• Research Highlight
People with psychotic disorders such as schizophrenia frequently experience cognitive difficulties, including problems with attention, concentration, and memory. These cognitive difficulties are usually early symptoms that appear before the onset of psychosis. In a study funded by the National Institute of Mental Health, researchers identified 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 doctors better understand the factors that lead to psychosis, informing earlier intervention and better treatments.
What did the researchers observe 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 examined data from two large multicenter studies. The studies, the Human Connectome Project for Early Psychosis (HCP-EP) and the North American Prodrome Longitudinal Study 2 (NAPLS2), include participants with early psychosis or at high risk for psychosis, as well as healthy participants with no known risk for psychosis. .
The research team conducted a comprehensive analysis of the participants’ neural connections, or connectomes, to identify strong associations between brain connectivity and attention. Attention was measured using an auditory task developed specifically to assess sustained attention in people with or at risk for psychotic disorders. The task measures three aspects of attention: vigilance, memory, and the ability to manage interference.
In total, 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 at 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, consistent with the researchers’ hypothesis. Specifically, lower connectivity between an area of the medial prefrontal cortex and a region of the somatomotor cortex was associated with worse performance on the attention task. The researchers found a similar association between connectivity and cognition among participants who were at higher risk for (and eventually developed) psychosis.
Data from the two studies showed no associations between connectivity and cognition 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 develops. However, these links do not provide evidence of a causal relationship. The researchers suggest that experimental studies using non-invasive brain stimulation techniques could help determine whether changes in these brain circuits directly impact cognitive performance. If so, these circuits may serve as specific targets for therapeutic intervention.
Ward, Brady, Lewandowski, and their colleagues note that recruiting participants is a particular challenge in this area of research, requiring considerable time, effort, and resources. Only a small proportion of people who are at risk for psychosis eventually develop psychosis, and at-risk participants are often difficult to identify. According to the researchers, these findings underscore how valuable large multisite studies such as HCP-EP and NAPLS2 are in improving our understanding of the factors that predict and contribute to psychosis.
Reference
Ward, H.B., Beermann, A., Xie, J., Yildiz, G., Manzanarez Felix, K., Addington, J., Bearden, C.E., Cadenhead, K., Cannon, T.D., Cornblatt, B., Keshavan, M., Mathalon, D., Perkins, DO, Seidman, L., Stone, WS, Tsuang, MT, Walker, EF, Woods, S., Coleman, MJ,…Brady, RO, Jr. (2024). A robust brain correlates with cognitive performance in psychosis and its prodromes. Biological psychiatry, 97(2), 139-147. https://doi.org/10.1016/j.biopsych.2024.07.012
Subsidies
MH066134 , MH066286 , MH120588-01A1 , MH081902 , MH081857 , MH117012 , MH109977 , MH082022 , MH081944 , MH066069 , MH076989 , MH081928 , MH081988 , MH116170
