Abstract
Functional and structural brain changes associated with the cognitive processing of emotional visual stimuli were assessed in schizophrenic patients after 16 weeks of antipsychotic treatment with ziprasidone. Forty-five adults aged 18 to 40 were recruited: 15 schizophrenia patients (DSM-IV criteria) treated with ziprasidone (mean daily dose = 120 mg), 15 patients treated with other antipsychotics, and 15 healthy controls who did not receive any medication. Functional and structural neuroimaging data were acquired at baseline and 16 weeks after treatment initiation. In each session, participants selected stimuli, taken from standardized sets, based on their emotional valence. After ziprasidone treatment, several prefrontal regions, typically involved in cognitive control (anterior cingulate and ventrolateral prefrontal cortices), were significantly activated in patients in response to positive versus negative stimuli. This effect was greater whenever they had to select negative compared to positive stimuli, indicating an asymmetric effect of cognitive treatment of emotionally laden information. No such changes were observed for patients under other antipsychotics. In addition, there was an increase in the brain volume commonly recruited by healthy controls and patients under ziprasidone, in response to cognitive processing of emotional information. The structural analysis showed no significant changes in the density of gray and white matter in ziprasidone-treated patients compared to patients receiving other antipsychotic treatments. Our results suggest that functional changes in brain activity after ziprasidone medication precede structural and clinical manifestations, as markers that the treatment is efficient in restoring the functionality of prefrontal circuits involved in processing emotionally laden information in schizophrenia.
Similar content being viewed by others
References
Abdi Z, Sharma T (2004) Social cognition and its neural correlates in schizophrenia and autism. CNS spectrums 9:335–343
Addington D, Addington J, Schissel B (1990) A depression rating scale for schizophrenics. Schizophr Res 3:247–251
Adell A, Castro E, Celada P, Bortolozzi A, Pazos A, Artigas F (2005) Strategies for producing faster acting antidepressants. Drug Discov Today 10:578–585. doi:10.1016/S1359-6446(05)03398-2
Akil M, Pierri JN, Whitehead RE, Edgar CL, Mohila C, Sampson AR, Lewis DA (1999) Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. Am J Psychiatry 156:1580–1589
Badre D, Hoffman J, Cooney JW, D'Esposito M (2009) Hierarchical cognitive control deficits following damage to the human frontal lobe. Nat Neurosci 12:515–522
Barbas H (2000) Complementary roles of prefrontal cortical regions in cognition, memory, and emotion in primates. Adv Neurol 84:87–110
Beer JS, John OP, Scabini D, Knight RT (2006) Orbitofrontal cortex and social behavior: integrating self-monitoring and emotion-cognition interactions. J Cogn Neurosci 18:871–879. doi:10.1162/jocn.2006.18.6.871
Blasi G et al (2009) Changes in prefrontal and amygdala activity during olanzapine treatment in schizophrenia. Psychiatry Res 173:31–38. doi:10.1016/j.pscychresns.2008.09.001
Bonelli RM, Cummings JL (2007) Frontal-subcortical circuitry and behavior. Dialogues Clin Neurosci 9:141–151
Bush G, Luu P, Posner MI (2000) Cognitive and emotional influences in anterior cingulate cortex. Trends Cogn Sci 4:215–222
Davis KL, Kahn RS, Ko G, Davidson M (1991) Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 148:1474–1486
Dolcos F, LaBar KS, Cabeza R (2004) Dissociable effects of arousal and valence on prefrontal activity indexing emotional evaluation and subsequent memory: an event-related fMRI study. NeuroImage 23:64–74. doi:10.1016/j.neuroimage.2004.05.015
Duncan J, Owen AM (2000) Common regions of the human frontal lobe recruited by diverse cognitive demands. Trends Neurosci 23:475–483
