title: Accelerated brain aging in schizophrenia and beyond: a neuroanatomical marker of psychiatric disorders.
abstract: Structural brain abnormalities are central to schizophrenia (SZ), but it remains unknown whether they are linked to dysmaturational processes crossing diagnostic boundaries, aggravating across disease stages, and driving the neurodiagnostic signature of the illness. Therefore, we investigated whether patients with SZ (N = 141), major depression (MD; N = 104), borderline personality disorder (BPD; N = 57), and individuals in at-risk mental states for psychosis (ARMS; N = 89) deviated from the trajectory of normal brain maturation. This deviation was measured as difference between chronological and the neuroanatomical age (brain age gap estimation [BrainAGE]). Neuroanatomical age was determined by a machine learning system trained to individually estimate age from the structural magnetic resonance imagings of 800 healthy controls. Group-level analyses showed that BrainAGE was highest in SZ (+5.5 y) group, followed by MD (+4.0), BPD (+3.1), and the ARMS (+1.7) groups. Earlier disease onset in MD and BPD groups correlated with more pronounced BrainAGE, reaching effect sizes of the SZ group. Second, BrainAGE increased across at-risk, recent onset, and recurrent states of SZ. Finally, BrainAGE predicted both patient status as well as negative and disorganized symptoms. These findings suggest that an individually quantifiable "accelerated aging" effect may particularly impact on the neuroanatomical signature of SZ but may extend also to other mental disorders.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; nikolaos.koutsouleris@med.uni-muenchen.de.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Koutsouleris
authors.affiliation: Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, PA;
authors.forename: Christos
authors.initials: C
authors.lastname: Davatzikos
authors.affiliation: Department of Psychiatry, University of Basel, Basel, Switzerland;
authors.forename: Stefan
authors.initials: S
authors.lastname: Borgwardt
authors.affiliation: Structural Brain Imaging Group, Dep artment of Psychiatry and Neurology, Friedrich Schiller University, Jena, Germany;
authors.forename: Christian
authors.initials: C
authors.lastname: Gaser
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany;
authors.forename: Ronald
authors.initials: R
authors.lastname: Bottlender
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany;
authors.forename: Thomas
authors.initials: T
authors.lastname: Frodl
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany;
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Department of Psychiatry, University of Basel, Basel, Switzerland;
authors.forename: Anita
authors.initials: A
authors.lastname: Riecher-Rössler
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany;
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.affiliation: Department of Radiology, Ludwig-Maximilian University, Munich, Germany;
authors.forename: Maximilian
authors.initials: M
authors.lastname: Reiser
authors.affiliation: Melbourne Neuropsychiatry Center, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany;
authors.forename: Eva
authors.initials: E
authors.lastname: Meisenzahl
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000375:Aging / Q000473:pathology*; D015415:Biomarkers; D001883:Borderline Personality Disorder / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003865:Major Depressive Disorder / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000473:pathology*; D012306:Risk; D012559:Schizophrenia / Q000473:pathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: accelerated aging; biomarker; borderline personality disorder; depression; machine learning; neuroanatomical dysmaturation; schizophrenia