Reduction of cortical GABAergic inhibition correlates with working memory impairment in recent onset schizophrenia

Takahashi, Shun; Ukai, Shigeo; Kose, Asami; Hashimoto, Tadahiro; Iwatani, Jun; Okumura, Minoru; Tsuji, Takao; Shinosaki, Kazuhiro

doi:10.1016/j.schres.2013.02.033

Cited by 29 publications

(26 citation statements)

References 59 publications

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“…However, cross-sectional designs have limited the interpretation of these studies. One prior stud has investigated the relationship between CI and cognitive impairments in schizophrenia patients (Takahashi et al 2013). In this study, lower SICI levels were found to be associated with poor working memory performance (Takahashi et al 2013).…”

Section: Introductionmentioning

confidence: 70%

The relation of the change in symptoms and cognitive functions with the change in cortical inhibition parameters measured by transcranial magnetic stimulation: An eight-week follow-up study

Yıldız¹,

Temuçin²,

Ertuğrul³

2014

Turkish Journal of Psychiatry

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Previous transcranial magnetic stimulation (TMS) studies have demonstrated cortical inhibition (CI) abnormalities in patients with schizophrenia. However, the relationship between changes in CI and changes in psychopathology and cognition resulting from antipsychotic treatment is not known. This is an 8 week follow up study which aims to evaluate the relation of the CI with the symptoms and cognitive functions of the patients who are switched to new atypical antipsychotic treatment, and to compare the TMS measurements of patients with those of controls. Method: Thirteen patients and 13 control subjects matched according to age, sex, and educational level were included in the study. Patients were assessed with TMS, Positive and Negative Syndrome Scale (PANSS), and a neurocognitive battery at baseline and at 8 weeks post-treatment, while the control group was evaluated with the neurocognitive battery and TMS at baseline only. CI parameters evaluated by TMS include resting motor threshold, cortical silent period, ipsilateral silent period (ISP), short interval intracortical inhibition (SICI) and intracortical facilitation. Results: Intracortical facilitation (ICF) was weaker and ISP was longer in patients relative to control subjects both at baseline and at the end of the eight weeks. Intracortical facilitation decreased following 8 weeks of antipsychotic treatment, indicating an increase in CI. The decrease in PANSS general psychopathology score was directly correlated with the decrease in ICF. SICI positively correlated with cognitive test performance in both cross-sectional and longitudinal analyses. Conclusion: Our findings suggest that increase in CI is associated with the improvement in the symptoms and the action of the atypical antipsychotics.

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Section: Introductionmentioning

confidence: 70%

The relation of the change in symptoms and cognitive functions with the change in cortical inhibition parameters measured by transcranial magnetic stimulation: An eight-week follow-up study

Yıldız¹,

Temuçin²,

Ertuğrul³

2014

Turkish Journal of Psychiatry

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“…The severity of clinical symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Neurocognitive function was tested by experienced psychologists using the Brief Assessment of Cognition in Schizophrenia (BACS) Japanese version (Kaneda et al, ), which is widely used in Japan (Ikebuchi et al, ; Itakura et al, ; Satogami, Takahashi, Yamada, Ukai, & Shinosaki, ; Sawada et al, ; Takahashi et al, ). This battery includes six subtests: list learning test (verbal memory), digit sequencing test (working memory), token motor test, verbal fluency test, symbol coding test (attention), and the Tower of London test (executive function).…”

Section: Methodsmentioning

confidence: 99%

“…The severity of clinical symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Neurocognitive function was tested by experienced psychologists using the Brief Assessment of Cognition in Schizophrenia (BACS) Japanese version (Kaneda et al, 2007), which is widely used in Japan (Ikebuchi et al, 2017;Itakura et al, 2017;Satogami, Takahashi, Yamada, Ukai, & Shinosaki, 2017;Sawada et al, 2017;Takahashi et al, 2013 (Kaneda et al, 2013). The composite score was calculated by averaging all z-scores of six subcomponents.…”

