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J Am Acad Child Adolesc Psychiatry [journal]
- Battle royale. [Letter]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):1031.
- Reduced prefrontal efficiency for visuospatial working memory in attention-deficit/hyperactivity disorder. [Journal Article]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):1020-1030.e6.
Visuospatial working memory impairments have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). However, most ADHD research has focused on the neural correlates of nonspatial mnemonic processes. This study examined brain activation and functional connectivity for visuospatial working memory in youth with and without ADHD.Twenty-four youth with ADHD and 21 age- and sex-matched healthy controls were scanned with functional magnetic resonance imaging while performing an N-back test of working memory for spatial position. Block-design analyses contrasted activation and functional connectivity separately for high (2-back) and low (1-back) working memory load conditions versus the control condition (0-back). The effect of working memory load was modeled with linear contrasts.The 2 groups performed comparably on the task and demonstrated similar patterns of frontoparietal activation, with no differences in linear gains in activation as working memory load increased. However, youth with ADHD showed greater activation in the left dorsolateral prefrontal cortex (DLPFC) and left posterior cingulate cortex (PCC), greater functional connectivity between the left DLPFC and left intraparietal sulcus, and reduced left DLPFC connectivity with left midcingulate cortex and PCC for the high load contrast compared to controls (p < .01; k > 100 voxels). Reanalysis using a more conservative statistical approach (p < .001; k > 100 voxels) yielded group differences in PCC activation and DLPFC-midcingulate connectivity.Youth with ADHD show decreased efficiency of DLPFC for high-load visuospatial working memory and greater reliance on posterior spatial attention circuits to store and update spatial position than healthy control youth. Findings should be replicated in larger samples.
- Attention-deficit/hyperactivity disorder (ADHD) and motor timing in adolescents and their parents: familial characteristics of reaction time variability vary with age. [Journal Article]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):1010-1019.e4.
There is consistent evidence that attention-deficit/hyperactivity disorder (ADHD) is strongly related to impaired motor timing as reflected in decreased accuracy and increased reaction time variability (RTV). It is not known whether motor timing impairments are present in adolescents and adults with ADHD and their unaffected relatives to the same extent as has been reported in children, and whether ADHD and motor timing share familial underpinnings, as reflected in parent-offspring co-segregation and sibling cross-correlations.A total of 589 parents and 808 children/adolescents from families with ADHD and control families (parent/offspring average age: 48.6/17.3 years) were included. All participants were thoroughly assessed for ADHD and performed a 40-trial motor timing task (1-second interval production). Dependent neurocognitive measures included RT median (RTM: representing accuracy), RTV and ex-Gaussian component τ (τ: representing infrequent long response times). Generalized estimating equations were used for analyses.Unaffected children from families with ADHD had RTV (but not RTM or τ) scores in between those of affected and control children. However, during middle-to-late adolescence, unaffected offspring were not impaired compared to control offspring and differed from ADHD probands, whereas during late adolescence/early adulthood, all offspring groups performed equally. Affected and unaffected parents of families with ADHD showed increased RTV compared to controls, regardless of age (not significant after adjusting for IQ). There were indications for shared familiality between RTV and ADHD as reflected by sibling cross-correlations and between RTM and ADHD as reflected by sibling cross-correlations and a maternal parent-offspring relation (parent-of-origin effect).RTV and its familial characteristics are influenced by development during adolescence. Increased RTV in children with ADHD appears to reflect immaturities in their neurocognitive functioning. Maternal ADHD effects might be involved in transmission of RTM (not RTV), but overall RTM showed less compelling (familial) relationships with ADHD than RTV.
- Executive Function in Probands With Autism With Average IQ and Their Unaffected First-Degree Relatives. [Journal Article]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):1001-9.
This study aimed to characterize executive function (EF) in pedigrees of children with autism spectrum disorder (ASD) and average IQ. The authors examined the hypothesis that deficits in EF relate to lower levels of adaptive functioning, and they assessed evidence for a cognitive extended phenotype in unaffected relatives in a large, well-characterized sample.Proband EF was assessed by parent-report questionnaires (Behavior Rating Inventory of Executive Functioning [BRIEF], n = 109) and child neuropsychological tests (Delis-Kaplan Executive Functioning System [D-KEFS], n = 35). EF also was examined in parents (D-KEFS, n = 335) and unaffected siblings (BRIEF, n = 114; D-KEFS, n = 57). Adaptive functioning was assessed by the Vineland Adaptive Behavior Scales-II (n = 155). All data were obtained from the Autism Consortium Clinical Genetics Database.Individuals with ASD showed important EF weaknesses. Multiple regression analyses showed that parent-reported EF deficits were related to profound decreases in adaptive functioning even after controlling for age, IQ, and severity of ASD symptoms. Parent-reported EF also was related to adaptive skills in preschoolers. First-degree unaffected relatives did not demonstrate difficulties with EF compared with normative data.In this study, EF impairments do not appear to relate to broad familial risk factors for ASD but may be associated with factors relevant to the expression of ASD in probands. Results support the benefits of EF assessment as a way to identify potential therapeutic targets that could lead to improved adaptive behavior in children with ASD and average IQ.
