Luigi Giuliani ¹ Pasquale Pezzella ¹ Giulia M. Giordano ^1* Leonardo Fazio ^2,3 Armida Mucci ¹ Andrea Perrottelli ¹ Giuseppe Blasi ² Mario Amore ⁴ Paola Rocca ⁵ Alessandro Rossi ⁶ Alessandro Bertolino ² Silvana Galderisi ¹ Mario Maj ¹

• ¹ Department of Psychiatry, University of Campania 'Luigi Vanvitelli', Naples, Campania, Italy
• ² Department of Basic Medical Sciences, Neurosciences and Sensory Organs, School of Medicine, University of Bari Aldo Moro, Bari, Italy
• ³ Department of Medicine and Surgery, LUM University 'Giuseppe Degennaro', Casamassima, Italy
• ⁴ Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child, School of Medical and Pharmaceutical Sciences, University of Genoa, Genova, Liguria, Italy
• ⁵ Department of Neuroscience, School of Medicine, University of Turin, Turin, Piedmont, Italy
• ⁶ Department of Applied Clinical Sciences and Biotechnology, University of L'Aquila, L'Aquila, Abruzzo, Italy

The development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI).In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain resting-state (rs)-activity with disease-related features.Methods: Sixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables.Results: Attention/vigilance deficits were negatively associated with dorsal anterior cingulate rsactivity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity.Neurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes.