Aberrant salience is the incorrect assignment of salience, significance or value to different innocuous stimuli. It seems closely related with dysregulation of the dopamine system that in turn relates with proneness to develop psychosis.

To evaluate aberrant salience processing in a clinical trans-diagnostic sample, its relationship with anamnestic psychotic symptoms and current psychopathology, and possible variations of aberrant salience after three months of clinical-based treatment.

Twenty inpatient subjects attending the Psychiatric Unit (Florence University) were recruited: 3 with Major Depression Disease, 6 with Schizophrenia, 3 with Bipolar Disorder, 4 with Obsessive-Compulsive Disorder, 4 with Eating Disorders. Patients were assessed by means of a clinical interview (SCID-I/P) and several questionnaires (AMDP, MADRS, HAM-A, MRS, PANSS and Aberrant Salience Inventory-ASI) at enrolment (T0) and after an individual and clinical-based treatment lasting 3 months (T1).

At T0 subjects with positive ASI (cut-off>14) reported more frequently past and lifetime psychotic symptoms (p<0.05) and constituted a distinct cluster from patients with ASI score < 14. A positive anamnesis of psychotic symptoms was significantly correlated with AMDP susbscales (delusions and perception disturbances), PANSS pos, PANSS neg, PANSS tot scores (p<0.05). A significant reduction of mean MADRS, PANSS tot and HAM scores between T0 and T1 was found (p<0.05). No differencesin ASI scores between T0 and T1 were observed.

Aberrant salience is significatively associated to lifetime psychotic symptoms. It represents a relevant psychopathologic dimension that, unlike other symptoms, seems not to significatively modify after pharmacological treatment and could represent a stable lifetime.

The long-term clinical validity of the At Risk Mental State (ARMS) for the prediction of non-psychotic mental disorders is unknown.

Clinical register-based cohort study including all non-psychotic individuals assessed by the Outreach And Support in South London (OASIS) service (2002–2015). The primary outcome was risk of developing any mental disorder (psychotic or non-psychotic). Analyses included Cox proportional hazard models, Kaplan–Meier survival/failure function and C statistics.

A total of 710 subjects were included. A total of 411 subjects were at risk (ARMS+) and 299 not at risk (ARMS−). Relative to ARMS−, the ARMS+ was associated with an increased risk (HR = 4.825) of developing psychotic disorders, and a reduced risk (HR = 0.545) of developing non-psychotic disorders (mainly personality disorders). At 6-year, the ARMS designation retained high sensitivity (0.873) but only modest specificity (0.456) for the prediction of psychosis onset (AUC 0.68). The brief and limited intermittent psychotic symptoms (BLIPS) subgroup had a higher risk of developing psychosis, and a lower risk of developing non-psychotic disorders as compared to the attenuated psychotic symptoms (APS) subgroup (P < 0.001).

In the long-term, the ARMS specifically predicts the onset of psychotic disorders, with modest accuracy, but not of non-psychotic disorders. Individuals meeting BLIPS criteria have distinct clinical outcomes.

In the long-term, the ARMS designation is still significantly associated with an increased risk of developing psychotic disorders but its prognostic accuracy is only modest. There is no evidence that the ARMS is associated with an increased risk of developing non-psychotic mental disorders. The BLIPS subgroup at lower risk of developing non-psychotic disorders compared to the APS subgroup.

While incident diagnoses employed in this study are high in ecological validity they have not been subjected to formal validation with research-based criteria.

Subjects at ultra high-risk (UHR) for psychosis have an enhanced vulnerability to develop the disorder but the risk factors accounting for this accrued risk are undetermined.

Systematic review of associations between genetic or environmental risk factors for psychosis that are widely established in the literature and UHR state, based on comparisons to controls.

Forty-four studies encompassing 170 independent datasets and 54 risk factors were included. There were no studies on association between genetic or epigenetic risk factors and the UHR state that met the inclusion criteria. UHR subjects were more likely to show obstetric complications, tobacco use, physical inactivity, childhood trauma/emotional abuse/physical neglect, high perceived stress, childhood and adolescent low functioning, affective comorbidities, male gender, single status, unemployment and low educational level as compared to controls.

The increased vulnerability of UHR subjects can be related to environmental risk factors like childhood trauma, adverse life events and affective dysfunction. The role of genetic and epigenetic risk factors awaits clarification.