive Developmental Disorders; http://www.clinicaltrials.gov; NCT00080145.
Stimulants and cardiovascular events in youth with attention-deficit/hyperactivity disorder.
J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):147-56
Authors: Olfson M, Huang C, Gerhard T, Winterstein AG, Crystal S, Allison PD, Marcus SC
Abstract
OBJECTIVE: This study examined associations between stimulant use and risk of cardiovascular events and symptoms in youth with attention-deficit/hyperactivity disorder and compared the risks associated with methylphenidate and amphetamines.
METHOD: Claims were reviewed of privately insured young people 6 to 21 years old without known cardiovascular risk factors (n = 171,126). A day-level cohort analysis evaluated the risk of cardiovascular events after a diagnosis of attention-deficit/hyperactivity disorder in relation to stimulant exposures. Based on filled stimulant prescriptions, follow-up days were classified as current, past, and no stimulant use. Endpoints included an emergency department or inpatient diagnosis of angina pectoris, cardiac dysrhythmia, or transient cerebral ischemia (cardiac events) or tachycardia, palpitations, or syncope (cardiac symptoms).
RESULTS: There were 0.92 new cardiac events and 3.08 new cardiac symptoms per 1,000,000 days of current stimulant use. Compared with no stimulant use (reference group), the adjusted odds ratios of cardiac events were 0.69 (95% confidence interval 0.42-1.12) during current stimulant use and 1.18 (95% CI 0.83-1.66) during past stimulant use. The corresponding adjusted odds ratios for cardiac symptoms were 1.18 (95% CI 0.89-1.59) for current and 0.93 (95% CI 0.71-1.21) for past stimulant use. No significant differences were observed in risks of cardiovascular events (2.14, 95% CI 0.82-5.63) or symptoms (1.08, 95% CI 0.66-1.79) for current methylphenidate use compared with amphetamine use (reference group).
CONCLUSIONS: Clinical diagnoses of cardiovascular events and symptoms were rare and not associated with stimulant use. The results help to allay concerns over the cardiovascular safety of stimulant treatment for attention-deficit/hyperactivity disorder in young people without known pre-existing risk factors.
Risperidone and divalproex differentially engage the fronto-striato-temporal circuitry in pediatric mania: a pharmacological functional magnetic resonance imaging study.
J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):157-170.e5
Authors: Pavuluri MN, Passarotti AM, Fitzgerald JM, Wegbreit E, Sweeney JA
Abstract
OBJECTIVE: The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD).
METHOD: This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 ± 2.5 years of age). Functional magnetic resonance imaging (fMRI) outcomes were measured using a block design, affective, N-back task with angry, happy, and neutral face stimuli at baseline and at 6-week follow-up. Matched healthy controls (HC; n = 15, 14.5 ± 2.8 years) were also scanned twice.
RESULTS: In post hoc analyses on the significant interaction in a 3×2×2 analysis of variance (ANOVA) that included patient groups and HC, the risperidone group showed greater activation after treatment in response to the angry face condition in the left subgenual anterior cingulate cortex (ACC) and striatum relative to the divalproex group. The divalproex group showed greater activation relative to the risperidone group in the left inferior frontal gyrus and right middle temporal gyrus. Over the treatment course, the risperidone group showed greater change in activation in the left ventral striatum than the divalproex group, and the divalproex group showed greater activation change in left inferior frontal gyrus and right middle temporal gyrus than the risperidone group. Furthermore, each patient group showed increased activation relative to HC in fronto-striato-temporal regions over time. The happy face condition was potentially less emotionally challenging in this study and did not elicit notable findings.
CONCLUSIONS: When patients performed a working memory task under emotional duress inherent in the paradigm, divalproex enhanced activation in a fronto-temporal circuit whereas risperidone increased activation in the dopamine (D(2)) receptor-rich ventral striatum. Clinical trial registration information-Risperidone and Divalproex Sodium With MRI Assessment in Pediatric Bipolar; http://www.clinicaltrials.gov; NCT00176202.
