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322 REVERSIBLE DISORDERS OF BRAIN DEVELOPMENTgray/white matter ratios, ventricular size, and number of white matter hyperintensities(WMH; reviewed in Strakowski, DelBello, Adler, Cecil, & Sax, 2000).However, findings have not always been replicated, perhaps due to small samplesizes, differences in image acquisition, processing and analyses, and heterogeneityof subject samples. Neuroimaging studies have also indicated that subcorticalstructures are involved in the pathophysiology of this condition (Strakowski et al.,2000). Primarily, candidate regions have included the hippocampus, caudate,putamen, thalamus, and amygdala. These limbic and paralimbic structures haveall been implicated in circuits of mood regulation (Blumberg, Charney, & Krystal,2002; Mayberg, 1997), making them logical candidates for further study in BD.Thus, the prefrontal cortex, amygdala, and the circuits involving these two regionsare particularly of interest regarding neurobiological characteristics of BD thatmay serve as markers.Role of the Amygdala in Bipolar DisorderThe amygdala is particularly relevant to the pathophysiology of BD. In addition tohaving a prominent role in emotion perception and response, the amygdala demonstratesactivation abnormalities during functional imaging studies of adults with BD(Drevets et al., 2002; Yurgelun-Todd et al., 2000). Volumetric findings in adultswith BD have been equivocal, with reports of similar (Swayze, Andreasen, Alliger,Yuh, & Ehrhardt, 1992), decreased (Blumberg, Kaufman, et al., 2003; Pearlson et al.,1997), or increased (Altshuler et al., 2000; Strakowski et al., 1999) amygdalar volumes.Amygdalar findings in pediatric BD have been more consistent, as three studiesof adolescents with BD found decreased amygdalar volumes in patients comparedto healthy controls (Blumberg, Kaufman, et al., 2003; K. Chang, Karchemskiy,Barnea-Goraly, Garrett, et al., 2005; DelBello, Zimmerman, Mills, Getz, &Strakowski, 2004). Blumberg et al. (Blumberg, Kaufman et al., 2003) reported adecrease in amygdalar volume of 15.6% compared to controls in a combined groupof adolescents and adults with BD. DelBello et al. (2004) reported a 10.9% decreasein overall amygdalar volume in children and adolescents with BD. We recently reporteda similar 10.4% decrease in amygdalar volume in 20 bipolar offspring withBD compared to controls, a finding driven by reduction in gray matter volume (K.Chang, Karchemskiy, Barnea-Goraly, Garrett, et al., 2005). Furthermore, anotherstudy found a trend for decreased left amygdalar volume (mean decrease 13.6%) inadolescents and young adults with BD (B. K. Chen et al., 2004). The convergenceof structural and functional amygdalar abnormalities in children and adults with BDpoint to likely involvement of the amygdala in the pathophysiology of BD. Becausechildren with BD usually are temporally closer to their time of BD onset and thushave had less time than adults to accrue influence of external factors (medications,substances, or mood episodes) on brain morphometry and function, these abnormalitiescould represent trait markers, present before the onset of full BD, and thusmay also serve as risk factors for BD development.