Secondary negative symptoms across schizophrenia and bipolar disorder

Background Primary and secondary negative symptoms (NS) are core features of schizophrenia (SCZ) and can also be observed in bipolar-disorder-I (BD-I) patients. Secondary NS, due to other clinical factors, are frequently reported in clinical practice, yet systematic investigations into these symptoms remain sparse. In this study, we characterized potential sources of secondary NS as well as the association between NS and working memory (WM) capacity within the SCZ-BD spectrum. Methods We included 50 outpatients with SCZ and 49 with BD-I and assessed NS domains using SANS global scores for avolition-apathy, anhedonia-asociality, alogia and blunted affect. To identify clinical factors as potential sources of NS we applied multiple regression analyses including positive symptoms, disorganization, depressive symptoms, antipsychotic and mood stabilizer intake. We quantified their relative importance as sources for secondary NS through dominance analyses. Lastly, we used multiple regression to assess the relationship between NS domains and WM. Results Across SCZ and BD-I, disorganization was associated with avolition-apathy and anhedonia-asociality and depressive symptoms additionally predicted anhedonia-asociality. Antipsychotic dose was associated with blunted affect while group differences only predicted alogia. Avolition-apathy predicted impaired WM transdiagnostically and in BD-I higher anhedonia-asociality was associated with better WM capacity. Conclusion Secondary NS are prevalent across the SCZ-BD spectrum, with disorganization reflecting an important factor for avolition-apathy and anhedonia-asociality. Avolition-apathy emerged as a transdiagnostic predictor of WM impairment, while anhedonia-asociality was linked to better WM in BD-I. Altogether, these findings support the clinical relevance and need for future research of secondary NS across the SCZ-BD spectrum. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used only openly available human data from the UCLA CNP that can be downloaded at: https://openfmri.org/dataset/ds000030/ I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data used in the presented study are available online at https://openfmri.org/dataset/ds000030/