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Psychiatry Res. 2015 Jun 30;232(3):226-36. doi: 10.1016/j.pscychresns.2015.03.006. Epub 2015 Mar 31.

Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

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  • 1Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA; Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA; Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: jill_goldstein@hms.harvard.edu.
  • 2Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA. Electronic address: katie.lancaster@virginia.edu.
  • 3Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA. Electronic address: longenecker.julia@gmail.com.
  • 4Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA. Electronic address: brandon.abbs@gmail.com.
  • 5Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA; Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA; Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: lholsen@partners.org.
  • 6Connors Center for Women׳s Health and Gender Biology, Division of Women׳s Health, Brigham and Women׳s Hospital, Boston, MA, USA. Electronic address: scherkerzian@partners.org.
  • 7Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: swg@mit.edu.
  • 8Departments of Psychiatry and Medicine, Harvard Medical School, Boston, MA, USA; Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA. Electronic address: nmakris@partners.org.
  • 9Center for Behavior Genomics, Department of Psychiatry, University of California at San Diego, San Diego, CA, USA. Electronic address: mtsuang@ucsd.edu.
  • 10Department of Community Health, Brown University, Providence, RI, USA. Electronic address: stephen_buka@brown.edu.
  • 11Division of Psychiatric Neuroscience, Athinoula A. Martinos Center, Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Beth Israel Deaconess Medical Center, Division of Public Psychiatry, Massachusetts Mental Health Center and Harvard Medical School, Boston, MA, USA. Electronic address: lseidman@bidmc.harvard.edu.
  • 12Department of Medicine, Harvard Medical School, Boston, MA, USA; Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA. Electronic address: aklibanski@partners.org.

Abstract

Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

HPA axis; HPG axis; Negative valence affect; Schizophrenia; Sex differences; Stress response

PMID:
25914141
[PubMed - indexed for MEDLINE]
PMCID:
PMC4439265
[Available on 2016-06-30]
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