All Title Author
Keywords Abstract

Progesterone and Cerebral Function during Emotion Processing in Men and Women with Schizophrenia

DOI: 10.1155/2012/917901

Full-Text   Cite this paper   Add to My Lib


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 [4]. 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 [5]. 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 [6]. 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 [7],


[1]  J. M. Andreano and L. Cahill, “Menstrual cycle modulation of medial temporal activity evoked by negative emotion,” NeuroImage, vol. 53, no. 4, pp. 1286–1293, 2010.
[2]  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.
[3]  M. Zitzmann, “Testosterone and the brain,” Aging Male, vol. 9, no. 4, pp. 195–199, 2006.
[4]  G. A. van Wingen, L. Ossewaarde, T. B?ckstr?m, E. J. Hermans, and G. Fernández, “Gonadal hormone regulation of the emotion circuitry in humans,” Neuroscience, vol. 191, pp. 38–45, 2011.
[5]  J. R. Bostwick, S. K. Guthrie, and V. L. Ellingrod, “Antipsychotic-induced hyperprolactinemia,” Pharmacotherapy, vol. 29, no. 1, pp. 64–73, 2009.
[6]  V. Hendrick, L. L. Altshuler, and V. K. Burt, “Course of psychiatric disorders across the menstrual cycle,” Harvard Review of Psychiatry, vol. 4, no. 4, pp. 200–207, 1996.
[7]  D. R. Rubinow and P. J. Schmidt, “The neuroendocrinology of menstrual cycle mood disorders,” Annals of the New York Academy of Sciences, vol. 771, pp. 648–659, 1995.
[8]  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.
[9]  R. D. Brinton, R. F. Thompson, M. R. Foy et al., “Progesterone receptors: form and function in brain,” Frontiers in Neuroendocrinology, vol. 29, no. 2, pp. 313–339, 2008.
[10]  American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders DSM-IV-TR Fourth Edition, American Psychiatric Press, Washington, DC, USA, 1994.
[11]  R. C. Oldfield, “The assessment and analysis of handedness: the Edinburgh inventory,” Neuropsychologia, vol. 9, no. 1, pp. 97–113, 1971.
[12]  Census, The National Occupational Classification and the Career Handbook, 23: pp. 56–62, 2001,
[13]  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.
[14]  S. R. Kay, A. Fiszbein, and L. A. Opler, “The positive and negative syndrome scale (PANSS) for schizophrenia,” Schizophrenia Bulletin, vol. 13, no. 2, pp. 261–276, 1987.
[15]  S. W. Woods, “Chlorpromazine equivalent doses for the newer atypical antipsychotics,” Journal of Clinical Psychiatry, vol. 64, no. 6, pp. 663–667, 2003.
[16]  P.J. Lang, A. ?hman, and D. Vaitl, The International Affective Picture System (Photographic Slides), Center for Research in Psychophysiology, University of Florida, Gainesville, Fla, USA, 1988.
[17]  K. J. Friston, “Commentary and opinion: II. Statistical parametric mapping: ontology and current issues,” Journal of Cerebral Blood Flow and Metabolism, vol. 15, no. 3, pp. 361–370, 1995.
[18]  K. L. Phan, T. Wager, S. F. Taylor, and I. Liberzon, “Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI,” NeuroImage, vol. 16, no. 2, pp. 331–348, 2002.
[19]  E. M. Reiman, R. D. Lane, G. L. Ahern et al., “Neuroanatomical correlates of externally and internally generated human emotion,” American Journal of Psychiatry, vol. 154, no. 7, pp. 918–925, 1997.
[20]  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.
[21]  U. Habel, M. Klein, T. Kellermann, N. J. Shah, and F. Schneider, “Same or different? Neural correlates of happy and sad mood in healthy males,” NeuroImage, vol. 26, no. 1, pp. 206–214, 2005.
[22]  A. Bartels and S. Zeki, “The neural basis of romantic love,” NeuroReport, vol. 11, no. 17, pp. 3829–3834, 2000.
[23]  M. Beauregard, J. Lévesque, and P. Bourgouin, “Neural correlates of conscious self-regulation of emotion,” The Journal of Neuroscience, vol. 21, no. 18, Article ID RC165, 2001.
[24]  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.
[25]  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.
[26]  J. O'Doherty, E. T. Rolls, S. Francis, R. Bowtell, and F. McGlone, “Representation of pleasant and aversive taste in the human brain,” Journal of Neurophysiology, vol. 85, no. 3, pp. 1315–1321, 2001.
[27]  J. F. Monroe, M. Griffin, A. Pinkham et al., “The fusiform response to faces: explicit versus implicit processing of emotion,” Human Brain Mapping. In press.
[28]  O. S. Gbadebo, “Reduced maladaptive behavior and improved social function in a child with PDD-NOS treated with progesterone,” Clinical Medicine and Research, vol. 9, no. 2, pp. 100–102, 2011.
[29]  D. S. Reddy, B. W. O'Malley, and M. A. Rogawski, “Anxiolytic activity of progesterone in progesterone receptor knockout mice,” Neuropharmacology, vol. 48, no. 1, pp. 14–24, 2005.
[30]  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.
[31]  J. Kato, S. Hirata, A. Nozawa, and N. Yamada-Mouri, “Gene expression of progesterone receptor isoforms in the rat brain,” Hormones and Behavior, vol. 28, no. 4, pp. 454–463, 1994.
[32]  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.
[33]  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.
[34]  C. L. Bethea, M. Pecins-Thompson, W. E. Schutzer, C. Gundlah, and Z. N. Lu, “Ovarian steroids and serotonin neural function,” Molecular Neurobiology, vol. 18, no. 2, pp. 87–123, 1998.
[35]  C. N. Epperson, K. L. Wisner, and B. Yamamoto, “Gonadal steroids in the treatment of mood disorders,” Psychosomatic Medicine, vol. 61, no. 5, pp. 676–697, 1999.


comments powered by Disqus