Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania.

BACKGROUND: Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder. METHODS: We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression. RESULTS: This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint. CONCLUSIONS: These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.

Development and Implementation of a Suicide Prevention Checklist to Create a Safe Environment.

BACKGROUND: An increasing number of patients are admitted to general hospitals for injuries sustained in suicide attempts and for assessment of their ongoing risk for suicide. However, clinical staff may lack knowledge and expertise in the provision of a safe environment for potentially suicidal patients. OBJECTIVE: In an effort to follow the Joint Commission's recommendations on the care of suicidal patients, a Suicide Prevention Interdisciplinary Task Force was created. The task force sought to design and implement a suicide checklist that would facilitate creation of a safe environment for potentially suicidal inpatients on nonpsychiatric units in a general hospital. METHODS: We describe the development and implementation of a Care of the Suicide and Self-Injury Patient Checklist and report on data derived from incident reports related to self-harm/suicide attempts over a 4-year period. We also report results of a Research Electronic Data Capture survey of nurses' feedback on the checklist. RESULTS: After implementation of the Care of the Suicide and Self-Injury Patient Checklist, a total of 47 incidents of patient self-injury were reported over 4 years on nonpsychiatric inpatient units at a large general hospital; only three sustained permanent or serious harm. The Research Electronic Data Capture survey revealed that 88% of responding nurses believed that the Care of the Suicide and Self-Injury Patient Checklist guided creation of a safe environment and 90% believed that it supported consistent practice. CONCLUSIONS: The Care of the Suicide and Self-Injury Patient Checklist contributed to the creation of a safe environment while caring for potentially suicidal patients on nonpsychiatric inpatient units and guided clinicians on the management of potentially self-injurious individuals.

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.

High Correspondence Between Child Behavior Checklist Rule Breaking Behavior Scale with Conduct Disorder in Males and Females.

This study investigated the diagnostic utility of the Child Behavior Checklist (CBCL) Rule-Breaking Behavior scale to identify children of both sexes with conduct disorder (CD). Participants were derived from four independent datasets of children with and without attention deficit hyperactivity disorder and bipolar-I disorder of both sexes. Participants had structured diagnostic interviews with raters blinded to subject ascertainment status. Receiver operating characteristic (ROC) curves were used to examine the scale's ability to identify children with and without CD. The sample consisted of 674 participants (mean age of 11.7 ± 3.3 years, 57% male, 94% Caucasian). The interaction to test if CBCL Rule-Breaking Behavior scores identified males and females with CD differently was not significant, thus we performed ROC analysis in the combined group. The ROC analysis of the scale yielded an area under the curve of 0.9. A score of ≥ 60 on the scale correctly classified 82% of participants with CD with 85% sensitivity, 81% specificity, 48% positive predictive value, 96% negative predictive value. The CBCL Rule-Breaking Behavior scale was an efficient tool to identify children with CD.

The morbidity of subthreshold pediatric bipolar disorder: A systematic literature review and meta-analysis.

OBJECTIVE: The objective of this study was to evaluate the morbidity of subthreshold pediatric bipolar (BP) disorder. METHODS: We performed a systematic literature search in November 2017 and included studies examining the morbidity of pediatric subthreshold BP. Extracted outcomes included functional impairment, severity of mood symptoms, psychiatric comorbidities, suicidal ideation and behaviors, and mental health treatment. We used meta-analysis to compute the pooled standardized mean difference (SMD) for continuous measures and the pooled risk ratio (RR) for binary measures between two paired groups: subthreshold pediatric BP vs controls and subthreshold pediatric BP vs pediatric BP-I. RESULTS: Eleven papers, consisting of seven datasets, were included. We compared subthreshold pediatric BP (N = 244) to non-BP controls (N = 1125) and subthreshold pediatric BP (N = 643) to pediatric BP-I (N = 942). Subthreshold pediatric BP was associated with greater functional impairment (SMD = 0.61, CI 0.25-0.97), greater severity of mood symptomatology (mania: SMD = 1.88, CI 1.38-2.38; depression: SMD = 0.66, CI 0.52-0.80), higher rates of disruptive behavior (RR = 1.75, CI 1.17-2.62), mood (RR = 1.78, CI 1.29-2.79) and substance use (RR = 2.27, CI 1.23-4.21) disorders, and higher rates of suicidal ideation and attempts (RR = 7.66, CI 1.71-34.33) compared to controls. Pediatric BP-I was associated with greater functional impairment, greater severity of manic symptoms, higher rates of suicidal ideation and attempts, and higher rates of mental health treatment compared to subthreshold pediatric BP. There were no differences between full and subthreshold cases in the severity of depressive symptoms or rates of comorbid disorders. CONCLUSIONS: Subthreshold pediatric BP disorder is an identifiable morbid condition associated with significant functional impairment including psychiatric comorbidities and high rates of suicidality.

