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Standardized Data Acquisition for Neuromelanin-Sensitive Magnetic Resonance Imaging of the Substantia Nigra
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In vivo brain macromolecules in schizophrenia spectrum disorders.

Joshua Chiappelli1, Hongji Chen1, Stephanie A Korenic1,2

  • 1Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.

Schizophrenia (Heidelberg, Germany)
|May 19, 2026
PubMed
Summary

Macromolecule signals in the brain, detected using proton magnetic resonance spectroscopy (MRS), showed slight reductions in the hippocampus of individuals with schizophrenia spectrum disorders (SSD). These brain macromolecule levels did not correlate with cognitive function or inflammation markers.

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Area of Science:

  • Neuroimaging
  • Biomarkers
  • Neuropsychiatry

Background:

  • Proton magnetic resonance spectroscopy (MRS) detects brain macromolecule signals, often considered noise.
  • These signals may indicate pathophysiological processes like inflammation, impaired glymphatic clearance, and cellular damage.
  • Limited data exists on macromolecule levels in schizophrenia spectrum disorders (SSD).

Purpose of the Study:

  • To investigate macromolecule signal levels in the brain of individuals with SSD.
  • To explore associations between macromolecule levels, cognition, inflammation, and clinical factors in SSD.

Main Methods:

  • Metabolite-nulled proton MRS was used to measure macromolecule signals.
  • Four brain regions (anterior cingulate cortex, striatum, hippocampus, white matter) were analyzed.
  • 24 individuals with SSD and 22 healthy controls participated, alongside cognitive and C-reactive protein (CRP) assessments.

Main Results:

  • Significant differences in macromolecule levels were observed in the left hippocampus between individuals with SSD and controls.
  • No significant associations were found between macromolecule levels and cognition, symptom severity, or CRP levels.
  • Striatal macromolecule levels correlated with antipsychotic dose, and anterior cingulate levels correlated with sleep quality in the SSD group.

Conclusions:

  • Macromolecule levels in the brain may not be significantly altered in SSD, except for minor reductions in the hippocampus.
  • These findings suggest macromolecules may not substantially affect short echo time MRS metabolite measures in SSD.
  • Larger studies are required to validate these preliminary findings.