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Both unmedicated and medicated individuals with schizophrenia show impairments across a wide array of cognitive and reinforcement learning tasks

Published online by Cambridge University Press:  17 August 2020

Erin K. Moran ,
James M. Gold ,
Cameron S. Carter ,
Angus W. MacDonald III ,
J. Daniel Ragland ,
Steven M. Silverstein ,
Steven J. Luck  and
Deanna M. Barch
Erin K. Moran*
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA
James M. Gold
Affiliation:
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD, USA
Cameron S. Carter
Affiliation:
Department of Psychiatry, University of California, Davis, CA, USA
Angus W. MacDonald III
Affiliation:
Department of Psychology, University of Minnesota, Minneapolis, MN, USA
J. Daniel Ragland
Affiliation:
Department of Psychiatry, University of California, Davis, CA, USA
Steven M. Silverstein
Affiliation:
Department of Psychiatry, Rutgers Robert Wood Johnson Medical School Hospital, Piscataway, NJ, USA
Steven J. Luck
Affiliation:
Department of Psychology, University of California, Davis, CA, USA
Deanna M. Barch
Affiliation:
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA Department of Psychological & Brain Sciences, Washington University in St. Louis, St. Louis, MO, USA Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA
*
Author for correspondence: Erin K. Moran, E-mail: ekmoran@wustl.edu
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Abstract

Background

Schizophrenia is a disorder characterized by pervasive deficits in cognitive functioning. However, few well-powered studies have examined the degree to which cognitive performance is impaired even among individuals with schizophrenia not currently on antipsychotic medications using a wide range of cognitive and reinforcement learning measures derived from cognitive neuroscience. Such research is particularly needed in the domain of reinforcement learning, given the central role of dopamine in reinforcement learning, and the potential impact of antipsychotic medications on dopamine function.

Methods

The present study sought to fill this gap by examining healthy controls (N = 75), unmedicated (N = 48) and medicated (N = 148) individuals with schizophrenia. Participants were recruited across five sites as part of the CNTRaCS Consortium to complete tasks assessing processing speed, cognitive control, working memory, verbal learning, relational encoding and retrieval, visual integration and reinforcement learning.

Results

Individuals with schizophrenia who were not taking antipsychotic medications, as well as those taking antipsychotic medications, showed pervasive deficits across cognitive domains including reinforcement learning, processing speed, cognitive control, working memory, verbal learning and relational encoding and retrieval. Further, we found that chlorpromazine equivalency rates were significantly related to processing speed and working memory, while there were no significant relationships between anticholinergic load and performance on other tasks.

Conclusions

These findings add to a body of literature suggesting that cognitive deficits are an enduring aspect of schizophrenia, present in those off antipsychotic medications as well as those taking antipsychotic medications.

Keywords

Antipsychotic medicationscognitionreinforcement learningschizophrenia
Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 6 , April 2022 , pp. 1115 - 1125
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Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

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References

Amato, D., Vernon, A. C., & Papaleo, F. (2018). Dopamine, the antipsychotic molecule: A perspective on mechanisms underlying antipsychotic response variability. Neuroscience & Biobehavioral Reviews, 85, 146–159. https://doi.org/10.1016/J.NEUBIOREV.2017.09.027CrossRefGoogle ScholarPubMed