Similar familial underpinnings for full and subsyndromal pediatric bipolar disorder: A familial risk analysis.

OBJECTIVES: To examine the validity of subthreshold pediatric bipolar I disorder (BP-I), we compared the familial risk for BP-I in the child probands who had either full BP-I, subthreshold BP-I, ADHD, or were controls that neither had ADHD nor bipolar disorder. METHODS: BP-I probands were youth aged 6-17 years meeting criteria for BP-I, full (N=239) or subthreshold (N=43), and also included were their first-degree relatives (N=687 and N=120, respectively). Comparators were youth with ADHD (N=162), controls without ADHD or bipolar disorder (N=136), and their first-degree relatives (N=511 and N=411, respectively). We randomly selected 162 non-bipolar ADHD probands and 136 non-bipolar, non-ADHD control probands of similar age and sex distribution to the BP-I probands from our case-control ADHD family studies. Psychiatric assessments were made by trained psychometricians using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children Epidemiological Version (KSADS-E) and Structured Clinical Interview for DSM-IV (SCID) structured diagnostic interviews. We analyzed rates of bipolar disorder using multinomial logistic regression. RESULTS: Rates of full BP-I significantly differed between the four groups (χ23 =32.72, P<.001): relatives of full BP-I probands and relatives of subthreshold BP-I probands had significantly higher rates of full BP-I than relatives of ADHD probands and relatives of control probands. Relatives of full BP-I, subthreshold BP-I, and ADHD probands also had significantly higher rates of major depressive disorder compared to relatives of control probands. CONCLUSIONS: Our results showed that youth with subthreshold BP-I had similarly elevated risk for BP-I and major depressive disorder in first-degree relatives as youth with full BP-I. These findings support the diagnostic continuity between subsyndromal and fully syndromatic states of pediatric BP-I disorder.

The International Society for Bipolar Disorders Task Force report on pediatric bipolar disorder: Knowledge to date and directions for future research.

OBJECTIVES: Over the past two decades, there has been tremendous growth in research regarding bipolar disorder (BD) among children and adolescents (ie, pediatric BD [PBD]). The primary purpose of this article is to distill the extant literature, dispel myths or exaggerated assertions in the field, and disseminate clinically relevant findings. METHODS: An international group of experts completed a selective review of the literature, emphasizing areas of consensus, identifying limitations and gaps in the literature, and highlighting future directions to mitigate these gaps. RESULTS: Substantial, and increasingly international, research has accumulated regarding the phenomenology, differential diagnosis, course, treatment, and neurobiology of PBD. Prior division around the role of irritability and of screening tools in diagnosis has largely abated. Gold-standard pharmacologic trials inform treatment of manic/mixed episodes, whereas fewer data address bipolar depression and maintenance/continuation treatment. Adjunctive psychosocial treatment provides a forum for psychoeducation and targets primarily depressive symptoms. Numerous neurocognitive and neuroimaging studies, and increasing peripheral biomarker studies, largely converge with prior findings from adults with BD. CONCLUSIONS: As data have accumulated and controversy has dissipated, the field has moved past existential questions about PBD toward defining and pursuing pressing clinical and scientific priorities that remain. The overall body of evidence supports the position that perceptions about marked international (US vs elsewhere) and developmental (pediatric vs adult) differences have been overstated, although additional research on these topics is warranted. Traction toward improved outcomes will be supported by continued emphasis on pathophysiology and novel therapeutics.

A Prospective Open-Label Trial of Memantine Hydrochloride for the Treatment of Social Deficits in Intellectually Capable Adults With Autism Spectrum Disorder.