- Subthreshold psychotic symptoms in 22q11.2 deletion syndrome. [Journal Article]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):991-1000.e2.
Chromosome 22q11.2 deletion syndrome (22q11DS) confers 25% risk for psychosis and is an invaluable window for understanding the neurobiological substrate of psychosis risk. The Structured Interview for Prodromal Syndromes (SIPS) is well validated in nondeleted populations for detecting clinical risk but has only recently been applied to 22q11DS. We assessed the largest 22q11DS cohort to date and report on SIPS implementation and symptoms elicited.The SIPS, including its 19 subscales, was administered to 157 individuals with 22q11DS aged 8 to 25 years. Youth and caregiver interviews were conducted and rated separately, then compared for agreement. Implementation of the SIPS in 22q11DS was challenging because of the prevalence of developmental delay and comorbid conditions. However, by explaining questions and eliciting examples, we were able to help youths and caregivers understand and respond appropriately. Consensus ratings were formulated and analyzed with itemwise and factor analysis.Subthreshold symptoms were common, with 85% of individuals endorsing 1 or more. The most commonly rated items were ideational richness (47%) and trouble with focus and attention (44%). Factor analysis revealed a 3-factor solution with positive, negative, and disorganized components. Youth-caregiver comparisons suggested that youths report greater symptoms of perceptual abnormalities, suspiciousness, trouble with emotional expression, and bizarre thinking. Caregivers reported more impaired tolerance to normal stress, poor hygiene, and inattention.The SIPS was adapted for 22q11DS through comprehensive and semi-structured administration methods, yielding a high prevalence of subthreshold psychotic symptoms. The significance and predictive validity of these symptoms require future longitudinal analysis.
- Racial/Ethnic Differences in Perceived Reasons for Mental Health Treatment in US Adolescents With Major Depression. [Journal Article]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):980-90.
Racial/ethnic differences in the course of treatment for a major depressive episode (MDE) among adolescents may arise, in part, from variation in the perceived rationale for treatment. We examined racial/ethnic differences in the perceived reasons for receiving mental health (MH) treatment among adolescents with an MDE.A total of 2,789 adolescent participants who experienced an MDE and received MH treatment in the past year were drawn from the 2005 to 2008 National Survey on Drug Use and Health. Adolescents reported the settings in which they received care and reasons for their most recent visit to each setting. Distributions of specific depressive symptoms were compared across racial/ethnic groups. Racial/ethnic differences in endorsing each of 11 possible reasons for receiving treatment were examined using weighted probit regressions adjusted for sociodemographic characteristics, health and mental health status, treatment setting, and survey year.Despite similar depressive symptom profiles, Hispanic adolescents were more likely than whites to endorse "breaking rules" or getting into physical fights as reasons for MH treatment. Black adolescents were more likely than white adolescents to endorse "problems at school" but less likely to endorse "felt very afraid or tense" or "eating problems" as reasons for treatment. Asian adolescents were more likely to endorse "problems with people other than friends or family" but less likely than whites to endorse "suicidal thoughts/attempt" and "felt depressed" as reasons for treatment.Racial/ethnic minority participants were more likely than white participants to endorse externalizing or interpersonal problems and less likely to endorse internalizing problems as reasons for MH treatment. Understanding racial/ethnic differences in the patient's perceived treatment rationale can offer opportunities to enhance outcomes for depression among diverse populations.
- Risk of diabetes in children and adolescents exposed to antipsychotics: a nationwide 12-year case-control study. [Journal Article]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):971-979.e6.
