TY - JOUR
T1 - Associations Between Cognitive Function and Levels of Glutamatergic Metabolites and Gamma-Aminobutyric Acid in Antipsychotic-Naïve Patients With Schizophrenia or Psychosis
AU - Bojesen, Kirsten Borup
AU - Broberg, Brian Villumsen
AU - Fagerlund, Birgitte
AU - Jessen, Kasper
AU - Thomas, Marie Bjerregaard
AU - Sigvard, Anne
AU - Tangmose, Karen
AU - Nielsen, Mette Ødegaard
AU - Andersen, Gitte Saltoft
AU - Larsson, Henrik Bo Wiberg
AU - Edden, Richard A.E.
AU - Rostrup, Egill
AU - Glenthøj, Birte Yding
N1 - Funding Information:
Funding for the study was provided by a Ph.D. grant from the Faculty of Health and Medical Sciences , University of Copenhagen (to KBB), Ph.D. grants and a postdoctoral grant from the Mental Health Services in the Capital Region of Denmark (to KJ, AS, KT, and MØN), a Ph.D. grant from the Faculty of Social Sciences , University of Copenhagen (to MBT), an independent grant from the Lundbeck Foundation (Grant No. R155-2013-16337 ) to the Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (to BYG), support from the Mental Health Services , Capital Region of Denmark (to BYG), and a grant from the Gangsted Foundation (to BYG). RAEE received support from the National Institute of Health (Grant Nos. P41EB015909 , R01EB016089 , R01EB023963 , R01MH106564 , and R21MH098228 ). The funding sources played no further role in the study design; collection, analysis, and interpretation of data; writing of the manuscript; or decision to submit the manuscript for publication.
Funding Information:
BYG is the head of the Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, which is partially financed by an independent grant from the Lundbeck Foundation (Grant No. R155-2013-16337), which is based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. Her group has also received a research grant from Lundbeck A/S for an additional independent investigator-initiated study. All grants are the property of, and administrated by, the Mental Health Services. All other authors report no biomedical financial interests or potential conflicts of interest.
PY - 2020
Y1 - 2020
N2 - 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-naïve patients. Methods: In total, 56 antipsychotic-naïve 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-naïve 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.
AB - 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-naïve patients. Methods: In total, 56 antipsychotic-naïve 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-naïve 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.
KW - Anterior cingulate cortex
KW - Antipsychotic-naïve schizophrenia
KW - Cognition
KW - GABA
KW - Glutamate
KW - Magnetic resonance spectroscopy
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U2 - 10.1016/j.biopsych.2020.06.027
DO - 10.1016/j.biopsych.2020.06.027
M3 - Article
C2 - 32928500
AN - SCOPUS:85090708888
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
ER -