Despite a large number of functional neuroimaging investigations of emotion processing in schizophrenia, very few have included women. In the present study 21 schizophrenia and 23 healthy women underwent functional MRI (3T) on two occasions (during the follicular and luteal phase of their menstrual cycle) while viewing blocks of emotionally negative, positive and neutral images. During exposure to negatively charged images patients showed relatively less activations than controls during the luteal phase, but no between-group differences were observed during the follicular phase. In contrast, the exposure to positively valenced material produced no significant interaction, but the main effect of group; schizophrenia patients exhibited less activation than healthy controls during both phases of the menstrual cycle. This is the first study demonstrating that atypical neural activations associated with emotion processing in women diagnosed with schizophrenia depend on the menstrual cycle phase and on the affective valence of presented stimuli. 1. Introduction Schizophrenia is a complex and clinically heterogeneous psychiatric disorder with unknown etiology, age at onset in late adolescence/early adulthood, and a lifetime prevalence of approximately 1% [1, 2]. One of the hallmark characteristics of this devastating disorder is a disturbance in emotion processing, which has been demonstrated in numerous behavioral, physiological, and functional neuroimaging investigations that employed tasks ranging from passive viewing of emotional material, through to facial emotion identification and emotional memory [3–8]. Although widely investigated, the neural correlates of atypical emotion processing in schizophrenia patients are still not well understood. For instance, while the majority of studies report diminished activations in patients relative to healthy subjects in several regions implicated in affect (e.g., hippocampus, amygdala, medial prefrontal, orbitofrontal cortex, and cingulate cortices) (e.g., [9–12]), others have found no effect or increased neural reactivity to emotionally charged material (e.g., [13–15]). In our recent study we have observed diminished activations during retrieval of negatively valenced emotional material but enhanced activations during positively valenced condition in clinically stable schizophrenia patients relative to controls [8]. Thus, one important factor to consider is affective valence of presented stimuli. Another important variable is gender of tested individuals, as numerous studies in the general population have
References
[1]
W. T. Carpenter Jr., “Targeting schizophrenia research to patient outcomes,” American Journal of Psychiatry, vol. 163, no. 3, pp. 353–355, 2006.
[2]
J. van Os and S. Kapur, “Schizophrenia,” The Lancet, vol. 374, no. 9690, pp. 635–645, 2009.
[3]
A. E. Pinkham, R. E. Gur, and R. C. Gur, “Affect recognition deficits in schizophrenia: neural substrates and psychopharmacological implications,” Expert Review of Neurotherapeutics, vol. 7, no. 7, pp. 807–816, 2007.
[4]
M. Hoekert, R. S. Kahn, M. Pijnenborg, and A. Aleman, “Impaired recognition and expression of emotional prosody in schizophrenia: review and meta-analysis,” Schizophrenia Research, vol. 96, no. 1–3, pp. 135–145, 2007.
[5]
R. W. Morris, C. S. Weickert, and C. M. Loughland, “Emotional face processing in schizophrenia,” Current Opinion in Psychiatry, vol. 22, no. 2, pp. 140–146, 2009.
[6]
S. Kalkstein, I. Hurford, and R. C. Gur, “Neurocognition in schizophrenia,” Current Topics in Behavioral Neurosciences, vol. 4, pp. 373–390, 2010.
[7]
M. F. Green, C. E. Bearden, T. D. Cannon, et al., “Social cognition in schizophrenia, part 1: performance across phase of illness,” Schizophr Bull. In press.
[8]
N. Lakis, J. A. Jiménez, A. Mancini-Mar？e, E. Stip, M. E. Lavoie, and A. Mendrek, “Neural correlates of emotional recognition memory in schizophrenia: effects of valence and arousal,” Psychiatry Research, vol. 194, no. 3, pp. 245–256, 2011.
[9]
F. Schneider, U. Weiss, C. Kessler et al., “Differential amygdala activation in schizophrenia during sadness,” Schizophrenia Research, vol. 34, no. 3, pp. 133–142, 1998.
[10]
R. E. Gur, C. McGrath, R. M. Chan et al., “An fMRI study of facial emotion processing in patients with schizophrenia,” American Journal of Psychiatry, vol. 159, no. 12, pp. 1992–1999, 2002.
[11]
S. Paradiso, N. C. Andreasen, B. Crespo-Facorro et al., “Emotions in unmedicated patients with schizophrenia during evaluation with positron emission tomography,” American Journal of Psychiatry, vol. 160, no. 10, pp. 1775–1783, 2003.
[12]
H. Takahashi, M. Koeda, K. Oda et al., “An fMRI study of differential neural response to affective pictures in schizophrenia,” NeuroImage, vol. 22, no. 3, pp. 1247–1254, 2004.
