Cognitive Control Deficits in Schizophrenia: Mechanisms and Meaning

Overview

Journal Neuropsychopharmacology

Date 2010 Sep 17

PMID 20844478

Citations 243

Authors

Tyler A Lesh

Tara A Niendam

Michael J Minzenberg

Cameron S Carter

Affiliations

Soon will be listed here.

Abstract

Although schizophrenia is an illness that has been historically characterized by the presence of positive symptomatology, decades of research highlight the importance of cognitive deficits in this disorder. This review proposes that the theoretical model of cognitive control, which is based on contemporary cognitive neuroscience, provides a unifying theory for the cognitive and neural abnormalities underlying higher cognitive dysfunction in schizophrenia. To support this model, we outline converging evidence from multiple modalities (eg, structural and functional neuroimaging, pharmacological data, and animal models) and samples (eg, clinical high risk, genetic high risk, first episode, and chronic subjects) to emphasize how dysfunction in cognitive control mechanisms supported by the prefrontal cortex contribute to the pathophysiology of higher cognitive deficits in schizophrenia. Our model provides a theoretical link between cellular abnormalities (eg, reductions in dentritic spines, interneuronal dysfunction), functional disturbances in local circuit function (eg, gamma abnormalities), altered inter-regional cortical connectivity, a range of higher cognitive deficits, and symptom presentation (eg, disorganization) in the disorder. Finally, we discuss recent advances in the neuropharmacology of cognition and how they can inform a targeted approach to the development of effective therapies for this disabling aspect of schizophrenia.

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References

Mei L, Xiong W . Neuregulin 1 in neural development, synaptic plasticity and schizophrenia. Nat Rev Neurosci. 2008; 9(6):437-52. PMC: 2682371. DOI: 10.1038/nrn2392. View

Cosway R, Byrne M, Clafferty R, Hodges A, Grant E, Abukmeil S . Neuropsychological change in young people at high risk for schizophrenia: results from the first two neuropsychological assessments of the Edinburgh High Risk Study. Psychol Med. 2002; 30(5):1111-21. DOI: 10.1017/s0033291799002585. View

Bowen L, Wallace C, Glynn S, Nuechterlein K, Lutzker J, Kuehnel T . Schizophrenic individuals' cognitive functioning and performance in interpersonal interactions and skills training procedures. J Psychiatr Res. 1994; 28(3):289-301. DOI: 10.1016/0022-3956(94)90012-4. View

Cannon T, Huttunen M, Lonnqvist J, Tuulio-Henriksson A, Pirkola T, Glahn D . The inheritance of neuropsychological dysfunction in twins discordant for schizophrenia. Am J Hum Genet. 2000; 67(2):369-82. PMC: 1287184. DOI: 10.1086/303006. View

Aleman A, Hijman R, de Haan E, Kahn R . Memory impairment in schizophrenia: a meta-analysis. Am J Psychiatry. 1999; 156(9):1358-66. DOI: 10.1176/ajp.156.9.1358. View

Smith T, Hull J, Huppert J, Silverstein S . Recovery from psychosis in schizophrenia and schizoaffective disorder: symptoms and neurocognitive rate-limiters for the development of social behavior skills. Schizophr Res. 2002; 55(3):229-37. DOI: 10.1016/s0920-9964(01)00231-6. View

Harris J, Adler L, Young D, Cullum C, Rilling L, Cicerello A . Neuropsychological dysfunction in parents of schizophrenics. Schizophr Res. 1996; 20(3):253-60. DOI: 10.1016/0920-9964(96)00009-6. View

Brewer W, Wood S, McGorry P, Francey S, Phillips L, Yung A . Impairment of olfactory identification ability in individuals at ultra-high risk for psychosis who later develop schizophrenia. Am J Psychiatry. 2003; 160(10):1790-4. DOI: 10.1176/appi.ajp.160.10.1790. View

Manoach D, Press D, Thangaraj V, Searl M, Goff D, Halpern E . Schizophrenic subjects activate dorsolateral prefrontal cortex during a working memory task, as measured by fMRI. Biol Psychiatry. 1999; 45(9):1128-37. DOI: 10.1016/s0006-3223(98)00318-7. View

10.

Goldberg T, Goldman R, Burdick K, Malhotra A, Lencz T, Patel R . Cognitive improvement after treatment with second-generation antipsychotic medications in first-episode schizophrenia: is it a practice effect?. Arch Gen Psychiatry. 2007; 64(10):1115-22. DOI: 10.1001/archpsyc.64.10.1115. View

11.

Friedman J, Carpenter D, Lu J, Fan J, Tang C, White L . A pilot study of adjunctive atomoxetine treatment to second-generation antipsychotics for cognitive impairment in schizophrenia. J Clin Psychopharmacol. 2008; 28(1):59-63. DOI: 10.1097/jcp.0b013e318161318f. View

12.

Mohamed S, Paulsen J, OLeary D, Arndt S, Andreasen N . Generalized cognitive deficits in schizophrenia: a study of first-episode patients. Arch Gen Psychiatry. 1999; 56(8):749-54. DOI: 10.1001/archpsyc.56.8.749. View

13.

Otani S, Daniel H, Roisin M, Crepel F . Dopaminergic modulation of long-term synaptic plasticity in rat prefrontal neurons. Cereb Cortex. 2003; 13(11):1251-6. DOI: 10.1093/cercor/bhg092. View

14.

Carter C, Botvinick M, Cohen J . The contribution of the anterior cingulate cortex to executive processes in cognition. Rev Neurosci. 1999; 10(1):49-57. DOI: 10.1515/revneuro.1999.10.1.49. View

15.

MacDonald 3rd A, Carter C, Kerns J, Ursu S, Barch D, Holmes A . Specificity of prefrontal dysfunction and context processing deficits to schizophrenia in never-medicated patients with first-episode psychosis. Am J Psychiatry. 2005; 162(3):475-84. DOI: 10.1176/appi.ajp.162.3.475. View

16.

Jung W, Kim J, Jang J, Choi J, Jung M, Park J . Cortical thickness reduction in individuals at ultra-high-risk for psychosis. Schizophr Bull. 2009; 37(4):839-49. PMC: 3122277. DOI: 10.1093/schbul/sbp151. View

17.

Ranganath C, Minzenberg M, Ragland J . The cognitive neuroscience of memory function and dysfunction in schizophrenia. Biol Psychiatry. 2008; 64(1):18-25. PMC: 2474810. DOI: 10.1016/j.biopsych.2008.04.011. View

18.

Zirnheld P, Carroll C, Kieffaber P, ODonnell B, Shekhar A, Hetrick W . Haloperidol impairs learning and error-related negativity in humans. J Cogn Neurosci. 2004; 16(6):1098-112. DOI: 10.1162/0898929041502779. View

19.

Weinberger D, Gallhofer B . Cognitive function in schizophrenia. Int Clin Psychopharmacol. 1997; 12 Suppl 4:S29-36. DOI: 10.1097/00004850-199709004-00006. View

20.

van Erp T, Saleh P, Huttunen M, Lonnqvist J, Kaprio J, Salonen O . Hippocampal volumes in schizophrenic twins. Arch Gen Psychiatry. 2004; 61(4):346-53. DOI: 10.1001/archpsyc.61.4.346. View