Fahim C et al (2005) Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study. Psychiatry Res 140:1–15. doi:10.1016/j.pscychresns.2005.06.003
Fornito A, Yucel M, Patti J, Wood SJ, Pantelis C (2009) Mapping grey matter reductions in schizophrenia: an anatomical likelihood estimation analysis of voxel-based morphometry studies. Schizophr Res 108:104–113. doi:10.1016/j.schres.2008.12.011
Fusar-Poli P et al (2009) Functional atlas of emotional faces processing: a voxel-based meta-analysis of 105 functional magnetic resonance imaging studies. Journal of psychiatry & neuroscience : JPN 34:418–432
Garver DL, Holcomb JA, Christensen JD (2005) Cerebral cortical gray expansion associated with two second-generation antipsychotics. Biol Psychiatry 58:62–66. doi:10.1016/j.biopsych.2005.02.008
Gessa GL, Devoto P, Diana M, Flore G, Melis M, Pistis M (2000) Dissociation of haloperidol, clozapine, and olanzapine effects on electrical activity of mesocortical dopamine neurons and dopamine release in the prefrontal cortex. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 22:642–649. doi:10.1016/S0893-133X(00)00087-7
Goldman-Rakic PS (1987) Development of cortical circuitry and cognitive function. Child Dev 58:601–622
Grimm S et al (2006) Segregated neural representation of distinct emotion dimensions in the prefrontal cortex-an fMRI study. NeuroImage 30:325–340. doi:10.1016/j.neuroimage.2005.09.006
Guillaume F, Guillem F, Tiberghien G, Stip E (2012) ERP investigation of study-test background mismatch during face recognition in schizophrenia. Schizophr Res 134:101–109. doi:10.1016/j.schres.2011.10.010
Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276
Kim GW, Yang JC, Jeong GW (2015) Emotional effect on cognitive control in implicit memory tasks in patients with schizophrenia. Neuroreport 26:647–655. doi:10.1097/WNR.0000000000000405
Kumari V, Anilkumar A, Ffytche D, Mehrotra R, Mitterschiffthaler M, Sharma T (2008) Neural effects of ziprasidone monotherapy in first-episode schizophrenia: a longitudinal study using fMRI and a procedural learning paradigm. Clinical Schizophrenia & Related Psychoses 1:317–327. doi:10.3371/CSRP.1.4.3
Lang PJ, Öhman A, Vaitl D (1988) The International Affective Picture System (photographic slides). Center for Research in Psychophysiology University of Florida, Gainesville
Lesh TA, Niendam TA, Minzenberg MJ, Carter CS (2011) Cognitive control deficits in schizophrenia: mechanisms and meaning. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 36:316–338. doi:10.1038/npp.2010.156
Mayberg HS et al (1999) Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 156:675–682
Meltzer H (1989) Serotonergic dysfunction in depression. Br J Psychiatry Suppl:25–31
Mendrek A, Mancini-Marie A, Fahim C, Stip E (2007) Sex differences in the cerebral function associated with processing of aversive stimuli by schizophrenia patients. Aust N Z J Psychiatry 41:136–141. doi:10.1080/00048670601109907
Miller EK, Cohen JD (2001) An integrative theory of prefrontal cortex function. Annu Rev Neurosci 24:167–202
Mnie-Filali O, Lambas-Senas L, Zimmer L, Haddjeri N (2007) 5-HT7 receptor antagonists as a new class of antidepressants. Drug News Perspect 20:613–618. doi:10.1358/dnp.2007.20.10.1181354
Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9:97–113
Orban P, Desseilles M, Mendrek A, Bourque J, Bellec P, Stip E (2016) Altered brain connectivity in schizophrenia is consistent regardless of cognitive context similarity. Journal of Psychiatry and Neuroscience (in press)
Papakostas GI, Fava M, Baer L, Swee MB, Jaeger A, Bobo WV, Shelton RC (2015) Ziprasidone augmentation of escitalopram for major depressive disorder: efficacy results from a randomized, double-blind, placebo-controlled study. Am J Psychiatry 172:1251–1258. doi:10.1176/appi.ajp.2015.14101251
