Amygdala and Hippocampal Volumes in Relatives of Patients with Bipolar Disorder: A High—Risk Study

Abstract

M esiotemporal structures including hippocampus and amygdala have been implicated in the pathophysiology of BD by converging evidence from structural, 1 functional neuroimaging, 2 neuropathological, 3 and neurocognitive 4 studies. Structural neuroimaging findings regarding the amygdala are markedly heterogeneous, with findings of decreased, 5-8 unchanged, 9-13 as well as increased 14-18 amygdala volumes in patients with BD relative to control subjects. Similarly, the literature regarding hippocampal volumes is inconsistent with most studies reporting lack of hippocampal volume changes, 7,14-16 but also with findings of decreased 10 as well as increased 5,19 hippocampal volumes in patients with BD. These discrepancies likely reflect clinical and treatment heterogeneity. 20,21

Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis

“…This is in contrast to the majority of previous studies, 19,[21][22][23][24][25] as well as to 8 previous meta-analyses, [33][34][35][36][37][38][39][40] all of which reported comparable hippocampal volumes between patients with bipolar disorder and controls.…”

“…[15][16][17][18] In contrast, studies of patients with bipolar disorder have been contradictory, with findings of mostly comparable, [19][20][21][22][23][24][25] but also smaller [26][27][28][29] or even larger [30][31][32] hippocampal volumes in patients with bipolar disorder relative to controls. As a result, all 8 published metaanalyses found preserved hippocampal volumes in patients with bipolar disorder.…”

“…We also extracted variables that are import ant for interpretation of the results, including treatmentrelated factors such as the duration, dose and compliance with the Li treatment and previous exposure to Li, as well as information about illness burden such as duration of illness and number of episodes. This is important as, regardless of medication exposure, hippocampal volume abnormalities are unlikely to be present in the early stages of illness 24,49,50 and tend to appear only after a substantial illness burden. 15,51 Thus, differences in the duration of illness or the numbers of episodes could confound the results.…”

“…19,[21][22][23][24][25][33][34][35][36][37][38][39][40] The previously reported differences between unipolar depression and bipolar disorder in hippocampal volumes 14 were perhaps not related to any unique genetic or pathophysiological under pinning of each of these mood disorders, but rather to a different exposure to Li. Our results suggest that once current exposure to Li is accounted for, smaller hippocampal volumes are present in patients with bipolar disorder to a similar extent as in those with unipolar depression.…”

Emotional and Motivational Processes in Bipolar Disorder: A Neural Network Perspective

“…However, increased volume [106] and no alterations [216] in caudate volume have also been reported. Whereas there seem to be no volumetric alterations in the amygdala of relatives of patients with bipolar disorder [217,218], there are reports of reduced hippocampal volume [218] and also reports of no apparent alterations in the hippocampus [217]. Furthermore, one study observed reduced thalamic volumes in relatives of bipolar disorder patients [215].…”