Antipsychotics are associated with weight gain and diabetes. The risk and rate of diabetes in children and adolescents treated with antipsychotics is unclear.A longitudinal register linkage case-control study of diabetes in all psychiatric patients aged <18 years in Denmark was performed from January 1999 through the end of June 2010. Patients with and without antipsychotic exposure were compared regarding the occurrence of type 2 diabetes, defined as the prescription of oral antidiabetic medication. Regression analyses with type 2 diabetes as the dependent variable were conducted with sex, age, and diagnoses as covariates.We compared the risk of diabetes in 48,299 psychiatrically ill youth. Of 7,253 youth exposed to antipsychotics, 52 (0.72%; 95% CI = 0.52% - 0.91%) developed type 2 diabetes. Of 41,046 youth without exposure to antipsychotics, 111 (0.27%; 95% CI = 0.22% - 0.32%) developed type 2 diabetes. In a 25,033 + 16,013 logistic regression analysis, type 2 diabetes development was associated with antipsychotic drug exposure (odds ratio [OR] = 1.60; 95% CI = 1.08 - 2.36, p < .05) female sex, (OR = 4.48; 95% CI = 2.90 - 6.91, p < 0.001) and older age at first psychiatric diagnosis (OR = 1.19; 95% CI = 1.12 - 1.27, p < 0.001), but not with psychiatric diagnosis. In a Cox-regression analysis, shorter time to type 2 diabetes onset was associated with female sex (Hazard Ratio (HR) = 4.83; 95% CI = 3.05-7.66, p = 0.001), and older age at first psychiatric diagnosis (HR = 1.19; 95% CI = 1.12-1.28, p = 0.001), while antipsychotic exposure (HR) = 1.41; 95% CI = 0.92-2.16, p = 0.11) trended towards increasing the rate of diabetes.Antipsychotic treatment, female sex, and older age at psychiatric diagnosis were associated with a significantly more frequent type 2 diabetes onset in children and adolescents. Strict indications for antipsychotic treatment and routine cardiometabolic monitoring are crucial.
- Growth in the concurrent use of antipsychotics with other psychotropic medications in medicaid-enrolled children. [Journal Article]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):960-970.e2.
Second-generation antipsychotics (SGAs) have increasingly been prescribed to Medicaid-enrolled children; however, there is limited understanding of the frequency of concurrent SGA prescribing with other psychotropic medications. This study describes the epidemiology of concurrent SGA use with 4 psychotropic classes (stimulants, antidepressants, mood stabilizers, and α-agonists) among a national sample of Medicaid-enrolled children and adolescents 6 to 18 years old between 2004 and 2008.Repeated cross-sectional design was used, with national Medicaid Analytic eXtract data (10.6 million children annually). Logit and Poisson regression, standardized for year, demographics, and Medicaid eligibility group, estimated the probability and duration of concurrent SGA use with each medication class over time and examined concurrent SGAs in relation to clinical and demographic characteristics.While SGA use overall increased by 22%, 85% of such use occurred concurrently. By 2008, the probability of concurrent SGA use ranged from 0.22 for stimulant users to 0.52 for mood stabilizer users. Concurrent SGA use occurred for long durations (69%-89% of annual medication days). Although the highest users of concurrent SGA were participants in foster care and disability Medicaid programs or those with behavioral hospitalizations, the most significant increases over time occurred among participants who were income-eligible for Medicaid (+13%), without comorbid ADHD (+15%), were not hospitalized (+13%), and did not have comorbid intellectual disability (+45%).Concurrent SGA use with other psychotropic classes increased over time, and the duration of concurrent therapy was consistently long term. Concurrent SGA regimens will require further research to determine efficacy and potential drug-drug interactions, given a practice trend toward more complex regimens in less-impaired children/adolescents.
- Risperidone added to parent training and stimulant medication: effects on attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder, and peer aggression. [Journal Article]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):948-959.e1.
In this study, we aimed to expand on our prior research into the relative efficacy of combining parent training, stimulant medication, and placebo (Basic therapy) versus parent training, stimulant, and risperidone (Augmented therapy) by examining treatment effects for attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) symptoms and peer aggression, symptom-induced impairment, and informant discrepancy.Children (6-12 years of age; N = 168) with severe physical aggression, ADHD, and co-occurring ODD/CD received an open trial of parent training and stimulant medication for 3 weeks. Participants failing to show optimal clinical response were randomly assigned to Basic or Augmented therapy for an additional 6 weeks.Compared with Basic therapy, children receiving Augmented therapy experienced greater reduction in parent-rated ODD severity (p = .002, Cohen's d = 0.27) and peer aggression (p = .02, Cohen's d = 0.32) but not ADHD or CD symptoms. Fewer children receiving Augmented (16%) than Basic (40%) therapy were rated by their parents as impaired by ODD symptoms at week 9/endpoint (p = .008). Teacher ratings indicated greater reduction in ADHD severity (p = .02, Cohen's d = 0.61) with Augmented therapy, but not for ODD or CD symptoms or peer aggression. Although both interventions were associated with marked symptom reduction, a relatively large percentage of children were rated as impaired for at least 1 targeted disorder at week 9/endpoint by parents (Basic 47%; Augmented 27%) and teachers (Basic 48%; Augmented 38%).Augmented therapy was superior to Basic therapy in reducing severity of ADHD and ODD symptoms, peer aggression, and symptom-induced impairment, but clinical improvement was generally context specific, and effect sizes ranged from small to moderate. Clinical trial registration information-Treatment of Severe Childhood Aggression (The TOSCA Study); http://clinicaltrails.gov/; NCT00796302.
- Measuring prodromal symptoms in youth with developmental disabilities: a lesson from 22q11 deletion syndrome. [Editorial]
- J Am Acad Child Adolesc Psychiatry 2014 Sep; 53(9):945-7.