Paranoia is a frequent and highly distressing experience in psychosis. Models of paranoia suggest limbic circuit pathology. Here, we tested whether resting-state functional connectivity (rs-fc) in the limbic circuit was altered in schizophrenia patients with current paranoia. We collected MRI scans in 165 subjects including 89 patients with schizophrenia spectrum disorders (schizophrenia, schizoaffective disorder, brief psychotic disorder, schizophreniform disorder) and 76 healthy controls. Paranoia was assessed using a Positive And Negative Syndrome Scale composite score. We tested rs-fc between bilateral nucleus accumbens, hippocampus, amygdala and orbitofrontal cortex between groups and as a function of paranoia severity. Patients with paranoia had increased connectivity between hippocampus and amygdala compared to patients without paranoia. Likewise, paranoia severity was linked to increased connectivity between hippocampus and amygdala. Furthermore, paranoia was associated with increased connectivity between orbitofrontal and medial prefrontal cortex. In addition, patients with paranoia had increased functional connectivity within the frontal hubs of the default mode network compared to healthy controls. These results demonstrate that current paranoia is linked to aberrant connectivity within the core limbic circuit and prefrontal cortex reflecting amplified threat processing and impaired emotion regulation. Future studies will need to explore the association between limbic hyperactivity, paranoid ideation and perceived stress.

Background Personal space is the safe area around us causing discomfort when violated by others. Previous research has shown that our need for personal space can be shaped by previous and current experiences. For instance, childhood maltreatment is associated with altered personal space in healthy controls. Additionally, space regulation is altered in schizophrenia (with personal space being increased in patients with paranoia). Whether childhood maltreatment and dimensions of delusions are associated with increased safety behaviour in patients with schizophrenia is unknown. We therefore aim to test the association of childhood trauma and delusions with interpersonal distance in schizophrenia patients and healthy controls. Methods We assessed childhood trauma (CT) in both, healthy subjects and schizophrenia patients (matched for age, gender and education) with the childhood trauma scale. This scale is a self-report screening tool for experiences of abuse & neglect during childhood. Additionally, we assessed delusions in schizophrenia patients, using the dimensions of delusional experience scale (DDE), which includes ‘conviction’, ‘extension’, ‘bizarreness’, ‘disorganization’, and ‘pressure’ dimensions. We compared the interpersonal distance (stop-distance test) and comfort ratings at predetermined distances (fixed-distance test) between subjects with low/medium and high CT ratings. Likewise, interpersonal distance and comfort ratings of patients with and without delusions were compared. Results In our preliminary data (n = 27), subjects with high CT ratings showed an increased need for interpersonal space compared to subjects with low/medium CT. Additionally, the high CT group showed reduced comfort ratings at varying fixed distances. Likewise, patients with delusions had an increased interpersonal space and reduced comfort at fixed distances. Moreover, interpersonal space was associated with the severity of childhood trauma, and in particular with emotional neglect. Finally, interpersonal distance was associated with the degree to which the delusional belief involves various areas of patients’ lives (‘extension’ dimension of the DDE). Discussion Our preliminary data suggests that childhood maltreatment and dimensions of delusions are associated with increased safety behaviour in patients with schizophrenia. These findings are in line with previous studies, which found associations of interpersonal distance and childhood maltreatment in healthy controls as well as paranoia in patients with schizophrenia. Our findings are of particular interest, as increased safety behaviour may impact social functioning (i.e. lead to more social withdrawal) in patients with schizophrenia.

Background Schizophrenia is a disabling disorder with tremendous individual burden, reduced quality of life, leading to intense costs for society. Paranoia is a central feature of schizophrenia. In particular, paranoid experience is thought to be associated with aggressive behaviour, and poor social and functional outcome. Since paranoid threat is sometimes hard to detect in the clinical interview, a simple bedside test to identify patients suffering from paranoid experience was recently proposed: the interpersonal distance test. Methods For measuring interpersonal distance in patients with schizophrenia and age-, gender- and education-matched healthy controls, we performed a stop-distance paradigm. To accomplish the paradigm, we positioned experimenter and participant at opposite ends of the room with a distance of seven meters facing each other. The stop-distance paradigm contained four different conditions; two active conditions (i.e. participant is approaching experimenter) and two passive conditions (i.e. experimenter is approaching participant) both, with and without eye contact. Participants were instructed to stop or tell the experimenter to stop at a distance, at which they would start to feel less comfortable. Moreover, we assessed paranoid threat with the Bern Psychopathology Scale. We compared the interpersonal distance between patients with current experiences of paranoid threat, schizophrenic patients without paranoia and healthy controls. Results Patients with higher ratings in paranoid experience presented with higher interpersonal distance than patients without paranoid threat and matched healthy controls. This effect was most prominent in the passive conditions. Patients without paranoia did not differ from healthy controls in the interpersonal distance test. Discussion Interpersonal distance is a reliable indicator of current paranoid threat in patients with schizophrenia. In fact, interpersonal distance is not generally altered in schizophrenia. However, paranoid threat leads to impairments in interpersonal space regulation. This is of particular relevance as interpersonal distance might be predictive of social and functional outcome and aggressive behaviour in schizophrenia.

Negative symptoms (NS) are a core component of schizophrenia affecting community functioning and quality of life. We tested neural correlates of NS considering NS factors and consensus subdomains. We assessed NS using the Clinical Assessment Interview for Negative Symptoms and the Scale for Assessment of Negative Symptoms. Arterial spin labeling was applied to measure resting-state cerebral blood flow (rCBF) in 47 schizophrenia patients and 44 healthy controls. Multiple regression analyses calculated the relationship between rCBF and NS severity. We found an association between diminished expression (DE) and brain perfusion within the cerebellar anterior lobe and vermis, and the pre-, and supplementary motor area. Blunted affect was linked to fusiform gyrus and alogia to fronto-striatal rCBF. In contrast, motivation and pleasure was not associated with rCBF. These results highlight the key role of motor areas for DE. Considering NS factors and consensus subdomains may help identifying specific pathophysiological pathways of NS.

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