Baker, L. A., Cheng, L. Y., & Amara, I. B. (1983). The withdrawal of benztropine mesylate in chronic schizophrenic patients. The British Journal of Psychiatry, 143(6), 584–590. https://doi.org/10.1192/bjp.143.6.584CrossRefGoogle ScholarPubMed
Barch, D. M., Carter, C. S., Braver, T. S., Sabb, F. W., MacDonald, A., Noll, D. C., & Cohen, J. D. (2001). Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia. Archives of General Psychiatry, 58(3), 280. https://doi.org/10.1001/archpsyc.58.3.280CrossRefGoogle ScholarPubMed
Barch, D. M., Carter, C. S., Gold, J. M., Johnson, S. L., Kring, A. M., MacDonald, A. W. III., … Strauss, M. E. (2017). Explicit and implicit reinforcement learning across the psychosis spectrum. Journal of Abnormal Psychology, 126(5), 694–711. https://doi.org/10.1037/abn0000259CrossRefGoogle ScholarPubMed
Barch, D M, Carter, C. S., MacDonald, A. W., Braver, T. S., & Cohen, J. D. (2003). Context-processing deficits in schizophrenia: Diagnostic specificity, 4-week course, and relationships to clinical symptoms. Journal of Abnormal Psychology, 112(1), 132–143. Retrieved from https://insights.ovid.com/abnormal-psychology/jabnp/2003/02/000/context-processing-deficits-schizophrenia/13/00004468CrossRefGoogle ScholarPubMed
Barch, D. M., & Ceaser, A. (2012). Cognition in schizophrenia: Core psychological and neural mechanisms. Trends in Cognitive Sciences, 16(1), 27–34. https://doi.org/10.1016/J.TICS.2011.11.015CrossRefGoogle ScholarPubMed
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B (Methodological), 57(1), 289–300. https://doi.org/10.1111/j.2517-6161.1995.tb02031.xGoogle Scholar
Bilder, R. M., Goldman, R. S., Robinson, D., Reiter, G., Bell, L., Bates, J. A., … Lieberman, J. A. (2000). Neuropsychology of first-episode schizophrenia: Initial characterization and clinical correlates. American Journal of Psychiatry, 157(4), 549–559. https://doi.org/10.1176/appi.ajp.157.4.549CrossRefGoogle ScholarPubMed
Boustani, M., Campbell, N., Munger, S., Maidment, I., & Fox, C. (2008). Impact of anticholinergics on the aging brain: A review and practical application. Aging Health, 4(3), 311–320. https://doi.org/10.2217/1745509X.4.3.311CrossRefGoogle Scholar
Braff, D. L., & Saccuzzo, D. P. (1982). Effect of antipsychotic medication on speed of information processing in schizophrenic patients. American Journal of Psychiatry, 139(9), 1127–1130. https://doi.org/10.1176/ajp.139.9.1127Google ScholarPubMed
Brandt, J. (1991). The hopkins verbal learning test: Development of a new memory test with six equivalent forms. Clinical Neuropsychologist, 5(2), 125–142. https://doi.org/10.1080/13854049108403297CrossRefGoogle Scholar
Braver, T. S., & Barch, D. M. (2002). A theory of cognitive control, aging cognition, and neuromodulation. Neuroscience & Biobehavioral Reviews, 26(7), 809–817. https://doi.org/10.1016/S0149-7634(02)00067-2CrossRefGoogle ScholarPubMed
Broadway, J. M., & Engle, R. W.. (2010). Validating running memory span: Measurement of working memory capacity and links with fluid intelligence. Behavior Research Methods, 42, 563–570.CrossRefGoogle ScholarPubMed
Butler, P. D., Abeles, I. Y., Silverstein, S. M., Dias, E. C., Weiskopf, N. G., Calderone, D. J., & Sehatpour, P. (2013). An event-related potential examination of contour integration deficits in schizophrenia. Frontiers in Psychology, 4, 132. https://doi.org/10.3389/fpsyg.2013.00132CrossRefGoogle Scholar
Butler, P. D., Silverstein, S. M., & Dakin, S. C. (2008). Visual perception and Its impairment in schizophrenia. Biological Psychiatry, 64(1), 40–47. https://doi.org/10.1016/j.biopsych.2008.03.023CrossRefGoogle Scholar
Byerly, M. J., Nakonezny, P. A., & Lescouflair, E. (2007). Antipsychotic medication adherence in schizophrenia. Psychiatric Clinics of North America, 30(3), 437–452. https://doi.org/10.1016/J.PSC.2007.04.002CrossRefGoogle Scholar
Cadenhead, K. S., Geyer, M. A., Butler, R. W., Perry, W., Sprock, J., & Braff, D. L. (1997). Information processing deficits of schizophrenia patients: Relationship to clinical ratings, gender and medication status. Schizophrenia Research, 28(1), 51–62. https://doi.org/10.1016/S0920-9964(97)00085-6CrossRefGoogle ScholarPubMed
