title: Amygdala subnuclei resting-state functional connectivity sex and estrogen differences.
abstract: The amygdala is a hub in emotional processing, including that of negative affect. Healthy men and women have distinct differences in amygdala responses, potentially setting the stage for the observed sex differences in the prevalence of fear, anxiety, and pain disorders. Here, we examined how amygdala subnuclei resting-state functional connectivity is affected by sex, as well as explored how the functional connectivity is related to estrogen levels. Resting-state functional connectivity was measured using functional magnetic resonance imaging (fMRI) with seeds placed in the left and right laterobasal (LB) and centromedial (CM) amygdala. Sex differences were studied in 48 healthy men and 48 healthy women, matched for age, while the association with estrogen was analyzed in a subsample of 24 women, for whom hormone levels had been assessed. For the hormone analyses, the subsample was further divided into a lower and higher estrogen levels group based on a median split. We found distinct sex differences in the LB and CM amygdala resting-state functional connectivity, as well as preliminary evidence for an association between estrogen levels and connectivity patterns. These results are potentially valuable in explaining why women are more afflicted by conditions of negative affect than are men, and could imply a mechanistic role for estrogen in modulating emotion.
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: jonas.engman@psyk.uu.se.
authors.forename: Jonas
authors.initials: J
authors.lastname: Engman
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Clas
authors.initials: C
authors.lastname: Linnman
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA; Department of Psychology, Center for Brain Science, Harvard University, Cambridge, MA, USA.
authors.forename: Koene R A
authors.initials: KR
authors.lastname: Van Dijk
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Milad
mesh_terms: D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000502:physiology; D066272:Basolateral Nuclear Complex / Q000502:physiology*; D016022:Case-Control Studies; D066274:Central Amygdaloid Nucleus / Q000502:physiology*; D004644:Emotions / Q000502:physiology; D004967:Estrogens / Q000097:blood*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D004967:Estrogens
keywords: Estradiol; Hormones; Intrinsic connectivity networks; Negative affect; Sex differences; Spontaneous fluctuations