Changes in patterns of age-related network connectivity are associated with risk for schizophrenia

This is the online data repository (in progress) accompanying the following manuscript: <strong>Changes in patterns of age-related network connectivity are associated with risk for schizophrenia</strong> Roberta Passiatore^a,b,c, Linda A. Antonucci^a, Thomas P. DeRamus^b, Leonardo Fazio^d, Giuseppe Stolfa^a, Leonardo Sportelli^a, Gianluca C. Kikidis^a, Giuseppe Blasi^a,e, Qiang Chen^f, Juergen Dukart^c,g, Aaron Goldman^f, Venkata S. Mattay^f,h, Teresa Popolizioⁱ, Antonio Rampino^a,e, Fabio Sambataro^j, Pierluigi Selvaggi^a,e, William Ulrich^f, Apulian Network on Risk for Psychosis, Daniel R. Weinberger^f, Alessandro Bertolino^a,e*, Vince D. Calhoun^b*, Giulio Pergola^a,f,k* ^a Department of Translational Biomedicine and Neuroscience – University of Bari Aldo Moro, Bari, IT. ^b Tri-institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS) – Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA, USA ^c Institute of Neuroscience and Medicine, Brain &amp; Behavior (INM-7), Research Centre Jülich, Jülich, DE ^d Department of Medicine and Surgery - LUM Jean Monnet, Casamassima, IT ^e Psychiatric Unit - University Hospital, Bari, IT ^fLieber Institute for Brain Development – Johns Hopkins Medical Campus, Baltimore, MD, USA ^g Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, DE ^h Department of Neurology and Radiology – Johns Hopkins Medical Campus, Baltimore, MD, USA ⁱ Neuroradiology Unit - IRCCS Casa Sollievo della Sofferenza Hospital, S. Giovanni Rotondo, IT ^j Section of Psychiatry, Department of Neuroscience - University of Padova, Padua, IT ^k Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA Members of the Apulian Network on Risk for Psychosis include Ileana Andriola, Lucia Mare, Nicolò Parente, Alessandra Raio, Veronica D. Toro, (Department of Translational Biomedicine and Neuroscience – University of Bari Aldo Moro, Bari, IT), Mario Altamura, Marimar Castrigno, Melania Difino (Department of Mental Health, ASL Foggia, Foggia, IT; Department of Clinical and Experimental Medicine, University of Foggia, Foggia, IT), Flora Brudaglio, Sabino Savino, Rossana Vista (Department of Mental Health, ASL Barletta-Andria-Trani, Andria, IT), Angela Carofiglio, Barbara Gelao, Marina Mancini (Department of Mental Health, ASL Bari, Bari, IT), Alessandro Saponaro, Anna Manzari, Domenico Suma (Department of Mental Health, ASL Brindisi, Brindisi, IT). <strong>Abstract</strong> Alterations in fMRI-based brain functional network connectivity (FNC) are associated with schizophrenia (SCZ) and the genetic risk or subthreshold clinical symptoms preceding the onset of SCZ, which often occurs in early adulthood. Thus, age-sensitive FNC changes may be relevant to SCZ risk-related FNC. We used independent component analysis to estimate FNC from childhood to adulthood in 9,236 individuals. To capture individual brain features more accurately than single-session fMRI, we studied an average of three fMRI scans per individual. To identify potential familial risk-related FNC changes, we compared age-related FNC in first-degree relatives of SCZ patients including unaffected siblings (SIB) and with neurotypical controls (NC) at the same age-stage. Then, we examined how polygenic risk scores for SCZ influenced risk-related FNC patterns. Finally, we investigated the same risk-related FNC patterns in adult SCZ patients (oSCZ) and young individuals with subclinical psychotic symptoms (PSY). Age-sensitive risk-related FNC patterns emerge during adolescence and early adulthood, but not before. Young SIB always followed older NC patterns, with decreased FNC in a cerebellar-occipitoparietal circuit and increased FNC in two prefrontal-sensorimotor circuits when compared to young NC. Two of these FNC alterations were also found in oSCZ, with one exhibiting reversed pattern. All were linked to polygenic risk for SCZ in unrelated individuals (R2 varied from 0.02 to 0.09). Young PSY showed FNC alterations in the same direction as SIB when compared to NC. These results suggest that age-related neurotypical FNC correlate with genetic risk for SCZ and are detectable with MRI in young participants. Data files: <strong>FNC.zip</strong> Functional network connectivity matrices extracted at the group level for each fMRI session (resting state, working memory, episodic encoding and retrieval, emotion recognition) for UNIBA1 and UNIBA2 cohorts. Script is provided. For any data inquiries please contact: <strong>Giulio Pergola: </strong>[e-mail] <strong>Roberta Passiatore: </strong>[e-mail]