Summary: New research shows that cognitive deficits in psychotic disorders—including schizophrenia and bipolar disorder—are linked to how brain networks are organized. Crucially, this brain–cognition relationship appears before the first psychotic episode in people at clinical high risk, revealing potential pathways for earlier diagnosis and targeted intervention.
The findings describe a reproducible brain network signature associated with cognitive performance, pointing to new opportunities for treatments aimed at cognitive symptoms that are often resistant to medication.
Key Facts
- Cognitive impairment in psychotic disorders is associated with the organization of large-scale brain networks.
- The same brain–cognition association is detectable in individuals at clinical high risk before their first psychotic episode.
- These insights may enable earlier identification and novel interventions—such as noninvasive neuromodulation—targeting cognitive dysfunction.
Source: Elsevier
Overview
A new study published in Biological Psychiatry presents robust evidence that cognitive impairments in psychosis are tethered to specific patterns of brain connectivity. The research examined both people with early-course psychotic disorders and individuals identified as at-risk for psychosis, using a tailored cognitive test and advanced MRI connectome analysis. Results indicate that a reproducible link between connectivity and cognitive performance exists in those with psychotic disorders and emerges prior to clinical onset in future converters.
Lead author Heather Burrell Ward, MD, from Vanderbilt University Medical Center, emphasizes that cognitive deficits are common and disabling in schizophrenia and related disorders, yet effective medications for these problems are lacking. Because these impairments frequently appear by the time someone has a first psychotic break, recognizing brain signatures that precede psychosis could be critical for early detection and treatment development.
Many prior studies have explored cognitive deficits in psychosis using tests originally designed for healthy populations, but such approaches do not always clarify how cognitive constructs map onto measurable brain substrates. To address this gap, the current study used a psychosis-informed cognitive measure alongside a connectome-wide multivariate analysis of resting-state fMRI, drawing on two large research consortia for validation.
Co-senior author Roscoe O. Brady, Jr., MD, PhD, of Harvard Medical School and affiliated hospitals, explains that the team first identified connectivity patterns tied to cognition in individuals with early psychosis. They then tested whether the same brain-cognition signature could be detected in an independent sample of individuals at clinical high risk for psychosis. The signature—most notably connectivity between prefrontal and somatomotor regions—was present specifically in at-risk participants who later converted to psychosis, but not in nonconverters or healthy controls.
John Krystal, MD, Editor of Biological Psychiatry, notes that combining a data-driven connectome-wide approach with a disease-informed cognitive assessment enabled the researchers to uncover a novel, reproducible relationship between brain connectivity and cognitive performance—an advance that offers insight into early detection and potential intervention targets for psychotic disorders.
Co-senior author Kathryn E. Lewandowski, PhD, of McLean Hospital and Harvard Medical School, points out that international initiatives, including the Accelerating Medicines Partnership® Schizophrenia (AMP SCZ), are actively seeking biomarkers and treatment targets in people at risk for psychosis. The discovery of a reliable link between cognitive performance and brain network organization, detectable before clinical onset, suggests new avenues for early diagnosis and therapeutic strategies such as targeted, noninvasive neuromodulation.
About this psychosis and neuroscience research news
Author: Eileen Leahy
Source: Elsevier
Contact: Eileen Leahy – Elsevier
Image: The image is credited to Neuroscience News
Original Research: Open access.
Title: Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome by Heather Burrell Ward et al., Biological Psychiatry
Abstract
Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome
Background
Neurocognitive deficits are a hallmark of schizophrenia and often begin before psychosis becomes clinically apparent. Prior connectome-wide association studies have produced mixed results when relating resting-state fMRI connectivity to cognitive performance. The authors hypothesized that using a cognitive task designed for psychosis and focusing on a refined clinical population would improve the detection of reliable brain–behavior associations. They first conducted a connectome-wide analysis in early psychosis and then tested whether identified brain–cognition relationships generalized to an independent at-risk cohort.
Methods
The study used the Seidman Auditory Continuous Performance Task (ACPT), a cognitive measure that differentiates healthy individuals from those with psychosis. The Human Connectome Project for Early Psychosis (n = 183) served as the discovery sample to map connectivity associated with ACPT performance. The authors then applied these findings to the North American Prodrome Longitudinal Study 2 (n = 345), a multi-site prospective cohort of individuals at clinical high risk for psychosis, evaluating whether the same connectivity–cognition relationships appeared in converters, nonconverters, and controls.
Results
In early-course psychosis, better ACPT performance correlated with stronger connectivity between prefrontal and somatomotor networks (p < .005). The same prefrontal–somatomotor connectivity pattern predicted ACPT performance in at-risk individuals who later developed psychosis (converters, n = 17). This association did not appear in nonconverters (n = 196) or healthy controls (n = 132), suggesting the connectivity signature is specifically related to the prodromal phase that precedes conversion.
Conclusions
This connectome-wide association study identified reproducible links between brain connectivity and cognitive performance across separate samples of individuals with psychosis and those at clinical high risk who later converted. The results indicate that selecting cognitive measures grounded in the clinical phenotype, together with targeted population sampling, enhances the ability of connectome-wide approaches to reveal reliable brain–phenotype relationships. These findings support further development of brain-based biomarkers and early interventions aimed at cognitive deficits in psychotic disorders.