The Resilient Youth Program: a promising skills-based online program for resiliency and stress management.

BACKGROUND: Prevention programs that target resilience may help youth address mental health difficulties and promote well-being during public health crises. AIMS: To examine the preliminary efficacy of the Resilient Youth Program (RYP). METHOD: The RYP was delivered remotely from a US academic medical centre to youth in the community via a naturalistic pilot study. Data from 66 youth (ages 6-18, Mage = 11.65, SD = 3.02) and their parents were collected via quality assurance procedures (May 2020 to March 2021). Pre/post-intervention child/parent-reported psychological and stress symptoms as well as well-being measures were compared via Wilcoxon signed rank tests. Child/parent-reported skills use data were collected. RESULTS: Among child-reported outcomes, there were significant decreases in physical stress (p = .03), anxiety (p = .004), depressive symptoms (p < .001) and anger (p = .002), as well as increased life satisfaction (p = .02). There were no significant differences in child-reported psychological stress (p = .06) or positive affect (p = .09). Among parent-reported child outcomes, there were significant decreases in psychological (p < .001) and physical stress (p = .03), anxiety (p < .001), depressive symptoms (p < .001), and anger (p < .002) as well as increased positive affect (p < .001) and life satisfaction (p < .001). Effect sizes ranged from small to medium; 77% of youth (73% of parents) reported using RYP skills. Age and gender were not associated with outcome change. CONCLUSIONS: The RYP may help reduce psychological/stress symptoms and increase well-being among youth; further research is needed.

Anxiety and Disruptive Behavior Symptoms and Disorders in Preschool-Age Offspring of Parents With and Without Bipolar Disorder: Associations With Parental Comorbidity.

OBJECTIVE: We examined the relative contribution of parental bipolar disorder (BPD) and psychiatric comorbidities (disruptive behavior disorders [DBD] and anxiety disorders) in predicting psychiatric symptoms and disorders in 2-5-year-old offspring. METHODS: Participants were 60 families with a parent with BPD and 78 offspring and 70 comparison families in which neither parent had a mood disorder and 91 offspring. Parent and offspring diagnoses and symptoms were assessed using standardized diagnostic interviews and measures, with offspring assessors masked to parental diagnoses. RESULTS: Offspring of parents with BPD had significant elevations in behavioral, mood and anxiety disorders and symptoms. Both parental BPD and DBD contributed to elevations in child disruptive behavioral symptoms, whereas child anxiety symptoms were more strongly predicted by comorbid parental anxiety. Parental BPD was a stronger predictor than comorbid DBD of child DBDs. CONCLUSION: Some of the elevated risk for disorders in preschoolers is accounted for by parental comorbidity.

Screening Infants Through Adolescents for Social/Emotional/Behavioral Problems in a Pediatric Network.

OBJECTIVE: To assess changes in screening completion in a diverse, 7-clinic network after making annual screening for social/emotional/behavioral (SEB) problems the standard of care for all infant through late adolescent-aged patients and rolling out a fully automated screening system tied to the electronic medical record and patient portal. METHODS: In 2017, the Massachusetts General Hospital made SEB screening using the age-appropriate version of the Pediatric Symptom Checklist the standard of care in its pediatric clinics for all patients aged 2.0 months to 17.9 years. Billing records identified all well-child visits between January 1, 2016 and December 31, 2019. For each visit, claims were searched for billing for an SEB screen and the electronic data warehouse was queried for an electronically administered screen. A random sample of charts was reviewed for other evidence of screening. Chi-square analyses and generalized estimating equations assessed differences in screening over time and across demographic groups. RESULTS: Screening completion (billing and/or electronic) significantly increased from 2016 (37.2%) through 2019 (2017 [46.2%] vs 2018 [66.8%] vs 2019 [70.9%]; χ2 (3) =112652.33, P < .001), with an even higher prevalence found after chart reviews. Most clinics achieved screening levels above 90% by the end of 2019. Differences among demographic groups were small and dependent on whether data were aggregated at the clinic or system level. CONCLUSIONS: Following adoption of a best-practice policy and implementation of an electronic system, SEB screening increased in all age groups and clinics. Findings demonstrate that the AAP recommendation for routine psychosocial assessment is feasible and sustainable.

