Relationships between dorsolateral prefrontal cortex metabolic change and cognitive impairment in first-episode neuroleptic-naive schizophrenia patients

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Abstract

The present study aimed to explore the possible associations between the dorsolateral prefrontal cortex (DLPFC) metabolites and the cognitive function in first-episode schizophrenia (FES).

This study included 58 patients with FES (29 males and 29 females; mean age, 22.66 ± 7.64 years) recruited from the First Affiliated Hospital, College of Medicine, Zhejiang University, and 43 locally recruited healthy controls (16 males and 27 females; mean age, 23.07 ± 7.49 years). The single-voxel proton magnetic resonance spectroscopy was used to measure the levels of N-acetylaspartate (NAA); complex of glutamate, glutamine, and γ-aminobutyric acid (Glx); choline-containing compounds; and myo-inositol in the DLPFC. The ratios of metabolites to creatine (Cr) were calculated. The cognitive function was assessed by Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). Correlation analysis was used to assess the relationships between the DLPFC metabolites and the cognitive function.Compared with the healthy controls, the patients with FES showed significantly reduced scores in each part of the MCCB, significantly reduced NAA/Cr, and significantly increased Glx/Cr in the left DLPFC. Poor performance in verbal learning and visual learning was correlated to the reduced NAA/Cr ratio in the left DLPFC.

These findings suggest that a lower NAA/Cr ratio in the left DLPFC is associated with the cognitive deficits in patients with FES, and may be an early biochemical marker for the cognitive impairment in schizophrenia.

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Neurocognition in first-episode schizophrenia: a meta-analytic review.

Raquelle I Mesholam-Gately, Anthony J Giuliano, Kirsten P Goff … (2009)

Compromised neurocognition is a core feature of schizophrenia. Following Heinrichs and Zakzanis's (1998) seminal meta-analysis of middle-aged and predominantly chronic schizophrenia samples, the aim of this study is to provide a meta-analysis of neurocognitive findings from 47 studies of first-episode (FE) schizophrenia published through October 2007. The meta-analysis uses 43 separate samples of 2,204 FE patients with a mean age of 25.5 and 2,775 largely age- and gender-matched control participants. FE samples demonstrated medium-to-large impairments across 10 neurocognitive domains (mean effect sizes from -0.64 to -1.20). Findings indicate that impairments are reliably and broadly present by the FE, approach or match the degree of deficit shown in well-established illness, and are maximal in immediate verbal memory and processing speed. Larger IQ impairments in the FE compared to the premorbid period, but comparable to later phases of illness suggests deterioration between premorbid and FE phases followed by deficit stability at the group level. Considerable heterogeneity of effect sizes across studies, however, underscores variability in manifestations of the illness and a need for improved reporting of sample characteristics to support moderator variable analyses.

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Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates.

R M Bilder, R S Goldman, D Robinson … (2000)

Neuropsychological impairments are well documented in schizophrenia and are important targets of treatment. Information about the severity and pattern of deficits after treatment for the first psychotic episode and about relationships between these deficits and syndromal characteristics remains limited. Comprehensive neuropsychological assessments including 41 individual tests were given to 94 patients with first-episode schizophrenia after initial stabilization of psychosis and to a comparison group of 36 healthy volunteers. Profiles of neuropsychological deficits and the relationship of deficits to sex and handedness were examined. Correlations of neuropsychological deficit with a broad range of historical and clinical characteristics, including outcome, were explored. Patients had a large generalized neuropsychological deficit (1.5 standard deviations compared to healthy volunteers). Patients also had, superimposed on the generalized deficit, subtle relative deficits (less than 0.5 standard deviation compared to their own average profile) in memory and executive functions. Learning/memory dysfunction best distinguished patients from healthy individuals; after accounting for this difference, only motor deficits further distinguished the groups. Patients with higher neuropsychological ability had only memory deficits, and patients with lower ability had both memory and executive deficits. No sex differences were observed beyond the normal advantage for men in motor speed. Dextral patients had less severe generalized deficit. Severity of residual symptoms was associated with greater generalized deficit. Executive and attentional deficits were most linked to global functional impairment and poor outcome. The results document a large generalized deficit, and more subtle differential deficits, in clinically stabilized first-episode patients. Learning/memory deficits were observed even in patients with less severe generalized deficit, but the pattern was unlike the amnestic syndrome and probably reflects different mechanisms. Executive and attentional deficits marked the more severely disabled patients, and may portend relatively poor outcome. Failure to develop typical patterns of cerebral dominance may increase the risk for greater generalized deficit.