This prospective 12-week open-label trial evaluates the tolerability and efficacy of memantine hydrochloride for the treatment of core social and cognitive deficits in adults with high-functioning autism spectrum disorder (ASD). Measures for assessment of therapeutic response included the Social Responsiveness Scale-Adult Research Version (SRS-A), disorder-specific Clinical Global Impression scales, Behavior Rating Inventory of Executive Functioning-Adult Self-Report, Diagnostic Analysis of Nonverbal Accuracy Scale, and Cambridge Neuropsychological Test Automated Battery. Eighteen adults (mean age, 28 ± 9.5 years) with high-functioning ASD (SRS-A raw score, 99 ± 17) were treated with memantine (mean dose, 19.7 ± 1.2 mg/d; range, 15-20 mg), and 17 (94%) completed the trial. Treatment with memantine was associated with significant reduction on informant-rated (SRS-A, -28 ± 25; P < 0.001) and clinician-rated (Clinical Global Impression-Improvement subscale ≤2, 83%) measures of autism severity. In addition, memantine treatment was associated with significant improvement in ADHD and anxiety symptom severity. Significant improvement was noted in nonverbal communication on the Diagnostic Analysis of Nonverbal Accuracy Scale test and in executive function per self-report (Behavior Rating Inventory of Executive Functioning-Adult Self-Report Global Executive Composite, -6 ± 8.8; P < 0.015) and neuropsychological assessments (Cambridge Neuropsychological Test Automated Battery). Memantine treatment was generally well tolerated and was not associated with any serious adverse events. Treatment with memantine appears to be beneficial for the treatment of ASD and associated psychopathology and cognitive dysfunction in intellectually capable adults. Future placebo-controlled trials are warranted.

Stimulant Treatment and Potential Adverse Outcomes in Pediatric Populations With Bipolar Disorder: A Systematic Review of the Literature.

OBJECTIVE: To explore outcomes of stimulant treatment for ADHD in pediatric populations with particular attention to bipolar disorder (BPD). METHOD: We conducted a literature search of PubMed articles published prior to August 25, 2022 that focused on BPD, mania, and psychosis prior to, or as result of, stimulant treatment. We excluded studies: (1) unrelated to stimulants, (2) general stimulant research, (3) articles older than 40 years, (4) study protocols, or (5) case reports. RESULTS: A total of 11 articles met all inclusion/exclusion criteria. Some reports found stimulant treatment safe and well-tolerated in children with comorbid BPD and ADHD. Others found evidence of treatment-emergent mania (TEM), discontinuation, and other adverse events with stimulant treatment. CONCLUSION: Poor outcomes associated with stimulant treatment in pediatric populations with BPD necessitate work to identify patients at risk of serious stimulant-related adverse events. Our results were limited by automated search filters and a pediatric, primarily male sample.

In Memoriam: Professor Joseph Biederman's Contributions to Child and Adolescent Psychiatry.

OBJECTIVE: To provide an overview of Joe Biederman's contributions to child and adolescent psychiatry. METHOD: Nine colleagues described his contributions to: psychopharmacology, comorbidity and genetics, pediatric bipolar disorder, autism spectrum disorders, Tourette's and tic disorders, clinical and neuro biomarkers for pediatric mood disorders, executive functioning, and adult ADHD. RESULTS: Joe Biederman left us with many concrete indicators of his contributions to child and adolescent psychiatry. He set up the world's first pediatric psychopharmacology clinic and clinical research program in child adolescent psychiatry. As a young faculty member he began a research program that led to many awards and eventual promotion to full professor at Harvard Medical School. He was for many years the most highly cited researcher in ADHD. He achieved this while maintaining a full clinical load and was widely respected for his clinical acumen. CONCLUSION: The world is a better place because Joe Biederman was here.

Magnetic resonance spectroscopy study of the glutamatergic system in adolescent males with high-functioning autistic disorder: a pilot study at 4T.

