Background: Default mode network (DMN) dysfunction exists in psychosis and is associated with both systemic inflammation and impaired cognition. Here we examined whether inflammatory-based cognitive alterations in psychosis may be partially explained by DMN alterations.
Methods: Resting state functional MRI (rsfMRI) was examined in 95 probands (Schizophrenia/Schizoaffective, n=50; Psychotic Bipolar, n=45) and 42 healthy controls from the Bipolar-Schizophrenia Network of Intermediate Phenotypes. Empirical rsfMRI networks were derived using independent component analysis for the anterior, inferior- posterior and superior-posterior DMN. Cytokines (IL-1, IL-6, TNF, and CRP) were measured from serum and cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) composite score. The bootstrapping mediation method was conducted in the whole sample to examine DMN relationships between cytokines and cognition while covarying for age, sex, ancestry, and FD power.
Results: Increased IL-1 and IL-6 were associated with lower anterior DMN activity (r=- 0.24, p=0.005; r=-0.19, p=0.06). Higher CRP was negatively correlated with BACS (r=-0.14, p=0.01). Lower BACS significantly (p<0.05) correlated with decreased anterior, inferior- posterior, and superior-posterior DMN activity (r=0.18, r=0.19, r=0.20, respectively). We identified a significant mediation effect of anterior DMN on the relationship between IL-6 (ACME=-0.10, p=0.006), IL-1 (ACME=-0.07, p=0.008), or CRP (ACME=-0.04, p=0.04) and BACS. There were no direct effects (p>0.05). There were significant total effects for CRP (TE=-0.16, p=0.04) and IL-6 (TE=-0.29, p=0.05).
Conclusions: Lower anterior DMN activity mediates relationships between peripheral inflammation and cognition. DMN activity may serve as a target biomarker for anti- inflammatory treatment studies to improve cognitive deficits in patients with increased inflammation and psychosis.
Live Zoom Session – April 21st
Paulo Lizano, Sarah Keedy, Shashwath Meda, S Kristian Hill, Adam Lee, Olivia Lutz, Leah H. Rubin, Carol Tamminga, Brett Clementz, Godfrey Pearlson, Elliot Gershon, John Sweeney, Matcheri Keshavan, Jeffrey Bishop