Three-dimensional mapping of hippocampal and amygdalar structure in euthymic adults with bipolar disorder not treated with lithium

Abstract

Structural neuroimaging studies of the amygdala and hippocampus in bipolar disorder have been largely inconsistent. This may be due in part to differences in the proportion of subjects taking lithium or experiencing an acute mood state, as both factors have recently been shown to influence gray matter structure. To avoid these problems, we evaluated euthymic subjects not currently taking lithium. Thirty-two subjects with bipolar type I disorder and 32 healthy subjects were scanned using magnetic resonance imaging. Subcortical regions were manually traced, and converted to three-dimensional meshes to evaluate the main effect of bipolar illness on radial distance. Statistical analyses found no evidence for a main effect of bipolar illness in either region, although exploratory analyses found a significant age by diagnosis interaction in the right amygdala, as well as positive associations between radial distance of the left amygdala and both prior hospitalizations for mania and current medication status. These findings suggest that, when not treated with lithium or in an acute mood state, patients with bipolar disorder exhibit no structural abnormalities of the amygdala or hippocampus. Future studies, nevertheless, that further elucidate the impact of age, course of illness, and medication on amygdala structure in bipolar disorder are warranted.

Figure 1

Schematic of the mesh mapping method. The surface-based mesh mapping method relies on (A) manually tracing the subcortical structure (B) computing a three-dimensional parametric mesh model of the structure, (C) estimating the distance between the central core of the structure to each surface point (i.e., the radial distance), and recording radial distance estimates at each surface point to create subject and group average color-coded maps of the radial distance (D). These maps are then assessed statistically by fitting a statistical model separately at each surface point to provide group differences in radial distance, or associations with clinical and demographic variables (E).

Figure 2

Statistical maps showing regional positive associations between amygdala surface structure and current medication use (A) and prior hospitalizations for mania (B). Probability maps show thresholded, uncorrected p values in color. See the Results section of the text for corrected p values.

Figure 3

Associations between amygdala radial size and age in healthy controls (A) and bipolar subjects (B). The significance of these correlations is plotted as uncorrected color-coded p values, with cool colors indicating negative correlations and hot colors, positive correlations. Red areas in (C) indicate areas in areas of significant age by diagnosis interactions (i.e. areas in which age-related changes in radial size differ between groups).