Neuroimaging Studies in Bipolar Children and Adolescents

In vivo imaging studies that examined normal childhood and adolescence have started to characterize the key brain events involved in brain development and maturation of higher-order brain systems. From ages 3-6 years, the fastest growth rates occur in frontal networks. Peak growth rates in association and language cortices are attenuated after puberty, whereas there is pronounced loss of subcortical gray matter (Thompson et al., 2000). A rostrocaudal wave of growth in the corpus callosum during childhood and adolescence has been reported (Thompson et al., 2000). From adolescence to early adulthood, the main brain regions that appear to mature are dorsal, medial, and orbital frontal cortex, as well as lenticular nuclei (Sowell et al., 1999). There is evidence for postadolescence bilateral brain growth, primarily in the dorsal aspect of the frontal lobe and in the posterior temporo-occipital junction (Sowell et al., 2001). Neuronal events, such as increased myelination, play a prominent role in brain maturation during the postadolescent years, and synaptic pruning is also involved in maturation of frontal lobe cortical gray matter (Sowell et al., 2001, 2003). The emerging evidence from neuropsychological and neuroimaging studies suggests abnormalities in the frontal and temporal regions of BD youth. At this time, there is evidence that supports both a disruption in neurodevelopment and a neurodegenerative process. The amygdala in young patients with BD appears to be smaller compared to controls, but in adult subjects it is larger than controls, suggesting a developmental disruption. In vivo imaging studies conducted in healthy adolescent subjects have characterized the events that take place in early and late adolescence as far as changes in size of these brain structures. It is possible that BD in adolescence reflects disruption of critical events related to brain maturation (growth, myelination, and pruning) of these regions. However, no longitudinal data on brain development in BD patients are currently available. Findings of decreased cerebral volume in young multiple-episode patients (Strakowski et al., 2002) and studies noting the association of worse neuropsychological performance with illness severity (Cavanagh et al., 2002; Clark et al., 2002; van Gorp et al., 1998; Zubieta et al., 2001) suggest a neurodegenerative process. Similarly, in early-onset schizophrenia, a progression of neuroanatomic deficits from the parietal lobes to the temporal lobes, and sensorimotor and dorsolateral prefrontal cortices over a 5-year period has been noted (Thompson et al., 2001). The early detection of abnormalities in these areas could have important clinical implications. Future studies are needed to elucidate the effects of early treatment both acutely and chronically with BD patients. A number of functional imaging studies in adults have attempted to clarify neuroanatomical areas associated with specific mood states (Blumberg et al., 1999, 2000; Caligiuri et al., 2003; Dunn et al., 2002; Osuch et al., 2000). Similar studies in children and adolescents are lacking. There is still, therefore, the need to examine how the neuroanatomy, neurophysiology, and neuropsychology interact and affect the clinical presentation and course of illness. Lastly, further research on how environmental and genetic factors interact to determine brain development is necessary, as specific changes early in life may be important determinants of brain abnormalities that could be implicated in the pathophysiology of BD.