The pilot study aimed at examining the neural glutamatergic activity in autism. Seven adolescent males (mean age: 14 ± 1.8; age range: 12-17 years) with intact intellectual capacity (mean IQ: 108 ± 14.26; IQ range: 85-127) suffering from autistic disorder and an equal number of age- and sex-matched healthy controls underwent a two-dimensional magnetic resonance spectroscopy scan at 4T. Results indicated significantly high glutamate (Glu) levels in the anterior cingulate cortex of autistic disorder versus control subjects (paired t test p = 0.01) and a trend for lower Glu in the right medial temporal lobe, which was not statistically different between the groups (paired t test p = 0.06). These preliminary findings support the glutamatergic dysregulation hypothesis in autism and need to be replicated in a larger sample.

Growth Trajectories in Stimulant Treated Children and Adolescents: A Qualitative Review of the Literature from Comprehensive Datasets and Registries.

Objective: Attention-deficit/hyperactivity disorder (ADHD) treatment with stimulant products has been shown to be safe and effective; however, there are remaining concerns about their possible adverse effects on growth trajectories. We conducted a systematic review of the extant literature derived from ecologically valid databases and registries to assess the body of knowledge about the effects of stimulants on growth trajectories in naturalistic samples. Methods: Using PubMed and PsycINFO, we searched for articles published before February 8, 2023 that focused on growth findings associated with stimulant treatment in pediatric ADHD from comprehensive datasets derived from naturalistic population studies. Results: Of the 1070 articles initially identified, 12 met all inclusion criteria. Sample sizes ranged from 157 to 163,820 youths. Seven of 10 articles examining height found significant decreases in height associated with chronic stimulant treatment that normalized over time in 2 studies. Three articles found no significant association between stimulant treatment and height. No clear associations were identified between cumulative duration and dose of stimulant treatment and adult height. All articles examining weight and six of eight articles examining body mass index (BMI) found significant initial decreases that tended to normalize then increase over time. Longer duration of stimulant medication use was predominantly associated with significant weight and BMI reductions. The effects of stimulant dose on weight and BMI were mostly weak and clinically insignificant. Most studies found no significant association between age at start of stimulant treatment and change in height, weight, or BMI. Most studies did not find significant sex effects in relation to growth parameters. Conclusions: This review of ecologically informative samples revealed that the effects of stimulant treatment on growth trajectories are mainly small and transient. These effects seem to be clinically insignificant for most youth with ADHD who receive stimulant treatment from childhood onto adolescence and adulthood.

Examining the clinical correlates of conduct disorder in youth with bipolar disorder.

BACKGROUND: Conduct Disorder (CD) is highly comorbid with Bipolar Disorder (BP) and this comorbidity is associated with high morbidity and dysfunction. We sought to better understand the clinical characteristics and familiality of comorbid BP + CD by examining children with BP with and without co-morbid CD. METHODS: 357 subjects with BP were derived from two independent datasets of youth with and without BP. All subjects were evaluated with structured diagnostic interviews, the Child Behavior Checklist (CBCL), and neuropsychological testing. We stratified the sample of subjects with BP by the presence or absence of CD and compared the two groups on measures of psychopathology, school functioning, and neurocognitive functioning. First-degree relatives of subjects with BP +/- CD were compared on rates of psychopathology in relatives. RESULTS: Subjects with BP + CD compared to BP without CD had significantly more impaired scores on the CBCL Aggressive Behavior (p < 0.001), Attention Problems (p = 0.002), Rule-Breaking Behavior (p < 0.001), Social Problems (p < 0.001), Withdrawn/Depressed clinical scales (p = 0.005), the Externalizing Problems (p < 0.001), and Total Problems composite scales(p < 0.001). Subjects with BP + CD had significantly higher rates of oppositional defiant disorder (ODD) (p = 0.002), any SUD (p < 0.001), and cigarette smoking (p = 0.001). First-degree relatives of subjects with BP + CD had significantly higher rates of CD/ODD/ASPD and cigarette smoking compared to first-degree relatives of subjects without CD. LIMITATIONS: The generalization of our findings was limited due to a largely homogeneous sample and no CD only comparison group. CONCLUSIONS: Given the deleterious outcomes associated with comorbid BP + CD, further efforts in identification and treatment are necessary.

Are obstetrical, perinatal, and infantile difficulties associated with pediatric bipolar disorder?

