Neuroimaging and Clinical Phenotypes of Psychotic Disorders

Psychotic disorders, including schizophrenia and schizoaffective and bipolar presentations with psychotic features, are characterised by disturbances in perception, thought and social functioning. Neuroimaging has revealed heterogeneous patterns of brain structure and function that underlie these clinical phenotypes. Structural magnetic resonance imaging demonstrates regional grey matter reductions—most prominently in frontal, temporal and subcortical regions—alongside white matter disconnection in major association tracts. Functional MRI and resting-state techniques uncover altered connectivity within the default mode, salience and frontoparietal networks. Diffusion imaging further characterises microstructural white matter integrity, while spectroscopic methods probe neurochemical alterations in vivo. Machine learning and data-driven clustering approaches have begun to define biologically grounded subgroups, which correlate with symptom profiles, cognitive impairment and remission trajectories. Genetic risk profiles, integrated with multimodal imaging, yield intermediate biomarkers that may inform stratified treatment. Longitudinal analyses point to dynamic neuroprogressive changes in early illness phases and suggest critical windows for intervention. Together, this body of work supports a move towards precision psychiatry in which imaging-derived phenotypes guide prognosis and personalise therapeutic approaches.

Research from Nature Portfolio

Recent studies have identified two robust neurostructural subtypes in large international cohorts of individuals with schizophrenia, distinguished by early cortical versus subcortical grey matter loss trajectories. These subtypes are reproducible across continents and hold promise for redefining diagnostic boundaries based on biological signatures. In parallel, integration of schizophrenia polygenic risk scores with multimodal MRI has revealed a frontotemporal network biomarker. This gene-associated pattern of reduced grey matter volume and diminished functional activation distinguishes psychotic disorders from other conditions and predicts cognitive performance and symptom severity, offering a transdiagnostic imaging signature specific to schizophrenia spectrum illness.

Neuroimaging and Clinical Phenotypes of Psychotic Disorders publication trend

The graph below shows the total number of articles in neuroimaging and clinical phenotypes of psychotic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Structural magnetic resonance imaging (MRI): A non-invasive imaging technique that maps brain anatomy and measures volumes of grey and white matter.

Functional MRI (fMRI): A method to detect brain activity by measuring changes in blood oxygenation during tasks or at rest.

Diffusion tensor imaging (DTI): An MRI sequence that assesses the directional movement of water molecules to characterise white matter microstructure.

Cortical thickness: A measure of the thickness of the cerebral cortex, reflecting neuronal density and laminar organisation.

Polygenic risk score (PRS): A quantitative index of an individual’s inherited risk for a disorder, calculated from multiple genetic variants.

References

1. Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm. Nature Communications (2024).
2. Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium. Molecular Psychiatry (2023).
3. Brain structure, function, and neurochemistry in schizophrenia and bipolar disorder—a systematic review of the magnetic resonance neuroimaging literature. Schizophrenia (2017).
4. Neuroprogression across the Early Course of Psychosis †. Journal of Psychiatry and Brain Science (2020).
5. Derivation and utility of schizophrenia polygenic risk associated multimodal MRI frontotemporal network. Nature Communications (2022).
6. Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia. Molecular Psychiatry (2022).