Subcortical volumetric abnormalities in bipolar disorder

Abstract

Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case–control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=−0.232; P=3.50 × 10−7) and thalamus (d=−0.148; P=4.27 × 10−3) and enlarged lateral ventricles (d=−0.260; P=3.93 × 10−5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons.

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“…42,46 We used the ENIGMA pipeline to generate and inspect hippocampal volumes. This pipeline mandates careful inspection of each participant's data to ensure segmentation accuracy (for examples using this pipeline, see van Erp and colleagues 52 and Hibar and colleagues 53 ). Automated FreeSurfer hippocampal volumes have been shown to have high overlap and correlation with expert hand-drawn volumes of the hippocampus.…”

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“…However, the pathophysiological basis for their occurrence remains unclear [4,6]. More frequent observations include depression, psychotic and cognitive disorders [3,8,12].…”

“…Basal ganglia play an important role both in the direct realization of the motor function but also in the control of motor behavior on the motivation level [1][2][3][4][5][6][7][8][9][10].…”

612. Hippocampal Subfield Volumes in Mood Disorders

“…22,40,41 To be brief, any outlier (five standard deviations) of any hippocampal subfield was excluded. Then each segmented image, overlaid on the corresponding brain structural image, was visually inspected by two co-authors independently (BC and HT), in order to exclude segmentations with poor registration to the hippocampus location or with apparent wrong assignment of the subfields.…”

“…These inconsistent results could be related to the use of certain medication with neuroprotective effect, such as lithium and the heterogeneity of BD types in these studies. [19][20][21][22] A recent study, however, reported that patients with BD have reductions in hippocampus according to prior morbidity (number of manic episodes and hospitalization). 23 Regarding MDD, a recent meta-analysis of 32 magnetic resonance imaging (MRI) studies have confirmed the difference in hippocampal volume between patients and controls, but only among patients with MDD whose duration of illness was longer than two years or who had more than one mood episode.…”