Dysfunction of dorsolateral prefrontal cortex in antipsychotic-naïve schizophreniform psychosis

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Australia.
Psychiatry Research (Impact Factor: 2.47). 12/2006; 148(1):23-31. DOI: 10.1016/j.pscychresns.2006.02.006
Source: PubMed


Reports of abnormal activation of the dorsolateral prefrontal cortex (dlPFC) are common in functional neuroimaging studies of schizophrenia, although very few have examined brain activity in patients close to the onset of illness. In this H(2)(15)O PET study, eight young male patients with first-episode schizophreniform psychosis and age-matched control subjects performed a version of the Stroop task that we have previously shown to engage the middle-frontal gyrus. At the time of testing, patients were antipsychotic-naïve and were scanned within 1 week of initial contact with our clinical program. All patients received a later diagnosis of schizophrenia 6 months after participating in the study. Whole-brain (within-group) and region-of-interest (between-group) analyses were carried out and data underwent spatial reproducibility testing. Compared with healthy subjects, patients showed significantly greater reaction-time (RT) interference but normal RT accuracy on the Stroop task. This pattern correlated with significant under-activation of the posterior left middle-frontal gyri in the patient versus control group. These findings support an emerging model of impaired cognitive control in schizophrenia and suggest that there is significant dysfunction of the dlPFC close to the onset of illness that may coincide with, or be modulated by, the transition-to-illness phase.

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    • "Until recently, research on cognition in drug-naïve patients with schizophrenia has been hampered by small samples and by the great variety of cognitive tests used. Several of the reports have been imaging studies usually enrolling limited samples (Cleghorn et al., 1989; Andreasen et al., 1992; Buchsbaum et al., 1992; Parellada et al., 1994; Barch et al., 2001; Salgado-Pineda et al., 2003; Jones et al., 2004; Harrison et al., 2006). Although research on drug-naïve high risk to psychosis subjects has shown cognitive impairments even before psychosis onset (Bora and Murray, 2014; Bora et al., 2014) metaanalytic evidence from drug-naïve schizophrenia subjects is lacking. "
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    ABSTRACT: Cognitive deficits represent a significant characteristic of schizophrenia. However, a majority of the clinical studies have been conducted in antipsychotic drug treated patients. Thus, it remains unclear if significant cognitive impairments exist in the absence of medication. This is the first meta-analysis of cognitive findings in drug-naïve patients with schizophrenia. Cognitive data from 23 studies encompassing 1106 patients and 1385 controls published from 1992 to 2013 were included. Tests were to a large extent ordered in cognitive domains according to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery. Analysis was performed with STATA using the random-effects model and heterogeneity as well as Egger's publication bias was assessed. Overall the results show that patients performed worse than healthy controls in all cognitive domains with medium to large effect sizes. Verbal memory, speed of processing and working memory were three of the domains with the greatest impairments. The pattern of results is in line with previous meta-analytic findings in antipsychotic treated patients. The present meta-analysis confirms the existence of significant cognitive impairments at the early stage of the illness in the absence of antipsychotic medication.
    Schizophrenia Research 07/2014; 158(1-3). DOI:10.1016/j.schres.2014.06.034 · 3.92 Impact Factor
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    • "Many studies have reported brain structural alterations in FEP subjects, most often using magnetic resonance imaging (MRI) with region-of-interest (ROI) based volume measurements (Keshavan et al., 2005; Kubicki et al., 2002; Vita et al., 2006). Ventricular enlargement and whole brain or frontal/temporal regions volume reductions have been the most consistent findings (Flashman and Green, 2004; Steen et al., 2006; Vita et al., 2006). "
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    ABSTRACT: Neuropsychological deficits have been reported in association with first-episode psychosis (FEP). Reductions in grey matter (GM) volumes have been documented in FEP subjects compared to healthy controls. However, the possible inter-relationship between the findings of those two lines of research has been scarcely investigated. To investigate the relationship between neuropsychological deficits and GM volume abnormalities in a population-based sample of FEP patients compared to healthy controls from the same geographical area. FEP patients (n=88) and control subjects (n=86) were evaluated by neuropsychological assessment (Controlled Oral Word Association Test, forward and backward digit span tests) and magnetic resonance imaging using voxel-based morphometry. Single-group analyses showed that prefrontal and temporo-parietal GM volumes correlated significantly (p<0.05, corrected) with cognitive performance in FEP patients. A similar pattern of direct correlations between neocortical GM volumes and cognitive impairment was seen in the schizophrenia subgroup (n=48). In the control group, cognitive performance was directly correlated with GM volume in the right dorsal anterior cingulate cortex and inversely correlated with parahippocampal gyral volumes bilaterally. Interaction analyses with "group status" as a predictor variable showed significantly greater positive correlation within the left inferior prefrontal cortex (BA46) in the FEP group relative to controls, and significantly greater negative correlation within the left parahippocampal gyrus in the control group relative to FEP patients. Our results indicate that cognitive deficits are directly related to brain volume abnormalities in frontal and temporo-parietal cortices in FEP subjects, most specifically in inferior portions of the dorsolateral prefrontal cortex.
    Schizophrenia Research 08/2009; 113(2-3):200-9. DOI:10.1016/j.schres.2009.06.020 · 3.92 Impact Factor
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    ABSTRACT: Objective: Cognitive deficits, particularly those related to executive function and behavioural control, are a core feature of patients with schizophrenia and implicate disturbances of the prefrontal cortex (PFC). Consistent with this, functional imaging studies have identified abnormalities of PFC activity in chronically affected patients. The objective of the current study was to investigate executive-control related neural activity from first onset of the illness through to symptom stabilization.
    Australian and New Zealand Journal of Psychiatry 03/2007; 41(2):129-35. DOI:10.1080/00048670601109899 · 3.41 Impact Factor
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May 27, 2014