Clinical and research implications of panic-bipolar comorbidity in children and adolescents Gabriele Masi a, ⁎ , Giulio Perugi b,c , Stefania Millepiedi a , Cristina Toni c , Maria Mucci a , Nicoletta Bertini a , Chiara Pfanner a , Stefano Berloffa a , Cinzia Pari a , Kareen Akiskal d , Hagop S. Akiskal d,e a IRCCS Stella Maris, Scientific Institute Child Neurology and Psychiatry, Calambrone, Pisa, Italy b Department of Psychiatry, Neurobiology, Pharmacology and Biotechnologies, Psychiatry Section, University of Pisa, Pisa, Italy c Institute of Behavioral Sciences “G. De Lisio”, Carrara-Pisa, Italy d Union of Depressive and Manic-Depressive Associations, Rennes, France e International Mood Center, Department of Psychiatry, University of California at San Diego, and Veterans Administration Medical Center, La Jolla, CA, USA Received 26 January 2006; received in revised form 30 June 2006; accepted 24 October 2006 Abstract A substantial portion of patients with juvenile bipolar disorder (BD) have a comorbid panic disorder (PD). The aim of our study was to analyze the cross-sectional and longitudinal implications of such comorbidity in children and adolescents with BD. The sample comprised 224 referred children and adolescents with BD, 140 males (62.5%) and 84 females (37.5%), mean age 13.8±2.8 years, diagnosed with a clinical interview (K-SADS-PL), and followed up naturalistically for 6 months. Fifty-one BD patients (22.8%) had a lifetime diagnosis of comorbid PD. Subjects with BD + PD and those without BD (BD-noPD) did not differ according to index age, age at onset of BD and bipolar phenotype (episodic vs. continuous course, irritable vs. elated mood). BD + PD was more frequent in females, was less severe at baseline according to the Clinical Global Impression severity score, and was more frequently associated with BD type 2. Moreover, BD+PD presented higher rates of comorbid anxiety disorders (namely separation anxiety disorder) and lower rates of externalizing disorders, namely attention deficit disorder (ADHD) than BD-noPD. However, this different pattern of externalizing comorbidity did not affect severity and improvement. Our findings suggest that PD is frequently comorbid in juvenile BD and can influence severity, pattern of comorbidity and course of BD. The data are compatible with the hypothesis that Panic-BD and ADHD-BD might represent distinct developmental pathways of bipolar disorder. Further research on this question may prove rewarding. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Bipolar disorder; Panic disorder; Anxiety; Disruptive behavior disorders; Children; Adolescents 1. Introduction Anxiety comorbidity is a frequent marker of early- onset bipolarity, as indicated by systematic observations in children and adolescents with bipolar disorder (BD) (Masi et al., 2001; Johnson et al., 2000; Tillman et al., 2003), as well as by the psychopathological evaluation Psychiatry Research 153 (2007) 47 – 54 www.elsevier.com/locate/psychres ⁎ Corresponding author. IRCCS Stella Maris, Via dei Giacinti 2 56018 Calambrone (Pi) Italy. Tel.: +39 50 886111; fax: +39 50 886247. E-mail address: gabriele.masi@inpe.unipi.it (G. Masi). 0165-1781/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2006.10.010