OBJECTIVES: Despite increasing acknowledgement of bipolar disorder (BD) in childhood, there is a paucity of literature that has investigated obstetrical, perinatal, and infantile difficulties and their potential link with BD. To this end, we examined difficulties during delivery, immediate post-birth, and infancy and the association with BD in childhood. METHODS: From two similarly designed, ongoing, longitudinal, case-control family studies of pediatric BD (N = 327 families), we analyzed 338 children and adolescents [mean (± standard deviation) age: 12.00 ± 3.37 years]. We stratified them into three groups: healthy controls (N = 98), BD probands (N = 120), and their non-affected siblings (N = 120). All families were comprehensively assessed with a structured psychiatric diagnostic interview for psychopathology and substance use. Mothers were directly questioned regarding the pregnancy, delivery, and infancy difficulties that occurred with each child using a module from the Diagnostic Interview for Children and Adolescents-Parent Version (DICA-P). RESULTS: Mothers of BD subjects were more likely to report difficulties during infancy than mothers of controls [odds ratio (95% confidence interval) = 6.6 (3.0, 14.6)]. Specifically, children with BD were more likely to have been reported as a stiffened infant [7.2 (1.1, 47.1)] and more likely to have experienced 'other' infantile difficulties [including acting colicky; 4.9 (1.3, 18.8)] compared to controls. We found no significant differences between groups in regards to obstetrical or perinatal difficulties (all p values > 0.05). CONCLUSIONS: While our results add to previous literature on obstetrical and perinatal difficulties and BD, they also highlight characteristics in infancy that may be prognostic indicators for pediatric BD.

Examining the association between stimulant treatment and cognitive outcomes across the life cycle of adults with attention-deficit/hyperactivity disorder: a controlled cross-sectional study.

Few studies have evaluated the effects of stimulants on cognition in adults with attention-deficit/hyperactivity disorder (ADHD). We evaluated the impact of stimulant treatment on neurocognition in a cross-sectional sample of adults with ADHD. Comparisons were made between adults with ADHD who received (n = 105) and who had never received pharmacotherapy (n = 116) and 146 controls. The subjects were assessed cross-sectionally using a structured diagnostic interview and a neurocognitive battery. We modeled cognitive measures as a function of age and group status using linear regression. Treated ADHD subjects had statistically significantly better scores on measures of IQ than did untreated ones. The treated group also had better (not statistically significant) scores on neuropsychological measures. The direction of the effects of stimulant on neurocognition suggests that either good cognitive functioning may be a determinant of seeking treatment or that stimulant treatment may improve cognition in adults with ADHD. However, this does not indicate a clear causal relationship.

A systematic review of the literature on telepsychiatry for bipolar disorder.

OBJECTIVE: Bipolar (BP) disorder is a highly morbid disorder that is often misdiagnosed or undiagnosed and affects a large number of adults and children. Due to the coronavirus disease 2019 public health emergency stay at home orders, most outpatient mental health care was provided via telepsychiatry, and the many benefits of virtual care ensure that this will continue as an ongoing practice. The main aim of this review was to investigate what is currently known about the use of telepsychiatry services in the diagnosis and treatment of BP disorder across the lifespan. METHOD: A systematic literature review assessing the use of telepsychiatry in BP disorder was conducted in PubMed, PsychINFO, and Medline. RESULTS: Six articles were included in the final review. All included articles assessed populations aged 17 years or older. The literature indicates that BP disorder was addressed in telepsychiatry services at a similar rate as in-person services, reliable diagnoses can be made using remote interviews, satisfaction rates are comparable to in-person services, telepsychiatry services are able to reach and impact patients with BP disorder, are sustainable, and patient outcomes can improve using a telepsychiatry intervention. CONCLUSIONS: Given the morbidity of BP disorder, the research addressing the telepsychiatry diagnosis and treatment of BP disorder is sparse, with only emerging evidence of its reliability, effectiveness, and acceptance. There is no research assessing the safety and efficacy of telepsychiatry in pediatric populations with BP disorder. Given the morbidity associated with BP disorder at any age, further research is needed to determine how to safely and effectively incorporate telepsychiatry into clinical care for BP adult and pediatric patients.