Calev, A. (1984). Recall and recognition in mildly disturbed schizophrenics: The use of matched tasks. Psychological Medicine, 14(02), 425. https://doi.org/10.1017/S0033291700003676CrossRefGoogle ScholarPubMed
Chang, W. C., Waltz, J. A., Gold, J. M., Chan, T. C. W., & Chen, E. Y. H. (2016). Mild reinforcement learning deficits in patients with first-episode psychosis. Schizophrenia Bulletin, 42(6), 1476–1485. https://doi.org/10.1093/schbul/sbw060CrossRefGoogle ScholarPubMed
Cicero, D. C., Martin, E. A., Becker, T. M., & Kerns, J. G. (2014). Reinforcement learning deficits in people with schizophrenia persist after extended trials. Psychiatry Research, 220(3), 760–764. https://doi.org/https://doi.org/10.1016/j.psychres.2014.08.013CrossRefGoogle ScholarPubMed
Culbreth, A. J., Westbrook, A., Xu, Z., Barch, D. M., & Waltz, J. A. (2017). Intact ventral striatal prediction error signaling in medicated schizophrenia patients. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 1(5), 474–483. https://doi.org/10.1016/j.bpsc.2016.07.007Google Scholar
Daban, C., Amado, I., Bourdel, M.-C., Loo, H., Olié, J.-P., Poirier, M.-F., & Krebs, M.-O. (2005). Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia. Journal of Psychiatric Research, 39(4), 391–398. https://doi.org/10.1016/j.jpsychires.2004.09.001CrossRefGoogle ScholarPubMed
Dickinson, D., Ramsey, M. E., & Gold, J. M. (2007). Overlooking the obvious. Archives of General Psychiatry, 64(5), 532. https://doi.org/10.1001/archpsyc.64.5.532CrossRefGoogle ScholarPubMed
Dowd, E. C., Frank, M. J., Collins, A., Gold, J. M., & Barch, D. M. (2016). Probabilistic reinforcement learning in patients with schizophrenia: Relationships to anhedonia and avolition. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 1(5), 460–473. https://doi.org/https://doi.org/10.1016/j.bpsc.2016.05.005Google ScholarPubMed
Élie, D., Poirier, M., Chianetta, J., Durand, M., Grégoire, C., & Grignon, S. (2010). Cognitive effects of antipsychotic dosage and polypharmacy: A study with the BACS in patients with schizophrenia and schizoaffective disorder. Journal of Psychopharmacology, 24(7), 1037–1044. https://doi.org/10.1177/0269881108100777CrossRefGoogle ScholarPubMed
Eum, S., Hill, S. K., Rubin, L. H., Carnahan, R. M., Reilly, J. L., Ivleva, E. I., … Bishop, J. R. (2017). Cognitive burden of anticholinergic medications in psychotic disorders. Schizophrenia Research, 190, 129–135. https://doi.org/10.1016/j.schres.2017.03.034CrossRefGoogle ScholarPubMed
Everitt, B. J., & Robbins, T. W. (1997). Central cholinergic systems and cognition. Annual Review of Psychology, 48(1), 649–684. https://doi.org/10.1146/annurev.psych.48.1.649CrossRefGoogle ScholarPubMed
Fioravanti, M., Carlone, O., Vitale, B., Cinti, M. E., & Clare, L. (2005). A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia. Neuropsychology Review, 15(2), 73–95. https://doi.org/10.1007/s11065-005-6254-9CrossRefGoogle ScholarPubMed
Fox, C., Richardson, K., Maidment, I. D., Savva, G. M., Matthews, F. E., Smithard, D., … Brayne, C. (2011). Anticholinergic medication use and cognitive impairment in the older population: The medical research council cognitive function and ageing study. Journal of the American Geriatrics Society, 59(8), 1477–1483. https://doi.org/10.1111/j.1532-5415.2011.03491.xCrossRefGoogle ScholarPubMed
Frith, C. D., Stevens, M., Johnstone, E. C., Owens, D. G., & Crow, T. J. (1983). Integration of schematic faces and other complex objects in schizophrenia. Journal of Nervous and Mental Disease, 171(1), 34–39.CrossRefGoogle Scholar
Gold, J., Carpenter, C., Randolph, C., Goldberg, T. E., & Weinberger, D. R. (1997). Auditory working memory and Wisconsin card sorting test performance in schizophrenia. Archives of General Psychiatry, 54, 159–165.CrossRefGoogle Scholar
