High level of persistence of pediatric bipolar-I disorder from childhood onto adolescent years: A four year prospective longitudinal follow-up study
Introduction
A converging body of research supports the validity of pediatric bipolar (BP)-I disorder including unique clinical features (Biederman, 1995, Biederman et al., 2005a, Birmaher et al., 2006, Findling et al., 2001, Geller, 1994, Geller and Cook, 2000a, Geller et al., 2001, Geller et al., 2002a, Geller et al., 2002b, Geller and Tillman, 2005, Geller et al., 2008, Geller et al., 2004, Geller et al., 2000b, Wozniak, 2003, Wozniak et al., 1995, Wozniak et al., 2005), familial transmission (Faraone et al., 2003, Findling et al., 2001, Geller et al., 2006), selective treatment response to anti-manic agents (Biederman et al., 2008, Biederman et al., 2005b, Biederman et al., 2007, Kafantaris et al., 2004, Pavuluri et al., 2004, Tohen et al., 2007), and characteristic neuroimaging findings (Chang et al., 2004, Chang et al., 2005a, Chang et al., 2005b, Leibenluft et al., 2007, Moore et al., 2007, Pavuluri et al., 2007). Children and adolescents with bipolar disorder have a disabling and severe clinical picture that fully satisfies the diagnostic criteria for bipolar-I disorder as defined by DSM-IV (Birmaher et al., 2006, Wozniak et al., 1995, Wozniak et al., 2005).
In parallel to pediatric studies, an emerging literature in adults documents that a majority of adults with bipolar-I disorder have an onset of their disorder in childhood and adolescence and a full third of them have an onset before the age of 12 years (Nierenberg et al., 2005, Perlis et al., 2009). Adults with early onset bipolar disorder have clinical features very similar to those observed in youth with bipolar disorder including high rates of psychiatric comorbidity with ADHD, antisocial and anxiety disorders as well as high levels of functional impairment and mixed states. Furthermore, findings from the National Comorbidity Replication study (Kessler et al., 2006) document that adults with bipolar-I disorder in the community have a significantly increased risk for ADHD and vice versa. Despite these compelling findings, questions remain as to the validity of pediatric bipolar disorder.
As proposed by Robins and Guze (1970), a cornerstone in establishing the validity of a psychiatric disorder is for the disorder to have a unique course. Yet, only a limited literature has addressed the longitudinal course of pediatric bipolar disorder. In one of a very few studies of its kind, Geller et al. (2008) found that 44% of children with BP-I continued to suffer from the full disorder by the age of 18 years. While this study represents the first major report on the long-term follow-up of pediatric subjects with bipolar-I disorder, the study restricted recruitment to children meeting a phenotype based on the presence of euphoria or grandiosity, excluding other children who may have otherwise fully met DSM-IV bipolar-I disorder criteria. Unmodified DSM-IV criteria requires either a week or longer of irritability or euphoria along with concurrent criterion B symptoms (any 3 if mood is euphoric, any 4 if mood is irritable). Birmaher et al. (2009) followed-up 413 youth with bipolar I, II and NOS disorders over a four year period and reported a chronic course with high rates of relapse and recovery (63% and 82%, respectively) as well as high rates of persistence of subsyndromal presentations and episodes of depression.
As proposed by Keck et al. (1998) delineating different patterns of remission in psychiatric samples is of high scientific and clinical interest. These authors proposed three levels of remission for psychiatric disorders: syndromatic remission (or loss of full diagnostic status), symptomatic remission (or loss of partial diagnostic status) and functional remission (full recovery, including functioning well). For bipolar disorder, the additional component of recovery includes remission from syndromes and symptoms of depression as well as mania, as many subjects with bipolar disorder may remit from mania, but continue to suffer from impairing states of depression. Thus, questions remain as to whether children who no longer satisfy full diagnostic criteria for BP-I disorder should be considered remitters despite manifesting persistent symptoms of subsyndromal mania or depression. Since these are frequently seen in adults with BP-I disorder, a comprehensive assessment of the course of pediatric BP-I needs to address these outcomes.
