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The finding of glutamate/glutamine abnormalities in a group of subjects at high genetic risk for schizophrenia lends support for both the glutamate dysfunction and neurodevelopmental hypotheses for 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. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.OBJECTIVE To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites. DATA SOURCESThe MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. 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.STUDY SELECTION In total, 45 1H-MRS studies contributed data.DATA EXTRACTION AND SYNTHESIS Associations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor. Glu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL). MAIN OUTCOMES AND MEASURES RESULTSIn total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F 1,1211.9 = 4.311, P = .04) and Glx (F 1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F 1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F 1,1522.4 = 47.533, P < .001; cerebrospinal fluid-corrected Glu, F 1,1216.7 = 5.610, P = .02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, −0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose.CONCLUSIONS AND RELEVANCE F...

Despite the well-acknowledged problem of poor adherence to antipsychotic (AP) medication, long-acting injectables (LAIs) that could improve adherence are underused in Canada. Attitudes concerning LAIs among patients and psychiatrists may contribute to this underuse. Our objective was to investigate perceptions of and attitudes toward LAIs among patients in Canada. Method: Focus groups were conducted with 34 patients with a diagnosis of schizophrenia spectrum psychoses in 4 Canadian provinces. The focus groups inquired about experiences with and attitudes toward LAI APs. The sessions were audiotaped and transcribed verbatim, and transcripts were coded using a combination of deductive and inductive methods. Results: Four themes emerged: awareness of and knowledge about LAIs; perceptions about LAIs; cost and convenience considerations; and issues arising from the coercive context under which LAIs were often prescribed. Nine patients had never heard about LAIs, and some others reported not having understood what was discussed with them regarding LAIs. Patients had typically heard about LAIs in either a context of coercion or of medication nonadherence. Patients had positive and negative perceptions concerning LAIs. The positive perceptions centred on relapse prevention and reduced effort in ensuring adherence, and the negative perceptions centred on financial costs and the inconvenience of appointments to receive injections. Conclusion: To enhance LAI usage, some of the issues that need to be addressed are the inadequacy of information given to patients, the element of coercion involved in LAI introduction, the pragmatic barriers to LAI uptake by patients, and negative subjective perceptions about LAIs.