期刊
BIOLOGICAL PSYCHIATRY
卷 89, 期 3, 页码 278-287出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2020.06.027
关键词
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资金
- Faculty of Health and Medical Sciences, University of Copenhagen
- Mental Health Services in the Capital Region of Denmark
- Faculty of Social Sciences, University of Copenhagen
- Lundbeck Foundation [R155-2013-16337]
- Mental Health Services, Capital Region of Denmark
- Gangsted Foundation
- National Institute of Health [P41EB015909, R01EB016089, R01EB023963, R01MH106564, R21MH098228]
- University of Copenhagen
- Lundbeck A/S
The study found that antipsychotic-naive patients had lower GABA levels in the ACC and patients with schizophrenia had higher glutamate levels in the thalamus. There was a positive association between glutamatergic metabolites and cognitive function, with Glx levels in the ACC positively linked to working memory and attention.
BACKGROUND: Abnormal glutamate and GABA (gamma-aminobutyric acid) levels have been found in the early phase of schizophrenia and may underlie cognitive deficits. However, the association between cognitive function and levels of glutamatergic metabolites and GABA has not been investigated in a large group of antipsychotic-naive patients. METHODS: In total, 56 antipsychotic-naive patients with schizophrenia or psychotic disorder and 51 healthy control subjects underwent magnetic resonance spectroscopy to measure glutamate, glutamate+glutamine (Glx), and GABA levels in dorsal anterior cingulate cortex (ACC) and glutamate and Glx levels in left thalamus. The cognitive domains of attention, working memory, and IQ were assessed. RESULTS: The whole group of antipsychotic-naive patients had lower levels of GABA in dorsal ACC (p = .03), and the subgroup of patients with a schizophrenia diagnosis had higher glutamate levels in thalamus (p = .01), but Glx levels in dorsal ACC and thalamus did not differ between groups. Glx levels in dorsal ACC were positively associated with working memory (logarithmically transformed: b = -.016 [higher score indicates worse performance], p = .005) and attention (b = .056, p = .035) in both patients and healthy control subjects, although the association with attention did not survive adjustment for multiple comparisons. CONCLUSIONS: The findings suggest a positive association between glutamatergic metabolites and cognitive function that do not differ between patients and healthy control subjects. Moreover, our data indicate that decreased GABAergic levels in dorsal ACC are involved in schizophrenia and psychotic disorder, whereas increased glutamate levels in thalamus seem to be implicated in schizophrenia pathophysiology. The findings imply that first-episode patients with cognitive deficits may gain from glutamate-modulating compounds.
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