A better understanding of the course of pediatric BP-I disorder is of high clinical, public health and scientific importance. Understanding the degree to which pediatric BP-I persists in a naturalistic sample should help clinicians in the community understand the course of the disorder and whether its level of severity and persistence warrants early and aggressive treatment. Such knowledge should also encourage clinicians to carefully follow-up affected children with BP disorder and be mindful of the residual manifestations of the symptomatic picture over time. As described by Lewinsohn et al. (1995) in adolescent subjects and by Merikangas et al. (2007) in adult subjects, even subsyndromal forms of BP disorder are highly morbid, associated with significant dysfunction and merit clinical attention.
The main aim of the present study was to evaluate the longitudinal course of DSM-IV pediatric bipolar-I (BP-I) disorder attending to different definitions of remission at follow-up including persistence of the full diagnosis of BP-I disorder as well as the presence of subsyndromal mania and depression. To this end, we conducted a four year longitudinal follow-up study of a large sample of systematically ascertained children and adolescents of both sexes fully satisfying DSM-IV diagnostic criteria for BP-I disorder based on clinical assessment and structured diagnostic interview, followed prospectively onto adolescence. We hypothesized that pediatric BP-I disorder would be a persistent disorder. To the best of our knowledge this study represents one of only three comprehensive longitudinal studies that examined the course of pediatric bipolar disorder. While two previous longitudinal studies have addressed the longitudinal course of bipolar disorder, ours differs from Geller et al. (2008) in that it selects subjects based on unmodified DSM-IV criteria and from Birmaher et al. (2009) in that it attends to both syndromatic and symptomatic remission of both mania and depression, as well as stratifies syndromatic remitters into those who are treated vs untreated.
Section snippets
Subjects
We recruited 105 youth in a longitudinal follow-up study of BP-I disorder. The participants were children and adolescents 6–17 years of age of both sexes meeting full diagnostic criteria for bipolar (BP)-I disorder on structured diagnostic interview. All BP-I diagnoses were corroborated by clinical assessment by the lead author (JW), a board certified child and adolescent psychiatrist with expertise in the diagnosis of pediatric onset bipolar disorder. The clinical assessment was 2 h in length
Results
Of the 105 youth with BP-I disorder enrolled in a longitudinal follow-up study, 78 (74%) returned for follow-up assessments 4 years later (mean = 3.6 years, standard deviation = 1.2). There were no differences in baseline age (10.5 ± 3.2 vs 9.8 ± 3.5, p = 0.36), sex (76% male vs 89% male, p = 0.14) or functional impairment at baseline (GAF score 40.2 ± 5.9 vs 38.8 ± 6.5, p = 0.30) between the probands who were followed and lost to follow-up, respectively. However, there was a statistically
Discussion
This 4-year longitudinal follow-up study evaluated the course of DSM-IV pediatric bipolar-I disorder from childhood onto mid adolescence as well as its predictors and correlates. The majority of youth with BP-I disorder at baseline (73.1%) continued to meet full DSM-IV diagnostic criteria for BP-I disorder at follow-up (i.e., syndromatic persistence as defined by Keck et al. (1998). In addition, the overwhelming majority of the non-persistent cases had either subthreshold (6.4%) BP-I disorder,
Role of funding source
The funding sources had no role in the study design, had no role in the collection, analysis, or interpretation of data, had no role in the writing of the report, and had no role in the decision to submit the paper for publication.
Contributors
Janet Wozniak was the overall PI of the study. She provided general oversight of the study, training of the interviewers, and quality control. Joseph Biederman provided logistical and financial support, as well as administrative oversight. He played a key role in the interpretation of findings and drafting the manuscript. Stephen Faraone provided statistical consultation, as well as critical review of the final manuscript. Carter Petty provided statistical support, and analyzed the data from
Conflict of interest
All other authors report no conflict of interests.
Financial disclosures
Dr. Wozniak is the author of the book, “Is Your Child Bipolar” published May 2008, Bantam Books. She has been a speaker for McNeil, Primedia/MGH Psychiatry Academy, on the Advisory Board for Pfizer and Shire and received research support from NIMH, McNeil, Shire, Janssen and Lilly. Her spouse John Winkelman MD, PhD has been on the Speakers Bureau for Boehringer-Ingelheim, Cephalon, GlaxoSmithKline, King, Sanofi-Aventis, Sepracor, Takeda, on the Advisory Board for Axon Labs,
Acknowledgements
This study was partially supported by NIMH 5R01MH66237-5 (to JW), The Prechter Foundation, and the Pediatric Psychopharmacology Council Fund.
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