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328 REVERSIBLE DISORDERS OF BRAIN DEVELOPMENTKarchemskiy, Barnea-Goraly, Garrett, et al., 2005), one group did find decreasedhippocampal volume in pediatric BD (Frazier et al., 2005).However, these findings related to the val66met allele appear discrepant withassociation and linkage findings discussed above, which associate the val66 allelewith BD. The complexity of bipolar genetics may be underlying this discrepancy:for example, it may be that whereas the val66 allele does confer broadlyincreased risk for BD, those who have BD but have the vall66met allele may actuallybe prone to hippocampal and PFC abnormalities that lead to worsened executivefunction and episodic memory, which might worsen the course and severityof their illness. An interaction with the 5-HTT s-allele may partially explain thisdiscrepancy: Serotonin signaling appears to increase BDNF secretion (Coppell,Pei, & Zetterstrom, 2003; Nibuya, Nestler, & Duman, 1996), which then leads tomodification of serotonergic innervation in the brain (Goggi, Pullar, Carney, &Bradford, 2002; Mamounas et al., 2000). Those with the vall66met allele may haveimpaired sensitivity to this serotonin signaling such that if these patients also ares-allele carriers, the increase in serotonergic signaling may be offset by a lack ofresponsivity in BDNF that would have otherwise reorganized serotonergic innervationto increase risk for mood disorder development. In this way, it is possiblethat although possession of the BDNF val66met allele can lead to cognitive dysfunction,when combined with the 5–HTT s-allele it becomes protective againstmood disorders. Therefore, it is possible that whereas the val66met polymorphismis a moderator on the course and severity of bipolar illness, the val66 polymorphismis a risk factor for BD development (see figure 14-3), especially when combinedwith presence of the 5–HTT s-allele. It is this type of gene-gene-braininteraction that deserves further study for understanding the creation of risk factorsfor development of mood disorders, such as BD.In summary, although we are still years away from creating a definitive set ofbiological markers to help predict risk for BD, these early findings suggest thatabnormalities in prefrontal-amygdalar areas and polymorphisms in genes encodingfor relevant neuronal substrates may be good candidates for inclusion in this set.Early Intervention StrategiesAlthough we may eventually be able to more specifically target individuals forearly intervention based on neurobiology and genes, it appears prudent to developpotential intervention strategies now. As for the treatment of all psychiatric illnesses,interventions would be either pharmacologic or psychosocial.Pharmacologic InterventionWhen considering type of medication, at first it would seem logical to use the classof medication that treats the disease that is trying to be averted. This approach has