Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia

Sullivan, Edith V.; Shear, Paula K.; Lim, Kelvin O.; Zipursky, Robert B.; Pfefferbaum, Adolf

doi:10.1016/0006-3223(95)00135-2

Cited by 56 publications

(24 citation statements)

References 21 publications

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“…The general lack of a relationship between NP and MRI measures is consistent with at least some previous schizophrenia research employing NP and MRI measures (66). The NP measures were not designed to map on to specific brain region volumes, but rather were designed to assess relatively broad cognitive constructs, such as 'learning' or 'abstraction'.…”

Section: Discussionsupporting

confidence: 58%

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia^a

Jeste

McAdams

Palmer

et al. 1998

Acta Psychiatr Scand

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Age of onset of schizophrenia (AOS) may be largely determined by neurobiological factors. We examined in a diverse sample of schizophrenia out-patients the relationships of AOS with neuropsychological abilities and structural brain abnormalities as measured on cerebral magnetic resonance imaging (MRI). A total of 82 out-patients meeting DSM-111-R criteria for schizophrenia were evaluated with a comprehensive neuropsychological battery and semi-automated quantitatively analysed cerebral MRI. Earlier AOS correlated with poorer performance in learning and abstraction/ cognitive flexibility, and with larger volumes of caudate and lenticular nuclei, and smaller volume of thalamus on MRI. A model for predicting AOS consisting of abstraction and thalamic and caudate volumes'remained significant after controlling for duration of illness, current age and daily neuroleptic dose. In conclusion, AOS may be related to specific rather than general measures of cognitive performance and structural brain I abnormalities.

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Section: Discussionsupporting

confidence: 58%

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia^a

Jeste

McAdams

Palmer

et al. 1998

Acta Psychiatr Scand

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“…Regarding neurocognitive measures, GM was correlated with better performance on global and specific measures of neuropsychological functioning. 13,14 Gray matter was also correlated with higher IQ estimates in patients, 12 but not in healthy controls. Thus, there are suggestions that GM deficit in schizophrenia may relate to neurocognitive deficits and not to clinical variables associated with disease duration and severity.…”

Section: Arch Genmentioning

confidence: 88%

Reduced Gray Matter Volume in Schizophrenia

Gur¹,

Turetsky²,

Bilker³

et al. 1999

Arch Gen Psychiatry

154

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“…Individuals with schizophrenia also exhibit abnormalities in other cognitive, affective, sensory, and motor functions that depend on the circuitry of other cortical regions (15)(16)(17). Therefore, we sought to determine whether the specific pattern of changes in GABA-related transcript expression observed in the dorsolateral prefrontal cortex (i.e., decreased mRNA expression for GAD 67 , GAT-1, parvalbumin, somatostatin, GABA A α1, and GABA A δ and unaltered mRNA expression for calretinin and GAD 65 ) is specific to this area only or could also contribute to the dysfunction of other cortical areas in subjects with the illness.…”

Section: Introductionmentioning

confidence: 99%

“…In addition to these presynaptic markers of GABA neurotransmission, we recently reported decreased mRNA expression for several GABA A receptor subunits in the dorsolateral prefrontal cortex of subjects with schizophrenia (11), including the α1 and δ subunits, the major subunits in synaptic and extrasynaptic cortical GABA A receptors, respectively. Because normal working memory function depends upon GABA-mediated neurotransmission in the dorsolateral prefrontal cortex (14), these molecular alterations are thought to contribute to working memory disturbances in subjects with schizophrenia (3).Individuals with schizophrenia also exhibit abnormalities in other cognitive, affective, sensory, and motor functions that depend on the circuitry of other cortical regions (15)(16)(17). Therefore, we sought to determine whether the specific pattern of changes in GABA-related transcript expression observed in the dorsolateral prefrontal cortex (i.e., decreased mRNA expression for GAD 67 , GAT-1, parvalbumin, somatostatin, GABA A α1, and GABA A δ and unaltered mRNA expression for calretinin and GAD 65 ) is specific to this area only or could also contribute to the dysfunction of other cortical areas in subjects with the illness.…”

mentioning

confidence: 99%

Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects With Schizophrenia

Hashimoto

Bazmi²,

Mirnics

et al. 2008

AJP

416

330

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Objective-Individuals with schizophrenia exhibit disturbances in a number of cognitive, affective, sensory, and motor functions that depend on the circuitry of different cortical areas. The cognitive deficits associated with dysfunction of the dorsolateral prefrontal cortex result, at least in part, from abnormalities in GABA neurotransmission, as reflected in a specific pattern of altered expression of GABA-related genes. Consequently, the authors sought to determine whether this pattern of altered gene expression is restricted to the dorsolateral prefrontal cortex or could also contribute to the dysfunction of other cortical areas in subjects with schizophrenia.Method-Real-time quantitative polymerase chain reaction was used to assess the levels of eight GABA-related transcripts in four cortical areas (dorsolateral prefrontal cortex, anterior cingulate cortex, and primary motor and primary visual cortices) of subjects (N=12) with schizophrenia and matched normal comparison subjects.Results-Expression levels of seven transcripts were lower in subjects with schizophrenia, with the magnitude of reduction for each transcript comparable across the four areas. The largest reductions were detected for mRNA encoding somatostatin and parvalbumin, followed by moderate decreases in mRNA expression for the 67-kilodalton isoform of glutamic acid decarboxylase, the GABA membrane transporter GAT-1, and the α1 and δ subunits of GABA A receptors. In contrast, the expression of calretinin mRNA did not differ between the subject groups in any of the four areas.Conclusions-Because the areas examined represent the major functional domains (e.g., association, limbic, motor, and sensory) of the cerebral cortex, our findings suggest that a conserved set of molecular alterations affecting GABA neurotransmission contribute to the pathophysiology of different clinical features of schizophrenia.The core features of schizophrenia include disturbances in critical cognitive functions, such as working memory, that are mediated by the neural circuitry of the dorsolateral prefrontal cortex (1,2). In the dorsolateral prefrontal cortex of subjects with schizophrenia, markers of inhibitory neurotransmission appear to be impaired (3). For example, reduced levels of mRNA encoding the 67-kilodalton isoform of glutamic acid decarboxylase (GAD 67 ), the enzyme principally responsible for GABA synthesis (4), and the GABA membrane transporter GAT-1, which regulates the reuptake of synaptically released GABA, have been schizophrenia (5-12). These alterations in markers of GABA neurotransmission appear to involve specific subsets of GABA neurons. For example, mRNA encoding parvalbumin and somatostatin, each of which is expressed in a separate subset of GABA neurons, was decreased, whereas mRNA encoding calretinin, which is expressed in a third subset of GABA neurons, was unchanged in subjects with schizophrenia (11,13). Furthermore, reduced GABA synthesis might be selectively mediated by a deficit in GAD 67 , because neither mRNA nor protein leve...

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Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia

Cited by 56 publications

References 21 publications

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia^a

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia^a

Reduced Gray Matter Volume in Schizophrenia

Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects With Schizophrenia

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Cognitive and motor impairments are related to gray matter volume deficits in schizophrenia

Cited by 56 publications

References 21 publications

Relationship of neuropsychological and MRI measures to age of onset of schizophreniaa

Relationship of neuropsychological and MRI measures to age of onset of schizophreniaa

Reduced Gray Matter Volume in Schizophrenia

Conserved Regional Patterns of GABA-Related Transcript Expression in the Neocortex of Subjects With Schizophrenia

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Relationship of neuropsychological and MRI measures to age of onset of schizophrenia^a

Relationship of neuropsychological and MRI measures to age of onset of schizophrenia^a