Neuroimaging Studies of Schizophrenia and Psychosis

Neuroimaging has profoundly advanced our understanding of schizophrenia and psychosis by revealing structural and functional brain alterations that underpin symptoms and cognitive deficits. Structural MRI studies consistently report reduced grey-matter volumes in key regions such as the hippocampus, thalamus, amygdala and nucleus accumbens, together with cortical thinning in frontal and temporal lobes. Diffusion imaging highlights disrupted white-matter integrity and altered inter-hemispheric connectivity. Functional MRI reveals aberrant resting-state networks, notably in fronto-striatal and default-mode circuits, and task-based studies demonstrate abnormal activation patterns during cognitive and emotional challenges. Large-scale consortia and multisite mega-analyses have begun to identify subtle but reproducible effect sizes, while machine-learning approaches seek neuroimaging-based biotypes predictive of clinical outcome. Studies of individuals at clinical high-risk for psychosis explore prodromal neuromaturational deviations, guiding early intervention. Transdiagnostic investigations, for example comparing first-episode psychosis with Parkinson’s disease psychosis, point to common grey-matter covariance networks. Taken together, these advances offer objective biomarkers for diagnosis, prognosis and personalised treatment strategies, and illuminate the neurodevelopmental and neurodegenerative trajectories of psychotic disorders.

Research from Nature Portfolio

A large cohort investigation examined the volumes of subcortical nuclei in patients with schizophrenia versus healthy controls, replicating meta-analytic findings of smaller hippocampus, amygdala, thalamus and nucleus accumbens volumes. Importantly, individual differences in right nucleus accumbens volume correlated with processing-speed performance, and right thalamic volume predicted social functioning. These results underscore the pivotal role of limbic and basal ganglia structures in cognitive and socio-functional deficits and point to specific nuclei as potential targets for therapeutic modulation or biomarker development.

Neuroimaging Studies of Schizophrenia and Psychosis publication trend

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

Technical terms

Subcortical structures: Deep brain nuclei (e.g., hippocampus, thalamus, basal ganglia) involved in cognition, emotion and motor control.

Voxel-based morphometry (VBM): A neuroimaging analysis technique that assesses regional grey-matter volume or density on a voxel-wise basis.

Functional connectivity: Statistical dependence between activity time courses of spatially distinct brain regions, often measured during rest.

Structural covariance network (SCN): A pattern of coordinated grey-matter volume variations across individuals, reflecting shared developmental or pathological influences.

Cortical thickness: The distance between white-matter and pial surfaces, used as an index of neuronal and synaptic integrity.

Clinical high-risk (CHR): A defined state characterised by attenuated psychotic symptoms or genetic/familial vulnerability, indicating elevated risk of developing psychosis.

References

1. Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification. Molecular Psychiatry (2023).
2. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium. Proceedings of the National Academy of Sciences of the United States of America (2023).
3. A multicentre study on grey matter morphometric biomarkers for classifying early schizophrenia and parkinson’s disease psychosis. npj Parkinson's Disease (2023).
4. Role of subcortical structures on cognitive and social function in schizophrenia. Scientific Reports (2018).