Gold, J. M., Waltz, J. A., Matveeva, T. M., Kasanova, Z., Strauss, G. P., Herbener, E. S., … Frank, M. J. (2012). Negative symptoms and the failure to represent the expected reward value of actions: Behavioral and computational modeling evidence. Archives of General Psychiatry, 69(2), 129–138. https://doi.org/10.1001/archgenpsychiatry.2011.1269CrossRefGoogle ScholarPubMed
Goldberg, T. E., Goldman, R. S., Burdick, K. E., Malhotra, A. K., Lencz, T., Patel, R. C., … Robinson, D. G. (2007). Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: Is it a practice effect? Archives of General Psychiatry, 64(10), 1115–1122. https://doi.org/10.1001/archpsyc.64.10.1115CrossRefGoogle ScholarPubMed
Green, M. F., Kern, R. S., Braff, D. L., & Mintz, J. (2000). Neurocognitive deficits and functional outcome in schizophrenia: Are we measuring the right stuff? Schizophrenia Bulletin, 26(1), 119–136. https://doi.org/10.1093/oxfordjournals.schbul.a033430CrossRefGoogle ScholarPubMed
Grove, T. B., Yao, B., Mueller, S. A., McLaughlin, M., Ellingrod, V. L., McInnis, M. G., … Tso, I. F. (2018). A Bayesian model comparison approach to test the specificity of visual integration impairment in schizophrenia or psychosis. Psychiatry Research, 265(May), 271–278. https://doi.org/10.1016/j.psychres.2018.04.061CrossRefGoogle ScholarPubMed
Harvey, P. D., & Keefe, R. S. E. (2001). Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. American Journal of Psychiatry, 158(2), 176–184. https://doi.org/10.1176/appi.ajp.158.2.176CrossRefGoogle ScholarPubMed
Harvey, P. D., Velligan, D. I., & Bellack, A. S. (2007). Performance-Based measures of functional skills: Usefulness in clinical treatment studies. Schizophrenia Bulletin, 33(5), 1138–1148. https://doi.org/10.1093/schbul/sbm040CrossRefGoogle ScholarPubMed
Henderson, D., Poppe, A. B., Barch, D. M., Carter, C. S., Gold, J. M., Ragland, J. D., … MacDonald, A. W. (2012). Optimization of a goal maintenance task for use in clinical applications. Schizophrenia Bulletin, 38(1), 104–113. https://doi.org/10.1093/schbul/sbr172CrossRefGoogle ScholarPubMed
Hitri, A., Craft, R. B., Fallon, J., Sethi, R., & Sinha, D. (1987). Serum neuroleptic and anticholinergic activity in relationship to cognitive toxicity of antiparkinsonian agents in schizophrenic patients. Psychopharmacology Bulletin, 23(1), 33–37. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/2885890Google ScholarPubMed
Hori, H., Noguchi, H., Hashimoto, R., Nakabayashi, T., Omori, M., Takahashi, S., … Kunugi, H. (2006). Antipsychotic medication and cognitive function in schizophrenia. Schizophrenia Research, 86(1–3), 138–146. https://doi.org/10.1016/J.SCHRES.2006.05.004CrossRefGoogle Scholar
Hutton, S. B., Puri, B. K., Duncan, L. J., Robbins, T. W., Barnes, T. R. E., & Joyce, E. M. (1998). Executive function in first-episode schizophrenia. Psychological Medicine, 28(2), 463–473. Retrieved from https://www.cambridge.org/core/journals/psychological-medicine/article/executive-function-in-first-episode-schizophrenia/2562651D65E41DE97F2C07579B31B254CrossRefGoogle ScholarPubMed
Insel, C., Reinen, J., Weber, J., Wager, T. D., Jarskog, L. F., Shohamy, D., & Smith, E. E. (2014). Antipsychotic dose modulates behavioral and neural responses to feedback during reinforcement learning in schizophrenia. Cognitive, Affective, & Behavioral Neuroscience, 14(1), 189–201. https://doi.org/10.3758/s13415-014-0261-3CrossRefGoogle Scholar
Juckel, G., Schlagenhauf, F., Koslowski, M., Wüstenberg, T., Villringer, A., Knutson, B., … Heinz, A. (2006). Dysfunction of ventral striatal reward prediction in schizophrenia. NeuroImage, 29(2), 409–416. https://doi.org/10.1016/j.neuroimage.2005.07.051CrossRefGoogle Scholar
Keane, B. P., Paterno, D., Kastner, S., & Silverstein, S. M. (2016). Visual integration dysfunction in schizophrenia arises by first psychotic episode and worsens with illness duration. Journal of Abnormal Psychology, 125(4), 543–549.CrossRefGoogle ScholarPubMed
Keefe, R. S. E., Bilder, R. M., Davis, S. M., Harvey, P. D., Palmer, B. W., Gold, J. M., … Lieberman, J. A. (2007a). Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Archives of General Psychiatry, 64(6), 633. https://doi.org/10.1001/archpsyc.64.6.633CrossRefGoogle Scholar
