Bipolar disorder in children and adolescents – are we approaching the final frontier?

Recent studies suggest that the onset of bipolar disorder most commonly occurs before age 18 (1– 2). However, the clinical presentation of bipolar disorder in youth often differs from that in adults. Children and adolescents with bipolar disorder have higher rates of mixed episodes, rapid cycling, and co-occurring attention-deficit/hyperactivity disorder (ADHD) as compared to adults with bipolar disorder. It remains to be determined whether these age-related differences are the result of developmental differences in expression of the same symptoms or distinct underlying genetic and neurophysiological abnormalities marking pediatricand adult-onset bipolar disorder as two different disorders. The results of recent neuroimaging and pharmacological intervention investigations reveal that children and adolescents with bipolar disorder exhibit distinct patterns of pharmacological response and neurobiological alterations compared to adults with bipolar disorder (3–6). However, these differences might be due to reasons other than distinct neuropathophysiology between the two conditions. As discussed below, adults with bipolar disorder often have had many years of illness during which the sequlae of this devastating disorder may have exerted effects on the brain. While researchers continue to explore potential neurobiological and genetic etiologies of bipolar disorder through studies of adult probands, there are several advantages to including pediatric populations in these studies. First, family studies suggest that youth with bipolar disorder may have a greater genetic load for this illness than adults with bipolar disorder (7). Therefore, relatively small effects from single genetic polymorphisms may be amplified in samples of patients with pediatric bipolar disorder. Subsequently, this enhanced genetic susceptibility may be reflected in enhanced neurobiological abnormalities that may be more readily detected in sample sizes typically used for neuroimaging studies (12–40 subjects). Children and adolescents with bipolar disorder also are typically closer to their illness onset than adults, providing a window of opportunity for identifying genetic and neurobiological trait characteristics of the illness (i.e., disease biomarkers) that are independent of repeated affective episodes and other confounding factors associated with illness course, such as co-occurring substance use and medical disorders, as well as medication exposure. Longitudinal follow up from childhood to adulthood could then shed light on the developmental course of the disorder, linking findings from adult studies to those from pediatric studies. Finally, clarifying the genetic and neurophysiological characteristics of pediatric bipolar disorder may lead to identifying biomarkers that could serve as predictors of treatment response, targets for developing novel treatments, and signals for impending development of bipolar disorder. These signals could then be useful for identifying individuals who might benefit from early intervention to halt or delay the development of fully expressed bipolar disorder. During the past decade evidence-based research has shifted the debate from whether bipolar disorder in children and adolescents exists to how to best use biological research to determine core trait characteristics of bipolar disorder that might be used as predictors of illness development. In this special issue of Bipolar Disorders we begin with a broad overview examining the current controversies regarding the phenomenology of bipolar disorders in youth and then move beyond the confusion and take a journey into the next generation of research that will utilize innovative techniques to further advance our understanding of the genetic and neurobiological basis of this illness as it presents in children and adolescents. The first article is an eloquent meta-analysis of the phenomenological characteristics of mania in children and adolescents by Kowatch et al. (8). The enlightening findings of this paper suggest that, after statistically accounting for methodological differences among phenomenological studies, there is more consistency in the description of pediatric bipolar disorder over the last 25 years than disagreement. This conclusion is reassuring as we, as a field, need to establish diagnostic consistency in order to be able to confidently explore the biology of bipolar disorder. Soutullo et al. (9) provide an Bipolar Disorders 2005: 7: 479–482 Copyright a Blackwell Munksgaard 2005