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Amygdala volume typically is measured after BSD onset; thus, it is not known whether amygdala abnormalities predict BSD risk or relate to the disorder. Additionally, past literature often treated the amygdala as a homogeneous structure, and did not consider its distinct subnuclei and their differential connectivity to other brain regions. To address these issues, we used a behavioral high\u2010risk design and diffusion\u2010based subsegmentation to examine amygdala subnuclei among medication\u2010free individuals with, and at risk for, BSD. The behavioral high\u2010risk design (<jats:italic>N<\/jats:italic> = 114) included low\u2010risk (<jats:italic>N<\/jats:italic> = 37), high\u2010risk (<jats:italic>N<\/jats:italic> = 47), and BSD groups (<jats:italic>N<\/jats:italic> = 30). Diffusion\u2010based subsegmentation of the amygdala was conducted to determine whether amygdala volume differences related to particular subnuclei. Individuals with a BSD diagnosis showed greater whole, bilateral amygdala volume compared to Low\u2010Risk individuals. Examination of subnuclei revealed that the BSD group had larger volumes compared to the High\u2010Risk group in both the left medial and central subnuclei, and showed larger volume in the right lateral subnucleus compared to the Low\u2010Risk group. Within the BSD group, specific amygdala subnuclei volumes related to time since first episode onset and number of lifetime episodes. Taken together, whole amygdala volume analyses replicated past findings of enlargement in BSD, but did not detect abnormalities in the high\u2010risk group. Examination of subnuclei volumes detected differences in volume between the high\u2010risk and BSD groups that were missed in the whole amygdala volume. Results have implications for understanding amygdala abnormalities among individuals with, and at risk for, a BSD.<\/jats:p>","DOI":"10.1002\/hbm.25021","type":"journal-article","created":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T11:55:56Z","timestamp":1589025356000},"page":"3358-3369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Amygdala subnuclei volume in bipolar spectrum disorders: Insights from diffusion\u2010based subsegmentation and a high\u2010risk design"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4260-1528","authenticated-orcid":false,"given":"Katherine S. 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