Section: Neuropsychological Measurementsmentioning

confidence: 99%

Microstructural abnormalities in callosal fibers and their relationship with cognitive function in schizophrenia: A tract‐specific analysis study

et al. 2019

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Introduction The corpus callosum serves the essential role of relaying cognitive information between the homologous regions in the left and the right hemispheres of the brain. Cognitive impairment is a core dysfunction of schizophrenia, but much of its pathophysiology is unknown. The aim of this study was to elucidate the association between microstructural abnormalities of the corpus callosum and cognitive dysfunction in schizophrenia. Methods We examined stepwise multiple regression analysis to investigate the relationship of the fractional anisotropy (FA) of callosal fibers in each segment with z ‐scores of each brief assessment of cognition in schizophrenia subtest and cognitive composite score in all subjects (19 patients with schizophrenia [SZ group] and 19 healthy controls [HC group]). Callosal fibers were separated into seven segments based on their cortical projection using tract‐specific analysis of diffusion tensor imaging. Results The FA of callosal fibers in the temporal segment was significantly associated with z ‐scores of token motor test, Tower of London test, and the composite score. In the SZ group, the FA of callosal fibers in the temporal segment was significantly associated with the z ‐score of the Tower of London test. In addition, the FA of callosal fibers in temporal segment showed significant negative association with the positive and negative syndrome scale negative score in the SZ group. Compared to the HC group, the FA in temporal segment was significantly decreased in the SZ group. Conclusion Our results suggest that microstructural abnormalities in the callosal white matter fibers connecting bilateral temporal lobe cortices contribute to poor executive function and severe negative symptom in patients with schizophrenia.

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“…Some groups have found symptom correlations (less inhibition with greater symptom severity) (Daskalakis et al, 2002; Daskalakis et al, 2008; Liu et al, 2009), but this has not been found in other centers (see Table 3). Interestingly, one recent report found a correlation between greater SICI inhibition and working memory performance (Takahashi et al, 2013). Although these studies cannot rule out non-GABAergic causes of reduced SICI, this literature provides some of the most direct evidence for reduced inhibitory function predicted by the post-mortem GABA findings.…”

Section: 0 Tms Studies Of Gaba and Motor Activitymentioning

confidence: 99%

GABA abnormalities in schizophrenia: A methodological review of in vivo studies

Taylor

Tso

2015

Schizophrenia Research

104

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Abnormalities of GABAergic interneurons are some of the most consistent findings from post-mortem studies of schizophrenia. However, linking these molecular deficits with in vivo observations in patients – a critical goal in order to evaluate interventions that would target GABAergic deficits – presents a challenge. Explanatory models have been developed based on animal work and the emerging experimental literature in schizophrenia patients. This literature includes: neuroimaging ligands to GABA receptors, magnetic resonance spectroscopy (MRS) of GABA concentration, transcranial magnetic stimulation of cortical inhibitory circuits and pharmacologic probes of GABA receptors to dynamically challenge the GABA system, usually in combination with neuroimaging studies. Pharmacologic challenges have elicited behavioral changes, and preliminary studies of therapeutic GABAergic interventions have been conducted. This article critically reviews the evidence for GABAergic dysfunction from each of these areas. These methods remain indirect measures of GABAergic function, and a broad array of dysfunction is linked with the putative GABAergic measures, including positive symptoms, cognition, emotion, motor processing and sensory processing, covering diverse brain areas. Measures of receptor binding have not shown replicable group differences in binding, and MRS assays of GABA concentration have yielded equivocal evidence of large-scale alteration in GABA concentration. Overall, the experimental base remains sparse, and much remains to be learned about the role of GABAergic interneurons in healthy brains. Challenges with pharmacologic and functional probes show promise, and may yet enable a better characterization of GABAergic deficits in schizophrenia.

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Reduction of cortical GABAergic inhibition correlates with working memory impairment in recent onset schizophrenia

Cited by 29 publications

References 59 publications

The relation of the change in symptoms and cognitive functions with the change in cortical inhibition parameters measured by transcranial magnetic stimulation: An eight-week follow-up study

The relation of the change in symptoms and cognitive functions with the change in cortical inhibition parameters measured by transcranial magnetic stimulation: An eight-week follow-up study

Microstructural abnormalities in callosal fibers and their relationship with cognitive function in schizophrenia: A tract‐specific analysis study

GABA abnormalities in schizophrenia: A methodological review of in vivo studies

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