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Cognitive impairment in schizophrenia is the core of the disorder.

Emma Goldberg, B Elvevåg (1999)

Patients with schizophrenia exhibit an exceedingly wide range of symptoms from a variety of domains. The cardinal features are abnormal ideas (such as delusions); abnormal perceptions (such as hallucinations); formal thought disorder (as evidenced by disorganized speech); motor, volitional, and behavioral disorders; and emotional disorders (such as affective flattening or inappropriateness). In addition to these diverse, and sometimes bizarre symptoms, it has become increasingly apparent that the disorder is, to variable degrees, accompanied by a broad spectrum of cognitive impairments. This review addresses the question of whether the cognitive deficits seen in schizophrenic patients are the core features of the disorder. In other words, we explore whether schizophrenia is best characterized by symptoms or cognitive deficits (we suggest the latter) and moreover, whether there is a specific cognitive deficit profile that may assist in diagnosis. First, we discuss what the cognitive deficits are. Then we address in turn the reality, frequency, predictive validity, specificity, course and susceptibility to neuroleptic effects of these cognitive impairments. In brief, we argue that various cognitive deficits are enduring features of the schizophrenia illness, that they are not state-related and are not specific to subtypes of the illness, and, more specifically, that working memory and attention are characteristically impaired in patients with schizophrenia, irrespective of their level of intelligence. Last, we conclude that problems in these cognitive domains are at the very core of the dysfunction in this disease.

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Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: June 2017

Publication date (Electronic): 23 June 2017

Volume: 96

Issue: 25

Electronic Location Identifier: e7228

Affiliations

[a ]Department of Psychiatry, First Affiliated Hospital, College of Medicine, Zhejiang University, The Key Laboratory of Mental Disorder's Management of Zhejiang Province

[b ]College of Medicine, Zhejiang University

[c ]Department of Radiology, First Affiliated Hospital, College of Medicine, Zhejiang University, The Key Laboratory of Mental Disorder's Management of Zhejiang Province, Hangzhou, China.

Author notes

[∗ ]Correspondence: Yi Xu, Department of Psychiatry, First Affiliated Hospital, College of Medicine, Zhejiang University, The Key Laboratory of Mental Disorder's Management of Zhejiang Province, No. 79, Qingchun Road, Hangzhou 310003, China (e-mail: yixu1961@ 123456163.com ).

Article

Publisher ID: MD-D-17-01050 Accession ID: 07228

DOI: 10.1097/MD.0000000000007228

PMC ID: 5484227

PubMed ID: 28640119

SO-VID: 6bf37b6f-b424-4d03-9116-9b56c410006a

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This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0, which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. http://creativecommons.org/licenses/by-nd/4.0

History

Date received : 19 February 2017

Date revision received : 28 May 2017

Date accepted : 30 May 2017

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Keywords: 1h-mrs,cognition,dorsolateral prefrontal cortex,first-episode schizophrenia,mccb

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Keywords: 1h-mrs, cognition, dorsolateral prefrontal cortex, first-episode schizophrenia, mccb

Relationships between dorsolateral prefrontal cortex metabolic change and cognitive impairment in first-episode neuroleptic-naive schizophrenia patients

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Most cited references 48

Neurocognition in first-episode schizophrenia: a meta-analytic review.

Neuropsychology of first-episode schizophrenia: initial characterization and clinical correlates.

Cognitive impairment in schizophrenia is the core of the disorder.

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