Morphometry of the hippocampus and amygdala in bipolar disorder and schizophrenia

Epidemiologic and genetic studies suggest that bipolar disorder (BP) and schizophrenia (SCZ) may share common susceptibility genes (1). Volumetric neuroanatomical studies, however, do not indicate similarities between these two disorders. The hippocampus appears to be central to the pathophysiology of SCZ (2), and loss of gray matter in the hippocampus is often reported (3, 4). In contrast, there appears to be little change in hippocampal volume in BP. Rather, structural studies suggest that global measures of total cerebral and gray and white matter volumes in BP are largely normal (5). However, volumes of the amygdala are sometimes abnormal, compared to controls (CON) or SCZ patients (4, 5). Studying surface shape patterns can identify more subtle structural abnormalities not evident by volumetric studies. Surface shape abnormalities of the hippocampus have been reported in SCZ (6, 7), but no such studies have been conducted in BP. We used magnetic resonance imaging and a FreeSurfer-initiated fully automated brain segmentation method involving Large Deformation Diffeomorphic Metric Matching (8) to compare the volume and surface shape of the hippocampus and amygdala in SCZ and BP. We hypothesized that SCZ and BP would show similar shape patterns in the hippocampus and amygdala. Further, if SCZ and BP differed in the degree, but not the pattern, of structural irregularity, there would be an ordered relationship in surface shape among the SCZ, BP, and CON groups. Participants included individuals with bipolar I disorder (n = 12) and SCZ (n= 11), both based on DSM-IV criteria, as well as CON participants (n = 12). Participants were matched for age, gender, race, and handedness. Exclusion criteria included recent (within three months) substance dependence, mental retardation, and history of severe head injury. Principal component (PC) analysis was used to reduce the high dimensionality of structure surfaces, yielding an orthonormal set of PCs representing shape variation. Group differences in structure shapes were assessed using MANOVA with the weights from the first 10 PCs (> 82% shape variance) used as dependent variables. To test for an ordered variation in surface shape across the groups, we performed a canonical analysis using a general linear model with the PC scores as dependent variables and group as the predictor variable. The canonical analysis was designed to score BP subjects along a dimension of surface shape variation for each structure that maximized the difference between SCZ and CON (9). There was a trend-level significant effect for hippocampal volume [F(2,34) = 2.9, p = 0.07]. Post-hoc analysis of hippocampal volumes showed significant group difference on the left [F(2,34) = 3.5, p = 0.04] but not the right [F(2,34) = 2.0, p = 0.15]. Further analysis of the left hippocampus showed smaller volumes [mm (SD)] in SCZ [2,164 (370)] compared to BP [2,453 (174)] (p = 0.019) and CON [2,395 (252)] (p = 0.052). There was a significant hemisphere effect for hippocampal volume [right > left: F(1,34) = 91.7, p < 0.0001], but no hemisphere · diagnosis interaction. Covarying for cerebral volume eliminated the hemisphere · diagnosis interaction for the hippocampus. There were no group effects for amygdala volume [F(2,34) = 0.81, p = 0.45]. Significant hemispheric effects for amygdala volume were observed [right > left: F(1,34) = 16.5, p = 0.003], but no hemisphere · diagnosis interaction. MANOVA applied to the PC scores summarizing hippocampal surface variation, with hemisphere as a repeated factor, indicated a significant effect of group status (Wilks = 0.04, p = 0.004). Group comparisons based on the canonical shape score of the hippocampus did not show significant differences between BP and CON, while there were significant differences between BP and SCZ (p < 0.05). A visual representation of hippocampal shape in SCZ and BP compared to CON is shown in Figure 1. MANOVA applied to the PC scores Bipolar Disorders 2010: 12: 341–343 a 2010 The Authors Journal compilation a 2010 Blackwell Munksgaard