Identifying a neuroanatomical signature of schizophrenia, reproducible across sites and stages, using machine learning with structured sparsity

Amicie de Pierrefeu (1) , Tommy Löfstedt (2, 3) , Charles Laidi (1, 4, 3) , Fouad Hadj-Selem (5) , J. Bourgin (6, 7) , Tomas Hajek (8, 9) , Filip Spaniel (9) , Marian Kolenic (9) , Philippe Ciuciu (1, 10) , Nora Hamdani (3, 4, 11) , Marion Leboyer (3, 4, 11) , Thomas Fovet (12, 13) , Renaud Jardri (10, 12, 13) , Josselin Houenou (1, 3, 4, 11) , Edouard Duchesnay (1)

1 NEUROSPIN - Service NEUROSPIN
2 Umeå University
3 IMRB - Institut Mondor de Recherche Biomédicale
4 Fondation FondaMental [Créteil]
5 VeDeCom - VEhicule DEcarboné et COmmuniquant et sa Mobilité
6 Hôpital Louis Mourier - AP-HP [Colombes]
7 U894 / UMS 1266 - Institut de psychiatrie et neurosciences
8 Dalhousie University [Halifax]
9 NUDZ - National Institute of Mental Health [Topolova]
10 PARIETAL - Modelling brain structure, function and variability based on high-field MRI data
11 Pôle de Psychiatrie [Hôpital Henri Mondor]
12 SCALab - Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193
13 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]

Objective: Structural MRI (sMRI) increasingly offers insight into abnormalities inherent to schizophrenia. Previous machine learning applications suggest that individual classification is feasible and reliable and, however, is focused on the predictive performance of the clinical status in cross-sectional designs, which has limited biological perspectives. Moreover, most studies depend on relatively small cohorts or single recruiting site. Finally, no study controlled for disease stage or medication's effect. These elements cast doubt on previous findings' reproducibility. Method: We propose a machine learning algorithm that provides an interpretable brain signature. Using large datasets collected from 4 sites (276 schizophrenia patients, 330 controls), we assessed cross-site prediction reproducibility and associated predictive signature. For the first time, we evaluated the predictive signature regarding medication and illness duration using an independent dataset of first-episode patients. Results: Machine learning classifiers based on neuroanatomical features yield significant intersite prediction accuracies (72%) together with an excellent predictive signature stability. This signature provides a neural score significantly correlated with symptom severity and the extent of cognitive impairments. Moreover, this signature demonstrates its efficiency on first-episode psychosis patients (73% accuracy). Conclusion: These results highlight the existence of a common neuroanatomical signature for schizophrenia, shared by a majority of patients even from an early stage of the disorder.

Keywords: Structural MRI; Schizophrenia; First-episode psychosis; Classification; Psychoradiology

Domains: Statistics [stat]; Machine Learning [stat.ML]; Life Sciences [q-bio]; Human health and pathology; Psychiatrics and mental health; Computer Science [cs]; Artificial Intelligence [cs.AI]; Computer Science [cs]; Medical Imaging

Amicie de Pierrefeu, Tommy Löfstedt, Charles Laidi, Fouad Hadj-Selem, J. Bourgin, et al.. Identifying a neuroanatomical signature of schizophrenia, reproducible across sites and stages, using machine learning with structured sparsity. Acta Psychiatrica Scandinavica, 2018, 2018, pp.1 - 10. ⟨10.1111/acps.12964⟩. ⟨cea-01883283⟩