Risk Factors for Depression in Adolescents With ADHD: The Impact of Cognitive Biases and Stress.

Objective: Youth diagnosed with ADHD are at heightened risk of depression. However, many do not develop depression. Individuals with specific cognitive biases are more likely to develop depression yet it remains untested whether these vulnerability-stress models apply to depression risk in youth with ADHD. Method: We examined whether interpretation and attention biases moderated the relation between stressful life events and depressive symptoms in a sample of adolescents (Mage = 14.42) with ADHD (n = 59) and without ADHD (n = 36). Results: Youth with ADHD experienced more stressful life events compared with those without ADHD. Interpretation biases moderated the association between stress and depressive symptoms in youth with and without ADHD. Attention biases moderated the association between stress and depressive symptoms in the non-ADHD youth only. Conclusion: These results enhance our understanding of vulnerability for depression in adolescence with ADHD and inform targeted prevention and treatment models during this critical developmental juncture.

Exploring the stress sensitization theory with temperamentally inhibited children: a population-based study.

BACKGROUND: This study explored whether temperamentally inhibited children who experience early trauma are vulnerable to developing internalizing problems in the face of later life-stressors. METHODS: A validated screen for temperamental inhibition was distributed to parents of young children attending preschools in six government regions of Melbourne, Australia. Screening identified 11% of children as inhibited (703 of 6347 screened) and eligible for a prevention study. Participants were 545 parents of inhibited preschoolers (78% uptake), of whom 84% were followed into mid childhood (age 7-10 years: wave 1, n = 446; wave 2, n = 427; wave 3, n = 426). Parents and children then completed questionnaires for child internalizing (anxious and depressive) symptoms, and parents received a diagnostic interview for child anxiety disorder. In mid-childhood parents also completed questionnaires annually to describe recent life-stressors experienced by their child, and any potentially traumatic events in the first four years of life. RESULTS: Only one in 14 temperamentally inhibited children had experienced a potentially traumatic event in early childhood. In mid childhood 56% experienced recent life-stressors. Inhibited children who had early life trauma experienced slightly more anxiety disorder and symptoms in mid childhood. Those children with more recent life-stressors in mid childhood also had slightly more symptoms of anxiety and depression. In contrast to stress sensitization, inhibited children with early trauma plus recent stressors did not show especially high mid-childhood internalizing difficulties. CONCLUSIONS: Early life trauma and recent life-stressors each convey a small risk for children with an inhibited temperament to develop internalizing problems. Nevertheless, early life stress may not always result in negative sensitization for children in the general population.

Cingulum-Callosal white-matter microstructure associated with emotional dysregulation in children: A diffusion tensor imaging study.

Emotional dysregulation symptoms in youth frequently predispose individuals to increased risk for mood disorders and other mental health difficulties. These symptoms are also known as a behavioral risk marker in predicting pediatric mood disorders. The underlying neural mechanism of emotional dysregulation, however, remains unclear. This study used the diffusion tensor imaging (DTI) technique to identify anatomically specific variation in white-matter microstructure that is associated with pediatric emotional dysregulation severity. Thirty-two children (mean age 9.53 years) with varying levels of emotional dysregulation symptoms were recruited by the Massachusetts General Hospital and underwent the DTI scans at Massachusetts Institute of Technology. Emotional dysregulation severity was measured by the empirically-derived Child Behavior Checklist Emotional Dysregulation Profile that includes the Attention, Aggression, and Anxiety/Depression subscales. Whole-brain voxel-wise regression tests revealed significantly increased radial diffusivity (RD) and decreased fractional anisotropy (FA) in the cingulum-callosal regions linked to greater emotional dysregulation in the children. The results suggest that microstructural differences in cingulum-callosal white-matter pathways may manifest as a neurodevelopmental vulnerability for pediatric mood disorders as implicated in the clinical phenotype of pediatric emotional dysregulation. These findings may offer clinically and biologically relevant neural targets for early identification and prevention efforts for pediatric mood disorders.

Association of Intrinsic Brain Architecture With Changes in Attentional and Mood Symptoms During Development.

