• Research Highlights
People with psychotic disorders such as schizophrenia often experience cognitive difficulties, including problems with attention, concentration and memory. These cognitive difficulties are often early symptoms that appear before the onset of psychosis. In a study funded by the National Institute of Mental Health, researchers found consistent links between brain connectivity and cognitive function in people with early-stage psychosis and in high-risk people who later developed psychosis. This discovery could help researchers and clinicians better understand the factors that lead to psychosis, informing earlier intervention and improved treatments.
What did the researchers look at in the study?
Researchers Heather Burrell Ward, MD (Vanderbilt University Medical Center), Roscoe Brady, Jr., MD, Ph.D. (Beth Israel Deaconess Medical Center), Kathryn Eve Lewandowski, Ph.D. (McLean Hospital) and colleagues reviewed data from two large multisite studies. The studies – the Human Connectome Project for Early Psychosis (HCP-EP) and the North American Prodrome Longitudinal Study 2 (NAPLS2) – included participants with early psychosis or high risk for psychosis, as well as healthy participants with no known risk for psychosis.
The research team performed a comprehensive analysis of the participants’ neural connections, or connectome, to identify strong associations between brain connectivity and attention. Attention was measured using an auditory task specifically developed to assess sustained attention in individuals with or at risk for psychotic disorders. The task measures three aspects of attention: vigilance, memory, and the ability to manage interference.
Overall, the researchers analyzed data from 96 HCP-EP participants with early psychosis and 213 NAPLS2 participants at high risk for psychosis.
What did the study find?
Overall, participants with psychosis or increased risk for psychosis performed worse on the attention task than their peers who were not at risk for psychosis.
Data from participants with early psychosis revealed associations between their brain connectivity and attention, according to the researchers’ hypothesis. Specifically, lower connectivity between an area in the medial prefrontal cortex and an area in the somatomotor cortex was associated with poorer performance on the attention task. The researchers found a similar connectivity-cognition correlation among participants who were at increased risk for—and eventually developed—psychosis.
Data from the two studies showed no connectivity–cognition associations for high-risk participants who did not develop psychosis or for participants who were not at risk for psychosis.
What do the results mean?
These consistent links between brain connectivity and cognition point to specific brain circuits that may contribute to cognitive difficulties in people with psychotic disorders, even before psychosis occurs. However, these links do not provide evidence of causation. The researchers suggest that experimental studies using non-invasive brain stimulation techniques could help determine whether changes in these brain circuits directly affect cognitive performance. If so, these circuits may serve as specific targets for therapeutic intervention.
Ward, Brady, Lewandowski and colleagues note that recruiting participants is a particular challenge in this area of research, requiring significant time, effort and resources. Only a small percentage of people at risk for psychosis eventually develop psychosis, and at-risk participants are often difficult to identify. According to the researchers, these findings highlight how valuable large multisite studies such as the HCP-EP and NAPLS2 are in improving our understanding of the factors that predict and contribute to psychosis.
Reference
Ward, HB, Beermann, A., Xie, J., Yildiz, G., Manzanarez Felix, K., Addington, J., Bearden, CE, Cadenhead, K., Cannon, TD, Cornblatt, B., Keshavan, M., Mathalon, D., Perkins, DO, Seidman, L., Stone, WS, Tsuang, MT, Walker, EF, Woods, S., Coleman, MJ,…Brady, RO, Jr. (2024). Strong brain correlates of cognitive performance in psychosis and its progression. Biological Psychiatry, 97(2), 139–147. https://doi.org/10.1016/j.biopsych.2024.07.012
Grants
MH066134 , MH066286 , MH120588-01A1 , MH081902 , MH081857 , MH117012 , MH109977 , MH082022 , MH081944 , MH066069 , MH076989 , MH081928 , MH081988 , MH116170
