Schizophrenia has been associated with disturbed levels of sex-steroid hormones, including estrogen and testosterone. In the present study we have examined the implication of a less studied hormone progesterone. Forty-three patients with schizophrenia (21 women) and 43 control participants (21 women) underwent functional MRI while viewing emotionally positive, negative, and neutral images. Blood samples were taken prior to the scanning session to evaluate progesterone levels. Simple regression analyses between levels of progesterone and brain activations associated with emotion processing were performed using SPM5. A positive correlation was found between progesterone levels and brain activations during processing of emotionally charged images in both healthy and schizophrenia men, but no significant relationship was revealed in women. These preliminary results indicate that progesterone is significantly associated with brain activations during processing of positive and negative affect in healthy and schizophrenia men, but not in women. Further investigation is warranted. 1. Introduction There is some evidence of a relationship between sex-steroid hormones (i.e., estrogen, testosterone, and less commonly progesterone) and emotion processing in the general population [1–3]. Fluctuations in estrogen and progesterone have been linked with increased vulnerability to mood disorders in women, while elevated levels of testosterone have been primarily associated with antisocial behaviours, behaviours of dominance, and aggressiveness in both men and women . In schizophrenia, some studies have found abnormal levels of estrogens and testosterone in patients, but the results have been equivocal and sometimes attributed to the antipsychotic-induced hyperprolactinemia, which may alter levels of gonadal hormones . Despite numerous studies and clinical observations of lower relapse of clinical symptoms during pregnancy, high relapse postpartum, and the fluctuation of symptoms across the menstrual cycle (attributed typically to the changing levels of estrogens), a link between progesterone and affect in schizophrenia has yet to be examined . The little emphasis that has been placed on the relationship between progesterone and emotional functioning has been explored primarily in healthy women because this hormone is a female reproductive hormone. Nonetheless, it is produced in both men and women, and recent evidence suggests that it is implicated in brain function of both sexes. Thus, progesterone has been shown to play an important role in mood regulation ,
V. G. Guapo, F. G. Graeff, A. C. T. Zani, C. M. Labate, R. M. dos Reis, and C. M. Del-Ben, “Effects of sex hormonal levels and phases of the menstrual cycle in the processing of emotional faces,” Psychoneuroendocrinology, vol. 34, no. 7, pp. 1087–1094, 2009.
E. S. Leblanc, J. Janowsky, B. K. S. Chan, and H. D. Nelson, “Hormone replacement therapy and cognition: systematic review and meta-analysis,” Journal of the American Medical Association, vol. 285, no. 11, pp. 1489–1499, 2001.
R. L. Spitzer, J. B. Williams, M. Gibbon, and M. B. First, “The structured clinical interview for DSM-III-R (SCID), I: history, rationale, and description,” Archives of General Psychiatry, vol. 49, no. 8, pp. 624–629, 1992.
M. Liotti, H. S. Mayberg, S. K. Brannan, S. McGinnis, P. Jerabek, and P. T. Fox, “Differential limbic-cortical correlates of sadness and anxiety in healthy subjects: implications for affective disorders,” Biological Psychiatry, vol. 48, no. 1, pp. 30–42, 2000.
X. Protopopescu, H. Pan, M. Altemus et al., “Orbitofrontal cortex activity related to emotional processing changes across the menstrual cycle,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 44, pp. 16060–16065, 2005.
G. Northoff, A. Richter, M. Gessner et al., “Functional dissociation between medial and lateral prefrontal cortical spatiotemporal activation in negative and positive emotions: a combined fMRI/MEG study,” Cerebral Cortex, vol. 10, no. 1, pp. 93–107, 2000.
C. Guerra-Araiza, A. Coyoy-Salgado, and I. Camacho-Arroyo, “Sex differences in the regulation of progesterone receptor isoforms expression in the rat brain,” Brain Research Bulletin, vol. 59, no. 2, pp. 105–109, 2002.
C. Guerra-Araiza, O. Villamar-Cruz, A. González-Arenas, R. Chavira, and I. Camacho-Arroyo, “Changes in progestrone receptor isoforms content in the rat brain during the oestrous cycle and after oestradiol and progesterone treatments,” Journal of Neuroendocrinology, vol. 15, no. 10, pp. 984–990, 2003.
M. Bixo, A. Andersson, B. Winblad, R. H. Purdy, and T. B？ckstr？m, “Progesterone, 5 α-pregnane-3,20-dione and 3 α-hydroxy-5 α-pregnane- 20-one in specific regions of the human female brain in different endocrine states,” Brain Research, vol. 764, no. 1-2, pp. 173–178, 1997.