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Background Elevated incidence rates of non-affective psychosis and psychotic symptoms in densely populated urban areas have been reported by many epidemiological studies. It has been proposed that social characteristics of the urban environment underlie the association with the development of psychotic disorders. Individuals at risk for psychosis may be particularly susceptible to these conditions, given that psychosis is associated with deficits in social information processing. It has been suggested that the urban environment affects the neural mechanisms for social stress processing, including the amygdala (Lederbogen et al. 2011). Increased sensitivity to social stress (negative feedback) is a key characteristic of psychosis and may further contribute to problems during social interactions (Myin-Germeys et al. 2005). Additionally, city living was associated with altered activation and modulation of brain regions involved in reward processing (Krämer et al. 2017). This functional magnetic resonance imaging (fMRI) study investigates if reduced trust in patients with psychotic disorder is associated with urban upbringing. Methods Thirty-nine patients (22 first-episode and 17 clinical high-risk) and 30 healthy controls, aged 16 – 29 performed two multi-round trust games during fMRI scanning, with a cooperative and unfair partner. Baseline trust in an unknown other, and responses to positive and negative social feedback were investigated. Urban exposure during upbringing (0–15 years) was defined as higher-urban (>2500 inhabitants/km2) or lower-urban (<2500 inhabitants/km2). Region of interest analyses were conducted in areas related to stress processing, mentalizing, and reward processing. Associations of symptom measures with behavioral and neural outcomes were investigated. Results Patients displayed lower baseline trust (first investment) than controls, regardless of urbanicity exposure. Urbanicity exposure was associated with differential learning from positive social feedback in patients, with a steeper increase in investments in lower compared to higher urban patients. Negative symptoms impacted on learning from positive feedback only in patients brought up in higher-urban areas. During cooperative interactions higher urbanicity was associated with decreased activation of the left amygdala in patients and controls, and with increased activation of the right amygdala in patients only. In unfair interactions, no associations of brain activation and urbanicity were found. Discussion Urbanicity was unrelated to baseline trust. Higher-urban patients failed to compensate for the initial distrust during repeated cooperative interactions. The results tentatively suggest that low urbanicity during upbringing might act as a protective factor on the sensitivity to cooperation, where steep increases of trust counteracted initial distrust. On the neural level, urbanicity was linked to differential amygdala activation, a region associated with (negative) emotions, fear, and stress processing. Impaired learning from positive social feedback suggests that urbanicity is a proxy for social stress, possibly resulting in distrust. However, this could not explain behavioral differences. Patients appear to be more susceptible to urbanicity effects than controls, especially during positive social interactions and trust building. Alternatively, these differences might be due to the increased genetic risk levels for psychosis in participants with high-urban upbringing, due to selective migration. We did not find evidence for the hypothesis that urbanicity increases the sensitivity to negative social feedback. [ABSTRACT FROM AUTHOR]