While there has long been controversy surrounding the diagnosis of pediatric bipolar disorder, data from family studies, longitudinal studies, studies of high-risk offspring of parents with bipolar disorder, treatment studies and biomarker studies all support the validity of this diagnosis. While the onset of bipolar illness historically has been considered to occur during late adolescence and young adulthood, it is increasingly clear from converging studies that many adults with bipolar disorder experience the onset of symptoms in childhood (29%) and adolescence (38%) (Perlis et al, 2009). Information on the long-term outcomes of pediatric bipolar disorder is limited; previous studies have suggested that individuals with early onset bipolar disorder are more likely to experience more recurrent illness, chronicity, and greater functional impairment.
A recent study from Janet Wozniak, MD and her colleagues from the Clinical and Research Program in Pediatric Psychopharmacology and Adult ADHD at Mass General, follows the trajectories of a group of youths between the ages of 6 and 17 with bipolar I disorder (BP-I). This group was ascertained from the Clinical and Research Programs in Pediatric Psychopharmacology at MGH, advertisements in the community, and referrals from local clinicians.
Psychiatric assessments of participants younger than 18 years of age were made with the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children, Epidemiologic Version (K-SADS-E) (Orvaschel and Lauderdale, 1994). Psychiatric assessments of participants 18 years of age or older were made with the Structured Clinical Interview for DSM-IV (SCID) (First et al., 1997) supplemented with modules from the K-SADS-E to cover childhood disorders.
Pediatric bipolar participants were diagnosed with BP-I disorder if they met DSM-IV criteria. The DSM-IV criteria required subjects to meet criterion A for a distinct period of extreme and persistently elevated, expansive, or irritable mood lasting at least one week, plus criterion B, manifested by three (four if the mood is irritable only) of seven symptoms during the period of mood disturbance.
Subjects included in this prospective study were 6 to 17 years at entry and were assessed at baseline and subsequently at four, five, and six years of follow-up. Assessments included structured diagnostic interviews and measures of psychosocial and educational functioning. Of the 105 probands with BP-I disorder enrolled at baseline, 88 (84%) returned for at least one follow-up assessment. The average follow-up time was 5.8 ± 1.8 years.
High Rates of Persistent Symptoms, Low Rates of Functional Recovery
Pediatric BP-I disorder and subsyndromal states persisted at a high rate. About half of the youth (48%) continued to meet full diagnostic criteria for BP-I disorder (i.e. syndromatic persistence). These individuals had experienced an episode of mania during the previous year.
In this cohort, 28% experienced symptomatic persistence, defined as meeting subthreshold diagnostic criteria for mania or full or subthreshold diagnostic criteria for major depressive disorder (MDD) during the previous year.
About one-fourth of the youth (24%) experienced remission (defined as not meeting full or subthreshold criteria for a manic or depressive episode during the previous year). However, the probability of functional recovery from pediatric BP-I disorder was very low. Of the 88 youths assessed, only 6% (N = 5) of the sample were euthymic with normal functioning during the year prior to their last follow-up assessment. Given high rates of psychiatric comorbidity in this cohort, the authors speculate that this comorbidity may contribute to low rates of functional recovery.
Youth with at least one comorbid disorder at follow-up had an increased risk of experiencing the persistence of mania. While this study did not identify any statistically significant baseline predictors of persistent BP-I disorder (all p > 0.05), there were a number of factors associated with clinically meaningful increases in risk, including socioeconomic status, prepubertal onset, and family history of bipolar disorder, oppositional defiant disorder, and cigarette smoking.
What’s Next?
The current study provides compelling evidence for the high level of persistence of pediatric BP-I disorder. Symptomatic and functional remission were uncommon and most subjects continued to demonstrate high morbidity into late adolescence and early adulthood. In the current study, about three-quarters of youth continued to have persistent symptoms, and even among those who attained remission, rates of functional recovery were very low. These findings are consistent with longitudinal studies of pediatric bipolar disorder from three other sites.
Because many of the youth participating in this study were drawn from clinical populations, these findings may be generalizable to other populations. This study may not represent pediatric bipolar disorder with milder or misdiagnosed symptoms. However, this study does give us information on the clinical course of youth with pediatric bipolar disorder whose symptoms are severe enough to merit clinical attention. Epidemiologic studies with well-established diagnostic criteria are needed to better understand the prevalence and clinical course of pediatric bipolar disorder.
The consistency of findings across four studies from four separate sites with differing methodologies supports the validity of a high level of persistence of pediatric BP-I disorder, as well as associated subsyndromal states, extending from childhood into adolescence and early adulthood. The findings of this study highlight the importance of early identification and the development of interventions with psychotherapies, natural treatments and pharmacotherapy with the goal of reducing symptom burden and improving long-term outcomes. Given the morbidity of bipolar disorder occurring at any age, predictors of persistence from childhood into later years will help to clarify treatment guidelines. Future work will test the hypothesis that pediatric onset bipolar disorder is a distinct genetic and neurobiological subtype of bipolar disorder which shares clinical characteristics with the adult onset form of the disorder.
Co-Authors: Maura DiSalvo, MPH; Abigail Farrell, BS; Gagan Joshi, MD; Mai Uchida, MD; Stephen V Faraone, PhD; Emmaline Cook, BA; Joseph Biederman, MD
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Perlis RH, Dennehy EB, Miklowitz DJ, Delbello MP, et al. Retrospective age at onset of bipolar disorder and outcome during two-year follow-up: results from the STEP-BD study. Bipolar Disord. 2009 Jun;11(4):391-400.
Wozniak J, DiSalvo M, Farrell A, Joshi G, Uchida M, Faraone SV, Cook E, Biederman J. Long term outcomes of pediatric Bipolar-I disorder: A prospective follow-up analysis attending to full syndromatic, subsyndromal and functional types of remission. J Psychiatr Res. 2022 Jul; 151:667-675.
Janet Wozniak, MD is the Director of the Child and Adolescent Outpatient Service and Director of the Pediatric Bipolar Disorder Clinical and Research Program at Mass General. Dr. Wozniak is an Associate Professor of Psychiatry at Harvard Medical School. Her current research focuses on the course, characteristics, and pharmacological treatment of juvenile onset bipolar disorder.