Keefe, R. S. E., Goldberg, T. E., Harvey, P. D., Gold, J. M., Poe, M. P., & Coughenour, L. (2004). The brief assessment of cognition in schizophrenia: Reliability, sensitivity, and comparison with a standard neurocognitive battery. Schizophrenia Research, 68(2–3), 283–297. https://doi.org/10.1016/j.schres.2003.09.011CrossRefGoogle ScholarPubMed
Keefe, R. S. E., Sweeney, J. A., Gu, H., Hamer, R. M., Perkins, D. O., McEvoy, J. P., & Lieberman, J. A. (2007b). Effects of olanzapine, quetiapine, and risperidone on neurocognitive function in early psychosis: A randomized, double-blind 52–week comparison. American Journal of Psychiatry, 164(7), 1061–1071. https://doi.org/10.1176/ajp.2007.164.7.1061CrossRefGoogle Scholar
Keri, S., Kiss, I., Kelemen, O., Benedek, G., & Janka, Z. (2005). Anomalous visual experiences, negative symptoms, perceptual organization and the magnocellular pathway in schizophrenia: A shared construct? Psychological Medicine, 35(10), 1445–1455. https://doi.org/10.1017/S0033291705005398CrossRefGoogle ScholarPubMed
Knight, R. A. (1992). Specifying cognitive deficiencies in poor premorbid schizophrenics. In Walker, E. F., Dworkin, R., & Cornblatt, B. (Eds.), Progress in experimental psychology & psychopathology (15th ed., pp. 252–289). New York, NY: Springer.Google Scholar
Kring, A. M., Gur, R. E., Blanchard, J. J., Horan, W. P., & Reise, S. P. (2013). The Clinical Assessment Interview for Negative Symptoms (CAINS): Final development and validation. American Journal of Psychiatry, 170(2), 165–172. https://doi.org/10.1176/appi.ajp.2012.12010109CrossRefGoogle ScholarPubMed
Lee, J., & Park, S. (2005). Working memory impairments in schizophrenia: A meta-analysis. Journal of Abnormal Psychology, 114(4), 599–611. https://doi.org/10.1037/0021-843X.114.4.599CrossRefGoogle ScholarPubMed
Lesh, T. A., Niendam, T. A., Minzenberg, M. J., & Carter, C. S. (2011). Cognitive control deficits in schizophrenia: Mechanisms and meaning. Neuropsychopharmacology, 36(1), 316–338. https://doi.org/10.1038/npp.2010.156CrossRefGoogle ScholarPubMed
Lesh, T. A., Tanase, C., Geib, B. R., Niendam, T. A., Yoon, J. H., Minzenberg, M. J., … Carter, C. S. (2015). A multimodal analysis of antipsychotic effects on brain structure and function in first-episode schizophrenia. JAMA Psychiatry, 72(3), 226. https://doi.org/10.1001/jamapsychiatry.2014.2178CrossRefGoogle ScholarPubMed
Lussier, I., & Stip, E. (2001). Memory and attention deficits in drug naive patients with schizophrenia. Schizophrenia Research, 48(1), 45–55. https://doi.org/10.1016/S0920-9964(00)00102-XCrossRefGoogle ScholarPubMed
Macdonald, A. W., & Carter, C. S. (2003). Event-related fmri study of context processing in dorsolateral prefrontal cortex of patients with schizophrenia. Journal of Abnormal Psychology, 112(4), 689–697. Retrieved from https://insights.ovid.com/abnormal-psychology/jabnp/2003/11/000/event-related-fmri-study-context-processing/14/00004468CrossRefGoogle ScholarPubMed
Maia, T. V. (2009). Reinforcement learning, conditioning, and the brain: Successes and challenges. Cognitive, Affective, & Behavioral Neuroscience, 9(4), 343–364. https://doi.org/10.3758/CABN.9.4.343CrossRefGoogle ScholarPubMed
McKendrick, A. M., Weymouth, A. E., & Battista, J. (2010). The effect of normal aging on closed contour shape discrimination. Journal of Vision, 10(2), 1–9. https://doi.org/10.1167/10.2.1CrossRefGoogle ScholarPubMed
Meltzer, H. Y., & McGurk, S. R. (1999). The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophrenia Bulletin, 25(2), 233–255. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10416729CrossRefGoogle Scholar
Mesholam-Gately, R. I., Giuliano, A. J., Goff, K. P., Faraone, S. V., & Seidman, L. J. (2009). Neurocognition in first-episode schizophrenia: A meta-analytic review. Neuropsychology, 23(3), 315–336. https://doi.org/10.1037/a0014708CrossRefGoogle ScholarPubMed