[13]
M. Reske, U. Habel, T. Kellermann et al., “Differential brain activation during facial emotion discrimination in first-episode schizophrenia,” Journal of Psychiatric Research, vol. 43, no. 6, pp. 592–599, 2009.
[14]
E. C. Dowd and D. M. Barch, “Anhedonia and emotional experience in schizophrenia: neural and behavioral indicators,” Biological Psychiatry, vol. 67, no. 10, pp. 902–911, 2010.
[15]
K. Sergerie, J. L. Armony, M. Menear, H. Sutton, and M. Lepage, “Influence of emotional expression on memory recognition bias in schizophrenia as revealed by fMRI,” Schizophrenia Bulletin, vol. 36, no. 4, pp. 800–810, 2010.
[16]
T. D. Wager, K. L. Phan, I. Liberzon, and S. F. Taylor, “Valence, gender, and lateralization of functional brain anatomy in emotion: a meta-analysis of findings from neuroimaging,” NeuroImage, vol. 19, no. 3, pp. 513–531, 2003.
[17]
L. Cahill, “Sex influences on brain and emotional memory: the burden of proof has shifted,” Progress in Brain Research, vol. 186, pp. 29–40, 2010.
[18]
B. Derntl, A. Finkelmeyer, S. Eickhoff et al., “Multidimensional assessment of empathic abilities: neural correlates and gender differences,” Psychoneuroendocrinology, vol. 35, no. 1, pp. 67–82, 2010.
[19]
G. Domes, L. Schulze, M. B？ttger et al., “The neural correlates of sex differences in emotional reactivity and emotion regulation,” Human Brain Mapping, vol. 31, no. 5, pp. 758–769, 2010.
[20]
M. Mather, N. R. Lighthall, L. Nga, and M. A. Gorlick, “Sex differences in how stress affects brain activity during face viewing,” NeuroReport, vol. 21, no. 14, pp. 933–937, 2010.
[21]
K. M. Abel, R. Drake, and J. M. Goldstein, “Sex differences in schizophrenia,” International Review of Psychiatry, vol. 22, no. 5, pp. 417–428, 2010.
[22]
A. Mendrek, A. Mancini-Mari？, C. Fahim, and E. Stip, “Sex differences in the cerebral function associated with processing of aversive stimuli by schizophrenia patients,” Australian and New Zealand Journal of Psychiatry, vol. 41, no. 2, pp. 136–141, 2007.
[23]
A. Mendrek, N. Lakis, and J. Jimenez, “Associations of sex steroid hormones with cerebral activations during mental rotation in men and women with schizophrenia,” Psychoneuroendocrinology, vol. 36, pp. 1422–1426, 2011.
[24]
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.
[25]
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.
[26]
M. A. Farage, T. W. Osborn, and A. B. MacLean, “Cognitive, sensory, and emotional changes associated with the menstrual cycle: a review,” Archives of Gynecology and Obstetrics, vol. 278, no. 4, pp. 299–307, 2008.
[27]
J. Kulkarni, “Oestrogen—a new treatment approach for schizophrenia?” Medical Journal of Australia, vol. 190, supplement 4, pp. S37–S38, 2009.
[28]
A. Mendrek, “Reversal of normal cerebral sexual dimorphism in schizophrenia: evidence and speculations,” Medical Hypotheses, vol. 69, no. 4, pp. 896–902, 2007.
[29]
A. M. Mortimer, “Relationship between estrogen and schizophrenia,” Expert Review of Neurotherapeutics, vol. 7, no. 1, pp. 45–55, 2007.
[30]
L. Ossewaarde, S. Qin, H. J. F. Van Marle, G. A. van Wingen, G. Fernández, and E. J. Hermans, “Stress-induced reduction in reward-related prefrontal cortex function,” NeuroImage, vol. 55, no. 1, pp. 345–352, 2011.
[31]
J. M. Goldstein, M. Jerram, R. Poldrack et al., “Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging,” Journal of Neuroscience, vol. 25, no. 40, pp. 9309–9316, 2005.
[32]
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.
[33]
N. Bergemann, C. Mundt, P. Parzer et al., “Estrogen as an adjuvant therapy to antipsychotics does not prevent relapse in women suffering from schizophrenia: results of a placebo-controlled double-blind study,” Schizophrenia Research, vol. 74, no. 2-3, pp. 125–134, 2005.
[34]
T. J. Huber, M. Borsutzky, U. Schneider, and H. M. Emrich, “Psychotic disorders and gonadal function: evidence supporting the oestrogen hypothesis,” Acta Psychiatrica Scandinavica, vol. 109, no. 4, pp. 269–274, 2004.
[35]
J. H. Zhang-Wong and M. V. Seeman, “Antipsychotic drugs, menstrual regularity and osteoporosis risk,” Archives of Women's Mental Health, vol. 5, no. 3, pp. 93–98, 2002.
