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Developmental Pathways for Different Subtypes of Early-Onset Bipolarity in Youths

Gabriele Masi, MD; Maria Mucci, MD; Chiara Pfanner, MD; Stefano Berloffa, MD; Angela Magazù, MD; and Giulio Perugi, MD

Published: September 4, 2012

Article Abstract

Objective: Two main patterns of comorbidity have been described in bipolar disorder in children and adolescents: the first including preexisting attention-deficit/hyperactivity disorder (ADHD) and related disruptive behavior disorders and the second including anxiety disorders, namely, the association of co-occurring multiple anxiety disorders, usually predating the onset of bipolarity. This study was aimed at exploring whether ADHD and multiple anxiety disorders may exhibit different pathways to specific bipolar phenotypes.

Method: We compared 49 youths (7 to 18 years) with bipolar disorder + ADHD without anxiety, 76 youths with bipolar disorder + multiple anxiety disorders without ADHD, and 52 youths with bipolar disorder without ADHD or multiple anxiety disorders who were referred to a third-level hospital and diagnosed according to DSM-IV-TR in the period 2005-2011. Subjects were evaluated for current and lifetime Axis I psychiatric disorders by using a structured clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version) and followed up for at least 6 months.

Results: Compared to both patients with bipolar disorder + multiple anxiety disorders and patients with bipolar disorder without ADHD and multiple anxiety disorders, patients with bipolar disorder + ADHD without anxiety were more frequently male, were younger, had an earlier onset of bipolar disorder, had a prevalent chronic course and irritable mood, were more likely to present with a bipolar disorder not otherwise specified diagnosis, had a greater clinical severity and functional impairment, had a manic/mixed index episode, had a higher risk of conduct disorder, and were more resistant to treatments, according to the CGI-Improvement scores (P<.0001). Patients with bipolar disorder + multiple anxiety disorders were similar to those with bipolar disorder without ADHD or multiple anxiety disorders, except for a higher rate of diagnosis of bipolar II disorder, more use of antidepressants, and less use of atypical antipsychotics.

Conclusions: The presence of comorbid ADHD versus anxiety disorders is indicative of fundamental differences in the phenomenology of bipolar disorder in youth. While ADHD prior to bipolar disorder is associated with a specific bipolar phenotype, bipolar patients with multiple anxiety disorders are similar to “typical” bipolar patients.

J Clin Psychiatry

Submitted: November 1, 2011; accepted March 28, 2012.

Online ahead of print: September 4, 2012 (doi:10.4088/JCP.11m07504).

Corresponding author: Gabriele Masi, MD, IRCCS Stella Maris, Via dei Giacinti 2, 56018 Calambrone (Pisa), Italy (

Volume: 73

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