Minzenberg, M. J., Firl, A. J., Yoon, J. H., Gomes, G. C., Reinking, C., & Carter, C. S. (2010). Gamma oscillatory power is impaired during cognitive control independent of medication Status in first-episode schizophrenia. Neuropsychopharmacology, 35(13), 2590–2599. https://doi.org/10.1038/npp.2010.150CrossRefGoogle ScholarPubMed
Minzenberg, M. J., Laird, A. R., Thelen, S., Carter, C. S., & Glahn, D. C. (2009). Meta-analysis of 41 functional neuroimaging studies of executive function in schizophrenia. Archives of General Psychiatry, 66(8), 811. https://doi.org/10.1001/archgenpsychiatry.2009.91CrossRefGoogle Scholar
Minzenberg, M. J., Poole, J. H., Benton, C., & Vinogradov, S. (2004). Association of anticholinergic load with impairment of complex attention and memory in schizophrenia. American Journal of Psychiatry, 161(1), 116–124. https://doi.org/10.1176/appi.ajp.161.1.116CrossRefGoogle Scholar
Mishara, A. L., & Goldberg, T. E. (2004). A meta-analysis and critical review of the effects of conventional neuroleptic treatment on cognition in schizophrenia: Opening a closed book. Biological Psychiatry, 55(10), 1013–1022. https://doi.org/10.1016/j.biopsych.2004.01.027CrossRefGoogle ScholarPubMed
Montague, P. R., Dayan, P., & Sejnowski, T. J. (1996). A framework for mesencephalic dopamine systems based on predictive Hebbian learning. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 16(5), 1936–1947. https://doi.org/10.1523/JNEUROSCI.16-05-01936.1996CrossRefGoogle ScholarPubMed
Murray, G. K., Cheng, F., Clark, L., Barnett, J. H., Blackwell, A. D., Fletcher, P. C., … Jones, P. B. (2008). Reinforcement and reversal learning in first-episode psychosis. Schizophrenia Bulletin, 34(5), 848–855. https://doi.org/10.1093/schbul/sbn078CrossRefGoogle ScholarPubMed
Naveh-Benjamin, M., Hussain, Z., Guez, J., & Bar-On, M. (2003). Adult age differences in episodic memory: Further support for an associative-deficit hypothesis. Journal of Experimental Psychology. Learning, Memory, and Cognition, 29(5), 826–837. https://doi.org/10.1037/0278-7393.29.5.826CrossRefGoogle ScholarPubMed
Nejad, A. B., Ebdrup, B. H., Siebner, H. R., Rasmussen, H., Aggernæs, B., Glenthøj, B. Y., & Baaré, W. F. C. (2011). Impaired temporoparietal deactivation with working memory load in antipsychotic-naïve patients with first-episode schizophrenia. The World Journal of Biological Psychiatry, 12(4), 271–281. https://doi.org/10.3109/15622975.2010.556199CrossRefGoogle ScholarPubMed
Nuechterlein, K. H., Barch, D. M., Gold, J. M., Goldberg, T. E., Green, M. F., & Heaton, R. K. (2004). Identification of separable cognitive factors in schizophrenia. Schizophrenia Research, 72(1), 29–39. https://doi.org/10.1016/j.schres.2004.09.007CrossRefGoogle Scholar
Overall, J. E., & Gorham, D. R. (1962). The brief psychiatric rating scale. Psychological Reports, 10(3), 799–812. https://doi.org/10.2466/pr0.1962.10.3.799CrossRefGoogle Scholar
Perlick, D., Stastny, P., Katz, I., Mayer, M., & Mattis, S. (1986). Memory deficits and anticholinergic levels in chronic schizophrenia. American Journal of Psychiatry, 143(2), 230–232. https://doi.org/10.1176/ajp.143.2.230Google ScholarPubMed
Pizzagalli, D. A., Jahn, A. L., & O'Shea, J. P. (2005). Toward an objective characterization of an anhedonic phenotype: A signal-detection approach. Biological Psychiatry, 57(4), 319–327. https://doi.org/10.1016/j.biopsych.2004.11.026CrossRefGoogle ScholarPubMed
Ragland, J. D., Ranganath, C., Barch, D. M., Gold, J. M., Haley, B., MacDonald, A. W. I., … Carter, C. S. (2012). Relational and Item-Specific Encoding (RISE): Task development and psychometric characteristics. Schizophrenia Bulletin, 38(1), 114–124. https://doi.org/10.1093/schbul/sbr146CrossRefGoogle ScholarPubMed
Reinen, J. M., Van Snellenberg, J. X., Horga, G., Abi-Dargham, A., Daw, N. D., & Shohamy, D. (2016). Motivational context modulates prediction error response in schizophrenia. Schizophrenia Bulletin, 42(6), 1467–1475.CrossRefGoogle Scholar