Importance: Understanding the neurodevelopmental trajectory of psychiatric symptoms is important for improving early identification, intervention, and prevention of mental disorders. Objective: To test whether the strength of the coupling of activation between specific brain regions, as measured by resting-state functional magnetic resonance imaging (fMRI), predicted individual children's developmental trajectories in terms of attentional problems characteristic of attention-deficit/hyperactivity disorder and internalizing problems characteristics of major depressive disorder (MDD). Design, Setting, and Participants: A community cohort of 94 children was recruited from Vanderbilt University between 2010 and 2013. They were followed up longitudinally for 4 years and the data were analyzed from 2016 to 2019. Based on preregistered hypotheses and an analytic plan, we examined whether specific brain connectivity patterns would be associated with longitudinal changes in scores on the Child Behavior Checklist (CBCL), a parental-report assessment used to screen for emotional, behavioral, and social problems and to predict psychiatric illnesses. Main Outcomes and Measures: We used the strength of resting-state fMRI connectivity at age 7 years to predict subsequent changes in CBCL measures 4 years later and investigated the mechanisms of change by associating brain connectivity changes with changes in the CBCL. Results: We analyzed data from a longitudinal brain development study involving children assessed at age 7 years (n = 94; 41 girls [43.6%]) and 11 years (n = 54; 32 girls [59.3%]). As predicted, less positive coupling at age 7 years between the medial prefrontal cortex and dorsolateral prefrontal cortex (DLPFC) was associated with a decrease in attentional symptoms by age 11 years (t49 = 2.38; P = .01; ß = 0.32). By contrast, a less positive coupling between a region implicated in mood, the subgenual anterior cingulate cortex (sgACC), and DLPFC at age 7 years was associated with an increase in internalizing (eg, anxiety/depression) behaviors by age 11 years (t49 = -2.4; P = .01; ß = -0.30). Logistic regression analyses revealed that sgACC-DLPFC connectivity was a more accurate predictor than baseline CBCL measures for progression to a subclinical score on internalization (t50 = -2.61; P = .01; ß = -0.29). We then replicated and extended the sgACC-DLPFC result in an independent sample of children with (n = 25) or without (n = 18) familial risk for MDD. Conclusions and Relevance: These resting-state fMRI metrics are promising biomarkers for the early identification of children at risk of developing MDD or attention-deficit/hyperactivity disorder.

Intrinsic Functional Brain Connectivity Predicts Onset of Major Depression Disorder in Adolescence: A Pilot Study.

Children with familial risk for major depressive disorder (MDD) have elevated risk for developing depression as adolescents. Here, we investigated longitudinally whether resting-state functional connectivity (RSFC) could predict the onset of MDD. In this pilot study, we followed a group of never-depressed children with familial risk for MDD and a group of age-matched controls without familial risk who had undergone an MRI study at 8-14 years of age. Participants were reassessed 3-4 years later with diagnostic interviews. We first investigated group differences in RSFC from regions in the emotion regulation, cognitive control, and default mode networks in the children who later developed MDD (converted), the children who did not develop MDD (nonconverted), and the control group. We then built a prediction model based on baseline RSFC that was independent of the group differences to classify the individuals who later developed MDD. Compared with the nonconverted group, the converted group exhibited hypoconnectivity between subgenual anterior cingulate cortex (sgACC) and inferior parietal lobule (IPL) and between left and right dorsolateral prefrontal cortices. The nonconverted group exhibited higher sgACC-IPL connectivity than did both the converted and control groups, suggesting a possible resilience factor to MDD. Classification between converted and nonconverted individuals based on baseline RSFC yielded high predictive accuracy with high sensitivity and specificity that was superior to classification based on baseline clinical rating scales. Intrinsic brain connectivity measured in healthy children with familial risk for depression has the potential to predict MDD onset, and it can be a useful neuromarker in early identification of children for preventive treatment.

Neural markers of depression risk predict the onset of depression.

