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Original Investigation |

Greater Monoamine Oxidase A Binding in Perimenopausal Age as Measured With Carbon 11–Labeled Harmine Positron Emission Tomography

Paraskevi Vivien Rekkas, PhD1; Alan A. Wilson, PhD1; Vivian Wai Han Lee, BSc1; Priyanga Yogalingam, BSc1; Julia Sacher, MD, PhD2; Pablo Rusjan, PhD1; Sylvain Houle, MD, PhD1; Donna E. Stewart, MD3; Nathan J. Kolla, MSc, MD1; Stephen Kish, PhD1; Lina Chiuccariello, MSc1; Jeffrey H. Meyer, MD, PhD1
[+] Author Affiliations
1Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
2Max Planck Institute for Human Cognitive and Brain Sciences and Clinic of Cognitive Neurology, University of Leipzig, Leipzig, Germany
3Department of Psychiatry, Women’s Health Program, and Toronto General Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada
JAMA Psychiatry. 2014;71(8):873-879. doi:10.1001/jamapsychiatry.2014.250.
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Importance  Perimenopause is a period of high risk for mood disorders, and it has been proposed that perimenopause is also a window of risk for processes linked to later dementia. However, in human perimenopause, the neurobiological changes implicated in the genesis of mood disorders or dementia have not been identified. Monoamine oxidase A (MAO-A) is an important brain enzyme that creates oxidative stress, influences apoptosis, and metabolizes monoamines. After declines in estrogen level, MAO-A density may be elevated for a month or longer, and repeated declines in estrogen level occur with greater magnitude during perimenopause.

Objective  To investigate whether MAO-A total distribution volume (VT), an index of MAO-A density, is elevated in women of perimenopausal age (41-51 years).

Design, Setting, and Participants  In a cross-sectional study at a tertiary care psychiatric hospital, 58 women underwent carbon 11–labeled harmine positron emission tomography. These included 19 young women of reproductive age (mean [SD], 28.26 [5.05] years), 27 women of perimenopausal age (mean [SD] age, 45.21 [3.41] years; including 14 women with change in menstrual cycle length with a mean [SD] age of 45.50 [4.00] years and 13 women with no change in menstrual cycle length with a mean [SD] age of 44.92 [2.81] years), and 12 women in menopause (mean [SD] age, 56.25 [3.19] years).

Main Outcomes and Measures  Values of MAO-A VT in the prefrontal cortex, anterior cingulate cortex, dorsal striatum, ventral striatum, thalamus, hippocampus, and midbrain.

Results  On average, MAO-A VT in perimenopausal age was elevated by 34% compared with reproductive age and by 16% compared with menopause (multivariate analysis of variance, group effect, F16,94 = 3.03; P < .001). Within the perimenopausal age group, meeting Stages of Reproductive Aging Workshop criteria for perimenopause, which is mainly based on menstrual cycle length, was not associated with MAO-A VT (F8,18 = 0.548; P = .81) but tendency to cry was positively correlated with MAO-A VT in the prefrontal cortex (r = 0.54; P = .008).

Conclusions and Relevance  To our knowledge, this is the first report of a change in a central biomarker during perimenopausal age that is also present during major depressive episodes and high-risk states for major depressive episodes. The functions of MAO-A influence oxidative stress and apoptosis, 2 processes implicated as excessive in both mood disorders and dementia. Hence, greater MAO-A VT during perimenopause may represent a new target for assessing novel interventions to prevent mood disorders and reduce longer-term risk of neurodegenerative disease.

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Figure 1.
Monoamine Oxidase A (MAO-A) Total Distribution Volume (VT) in Women of Young Reproductive Age, Women of Perimenopausal Age (All Women Regardless of Cycle Length), and Older Women in Menopause

On average, MAO-A VT in perimenopausal age was 34% greater compared with reproductive age and 16% greater compared with menopause (multivariate analysis of variance, group effect, F16,94 = 3.03; P < .001). Horizontal lines indicate mean MAO-A VT.

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Figure 2.
Comparison of Monoamine Oxidase A (MAO-A) Total Distribution Volume (VT) in the Prefrontal Cortex and Anterior Cingulate Cortex in Women in the Perimenopausal Age Group With No Change in Menstrual Cycle Length vs Those With a Significant Change in Menstrual Cycle Length

Within the perimenopausal age group, MAO-A VT was not associated with meeting Stages of Reproductive Aging Workshop criteria for perimenopause (F8,18 = 0.548; P = .81). Horizontal lines indicate mean MAO-A VT.

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Figure 3.
Positive Correlation Between Monoamine Oxidase A (MAO-A) Total Distribution Volume (VT) in the Prefrontal Cortex and Scores on the Adult Crying Inventory in the Perimenopausal Age Group

For the correlation between MAO-A VT in the prefrontal cortex and scores on the Adult Crying Inventory, r = 0.54 (2-tailed P = .008).

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