A Randomized, Double-Blind, Controlled Clinical Trial of Omega-3 Fatty Acids and Inositol as Monotherapies and in Combination for the Treatment of Pediatric Bipolar Spectrum Disorder in Children Age 5-12.

Objectives: The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (FAs) and inositol alone and in combination for the treatment of pediatric bipolar (BP) spectrum disorder in young children. Methods: Participants were male and female children ages 5-12 meeting DSM-IV diagnostic criteria for a BP spectrum disorder and displaying mixed, manic, or hypomanic symptoms without psychotic features at the time of evaluation. Results: Participants concomitantly taking psychotropic medication were excluded from efficacy analyses. There were significant reductions in YMRS and HDRS mean scores in the inositol and combination treatment groups (all p < 0.05) and in CDRS mean scores in the combination treatment group (p < 0.001), with the largest changes seen in the combination group. Those receiving the combination treatment had the highest rates of antimanic and antidepressant response. The odds ratios for the combination group compared to the omega-3 FAs and inositol groups were clinically meaningful (ORs ≥2) for 50% improvement on the YMRS, normalization of the YMRS (score <12) (vs. inositol group only), 50% improvement on the HDRS, 50% improvement on CDRS (vs. omega-3 FAs group only), and CGI-I Mania, CGI-I MDD, and CGI-I Anxiety scores <2. Conclusion: The antimanic and antidepressant effects of the combination treatment of omega-3 FAs and inositol were consistently superior to either treatment used alone. This combination may offer a safe and effective alternative or augmenting treatment for youth with BP spectrum disorder, but more work is needed to confirm the statistical significance of this finding.

Can pediatric bipolar disorder be successfully treated when comorbid with conduct disorder? A secondary analysis of clinical trials of risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole.

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 = 89) met criteria for comorbid CD. The antimanic effects observed did not significantly differ between BP youths with and without comorbid CD, as measured either by a reduction in Young Mania Rating Scale (YMRS) ⩾ 30% or Clinical Global Impression (CGI)-Improvement ⩽ 2 (p = 0.23), or by the more stringent definition of a reduction in YMRS ⩾ 50% (p = 0.61). CONCLUSION: Pediatric BP can be effectively treated with the abovementioned medications in the context of comorbid CD. Based on previous research showing that remission of BP is associated with remission of CD, if confirmed, these findings raise the possibility that antimanic treatment of youth with BP comorbid with CD could have secondary benefits in mitigating the morbidity associated with CD. This is a pilot scale finding, the results of which are promising and should be confirmed by larger and long-term follow-up studies.

Disentangling the heterogeneity of emotional dysregulation in referred youth using the Child Behavior Checklist attending to age and sex effects.

PURPOSE: To assess the utility of the Child Behavior Checklist (CBCL) to identify meaningful subtypes of emotional dysregulation in an outpatient pediatric psychiatry clinic. METHODS: The sample consisted of 417 newly referred youth 6-18 years of age. Parents completed the CBCL and rating scales measuring executive function deficits, social functioning, and quality of life. Patients were stratified into subtypes of emotional dysregulation and compared on clinical correlates based on the A-A-A profile consisting of the CBCL Anxious/Depressed, Aggressive Behavior, and Attention Problems (A-A-A) scales. RESULTS: 67% of youth had emotional dysregulation (CBCL A-A-A T-score ≥ 180) and of these, 39% had a positive CBCL-Bipolar (BP) profile (A-A-A T-score ≥ 210), 24% had depression without the BP profile (CBCL Anxious/Depressed and/or Withdrawn/Depressed T-scores ≥70 and A-A-A T-score ≥ 180 and ã€ˆ210), and 37% had emotional impulsivity (A-A-A T-score ≥ 180 and <210) with normal CBCL Anxious/Depressed and Withdrawn/Depressed T-scores. Patients with the CBCL-BP profile were significantly more impaired on all measures of social and executive functioning compared to the other two groups. LIMITATIONS: Since our findings relied on the CBCL, other instruments may have led to different results. Because we included youth from a single clinic, largely Caucasian and referred, our findings may not generalize to other ethnic groups or settings. CONCLUSIONS: The CBCL can aid in the identification of subtypes of emotional dysregulation affecting youth seeking mental health services.