Although research highlights neural correlates of Major Depressive Disorder (MDD), it is unclear whether these correlates reflect the state of depression or a pre-existing risk factor. The current study examined whether baseline differences in brain activations, resting-state connectivity, and brain structural differences between non-symptomatic children at high- and low-risk for MDD based on familial depression prospectively predict the onset of a depressive episode or increases in depressive symptomatology. We re-assessed 44 participants (28 high-risk; 16 low-risk) who had undergone neuroimaging in a previous study 3-4 years earlier (Mean age at follow-up = 14.3 years, SD = 1.9 years; 45% females; 70% Caucasian). We investigated whether baseline brain imaging data (including an emotional face match task fMRI, resting-state fMRI and structural MRI) that differentiated the risk groups also predicted the onset of depression. Resting-state functional connectivity abnormalities in the default mode and cognitive control network that differentiated high-risk from low-risk youth at baseline predicted the onset of MDD during adolescence, after taking risk status into account. Increased functional activation to both happy and fearful faces was associated with greater decreases in self-reported depression symptoms at follow-up. This preliminary evidence could be used to identify youth at-risk for depression and inform early intervention strategies.

Very early family-based intervention for anxiety: two case studies with toddlers.

Anxiety disorders represent the most common category of psychiatric disorder in children and adolescents and contribute to distress, impairment and dysfunction. Anxiety disorders or their temperamental precursors are often evident in early childhood, and anxiety can impair functioning, even during preschool age and in toddlerhood. A growing number of investigators have shown that anxiety in preschoolers can be treated efficaciously using cognitive-behavioural therapy (CBT) administered either by training the parents to apply CBT strategies with their children or through direct intervention with parents and children. To date, most investigators have drawn the line at offering direct CBT to children under the age of 4. However, since toddlers can also present with impairing symptoms, and since behaviour strategies can be applied in older preschoolers with poor language ability successfully, it ought to be possible to apply CBT for anxiety to younger children as well. We therefore present two cases of very young children with impairing anxiety (ages 26 and 35 months) and illustrate the combination of parent-only and parent-child CBT sessions that comprised their treatment. The treatment was well tolerated by parents and children and showed promise for reducing anxiety symptoms and improving coping skills.

Family functioning in the context of parental bipolar disorder: associations with offspring age, sex, and psychopathology.

Previous research has shown that families with a parent who has bipolar disorder (BD) may experience family functioning difficulties. However, the association between family functioning and psychopathology among offspring of parents with BD, and offspring characteristics that may moderate this association, remains poorly understood. This study examined the cross-sectional associations between family functioning (cohesion, expressiveness, and conflict) and psychopathology in 117 offspring (ages 5-18) of 75 parents with BD. We also examined whether age and sex differences moderated these associations. We measured offspring psychopathology by examining current dimensional symptoms and DSM-IV emotional and behavioral disorders. Correlational analyses indicated that higher family conflict and lower cohesion were associated with higher internalizing and externalizing symptoms in offspring. Lower family cohesion was also associated with current offspring mood disorders. Moderation analyses indicated, first, that the link between lower family cohesion and internalizing symptoms was stronger for younger offspring compared to older offspring. Second, higher family conflict and current mood disorder were associated in younger males but not in older males or in females. Results remained the same after controlling for parental anxiety or substance use disorder comorbidity. Our study highlights the importance of accounting for family functioning when working with offspring at risk for BD, while also recognizing that the connections between family functioning and offspring outcomes are complex and differ based on offspring sex and developmental stage.

Efficacy of Interpretation Bias Modification in Depressed Adolescents and Young Adults.

This study evaluated the efficacy of a four-session Cognitive Bias Modification-Interpretation program for 45 depressed adolescents and young adults (14-21 years old; 12 males, 33 females; Beck Depressive Inventory, Second Edition ≥ 14) randomized to an active intervention condition (repeated exposure to positive outcomes of depression-relevant ambiguous scenarios; n=23) or a control condition (n=22). Both conditions experienced reductions on a Test of Interpretation Bias at post-treatment, with no significant between-group differences. When limited to those with negative bias at baseline, the intervention group showed greater improvement in interpretation bias at mid- and post-treatment. In addition, the intervention group overall had greater improvements in self-reported negative cognitions than the control group at post-intervention and two-week follow-up. However, there were no differences between groups in depression or anxiety symptom change. Potential factors contributing to mixed findings are discussed.

The human ortholog of acid-sensing ion channel gene ASIC1a is associated with panic disorder and amygdala structure and function.

