Negative symptoms in psychotic outpatients: insights from the Geneva Psychosis Cohort

Background

Negative symptoms are increasingly recognized as transdiagnostic features associated with impaired functioning and reduced quality of life [1]. While central to schizophrenia-spectrum disorders, they are also observed across other psychiatric conditions. Contemporary models distinguish two main dimensions: the motivation and pleasure (MAP) domain, including avolition, anhedonia and asociality, and the expression (EXP) domain, including blunted affect and alogia. Current frameworks also emphasise the distinction between primary and secondary negative symptoms, the latter being influenced by factors such as depressive symptoms or antipsychotic side effects [2]. Despite increasing recognition of their clinical importance, negative symptoms remain underdetected and insufficiently characterised in routine outpatient settings. Better understanding their clinical correlates may contribute to improving assessment and treatment strategies in psychotic disorders.

Aims

This study aimed to characterise the prevalence and clinical correlates of negative symptoms in a naturalistic cohort of psychotic outpatients, to explore associations between negative symptom dimensions and estimated dopamine D2 receptor occupancy, and to assess the contribution of depressive symptoms.

Methods

We conducted an observational cross-sectional analysis of outpatients enrolled in the Geneva Psychosis Cohort at Geneva University Hospitals. Participants underwent a standardised clinical assessment integrated into routine psychiatric care. Negative symptoms were assessed using the Brief Negative Symptom Scale (BNSS), depressive symptoms with the Montgomery–Åsberg Depression Rating Scale (MADRS), and medication side effects with the UKU Side Effect Rating Scale. Antipsychotic exposure was modelled using drug-specific receptor affinity profiles, with estimation of D2 receptor occupancy. Group comparisons between affective and non-affective psychoses were performed using t-tests or ANOVA, and associations between D2 receptor occupancy and BNSS scores were examined using correlation and regression analyses. Statistical significance was defined as p < 0.05.

Results

A total of 163 outpatients were included. Schizophrenia was the most prevalent diagnosis (57%), followed by schizoaffective disorder (21%) and other psychotic disorders (14%). Negative symptoms were highly prevalent in this outpatient cohort. Depressive symptoms were generally mild, and the burden of antipsychotic side effects was low, as assessed with the UKU scale. Patients with non-affective psychosis exhibited higher negative symptom severity compared with those with affective psychosis, particularly within the EXP domain (blunted affect, alogia) and MAP domain (avolition, asociality), whereas differences in anhedonia and distress were less pronounced. Higher estimated D2 receptor occupancy was negatively correlated with BNSS scores, particularly within the MAP domain, suggesting dopaminergic involvement in motivational negative symptoms.

Conclusions

This study provides a real-world clinical characterisation of negative symptoms across psychotic disorders within the Geneva Psychosis Cohort. Negative symptoms were frequent and particularly pronounced in non-affective psychoses. The observed association between higher estimated D2 receptor occupancy and lower MAP symptoms supports a potential dopaminergic contribution to motivational deficits. These findings highlight the importance of systematic assessment of negative symptoms in routine care and may contribute to improving the distinction between primary and secondary negative symptoms and functional outcomes.

References

Strauss, G. P., & Cohen, A. S. (2017). A transdiagnostic review of negative symptom phenomenology and etiology. Schizophrenia Bulletin, 43(4), 712–719. https://doi.org/10.1093/schbul/sbx066
Kirschner, M., Aleman, A., & Kaiser, S. (2017). Secondary negative symptoms: A review of mechanisms, assessment and treatment. Schizophrenia Research, 186, 29–38. https://doi.org/10.1016/j.schres.2016.05.003