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.

A Familial Risk Analysis of Emotional Dysregulation: A Controlled Study.

OBJECTIVE: Children with deficits in emotional regulation operationalized by scores on the Child Behavior Checklist (CBCL) Attention Problems, Aggressive Behavior, and Anxious-Depressed subscales are more likely than others to manifest adverse outcomes. However, the transmission of this profile has not been well studied. The main aim of this study was to investigate the familiality of this profile. METHOD: Participants were youth probands with bipolar I (BP-I) disorder ( N = 140), ADHD ( N = 83), and controls ( N = 117) and their siblings. Based on the CBCL emotional dysregulation profile, we classified children with severe emotional dysregulation (aggregate cut-off score ≥210) and emotional dysregulation (aggregate cut-off score ≥ 180 and <210). RESULTS: Emotional dysregulation profile scores correlated positively between probands and siblings. CONCLUSION: Youth with emotional dysregulation are at increased risk to have siblings with similar deficits, suggesting that emotional dysregulation runs in families.

Further evidence that severe scores in the aggression/anxiety-depression/attention subscales of child behavior checklist (severe dysregulation profile) can screen for bipolar disorder symptomatology: a conditional probability analysis.

BACKGROUND: Previous work shows that children with high scores (2SD, combined score≥210) on the Attention Problems, Aggressive Behavior, and Anxious-Depressed (A-A-A) subscales of the Child Behavior Checklist (CBCL) are more likely than other children to meet criteria for bipolar (BP)-I disorder. However, the utility of this profile as a screening tool has remained unclear. METHODS: We compared 140 patients with pediatric BP-I disorder, 83 with attention deficit hyperactivity disorder (ADHD), and 114 control subjects. We defined the CBCL-Severe Dysregulation profile as an aggregate cutoff score of ≥210 on the A-A-A scales. Patients were assessed with structured diagnostic interviews and functional measures. RESULTS: Patients with BP-I disorder were significantly more likely than both control subjects (Odds Ratio [OR]: 173.2; 95% Confidence Interval [CI], 21.2 to 1413.8; P<0.001) and those with ADHD (OR: 14.6; 95% CI, 6.2 to 34.3; P<0.001) to have a positive CBCL-Severe Dysregulation profile. Receiver Operating Characteristics analyses showed that the area under the curve for this profile comparing children with BP-I disorder against control subjects and those with ADHD was 99% and 85%, respectively. The corresponding positive predictive values for this profile were 99% and 92% with false positive rates of <0.2% and 8% for the comparisons with control subjects and patients with ADHD, respectively. LIMITATIONS: Non-clinician raters administered structured diagnostic interviews, and the sample was referred and largely Caucasian. CONCLUSIONS: The CBCL-Severe Dysregulation profile can be useful as a screen for BP-I disorder in children in clinical practice.

Personal and familial correlates of bipolar (BP)-I disorder in children with a diagnosis of BP-I disorder with a positive child behavior checklist (CBCL)-severe dysregulation profile: a controlled study.

BACKGROUND: Although the DSM-IV provides explicit criteria for the diagnosis of BP-I disorder, this is a complex diagnosis that requires high levels of clinical expertise. Previous work shows children with a unique profile of the CBCL of high scores (2SD) on the attention problems (AP), aggressive behavior (AGG), and anxious-depressed (AD) (A-A-A) subscales are more likely than other children to meet criteria for BP-I disorder in both epidemiological and clinical samples. However, since not all BP-I disorder children have a positive profile questions remain as to its informativeness, particularly in the absence of an expert diagnostician. METHODS: Analyses were conducted comparing personal and familial correlates of BP-I disorder in 140 youth with a structured interview and an expert clinician based DSM-IV diagnosis of BP-I disorder with (N=80) and without (N=60) a positive CBCL- Severe Dysregulation profile, and 129 controls of similar age and sex without ADHD or a mood disorder. Subjects were comprehensively assessed with structured diagnostic interviews and wide range of functional measures. We defined the CBCL-severe dysregulation profile as an aggregate cut-off score of ≥ 210 on the A-A-A scales. RESULTS: BP-I probands with and without a positive CBCL-severe dysregulation profile significantly differed from Controls in patterns of psychiatric comorbidity, psychosocial and psychoeducational dysfunction, and cognitive deficits, as well as in their risk for BP-I disorder in first degree relatives. LIMITATIONS: Because the sample was referred and largely Caucasian, findings may not generalize to community samples and other ethnic groups. CONCLUSION: A positive CBCL-severe dysregulation profile identifies a severe subgroup of BP-I disorder youth.

Pharmacologic treatments for pediatric bipolar disorder: a review and meta-analysis.

OBJECTIVE: A growing body of literature has documented pediatric bipolar disorder to be a severely impairing form of psychopathology. However, concerns remain as to the inadequacy of the extant literature on its pharmacotherapy. Furthermore, treatment studies have not been systematically reviewed for treatment effects on core and associated symptoms. Thus, a systematic evaluation and synthesis of the available literature on the efficacy of antimanic pharmacotherapy for pediatric bipolar disorder on symptoms of mania, depression, and attention-deficit/hyperactivity disorder was undertaken. METHOD: A systematic search was conducted through PubMed from 1989 through 2010 for open-label and randomized controlled trials published in English on the pharmacotherapy of pediatric mania. RESULTS: There have been 46 open-label (n = 29) and randomized (n = 17) clinical trials of antimanic agents in pediatric bipolar disorder encompassing 2,666 subjects that evaluated a range of therapeutic agents, including traditional mood stabilizers, other anticonvulsants, second-generation antipsychotics, and naturopathic compounds. This literature has documented that the available armamentarium has different levels of efficacy in the treatment of pediatric mania. Because all psychotropic classes are associated with important adverse effects, a careful risk-benefit analysis is warranted when initiating pharmacologic treatment with any of these compounds. In the limited data available, the effects of antimanic agents on depression and symptoms of attention-deficit/hyperactivity disorder have been, in general, modest. Few studies have evaluated the effects of antimanic agents in children younger than 10 years. CONCLUSIONS: A substantial body of scientific literature has evaluated the safety and efficacy of various medicines and drug classes in the treatment of mania in pediatric bipolar disorder. More work is needed to assess the safety and efficacy of psychotropic drugs in children younger than 10 years, to further evaluate the efficacy of naturopathic compounds, and to further evaluate the effects of antimanic treatments for the management of depression and attention-deficit/hyperactivity disorder.