Paranoid ideation—the mistaken belief that intentional harm is likely to occur—spans a continuum, from mild suspicion to persecutory delusions. Among patients with schizophrenia and other psychosis disorders, elevated levels of paranoia are common, debilitating, and challenging to treat.

The cues (public environments, strangers) and processes (anxiety) that promote paranoia have grown increasingly clear, but the brain bases of these pathways are unknown, thwarting the development of mechanistic models and, ultimately, the development of more effective or tolerable biological interventions.

This multi-disciplinary project will use a combination of tools to clarify the factors governing paranoia. We will enroll the full spectrum of paranoia without gaps or discontinuities—including psychosis patients with frank persecutory delusions and matched community controls. These data will allow us to rigorously examine the hypothesized contribution of brain circuits responsible for triggering anxiety and evaluating the threat potential of everyday social cues. Integrating neuroimaging measures with smartphone experience-sampling data will enable us to extend these insights to the real world for the first time. It has become increasingly clear that traditional psychiatric diagnoses, like Schizophrenia, present significant barriers to understanding etiology. Our focus on dimensional measures of paranoia overcomes many of these barriers and dovetails with the HiTOP framework.

This project is led by Drs. Jack Blanchard, Jason Smith, and Alex Shackman at Maryland, and encompasses a collaboration with Dr. Alan Anticevic‘s group at Yale. The award is sponsored by the National Institute of Mental Health.