[36]
APA, American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, American Psychiatric Press, Washington, DC, USA, 4th edition, 1994.
[37]
R. C. Oldfield, “The assessment and analysis of handedness: the Edinburgh inventory,” Neuropsychologia, vol. 9, no. 1, pp. 97–113, 1971.
[38]
Census, “The National Occupational Classification and the Career Handbook,” vol. 23, pp. 56–62, 2001, http://www5.hrsdc.gc.ca/noc/English/CH/2001/IntroductionNOCandCH.aspx.
[39]
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.
[40]
R. L. Spitzer, J. B. W. 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.
[41]
P. J. Lang, A. ？hman, and D. Vaitl, The International Affective Picture System, Center for Research in Psychophysiology, University of Florida, Gainesville, Fla, USA, 1988.
[42]
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.
[43]
D. Sabatinelli, E. E. Fortune, Q. Li et al., “Emotional perception: meta-analyses of face and natural scene processing,” NeuroImage, vol. 54, no. 3, pp. 2524–2533, 2011.
[44]
P. Fusar-Poli, A. Placentino, F. Carletti et al., “Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies,” Journal of Psychiatry and Neuroscience, vol. 34, no. 6, pp. 418–432, 2009.
[45]
S. G. Costafreda, M. J. Brammer, A. S. David, and C. H. Y. Fu, “Predictors of amygdala activation during the processing of emotional stimuli: a meta-analysis of 385 PET and fMRI studies,” Brain Research Reviews, vol. 58, no. 1, pp. 57–70, 2008.
[46]
T. W. Buchanan, “Retrieval of emotional memories,” Psychological Bulletin, vol. 133, no. 5, pp. 761–779, 2007.
[47]
B. Walter, C. Blecker, P. Kirsch, et al., “MARINA: an easy to use tool for the creation of MAsks for region of INterest analyses,” in Proceedings of the 9th International Conference on Functional Mapping of the Human Brain, vol. 19, no. 2, New York, NY, USA, June 2003, Available on CD-Rom in NeuroImage.
[48]
N. Tzourio-Mazoyer, B. Landeau, D. Papathanassiou et al., “Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain,” NeuroImage, vol. 15, no. 1, pp. 273–289, 2002.
[49]
J. B. Poline, K. J. Worsley, A. C. Evans, and K. J. Friston, “Combining spatial extent and peak intensity to test for activations in functional imaging,” NeuroImage, vol. 5, no. 2, pp. 83–96, 1997.
[50]
R. E. Gur, J. Loughead, C. G. Kohler et al., “Limbic activation associated with misidentification of fearful faces and flat affect in schizophrenia,” Archives of General Psychiatry, vol. 64, no. 12, pp. 1356–1366, 2007.
[51]
D. K. Shayegan and S. M. Stahl, “Emotion processing, the amygdala, and outcome in schizophrenia,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 29, no. 5, pp. 840–845, 2005.
[52]
L. Pessoa and R. Adolphs, “Emotion processing and the amygdala: from a “low road” to “many roads” of evaluating biological significance,” Nature Reviews Neuroscience, vol. 11, no. 11, pp. 773–782, 2010.
[53]
P. Vuilleumier and J. Driver, “Modulation of visual processing by attention and emotion: windows on causal interactions between human brain regions,” Philosophical Transactions of the Royal Society B, vol. 362, no. 1481, pp. 837–855, 2007.
[54]
C. J. Stoodley and J. D. Schmahmann, “Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing,” Cortex, vol. 46, no. 7, pp. 831–844, 2010.
[55]
N. C. Andreasen and R. Pierson, “The role of the cerebellum in schizophrenia,” Biological Psychiatry, vol. 64, no. 2, pp. 81–88, 2008.
[56]
N. C. Andreasen, “A unitary model of schizophrenia. Bleuler's “fragmented phrene” as schizencephaly,” Archives of General Psychiatry, vol. 56, no. 9, pp. 781–787, 1999.
[57]
M. Endo, M. Daiguji, Y. Asano, I. Yamashita, and S. Takahashi, “Periodic psychosis recurring in association with menstrual cycle,” Journal of Clinical Psychiatry, vol. 39, no. 5, pp. 456–466, 1978.
[58]
J. D. Hallonquist, M. V. Seeman, M. Lang, and N. A. Rector, “Variation in symptom severity over the menstrual cycle of schizophrenics,” Biological Psychiatry, vol. 33, no. 3, pp. 207–209, 1993.
[59]
S. S. Chang and D. C. Renshaw, “Psychosis and pregnancy,” Comprehensive Therapy, vol. 12, no. 10, pp. 36–41, 1986.
[60]
R. E. Kendell, J. C. Chalmers, and C. Platz, “Epidemiology of puerperal psychoses,” British Journal of Psychiatry, vol. 150, pp. 662–673, 1987.
