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Evidence suggests that affect plays a role in the development of psychosis but the underlying mechanism requires further investigation. This study examines the moment-to-moment dynamics between negative affect (NA) and paranoia prospectively in daily life. A female general population sample (n = 515) participated in an experience sampling study. Time-lagged analyses between increases in momentary NA and subsequent momentary paranoia were examined. The impact of childhood adversity, stress sensitivity (impact of momentary stress on momentary NA), and depressive symptoms on these time-lagged associations, as well as associations with follow-up self-reported psychotic symptoms (Community Assessment of Psychic Experiences and the Symptom Checklist-90-Revised) were investigated. Moments of NA increase resulted in a significant increase in paranoia over 180 subsequent minutes. Both stress sensitivity and depressive symptoms impacted on the transfer of NA to paranoia. Stress sensitivity moderated the level of increase in paranoia during the initial NA increase, while depressive symptoms increased persistence of paranoid feelings from moment to moment. Momentary paranoia responses to NA increases were associated with follow-up psychotic symptoms. Examination of microlevel momentary experience may thus yield new insights into the mechanism underlying co-occurrence of altered mood states and psychosis. Knowledge of the underlying mechanism is required in order to determine source and place where remediation should occur.

Objective: Patients diagnosed with a psychotic disorder and their first-degree relatives display increased reactivity to stress. Theory predicts that experience of psychosocial stress is associated both with ventromedial prefrontal and mesolimbic dopamine neurotransmission. However, while there is evidence of aberrant striatal dopamine processing in psychotic disorder, the role of the prefrontal cortex remains under-researched. This study aimed at investigating stress-induced in vivo dopamine release in ventromedial prefrontal cortex (vmPFC) of individuals at familial risk for psychosis., Method: Fourteen healthy first-degree relatives of patients with a diagnosis of psychotic disorder and 10 control subjects underwent a single dynamic positron emission tomography (PET) scanning session after intravenous administration of 183.2 (SD = 7.6) MBq [(18)F]fallypride. Psychosocial stress was initiated at 100 min postinjection using a computerized mental arithmetic task with social evaluative threat components. PET data were analyzed using the linearized simplified reference region model. Regression analyses were performed to compare the spatial extent of task-related ligand displacement between control subjects and relatives and to find how it related to self-rated experiences of psychosocial stress and psychosis., Results: First-degree relatives displayed hyporeactive dopamine signaling in the vmPFC in response to stress. Increased levels of subjectively rated stress were associated with increased intensity of psychotic experiences. This effect was particularly pronounced in first-degree relatives., Conclusion: Although previous studies have hypothesized a role for prefrontal dopamine dysfunction in psychosis, this study, to our knowledge, is the first in vivo human imaging study showing attenuated (ie, hyporeactive) dopamine stress neuromodulation in vmPFC of individuals at familial risk for psychosis.

Background: Cross-sectional studies have indicated that alterations in social functioning, particularly interpersonal functioning, are associated with the occurrence of psychotic symptoms and experiences at different levels of the extended psychosis phenotype (ranging from population psychometric expression of liability to overt psychotic disorder). However, more research is needed on the development of this association over time., Methods: Cross-lagged path modeling was used to analyze bidirectional, longitudinal associations between 4 dimensions of subclinical psychotic experiences (persecutory ideation, bizarre experiences, perceptual abnormalities, and magical thinking) and interpersonal functioning in an adolescent general population sample (N = 881 at T1, N = 652 at T2, and N = 512 at T3) assessed 3 times in 3 years., Results: All symptom dimensions showed some association with interpersonal functioning over time, but only bizarre experiences and persecutory ideation were consistently and longitudinally associated with interpersonal functioning. Poorer interpersonal functioning predicted higher levels of bizarre experiences and persecutory ideation at later measurement points (both T1 to T2 and T2 to T3)., Conclusions: Poor interpersonal functioning in adolescence may reflect the earliest expression of neurodevelopmental alterations preceding expression of psychotic experiences in a symptom-specific fashion.

Previous evidence reviewed in Schizophrenia Bulletin suggests the importance of a range of different environmental factors in the development of psychotic illness. It is unlikely, however, that the diversity of environmental influences associated with schizophrenia can be linked to as many different underlying mechanisms. There is evidence that environmental exposures may induce, in interaction with (epi)genetic factors, psychological or physiological alterations that can be traced to a final common pathway of cognitive biases and/or altered dopamine neurotransmission, broadly referred to as "sensitization," facilitating the onset and persistence of psychotic symptoms. At the population level, the behavioral phenotype for sensitization may be examined by quantifying, in populations exposed to environmental risk factors associated with stress or dopamine-agonist drugs, (1) the increased rate of persistence (indicating lasting sensitization) of normally transient developmental expressions of subclinical psychotic experiences and (2) the subsequent increased rate of transition to clinical psychotic disorder.