Roudaia, E., Bennett, P. J., & Sekuler, A. B. (2008). The effect of aging on contour integration. Vision Research, 48(28), 2767–2774. https://doi.org/10.1016/J.VISRES.2008.07.026CrossRefGoogle ScholarPubMed
Saykin, A. J., Shtasel, D. L., Gur, R. E. R. C., Kester, D. B., Mozley, L. H., Stafiniak, P., & Gur, R. E. R. C. (1994). Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia. Archives of General Psychiatry, 51(2), 124. https://doi.org/10.1001/archpsyc.1994.03950020048005CrossRefGoogle ScholarPubMed
Schlagenhauf, F., Huys, Q. J. M., Deserno, L., Rapp, M. A., Beck, A., Heinze, H.-J. J., … Heinz, A. (2014). Striatal dysfunction during reversal learning in unmedicated schizophrenia patients. NeuroImage, 89, 171–180. https://doi.org/https://doi.org/10.1016/j.neuroimage.2013.11.034CrossRefGoogle ScholarPubMed
Schneider, L. C., & Struening, E. L. (1983). SLOF: A behavioral rating scale for assessing the mentally ill. Social Work Research and Abstracts, 19(3), 9–21. https://doi.org/10.1093/swra/19.3.9CrossRefGoogle ScholarPubMed
Schultz, W. (2007). Multiple dopamine functions at different time courses. Annual Review of Neuroscience, 30(1), 259–288. https://doi.org/10.1146/annurev.neuro.28.061604.135722CrossRefGoogle ScholarPubMed
Schultz, W. (2016a). Dopamine reward prediction error coding. Dialogues in Clinical Neuroscience, 18(1), 23–32. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/27069377CrossRefGoogle Scholar
Schultz, W. (2016b). Reward functions of the basal ganglia. Journal of Neural Transmission, 123(7), 679–693. https://doi.org/10.1007/s00702-016-1510-0CrossRefGoogle Scholar
Seeger, T., Fedorova, I., Zheng, F., Miyakawa, T., Koustova, E., Gomeza, J., … Wess, J. (2004). M2 muscarinic acetylcholine receptor knock-out mice show deficits in behavioral flexibility, working memory, and hippocampal plasticity. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 24(45), 10117–10127. https://doi.org/10.1523/JNEUROSCI.3581-04.2004CrossRefGoogle ScholarPubMed
Silverstein, S. M., All, S. D., Kasi, R., Berten, S., Essex, B., Lathrop, K. L., & Little, D. M. (2010). Increased fusiform area activation in schizophrenia during processing of spatial frequency-degraded faces, as revealed by fMRI. Psychological Medicine, 40(7), 1159–1169. https://doi.org/10.1017/S0033291709991735CrossRefGoogle ScholarPubMed
Silverstein, S. M., Berten, S., Essex, B., Kovacs, I., Susmaras, T., & Little, D. M. (2009). An fMRI examination of visual integration in schizophrenia. Journal of Integrative Neuroscience, 8(2), 175–202. https://doi.org/10.1142/S0219635209002113CrossRefGoogle Scholar
Silverstein, S. M., Harms, M. P., Carter, C. S., Gold, J. M., Keane, B. P., MacDonald, A., … Barch, D. M. (2015). Cortical contributions to impaired contour integration in schizophrenia. Neuropsychologia, 75, 469–480. https://doi.org/10.1016/J.NEUROPSYCHOLOGIA.2015.07.003CrossRefGoogle Scholar
Silverstein, S. M., Keane, B. P., Barch, D. M., Carter, C. S., Gold, J. M., Kovács, I., … Strauss, M. E. (2011). Optimization and validation of a visual integration test for schizophrenia research. Schizophrenia Bulletin, 38(1), 125–134. https://doi.org/10.1093/schbul/sbr141CrossRefGoogle ScholarPubMed
Silverstein, S. M., Keane, B. P., Barch, D. M., Carter, C. S., Gold, J. M., Kovacs, I., … Strauss, M. E. (2012). Optimization and validation of a visual integration test for schizophrenia Research. Schizophrenia Bulletin, 38(1), 125–134. https://doi.org/10.1093/schbul/sbr141CrossRefGoogle ScholarPubMed
Silverstein, S. M., Kovács, I., Corry, R., & Valone, C. (2000). Perceptual organization, the disorganization syndrome, and context processing in chronic schizophrenia. Schizophrenia Research, 43(1), 11–20. https://doi.org/10.1016/S0920-9964(99)00180-2CrossRefGoogle ScholarPubMed
Spagna, A., Dong, Y., Mackie, M.-A., Li, M., Harvey, P. D., Tian, Y., … Fan, J. (2015). Clozapine improves the orienting of attention in schizophrenia. Schizophrenia Research, 168(1–2), 285–291. https://doi.org/10.1016/j.schres.2015.08.009CrossRefGoogle Scholar
