BACKGROUND: Neuroimaging studies of early-onset bipolar disorder (BD) are important in order to establish a fuller understanding of the underlying pathophysiology of the illness. The advantages of studying BD in children and adolescents include the relative absence of some confounds present in adult-onset research, such as lengthy duration of illness and exposure to treatments, greater number of mood episodes, and the presence of substance abuse or dependence. Finally, studying youths with the disorder may enhance our knowledge about the neural mechanisms of affective dysregulation and may specifically elucidate whether there are abnormalities that are unique to the early-onset form of the illness. METHODS: PubMed was used to identify peer-reviewed publications from the past 15 years (January 1990 to January 2005) that used brain-imaging techniques (anatomic, functional, and biochemical) to research early-onset BD. RESULTS: Eleven studies using anatomic magnetic resonance imaging (MRI), seven using magnetic resonance spectroscopy (MRS), and two using functional MRI (fMRI) were identified. Structural abnormalities were reported in total cerebral, white matter, superior temporal gyrus, putamen, thalamus, amygdala, and hippocampal volumes. Deficits in cortical gray matter were also reported. Using MRS, abnormalities were reported in the dorsolateral prefrontal cortex, anterior cingulate, and basal ganglia. One fMRI study found increased activation in the putamen and thalamus of BD youths compared to controls, and a second found abnormal prefrontal-subcortical activation in familial pediatric BD. CONCLUSION: Published MRI studies of early-onset BD are few. Nonetheless, extant data implicate abnormalities in brain regions thought to regulate mood and cognition. Synthesis of the findings into an overall model of anatomic and functional disruption is difficult due to the methodological variations among studies and the limitations of individual studies, such as the use of small sample sizes, the heterogeneity of sample characteristics, and the wide range of brain structures selected for analysis. Recommendations are offered to guide future research. It will be important for future studies to reproduce prior findings and determine which findings are unique to early-onset BD, relative to adult-onset illness. In addition, studies will need to establish the extent to which early-onset BD may overlap with comorbid disruptive, mood, anxiety, or psychotic disorders.

BACKGROUND: Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities. METHOD: Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled. RESULTS: The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen. CONCLUSIONS: These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.