Cognitive Impairment in Psychotic Disorders Is Associated with Brain Reductive Stress and Impaired Energy Metabolism as Measured by 31P Magnetic Resonance Spectroscopy.
Level 4 - case-series / case-control
Cross-sectional comparative study analyzing subgroups within a clinical psychosis cohort.
PubMed 39869459 · doi:10.1093/schbul/sbaf003
What was done
Sixty-two participants with affective and non-affective psychosis (mean age 25.1 years) completed the MATRICS Consensus Cognitive Battery (MCCB) and a 4T phosphorus-31 magnetic resonance spectroscopy (31P-MRS) scan. Cluster analysis was used to separate participants into two groups: those with and without cognitive dysfunction. The clusters were compared on brain redox balance (NAD+/NADH ratio), creatine kinase enzymatic activity, and intracellular pH.
What was found
The cognitively impaired cluster showed a significantly lower brain NAD+/NADH ratio, indicating greater reductive stress, compared to the cognitively intact cluster (t = -2.60, P = .01). Creatine kinase activity was also significantly reduced in the impaired cognitive cluster (t = -2.19, P = .03). Intracellular pH showed no significant difference between groups (t = 1.31, P = .19). Mood and psychotic symptom severity did not differ between the clusters.
Why it matters
This study links in vivo markers of brain bioenergetics and reductive stress directly to cognitive impairment in psychotic disorders, highlighting potential metabolic targets for cognitive deficits.
Limits
The study is cross-sectional, precluding causal conclusions about whether metabolic abnormalities drive cognitive impairment. The sample size is modest (n = 62), encompasses mixed affective and non-affective diagnoses, and the abstract lacks details on medication status or comparison to healthy controls.
Cited by
- supports Researchers at McLean Hospital and Harvard have published data directly measuring bioenergetic impairment and energy resistance in the human brain in mental illnesses.