Spencer, K. M., Nestor, P. G., Perlmutter, R., Niznikiewicz, M. A., Klump, M. C., Frumin, M., … McCarley, R. W. (2004). Neural synchrony indexes disordered perception and cognition in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 101(49), 17288 LP–17293. https://doi.org/10.1073/pnas.0406074101CrossRefGoogle ScholarPubMed
Spohn, H. E., & Strauss, M. E. (1989). Relation of neuroleptic and anticholinergic medication to cognitive functions in schizophrenia. Journal of Abnormal Psychology, 98(4), 367–380. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/2574202CrossRefGoogle Scholar
Stoy, M., Schlagenhauf, F., Sterzer, P., Bermpohl, F., Hägele, C., Suchotzki, K., … Ströhle, A. (2012). Hyporeactivity of ventral striatum towards incentive stimuli in unmedicated depressed patients normalizes after treatment with escitalopram. Journal of Psychopharmacology, 26(5), 677–688. https://doi.org/10.1177/0269881111416686CrossRefGoogle ScholarPubMed
Strauss, G. P., Frank, M. J., Waltz, J. A., Kasanova, Z., Herbener, E. S., & Gold, J. M. (2011). Deficits in positive reinforcement learning and uncertainty-driven exploration are associated with distinct aspects of negative symptoms in schizophrenia. Biological Psychiatry, 69(5), 424–431. https://doi.org/10.1016/j.biopsych.2010.10.015CrossRefGoogle Scholar
Strauss, M. E., Reynolds, K. S., Jayaram, G., & Tune, L. E. (1990). Effects of anticholinergic medication on memory in schizophrenia. Schizophrenia Research, 3(2), 127–129. https://doi.org/10.1016/0920-9964(90)90045-9CrossRefGoogle Scholar
Tracy, J. I., Monaco, C., Giovannetti, T., Abraham, G., & Josiassen, R. C. (2001). Anticholinergicity and cognitive processing in chronic schizophrenia. Biological Psychology, 56(1), 1–22. https://doi.org/10.1016/S0301-0511(00)00083-1CrossRefGoogle ScholarPubMed
Tzavara, E. T., Bymaster, F. P., Felder, C. C., Wade, M., Gomeza, J., Wess, J., … Nomikos, G. G. (2003). Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice. Molecular Psychiatry, 8(7), 673–679. https://doi.org/10.1038/sj.mp.4001270CrossRefGoogle ScholarPubMed
Uchida, H., Rajji, T. K., Mulsant, B. H., Kapur, S., Pollock, B. G., Graff-Guerrero, A., … Mamo, D. C. (2009). D2 receptor blockade by risperidone correlates with attention deficits in late-life schizophrenia. Journal of Clinical Psychopharmacology, 29(6), 571–575. https://doi.org/10.1097/JCP.0b013e3181bf4ea3CrossRefGoogle ScholarPubMed
Vinogradov, S., Fisher, M., Warm, H., Holland, C., Kirshner, M. A., & Pollock, B. G. (2009). The cognitive cost of anticholinergic burden: Decreased response to cognitive training in schizophrenia. American Journal of Psychiatry, 166(9), 1055–1062. https://doi.org/10.1176/appi.ajp.2009.09010017CrossRefGoogle Scholar
Waltz, J. A., Demro, C., Schiffman, J., Thompson, E., Kline, E., Reeves, G., … Gold, J. M. (2017). Reinforcement learning performance and risk for psychosis in youth. The Journal of Nervous and Mental Disease, 203(12), 919. https://doi.org/10.1097/NMD.0000000000000420CrossRefGoogle Scholar
Waltz, J. A., Frank, M. J., Robinson, B. M., & Gold, J. M. (2007). Selective reinforcement learning deficits in schizophrenia support predictions from computational models of striatal-cortical dysfunction. Biological Psychiatry, 62(7), 756–764. https://doi.org/10.1016/j.biopsych.2006.09.042CrossRefGoogle ScholarPubMed
Wechsler, D. (2001). Wechsler: Wechsler test of adult reading: WTAR. San Antonio, TX: The Psychological Corporation.Google Scholar
Wood, S. J., Pantelis, C., Proffitt, T., Phillips, L. J., Stuart, G. W., Buchanan, J. A., … McGorry, P. D. (2003). Spatial working memory ability is a marker of risk-for-psychosis. Psychological Medicine, 33(7), 1239–1247. https://doi.org/10.1017/S0033291703008067CrossRefGoogle ScholarPubMed
Woods, S. W. (2003). Chlorpromazine equivalent doses for the newer atypical antipsychotics. Journal of Clinical Psychiatry, 64(6), 663–667. https://doi.org/10.4088/JCP.v64n0607CrossRefGoogle ScholarPubMed
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