A question of trust: Aberrant connectivity of the salience network in schizophrenia

Introduction: Patients with schizophrenia (SZ) show impaired social cognition, which may contribute to altered trust judgments and increased vulnerability to health risks like sexually transmitted infections. Along with aberrant salience attribution in SZ, the salience network, a key system for processing socially and emotionally relevant information, might contribute to altered social risk attribution.Methods: Patients with SZ, a clinical control group of patients with alcohol use disorder (AUD), and healthy controls (HC) were asked to rate the trustworthiness of persons pre-classified as HIV+ or HIV- based on a previous study, while imagining to be in a dating context. Behavioral ratings during fMRI, post-ratings of trustworthiness, attractiveness, and HIV probability were collected, and brain activity focusing on the salience network and its connectivity were analyzed.Results: All groups rated HIV+ pre-categorized person as less trustworthy than HIV− ones. SZ patients showed generally higher trust ratings, accompanied by reduced connectivity between the salience network and regions involved in social-cognitive processing. Activation in insula and nucleus accumbens was more influenced by attractiveness in SZ than HC. AUD patients exhibited increased insula connectivity during untrustworthy evaluations, and activation in reward-related brain regions was less modulated by perceived trustworthiness than in HC.Discussion: Our findings point to differential biases in trust evaluation across clinical groups, and suggest distinct patterns of salience attribution. In SZ, increased trust and stronger neural responses to attractiveness, paired with reduced integration of risk-related cues, may reflect a diminished ability to detect socially relevant threats. In contrast, AUD patients showed enhanced sensitivity to negative social cues. These results demonstrate how altered salience attribution in trust perception shows differently across disorders, with SZ being characterized by under-attribution of social risk and AUD by heightened threat sensitivity.