Association of Age, Antipsychotic Medication, and Symptoms W
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Lower brain glutamate levels may be associated with antipsychotic exposure rather than with greater age-related decline, whereas higher glutamate levels may serve as a biomarker of illness severity in patients with schizophrenia.

Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. The objective of this study was to assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.

The MEDLINE database was searched to identify journal articles. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data.

In total, 42 studies were included, with data for 1251 patients with schizophrenia.

--The MFC Glu and Glx levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant.

--In both patients and volunteers, the MFC Glu level was negatively associated with age, showing a 0.2-unit reduction per decade.

--In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu and MFC Glx levels.

--The MFC Glu to Cr ratio was positively associated with total symptom severity and positive symptom severity and was negatively associated with the level of global functioning.

--In the MTL, the Glx to Cr ratio was positively associated with total symptom severity, negative symptoms, and worse Clinical Global Impression score.

--The MFC creatine level increased with age but was not associated with either symptom severity or antipsychotic medication dose.

Findings from this meta-analysis suggest that lower brain Glu levels in patients with schizophrenia may be associated with antipsychotic medication exposure rather than with greater age-related decline. Higher brain Glu levels may act as a biomarker of illness severity in schizophrenia.

Source: https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2778479
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