BACKGROUND: Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide, possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that carbon dioxide-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid-sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. METHODS: We conducted a case-control analysis (n = 414 PD cases and 846 healthy controls) of ACCN2 single nucleotide polymorphisms and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n = 1048) or task-evoked reactivity to emotional stimuli (n = 103) in healthy individuals. RESULTS: Two single nucleotide polymorphisms at the ACCN2 locus showed evidence of association with PD: rs685012 (odds ratio = 1.32, gene-wise corrected p = .011) and rs10875995 (odds ratio = 1.26, gene-wise corrected p = .046). The association appeared to be stronger when early-onset (age ≤ 20 years) PD cases and when PD cases with prominent respiratory symptoms were compared with controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p = .035) as well as task-evoked amygdala reactivity to fearful and angry faces (p = .0048). CONCLUSIONS: Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to proneness to anxiety. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD.

Academic women faculty: are they finding the mentoring they need?

BACKGROUND: Although women comprise an increasing proportion of US medical school faculty, they are underrepresented at higher ranks. Lack of effective mentoring may contribute to this disparity. We examined the role of academic rank, research focus, parenting, and part-time work on mentoring importance, needs, and gaps. METHODS: In 2009, women faculty members of Harvard Medical School and Harvard School of Dental Medicine were invited by e-mail to participate in a 28-item structured questionnaire. Descriptive statistics and adjusted logistic regressions were used to identify relevant themes. RESULTS: Of the 1179 women faculty who responded, 54% had a mentor, and 72% without a mentor desired mentoring. The most important mentor characteristic identified was availability. Respondents endorsed most mentoring areas as important (range 51%-99%); 52% of respondents identified mentoring gaps (area important and unmet) in developing and achieving career goals and negotiation skills. Interest in mentorship for skills needed for advancement (research and lecturing skills and getting national recognition) was significantly associated with lower rank. Assistant professors were most likely to identify mentoring related to writing and publishing articles, whereas associate professors identified program development/strategic planning as important. Faculty who are parents identified gaps in finding collaborators and balancing work and family life. CONCLUSIONS: This survey identified a desire for both comprehensive and targeted mentoring to address gaps that varied by faculty rank, research focus, parenting, and work time status. Strategies to enhance mentoring should address career stages and include a structured framework for assessing mentoring gaps.

Psychopathology in adolescent offspring of parents with panic disorder, major depression, or both: a 10-year follow-up.

OBJECTIVE: The authors examined the specificity and course of psychiatric disorders from early childhood through adolescence in offspring of parents with confirmed panic disorder and major depressive disorder. METHOD: The authors examined rates of psychiatric disorders at 10-year-follow-up (mean age, 14 years) in four groups: offspring of referred parents with panic and depression (N=137), offspring of referred parents with panic without depression (N=26), offspring of referred parents with depression without panic (N=48), and offspring of nonreferred parents with neither disorder (N=80). Follow-up assessments relied on structured interviews with the adolescents and their mothers; diagnoses were rated present if endorsed by either. RESULTS: Parental panic disorder, independently of parental depression, predicted lifetime rates in offspring of multiple anxiety disorders, panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorder. Parental depression independently predicted offspring bipolar, drug use, and disruptive behavior disorders. Parental panic and depression interacted to predict specific phobia and major depressive disorder. Phobias were elevated in all at-risk groups, and depression was elevated in both offspring groups of parents with depression (with or without panic disorder), with the highest rates in the offspring of parents with depression only. Parental depression independently predicted new onset of depression, parental panic disorder independently predicted new onset of social phobia, and the two interacted to predict new onset of specific phobia and generalized anxiety disorder. CONCLUSIONS: At-risk offspring continue to develop new disorders as they progress through adolescence. These results support the need to screen and monitor the offspring of adults presenting for treatment of panic disorder or major depressive disorder.

Applying cognitive-behavioral therapy for anxiety to the younger child.

Cognitive-behavioral therapy (CBT) protocols for anxiety disorders have been shown to have efficacy with older children and adolescents; however, only recently have investigators begun to adapt and pilot such interventions for younger children. This article reviews data suggesting that even very young children can benefit from CBT for anxiety, discusses some of the necessary developmental adaptations when working with children of preschool and early elementary school age, and reviews studies that have implemented CBT for anxiety disorders with youngsters in this age range. The authors conclude with recommendations for future directions for research in this area.

Cognitive behavioral therapy for 4- to 7-year-old children with anxiety disorders: a randomized clinical trial.

