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Matthew J Kempton

Publications and source records attributed to Matthew J Kempton.

2 recordsLinked to original sources
PubMed2026

Neurometabolites and Antipsychotic Response in Psychosis: A Mega-Analysis.

IMPORTANCE: Revealing neurobiological markers of antipsychotic nonresponse in psychosis may aid outcome prediction and inform novel treatment targets. OBJECTIVE: To examine differences in neurometabolites in antipsychotic nonresponsive compared to antipsychotic-responsive psychosis using individual participant data and meta-analysis. DATA SOURCES: Web of Science was searched for studies published between January 1, 1980, and November 1, 2025. Authors of 21 eligible studies identified before August 2024 were invited to contribute individual participant data. STUDY SELECTION: Eighteen studies examining neurometabolites by treatment response in psychosis contributed individual participant data for the mega-analysis. These studies plus a further 5 studies were included in the meta-analyses of standardized mean differences and variability. DATA EXTRACTION AND SYNTHESIS: Individual participant data were analyzed using linear mixed models with study as a random effect. Subgroup analyses examined prospective designs and treatment-resistant samples. Published group means and standard deviations were extracted for meta-analyses. MAIN OUTCOMES AND MEASURES: Group differences in glutamate, glutamate plus glutamine, choline, myo-inositol, N-acetylaspartate, γ-aminobutyric acid, and glutathione in the medial frontal cortex, dorsolateral prefrontal cortex, thalamus, and basal ganglia. RESULTS: The mega-analysis included 1189 participants from 18 studies; of these, 476 were treatment nonresponders (mean [SD] age, 33.0 [12.5] years; 340 male), 427 were treatment responders (mean [SD] age, 30.3 [11.5] years; 299 male), and 286 were healthy control individuals (mean [SD] age, 31.0 [12.5] years; 170 male). Compared with the antipsychotic response group, nonresponders showed elevations in medial frontal glutamate (Glass Δ = 0.21; P = .02), glutamate plus glutamine (Glass Δ = 0.29; P = .002), choline (Glass Δ = 0.22; P = .03), and myo-inositol (Glass Δ = 0.35; P = .001); similar elevations were observed relative to control individuals. Elevated medial frontal glutamate plus glutamine in antipsychotic nonresponders compared with responders was also observed prospectively in first-episode psychosis (Glass Δ = 0.41; P = .002), whereas myo-inositol elevations were greatest in individuals meeting criteria for treatment-resistance (Glass Δ = 0.64; P = .001). The meta-analysis of 23 studies (1844 participants) also showed elevated medial frontal choline and myo-inositol in antipsychotic nonresponse compared with response. CONCLUSIONS AND RELEVANCE: These findings provide evidence of an association between antipsychotic nonresponse in psychosis with elevations in medial frontal glutamate, choline, and myo-inositol. The presence of elevations in these markers supports the continued investigation of glutamate-acting and inflammatory pathway-associated interventions for psychosis and schizophrenia.

Humans↗
PubMed2025

A whole-brain voxel-based analysis of structural abnormalities in PTSD: An ENIGMA-PGC study.

BACKGROUND: Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group. METHODS: T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9). RESULTS: PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges' g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges' g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (p corrected  = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (p corrected  = .001). CONCLUSIONS: PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.

Humans↗