Paquet F, Soucy JP, Stip E, Levesque M, Elie A, Bedard MA (2004) Comparison between olanzapine and haloperidol on procedural learning and the relationship with striatal D2 receptor occupancy in schizophrenia. The Journal of neuropsychiatry and clinical neurosciences 16:47–56
Patton JH, Stanford MS, Barratt ES (1995) Factor structure of the Barratt impulsiveness scale. J Clin Psychol 51:768–774
Penny WD, Holmes AJ (2003) Random-effects analysis. In: Frackowiak RSJ et al (eds) Human brain function, 2nd edn. Academic Press, London, pp 843–850
Pezze MA, Feldon J (2004) Mesolimbic dopaminergic pathways in fear conditioning. Prog Neurobiol 74:301–320. doi:10.1016/j.pneurobio.2004.09.004
Phan KL, Wager T, Taylor SF, Liberzon I (2002) Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. NeuroImage 16:331–348. doi:10.1006/nimg.2002.1087
Roth BL, Hanizavareh SM, Blum AE (2004) Serotonin receptors represent highly favorable molecular targets for cognitive enhancement in schizophrenia and other disorders. Psychopharmacology 174:17–24. doi:10.1007/s00213-003-1683-8
Sabatinelli D, Flaisch T, Bradley MM, Fitzsimmons JR, Lang PJ (2004) Affective picture perception: gender differences in visual cortex? Neuroreport 15:1109–1112
Sakurai H et al (2012) Dopamine D2 receptor occupancy and cognition in schizophrenia: analysis of the CATIE data. Schizophr Bull. doi:10.1093/schbul/sbr189
Scherer H et al (2004) Procedural learning in schizophrenia can reflect the pharmacologic properties of the antipsychotic treatments. Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology 17:32–40
Schneider MR et al (2012) The effects of ziprasidone on prefrontal and amygdalar activation in manic youth with bipolar disorder. The Israel journal of psychiatry and related sciences 49:112–120
Seamans JK, Yang CR (2004) The principal features and mechanisms of dopamine modulation in the prefrontal cortex. Prog Neurobiol 74:1–58. doi:10.1016/j.pneurobio.2004.05.006
Stip E, Chouinard S, Boulay LJ (2005) On the trail of a cognitive enhancer for the treatment of schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry 29:219–232. doi:10.1016/j.pnpbp.2004.11.004
Stip E, Zhornitsky S, Moteshafi H, Letourneau G, Stikarovska I, Potvin S, Tourjman V (2011) Ziprasidone for psychotic disorders: a meta-analysis and systematic review of the relationship between pharmacokinetics, pharmacodynamics, and clinical profile. Clin Ther 33:1853–1867. doi:10.1016/j.clinthera.2011.10.027
Talairach J, Tournoux P (1988) Co-planar stereotaxic atlas of the human brain. Thieme Medical Publishers, New York
Tikasz A, Potvin S, Lungu O, Joyal CC, Hodgins S, Mendrek A, Dumais A (2016) Anterior cingulate hyperactivations during negative emotion processing among men with schizophrenia and a history of violent behavior. Neuropsychiatr Dis Treat 12:1397–1410. doi:10.2147/NDT.S107545
Ursu S et al (2011) Prefrontal cortical deficits and impaired cognition-emotion interactions in schizophrenia. Am J Psychiatry 168:276–285. doi:10.1176/appi.ajp.2010.09081215
Zhornitsky S, Potvin S, Aubin G, Stip E (2011) Relationship between insight into cognition, extrapyramidal symptoms and mental illness in schizophrenia. Aust N Z J Psychiatry 45:604–605. doi:10.3109/00048674.2011.561483
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All participants were right-handed and they signed an informed detailed consent form approved by the ethics committee of the Centre de Recherche de l’Institut Universitaire de gériatrie de Montréal–CRIUGM (where neuroimaging sessions took place) prior to participation in the study.
Rights and permissions
About this article
Cite this article
Stip, E., Cherbal, A., Luck, D. et al. A neuroimaging study of emotion–cognition interaction in schizophrenia: the effect of ziprasidone treatment. Psychopharmacology 234, 1045–1058 (2017). https://doi.org/10.1007/s00213-017-4533-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-017-4533-9