OBJECTIVE: To examine the efficacy of a developmentally appropriate parent-child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4-7 years. DESIGN: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were randomized to a parent-child CBT intervention (n = 34) or a 6-month wait-list condition (n = 30). Children were assessed by interviewers blind to treatment assignment, using structured diagnostic interviews with parents, laboratory assessments of behavioral inhibition, and parent questionnaires. ANALYSIS: Chi-square analyses of outcome rates and linear and ordinal regression of repeated measures, examining time by intervention interactions. RESULTS: The response rate (much or very much improved on the Clinical Global Impression Scale for Anxiety) among 57 completers was 69% versus 32% (CBT vs. controls), p < .01; intent-to-treat: 59% vs. 30%, p = .016. Treated children showed a significantly greater decrease in anxiety disorders (effect size [ES] = .55) and increase in parent-rated coping (ES = .69) than controls, as well as significantly better CGI improvement on social phobia/avoidant disorder (ES = .95), separation anxiety disorder (ES = .82), and specific phobia (ES = .78), but not on generalized anxiety disorder. Results on the Child Behavior Checklist Internalizing scale were not significant and were limited by low return rates. Treatment response was unrelated to age or parental anxiety but was negatively predicted by behavioral inhibition. Gains were maintained at 1-year follow-up. CONCLUSIONS: Results suggest that developmentally modified parent-child CBT may show promise in 4- to 7-year-old children.

Familial and temperamental risk factors for social anxiety disorder.

Social anxiety disorder (SAD) is a common disorder that can lead to significant impairment. In this chapter, the author provides background on the disorder and reviews hypothesized familial and temperamental risk factors. In particular, it highlights the Massachusetts General Hospital (MGH) Longitudinal Study of Children at Risk for Anxiety, now in its fifteenth year, and describes how this study has identified some factors that contribute to risk for SAD.

Anxiety and depressive disorders in offspring at high risk for anxiety: a meta-analysis.

This paper presents a meta-analysis of studies examining prevalence of psychopathology among offspring of anxiety-disordered parents, with the purpose of determining overall risk among these offspring for developing anxiety and depressive disorders. Pooled odds ratios for these disorders among high-risk offspring, compared to offspring of psychiatric and non-psychiatric controls, were calculated. Sixteen papers (including three follow-up studies) were identified, encompassing 1892 offspring (ages 4-25 years). Results revealed that: (1) offspring of parents with anxiety disorders have greater risk for anxiety and depressive disorders than offspring of non-psychiatric controls (ORs=3.91 and 2.67, respectively) and greater risk for anxiety disorders than offspring of psychiatric controls (OR=1.84); (2) offspring of anxious parents have significantly greater odds of having each type of anxiety disorder and MDD compared to offspring of non-psychiatric controls (ORs range from 1.96 to 8.69); and (3) offspring of parents with anxiety only, anxiety plus MDD, and MDD only have similar odds of having anxiety and depressive disorders but significantly higher odds than offspring of parents without disorder. Results suggest that parental anxiety disorders confer significant risk for anxiety and depression in offspring. Additional studies are needed to examine whether there are differences among specific parental anxiety disorders.

Is psychopharmacologic treatment associated with neuropsychological deficits in bipolar youth?

OBJECTIVE: To evaluate the impact of psychopharmacologic treatments on neuropsychological functioning in bipolar youth. METHOD: Participants were 173 children (aged 6-17 years) with DSM-IV bipolar disorder. Participants were comprehensively assessed using structured diagnostic interviews (Schedule for Affective Disorders and Schizophrenia for School-Age Children) and neuropsychological measures (eg, subtests of the Wechsler Intelligence Scale for Children-III and Wechsler Adult Intelligence Scale-III) during the years 2001-2006. Comparisons were made in neuropsychological functioning between medicated and unmedicated youth with bipolar disorder. RESULTS: Children who were treated with mood stabilizers performed significantly (P < .05) more poorly than untreated children on measures of processing speed and working memory. Treatment with other classes of medication, including second-generation antipsychotics, was not significantly associated with neuropsychological impairments. CONCLUSIONS: Treatment with mood stabilizers may be associated with specific neuropsychological impairments. Cognitive side effects may need to be considered in selecting particular psychopharmacologic treatments for children with bipolar disorder.