Gender differences in α-[11C]MTrp brain trapping, an index of serotonin synthesis, in medication-free individuals with major depressive disorder: A positron emission tomography study
Received 14 January 2009; received in revised form 12 February 2010; accepted 13 May 2010.
Abstract
Women are at higher risk than men for developing major depressive disorder (MDD), but the mechanisms underlying this higher risk are unknown. Here, we report proportionally normalized α-[11C]methyl-L-tryptophan brain trapping constant (α-[11C]MTrp K*N), an index of serotonin synthesis, in 25 medication-free individuals with MDD and in 25 gender- and age-matched healthy subjects who were studied using positron emission tomography (PET). Comparisons of α-[11C]MTrp K*N values between the men and women were conducted at the voxel and cluster levels using Statistical Parametric Mapping 2 (SPM2) analysis. In addition, the α-[11C]MTrp K*N values on both sides of the brain were extracted and compared to identify the left to right differences, as well as the gender differences. Women with MDD displayed higher α-[11C]MTrp K*N than men in the inferior frontal gyrus, anterior cingulate cortex (ACC), parahippocampal gyrus, precuneus, superior parietal lobule, and occipital lingual gyrus. In a matched group of normal subjects the gender differences were opposite from those found in MDD patients. Significant hemispheric differences in fronto-limbic structures between men and women with MDD were also observed. The K*N extracted from the volumes identified in MDD patients and in male and female normal subjects suggested no significant differences between males and females. In conclusion, depressed women have higher serotonin synthesis in multiple regions of the prefrontal cortex and limbic system involved with mood regulation, as compared with depressed men. Gender differences in brain serotonin synthesis may be related to higher risk for MDD in women.
Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada H3A 2B4 and Montreal Neurological Institute, McGill University, Montreal, QC, Canada H3A 2B4
Corresponding author. Montreal Neurological Institute, 3801 University Street, Montreal, QC, Canada H3A 2B4. Tel.: +1 514 398 8526; fax: +1 514 398 8195.
1 Present address: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
2 Present address: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada.
3 Department of Neuropsychiatry, Fukushima Medical University School of Medicine, Fukushima, Japan.
4 Present address: Department of Social Education, Kawamura Gakuen Woman's University, Abiko, Chiba, Japan.
ABSTRACT