Neuroimaging and Structural Changes in Schizophrenia

Schizophrenia is associated with widespread alterations in brain structure that can be detected non‐invasively by magnetic resonance imaging. Cross‐sectional and longitudinal studies have consistently revealed reductions in cortical thickness and grey matter volume, particularly within prefrontal, temporal and limbic regions, alongside ventricular enlargement. White matter integrity is also compromised, with disruptions in major frontotemporal tracts contributing to impaired neural connectivity. Subcortical structures such as the caudate nucleus and thalamus exhibit volumetric shifts influenced by both disease processes and antipsychotic treatment. While some changes appear progressive—especially early in the disease—others may stabilise or partially reverse, reflecting a complex interplay of neurodevelopmental vulnerability, synaptic dysregulation, inflammation and treatment effects. Advances in morphometric techniques, surface‐based analysis and normative modelling have enabled finer mapping of individual deviations, paving the way for biomarkers that track clinical trajectories and guide personalised interventions.

Research from Nature Portfolio

Recent work has clarified how age of onset and medication interact to shape subcortical anatomy. In a large clinical cohort, both early-onset and adult-onset patients exhibited enlarged caudate volumes relative to healthy controls. Crucially, antipsychotic exposure was linked to further increases in the caudate among early-onset cases but not in adult-onset patients, suggesting a heightened vulnerability of the developing striatum to dopaminergic treatments. This finding delineates separate contributions of illness and medication to striatal morphology and highlights a potential biomarker for monitoring therapeutic effects in younger patients.

Neuroimaging and Structural Changes in Schizophrenia publication trend

The graph below shows the total number of articles in neuroimaging and structural changes in schizophrenia across all publications each year (not limited to Nature Index journals).

Technical terms

Voxel-based morphometry: An automated MRI analysis technique that quantifies local differences in brain tissue volume and concentration.

Cortical thickness: The distance between white matter and pial surfaces, used to assess regional grey matter integrity.

Normative modelling: A statistical framework that compares an individual’s brain measures against a large healthy reference to identify atypical deviations.

Caudate nucleus: A subcortical structure of the striatum involved in motor and cognitive functions and sensitive to dopaminergic modulation.

First-episode psychosis: The initial manifestation of psychotic symptoms, often studied to minimise confounding by chronic illness and long-term treatment.

References

1. Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study. Molecular Psychiatry (2024).
2. Transcriptional level of inflammation markers associates with short-term brain structural changes in first-episode schizophrenia. BMC Medicine (2023).
3. A 10-Year Longitudinal Study of Brain Cortical Thickness in People with First-Episode Psychosis Using Normative Models. Schizophrenia Bulletin (2024).
4. Caudate nucleus volume in medicated and unmedicated patients with early- and adult-onset schizophrenia. Scientific Reports (2024).