Functional connectome signature of general psychopathology in middle-aged and older adults: Evidence from…

Cohort studyImaging neuroscience (Cambridge, Mass.)· 2026

Functional connectome signature of general psychopathology in middle-aged and older adults: Evidence from multi-cohort, multi-ethnic analyses.

Thuan Tinh Nguyen, Kwun Kei Ng, Voon Hao Lew … Juan Helen Zhou

GeriatricsCohort studyPrognosisQ2IF 2.4

General psychopathology brain scores are linked to elevated mortality risk.

Functional connectome signature of general psychopathology in middle-aged and older adults: Evidence from multi-cohort, multi-ethnic analyses.

Thuan Tinh Nguyen … Juan Helen Zhou

Imaging neuroscience (Cambridge, Mass.) · 2026 · Q2 in General Medicine

Background

Mental health disorders are increasingly prevalent in middle-aged and older adults, a population undergoing substantial brain network reorganization.

Purpose

We aimed to identify whole-brain connectivity patterns associated with transdiagnostic psychiatric dimensions and their links to mental health trajectories and mortality.

Methods

We analyzed resting-state functional connectivity from the UK Biobank (N = 6529) using multivariate partial least squares analysis to identify latent variables linking brain networks with mental health symptoms.

n = 6529

Results

higher general psychopathology brain scores are linked to a higher risk of death

HR 1.31 (95% CI 1.06 to 1.62)

CI excludes the null - significant

More results

Associations with longitudinal mental health outcomes and mortality risk were examined.

The first represented a general psychopathology factor (p = 0.0006, 28.0% of the overall covariance), marked by altered connectivity in the somatomotor and default mode networks.

More results

The second (p < 0.0001, 17.2% of the overall covariance) distinguished affective disorders from alcohol use disorder via attentional and subcortical network patterns.

“

Conclusion

This work provides insight into mechanisms of vulnerability and suggests that brain-based markers may help indicate risk and differentiate patterns of symptom persistence, transition, and remission across disorders in aging populations.

Functional connectome signature of general psychopathology in middle-aged and older adults: Evidence from multi-cohort, multi-ethnic analyses.

Functional connectome signature of general psychopathology in middle-aged and older adults: Evidence from multi-cohort, multi-ethnic analyses.

Related papers