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Shift in the brain network of emotional regulation in midlife women: is the menopausal transition the turning point?

Frey, Benicio N. MD, PhD1,2; Hall, Geoffrey B. PhD2,3,4; Attard, Stefanie BA1,2; Yucel, Kaan MD, PhD2,3; Skelin, Ivan MD, PhD1; Steiner, Meir MD, PhD, FRCPC1,4; Soares, Claudio N. MD, PhD, FRCPC1,2,4

doi: 10.1097/gme.0b013e3181df840f
Special Section: Menopause, Cognition and Mental Health

Objective: The menopausal transition is marked by hormonal changes and is quite often accompanied by cognitive and emotional complaints. Recent data also suggest a heightened risk for depression. Little is known about the changes in emotional regulation that might contribute to the increased risk of depression in this population. The aim of this study was to examine the brain correlates of emotional regulation in healthy, nondepressed midlife women.

Methods: Functional magnetic resonance imaging was obtained in response to a standardized emotional regulation task. Levels of congruency were set and brain activation was measured during high- and low-conflict-resolution trials.

Results: Fourteen women aged 40 to 60 years were enrolled into the study, and 11 were included in the final analyses. Activity associated with resolution of emotional conflict was observed in the dorsolateral prefrontal cortex (P < 0.05). No regions were engaged in the generation/monitoring of emotional conflict. Moreover, there was a significant deactivation of the amygdala in response to fearful faces (P < 0.05).

Conclusions: Unlike similar studies in younger populations, these results suggest a more significant engagement of the dorsolateral prefrontal cortex and less amygdala activation in emotional regulation in midlife women. These findings are, however, consistent with previous studies in older populations. We hypothesize that a shift in emotional regulation circuitry might therefore occur in women during the menopausal transition and possibly contribute to the occurrence of mood and anxiety symptoms in women during/after this period in life.

This study investigated brain correlates of emotional regulation in healthy peri- and postmenopausal women using functional magnetic resonance imaging. The results suggest that a shift in the brain network involved with emotional regulation in women may occur during the menopausal transition, a finding that might have potential clinical and therapeutic implications.

From the 1Women's Health Concerns Clinic, St. Joseph Healthcare, Hamilton, Ontario, Canada; 2Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada; and 3Imaging Research Centre and 4Brain-Body Institute, St. Joseph's Healthcare, Hamilton, Ontario, Canada.

Received January 22, 2010; revised and accepted March 24, 2010.

Funding/support: This research was supported in part by investigator-initiated grants from Wyeth Pharmaceuticals (Dr. Soares), Eli Lilly (Dr.Soares), and Canadian Institutes of Health Research (CIHR) Wyeth Rx&D Fellowships (Drs. Frey, Skelin, and Soares).

Financial disclosure/conflicts of interest: Dr. Soares has received research support from the Allergen National Centre of Excellence, the CIHR, Eli Lilly, Pfizer, AstraZeneca, and the Hamilton Community Foundation. He has received honoraria as consultant and/or speaker for Wyeth, Pfizer, AstraZeneca, Eli Lilly, Lundbeck, and Bayer Shering Pharmaceuticals. Dr. Frey has received research support from the CIHR, the Stanley Medical Research Institute, the Father Sean O'Sullivan Research Centre, Bristol-Myers Squibb, Wyeth Pharmaceuticals, and Eli Lilly. He has worked on advisory boards and the speaker bureau for AstraZeneca and Wyeth Pharmaceuticals. Dr. Steiner has received honoraria as consultant for Wyeth Pharmaceuticals, Bayer Shering Pharmaceuticals, AstraZeneca, and Azevan Pharmaceuticals; grant/research support from Wyeth, GlaxoSmithKline, AstraZeneca, and Lundbeck; and honoraria from Azevan Pharmaceuticals and Ortho-McNeil.

Address correspondence to: Benicio N. Frey, MD, PhD, Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, 301 James St. South, FB 634, Hamilton, Ontario, Canada L8P 3B6. E-mail:

©2010The North American Menopause Society