Accelerated brain aging in schizophrenia and beyond: A neuroanatomical marker of psychiatric disorders

Nikolaos Koutsouleris*, Christos Davatzikos, Stefan Borgwardt, Christian Gaser, Ronald Bottlender, Thomas Frodl, Peter Falkai, Anita Riecher-Rössler, Hans Jürgen Möller, Maximilian Reiser, Christos Pantelis, Eva Meisenzahl

*Corresponding author for this work
211 Citations (Scopus)


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.

Original languageEnglish
JournalSchizophrenia bulletin
Issue number5
Pages (from-to)1140-1153
Number of pages14
Publication statusPublished - 09.2014


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