Assessing Brain Metabolism With 7-T Proton Magnetic Resonance Spectroscopy in Patients With First-Episode Psychosis

Abstract

IMPORTANCEThe use of high-field magnetic resonance spectroscopy (MRS) in multiple brain regions of a large population of human participants facilitates in vivo study of localized or diffusely altered brain metabolites in patients with first-episode psychosis (FEP) compared to healthy participants. OBJECTIVE To compare metabolite levels in 5 brain regions between patients with FEP (evaluated within 2 years of onset) and healthy controls, and to explore possible associations between targeted metabolite levels and neuropsychological test performance.DESIGN, SETTING, AND PARTICIPANTS Cross-sectional design used 7-T MRS at a research MR imaging facility in participants recruited from clinics at the Johns Hopkins Schizophrenia Center and the local population. Eighty-one patients who had received a DSM-IV diagnosis of FEP within the last 2 years and 91 healthy age-matched (but not sex-matched) volunteers participated.MAIN OUTCOMES AND MEASURES Brain metabolite levels including glutamate, glutamine, γ-aminobutyric acid (GABA), N-acetylaspartate, N-acetylaspartyl glutamate, and glutathione, as well as performance on neuropsychological tests. RESULTSThe mean (SD) age of 81 patients with FEP was 22.3 (4.4) years and 57 were male, while the mean (SD) age of 91 healthy participants was 23.3 (3.9) years and 42 were male. Compared with healthy participants, patients with FEP had lower levels of glutamate (F 1,162 = 8.63, P = .02), N-acetylaspartate (F 1,161 = 5.93, P = .03), GABA (F 1,163 = 6.38, P = .03), and glutathione (F 1,162 = 4.79, P = .04) in the anterior cingulate (all P values are corrected for multiple comparisons); lower levels of N-acetylaspartate in the orbitofrontal region (F 1,136 = 7.23, P = .05) and thalamus (F 1,133 = 6.78, P = .03); and lower levels of glutathione in the thalamus (F 1,135 = 7.57, P = .03). Among patients with FEP, N-acetylaspartate levels in the centrum semiovale white matter were significantly correlated with performance on neuropsychological tests, including processing speed (r = 0.48; P < .001), visual (r = 0.33; P = .04) and working (r = 0.38; P = .01) memory, and overall cognitive performance (r = 0.38; P = .01).CONCLUSIONS AND RELEVANCE Seven-tesla MRS offers insights into biochemical changes associated with FEP and may be a useful tool for probing brain metabolism that ranges from neurotransmission to stress-associated pathways in participants with psychosis.

Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate

“…This is not surprising, given that meta-analytic pooling of ACC GSH studies in schizophrenia reveal a small overall effect size [24], suggesting the possibility of heterogeneity in the GSH levels and thus redox status among patients. Our results suggest that such heterogeneity may map onto antipsychotic responsiveness, resulting in the conflicting findings of GSH levels reported to date in schizophrenia [23].…”

“…A previous 7T MRS study included FEP subjects with an average of 55 weeks of antipsychotic exposure [54], compared with 6 days of median exposure in our sample. A more recent study [23] included FEP subjects with up to 2 years of illness duration, while we recruited all subjects during the acute first episode (mean SOFAS score of 38.1). We report three major findings: (1) patients with FEP with higher GSH levels in ACC show a rapid symptom reduction upon starting antipsychotic treatment, (2) when compared with healthy controls, GSH levels in patients are dissociated from glutamate levels, and (3) Glutamate excess predicts the degree of Social and Occupational dysfunction seen at the time of presentation with FEP.…”

“…Glutathione (GSH), the brain's most prominent intracellular antioxidant, has been suspected to play a key protective role in free-radical-mediated damage to neurons [21], giving rise to the redox dysregulation hypothesis of schizophrenia [22]. Magnetic resonance spectroscopy (MRS) studies have found a small but significant GSH deficit in the ACC in patients with schizophrenia [23], indicating the presence of subgroups of patients with different redox profiles [24]. The most prominent reduction in GSH seems to occur particularly in patients with persistent residual symptoms, indicating that low levels of GSH may be associated with poor response to antipsychotics [25].…”

Dopamine and glutamate in schizophrenia: biology, symptoms and treatment

“…Higher field strength has greater sensitivity, enabling greater separation of glutamate and glutamine peaks, and allowing for more accurate quantification. Two studies in first‐episode patients have shown reduced glutamate concentrations in the anterior cingulate cortex, while another only found this in a subset of patients with predominantly negative symptoms. No difference has been observed in several other investigations.…”

LSD impairs working memory, executive functions, and cognitive flexibility, but not risk-based decision making

“…Most psychiatric and neurodegenerative illnesses are characterized by cognitive impairments (Claesdotter, et al, 2018;Jagust, 2018;Wang, et al, 2019;Wunderli, et al, 2016).…”