Neurobiological Signatures of Trauma, Personality, and Depressivity: A Transdiagnostic Machine Learning Study in Adolescents and Young Adults.
Authors
Affiliations (23)
Affiliations (23)
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany; Graduate School of Systemic Neurosciences (GSN), Munich, Germany.
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany; Max Planck Institute of Psychiatry, Munich, Germany; International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany.
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany.
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany; Max Planck Institute of Psychiatry, Munich, Germany.
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany; Centre for Youth Mental Health, University of Melbourne, Melbourne, Australia.
- Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy.
- Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
- Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany; Faculty of Psychology and Educational Sciences, Department of Psychology, LMU Munich, Munich, Germany.
- School of Psychology, University of Sussex, Brighton, United Kingdom.
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland; Department of Psychology, Faculty of Psychology, Airlangga University, Surabaya, Indonesia.
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany; Max Planck Institute of Psychiatry, Munich, Germany; Munich-Augsburg site of the German Centre for Mental Health (DZPG).
- Department of Translational Biomedicine and Neuroscience, University of Bari Aldo Moro, Bari, Italy; Lieber Institute for Brain Development - Johns Hopkins Medical Campus, Baltimore, MD, USA; Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.
- Department of Child and Adolescent Psychiatry, University of Münster, Münster, Germany.
- Department of Psychiatry and Psychotherapy, University of Lübeck, Germany; Institute for Translational Psychiatry, University of Münster, Münster, Germany.
- Institute for Translational Psychiatry, University of Münster, Münster, Germany.
- Department of Psychiatry, University of Oxford, Oxford, United Kingdom; Institute for Mental Health, University of Birmingham, Birmingham, United Kingdom; Early Intervention Service, Birmingham Women's and Children's NHS Trust, Birmingham, United Kingdom.
- Department of Psychiatry, University of Turku, Turku, Finland.
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia; Monash Institute of Pharmaceutical Sciences (MIPS), Monash University, Victoria, Australia.
- Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
- Orygen, the National Centre of Excellence for Youth Mental Health, Melbourne, Victoria, Australia.
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
- Department of Psychiatry and Psychotherapy, University of Lübeck, Germany.
- Department of Psychiatry and Psychotherapy, LMU University Hospital, LMU Munich, Munich, Germany; Max Planck Institute of Psychiatry, Munich, Germany; Munich-Augsburg site of the German Centre for Mental Health (DZPG); Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom. Electronic address: [email protected].
Abstract
Adolescence and early adulthood are vulnerable phases for psychiatric disorders, where trauma and personality development converge on shared and distinct, often unknown brain signatures. We used Sparse Partial Least Squares (SPLS) to identify multivariate signatures between voxel-wise grey matter volume (GMV) and three domains: childhood trauma, personality, and depressivity. We performed structural equation modeling (SEM) among these domains, predicted functional outcome at 9-month follow-up via support vector machine classification, and correlated the SPLS signatures with resilience, coping and visual dysfunctions. All models were cross-validated in the discovery (n=633; 52.9% female, mean(SD) age=25.41(5.98) years) and validated in the replication sample (n=343; 53.0% female, 24.69(5.72) years) of the multi-site prospective PRONIA cohort, comprising individuals with recent-onset depression or psychosis, psychosis risk syndromes, and healthy controls. We identified three signatures of interest: (1) depressivity, linked to reduced GMV in limbic regions; (2) childhood trauma, associated with GMV in thalamic, frontotemporal, and parietal regions; (3) a trauma-personality-depressivity signature relating childhood trauma, personality, and depressivity, to GMV in thalamic, occipital, temporal, and limbic regions. Through SEM, childhood trauma was directly associated with depressivity and indirectly via a maladaptive personality structure. The trauma-personality-depressivity signature was the strongest predictor of poor functional outcome (BAC<sub>Discovery</sub>=75.8%, BAC<sub>Replication</sub>=83.2%). The depressivity and trauma-personality-depressivity signatures were linked to deficient resilience and coping styles as well as visual dysfunctions. Childhood trauma, personality, and depressivity are associated with shared and distinct brain signatures spanning the affective-psychotic spectrum. If these factors converge, current and future mental health may be compromised.