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. K E Y W O R D Sbipolar disorder, child, pediatric, subthreshold | INTRODUC TI ONAs pediatric bipolar (BP) disorder tends to evolve over time, some youth may present to clinical attention with insufficient symptoms to fulfill full diagnostic criteria for a diagnosis of BP disorder.However, while much is known about full threshold pediatric BP disorder, little is known about subthreshold forms of pediatric BP disorder.

Objectives To examine the validity of subthreshold pediatric bipolar-I (BP-I) disorder, we compared the familial risk for BP-I disorder in child probands with full BP-I disorder, subthreshold BP-I disorder, ADHD, and non-ADHD/non-bipolar disorder controls. Methods Probands were youth ages 6–17 meeting criteria for BP-I disorder, full (N=239) or subthreshold (N=43), and their first degree relatives (N=687 and N=120, respectively). Comparators were youth with ADHD (N=162), controls (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 KSADS-E and SCID structured diagnostic interviews. We analyzed rates of bipolar disorder using multinomial logistic regression. Results Rates of full bipolar-I disorder significantly differed between the four groups (χ23 = 32.72, p<0.001): relatives of full BP-I and relatives of subthreshold BP-I probands had significantly higher rates of full BP-I disorder 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 (MDD) compared to relatives of control probands. Conclusions Our results showed that youth with subthreshold BP-I disorder had similarly elevated risk for BP-I disorder and MDD in first-degree relatives as youth with full BP-I disorder. These findings support the diagnostic continuity between subsyndromal and fully syndromatic states of pediatric BP-I disorder.

of bipolar I disorder and conduct disorder: a familial risk analysis Objective: To investigate the association between pediatric bipolar I (BP-I) disorder and conduct disorder (CD) using familial risk analysis. Method: We compared diagnoses in relatives of youth in four proband groups defined by the presence or absence of BP-I and CD: (1) probands with neither CD nor BP-I (probands: N = 550; relatives: N = 1656), (2) probands with CD and without BP-I (probands: N = 40; relatives: N = 127), (3) probands with BP-I and without CD (probands: N = 197; relatives: N = 579), and (4) probands with both CD and BP-I (probands: N = 176; relatives: N = 488). All subjects were evaluated with structured diagnostic interviews, and diagnoses of relatives were made blind to the diagnoses of probands. Results: Relatives of probands with BP-I disorder had high rates of BP-I, and relatives of probands with CD had high rates of CD irrespective of the comorbidity with the other disorder. Relatives of probands with the combined condition of CD and BP-I had high rates of the combined condition. Conclusion: The finding of cosegregation between BP-I disorder and CD is consistent with the hypothesis that the combined condition represents a distinct subtype of either disorder. Significant outcomes• The findings support the hypothesis that comorbid BP-I and CD may represent a distinct familial subtype of either BP-I disorder or CD. This information has high predictive value for future clinicians.

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