Transdiagnostic Neuroimaging Approaches in Psychiatric Disorders

Transdiagnostic neuroimaging seeks to identify neural features that underlie symptoms across traditional diagnostic boundaries, moving beyond categorical classifications to dimensional models of psychopathology. This paradigm rests on the observation that many psychiatric conditions share genetic, behavioural and neurobiological substrates, and that high rates of comorbidity often reflect common circuit-level dysfunctions. By employing structural MRI, resting-state and task-based functional MRI, diffusion imaging and multimodal integration, researchers aim to delineate patterns of brain structure and connectivity that correlate with symptom dimensions such as mood dysregulation, cognitive control deficits and thought disturbance. Advanced analytic frameworks—including multivariate techniques, normative modelling and network neuroscience—have facilitated the mapping of latent factors (for example the general psychopathology or ‘p’ factor) onto reproducible alterations in prefrontal development, default mode and executive networks, and white-matter pathways. Such transdiagnostic markers hold promise for stratifying patients, refining prognoses and guiding personalised interventions by pinpointing core circuits that transcend conventional categories.

Research from Nature Portfolio

Recent studies have demonstrated a unified neural substrate for comorbid symptoms across multiple disorders. One investigation used longitudinal multimodal connectome data from adolescence to early adulthood to derive a reproducible neuropsychopathological factor characterised by delayed prefrontal maturation and impaired executive function. This factor generalized across resting-state connectivity and independent clinical cohorts, suggesting a shared developmental trajectory underpinning externalizing and internalizing symptoms. Another study applied sparse canonical correlation analysis in a large youth sample to extract four dimensions of psychopathology—mood, psychosis, fear and externalizing behaviour—and linked each dimension to distinct patterns of functional network connectivity. A common finding was reduced segregation between default mode and executive networks, highlighting a convergent signature of network integration deficits across symptom dimensions.

Transdiagnostic Neuroimaging Approaches in Psychiatric Disorders publication trend

The graph below shows the total number of articles in transdiagnostic neuroimaging approaches in psychiatric disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Transdiagnostic approach: An investigative framework that focuses on underlying dimensions shared across multiple psychiatric disorders rather than on individual diagnostic categories.

Functional connectivity: Statistical dependence between activity patterns of distinct brain regions, often measured during rest or task performance to infer network interactions.

Connectome: A comprehensive map of neural connections in the brain, encompassing structural or functional links between regions.

General psychopathology factor (p-factor): A latent dimension capturing shared liability for diverse psychiatric symptoms, reflecting general vulnerability to mental illness.

Canonical correlation analysis (CCA): A multivariate statistical method that identifies pairs of linear combinations from two sets of variables that maximally correlate, used to link brain measures with behavioural or clinical data.

References

1. A shared neural basis underlying psychiatric comorbidity. Nature Medicine (2023).
2. Transdiagnostic biomarkers of mental illness across the lifespan: A systematic review examining the genetic and neural correlates of latent transdiagnostic dimensions of psychopathology in the general population. Neuroscience & Biobehavioral Reviews (2023).
3. Multivariate brain-behaviour associations in psychiatric disorders. Translational Psychiatry (2024).
4. Linked dimensions of psychopathology and connectivity in functional brain networks. Nature Communications (2018).
5. A Connectome-wide Functional Signature of Transdiagnostic Risk for Mental Illness. Biological Psychiatry (2018).