Parietal lobe volume deficits in adolescents with schizophrenia and adolescents with cannabis use disorders.
J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):171-80
Authors: Kumra S, Robinson P, Tambyraja R, Jensen D, Schimunek C, Houri A, Reis T, Lim K
Abstract
OBJECTIVE: In early-onset schizophrenia (EOS), the earliest structural brain volumetric abnormalities appear in the parietal cortices. Early exposure to cannabis may represent an environmental risk factor for developing schizophrenia. This study characterized cerebral cortical gray matter structure in adolescents in regions of interest (ROIs) that have been implicated in EOS and cannabis use disorders (CUD).
METHOD: T1-weighted magnetic resonance images were acquired from adolescents with EOS (n = 35), CUD (n = 16), EOS + CUD (n = 13), and healthy controls (HC) (n = 51). Using FreeSurfer, brain volume was examined within frontal, temporal, parietal and subcortical ROIs by a 2 (EOS versus no EOS) × 2 (CUD versus no CUD) design using multivariate analysis of covariance. In ROIs in which volumetric differences were identified, additional analyses of cortical thickness and surface area were conducted.
RESULTS: A significant EOS-by-CUD interaction was observed. In the left superior parietal region, both “pure” EOS and “pure” CUD had smaller gray matter volumes that were associated with lower surface area compared with HC. A similar alteration was observed in the comorbid group compared with HC, but there was no additive volumetric deficit found in the comorbid group compared with the separate groups. In the left thalamus, the comorbid group had smaller gray matter volumes compared with the CUD and HC groups.
CONCLUSIONS: These preliminary data indicate that the presence of a CUD may moderate the relationship between EOS and cerebral cortical gray matter structure in the left superior parietal lobe. Future research will follow this cohort over adolescence to further examine the impact of cannabis use on neurodevelopment.
Regional cerebral development at term relates to school-age social-emotional development in very preterm children.
J Am Acad Child Adolesc Psychiatry. 2012 Feb;51(2):181-91
Authors: Rogers CE, Anderson PJ, Thompson DK, Kidokoro H, Wallendorf M, Treyvaud K, Roberts G, Doyle LW, Neil JJ, Inder TE
Abstract
OBJECTIVE: Preterm children are at risk for social-emotional difficulties, including autism and attention-deficit/hyperactivity disorder. We assessed the relationship of regional brain development in preterm children, evaluated via magnetic resonance imaging (MRI) at term-equivalent postmenstrual age (TEA), to later social-emotional difficulties.
METHOD: MR images obtained at TEA from 184 very preterm infants (gestation <30 weeks or birth weight <1,250 g) were analyzed for white matter abnormalities, hippocampal volume, and brain metrics. A total of 111 infants underwent diffusion tensor imaging, which provided values for fractional anisotropy and apparent diffusion coefficient. Social-emotional development was assessed with the Infant Toddler Social and Emotional Assessment (ITSEA) at age 2 and the Strengths and Difficulties Questionnaire (SDQ) at age 5 years.
RESULTS: Higher apparent diffusion coefficient in the right orbitofrontal cortex was associated with social-emotional problems at age 5 years (peer problems, p < .01). In females, smaller hippocampal volume was associated with increased hyperactivity (p < .01), peer problems (p < .05), and SDQ total score (p < .01). In males, a smaller frontal region was associated with poorer prosocial (p < .05) scores. Many of the hippocampal findings remained significant after adjusting for birthweight z score, intelligence, social risk, immaturity at birth, and parental mental health. These associations were present in children who had social-emotional problems in similar domains at age 2 and those who did not.
CONCLUSIONS: Early alterations in regional cerebral development in very preterm infants relate to specific deficits in social-emotional performance by school-age. These results vary by gender. Our results provide further evidence for a neuroanatomical basis for behavioral challenges found in very preterm children.
PMID: 22265364 [PubMed - in process]
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