Spatial working memory deficits and their relationship to negative symptoms in unmedicated schizophrenia patients

Carter, Cameron S.; Robertson, Lynn C.; Nordahl, Thomas E.; Chaderjian, Marc; Kraft, Louis; O'Shora-Celaya, L.

doi:10.1016/s0006-3223(96)00350-2

Cited by 166 publications

(108 citation statements)

References 11 publications

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“…26 Moreover, the PLC-b1 null mutation disrupts signaling through multiple pathways implicated in schizophrenic pathogenesis, such as the muscarinic cholinergic pathways, resulting in a comprehensive behavioral phenotype which correlates with that observed in the human condition. [68][69][70][71][72] We show that this mouse model exhibits numerous endophenotypes characteristic of schizophrenia including locomotor hyperactivity, sensorimotor gating deficits and cognitive deficits. The beneficial effects of the antipsychotic treatment on PPI suggest that the model has predictive validity.…”

Section: Camentioning

confidence: 99%

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

et al. 2007

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Phospholipase C-b1 (PLC-b1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-b1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-b1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenialike symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-b1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene-environment interactions.

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Section: Camentioning

confidence: 99%

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

et al. 2007

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“…Deficits have been demonstrated throughout the course of schizophrenia, 26,27 in neuroleptic-naïve, medicated and unmedicated patients, and are relatively unaffected by antipsychotic treatment. 16,[28][29][30] Dopamine neurotransmission in the dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in working memory. Single unit recording studies in non-human primates as well as functional neuroimaging studies in humans have consistently demonstrated this relationship.…”

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confidence: 99%

Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow

et al. 2005

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The catechol-O-methyl transferase (COMT) gene is considered a leading schizophrenia candidate gene. Although its role in increasing schizophrenia susceptibility has been conflicting, recent studies suggest the valine allele may contribute to poor cognitive function in schizophrenia. V 158 M COMT genotype was obtained on 159 schizophrenia patients and 84 healthy controls. The effects of COMT genotype on four measures of working memory/ executive functions (Wisconsin Card Sorting, digit span backward, Trail Making and N-back tests) and on MRI frontal brain volumes were examined. Genotype distributions were not significantly different between patients and controls. There were no significant genotype or genotype-by-group effects on any working memory/executive function measures. No genotype or genotype-by-diagnosis interaction effects were found with MRI frontal lobe volumes. Randomization analyses using [ 15 O]H 2 O positron emission tomography (PET) cerebral blood flow data found Val/Val patients had higher frontal lobe activation than Met/Met patients while performing the one-back task. Overall, these findings do not support a major role for COMT in increasing susceptibility for schizophrenia or in mediating frontal lobe function. Age-related changes and phenotypic heterogeneity of schizophrenia may influence the complex relationships between COMT genotype and cognition.

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“…CONCENTRATION CARD GAME AND SCHIZOPHRENIA In previous studies, a correlation was observed between WM in patients and the negative symptom assessment score [4,10]. Meanwhile, WM deficits have been proposed as a functional marker of schizophrenia [34,35].…”

Section: Discussionmentioning

confidence: 99%

“…Much is known about WM deficits in patients with schizophrenia, which have been shown to persist even when clinical symptoms decrease, and they are suggested to be important for their clinical outcome [3][4][5][6]. Previous studies have demonstrated reduced lateralization of activation during WM tasks [7][8][9] and correlation between degree of WM impairment and negative symptoms in schizophrenic patients [4,10].…”

Section: Introductionmentioning

confidence: 99%

Characteristics of Cortical Activation in Schizophrenia during the Card Game ^|^ldquo;Concentration^|^rdquo;

et al. 2012

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Summary:Various functional imaging studies have demonstrated reduced lateralization of cortical activation during neurocognitive tasks in schizophrenia. -A well-known card game, "concentration", reflects working memory (WM). We compared characteristics of hemodynamic changes in the prefrontal to temporo-parietal areas of the brain during this card game between 24 outpatients with schizophrenia and 24 age-and gendermatched healthy control subjects. Using multi-channel near-infrared spectroscopy, we measured relative changes in oxygenated hemoglobin concentration (oxy-Hb changes), which reflects brain activity during this task. Patients showed reduced lateralization in the midfrontal area, which is involved in executive functions, and in the inferior parietal area, involved in WM subcomponents. We also found a significant negative correlation between left midfrontal region oxy-Hb changes and severity of negative symptoms of schizophrenia. Our results characterized disease-related features, suggesting the usefulness of oxy-Hb change measurement during this card game for assessing functional outcome in schizophrenic patients.

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Spatial working memory deficits and their relationship to negative symptoms in unmedicated schizophrenia patients

Cited by 166 publications

References 11 publications

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

Catechol-O-methyl transferase Val158Met gene polymorphism in schizophrenia: working memory, frontal lobe MRI morphology and frontal cerebral blood flow

Characteristics of Cortical Activation in Schizophrenia during the Card Game ^|^ldquo;Concentration^|^rdquo;

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