title: Two subgroups of antipsychotic-naive, first-episode schizophrenia patients identified with a Gaussian mixture model on cognition and electrophysiology.
abstract: Deficits in information processing and cognition are among the most robust findings in schizophrenia patients. Previous efforts to translate group-level deficits into clinically relevant and individualized information have, however, been non-successful, which is possibly explained by biologically different disease subgroups. We applied machine learning algorithms on measures of electrophysiology and cognition to identify potential subgroups of schizophrenia. Next, we explored subgroup differences regarding treatment response. Sixty-six antipsychotic-naive first-episode schizophrenia patients and sixty-five healthy controls underwent extensive electrophysiological and neurocognitive test batteries. Patients were assessed on the Positive and Negative Syndrome Scale (PANSS) before and after 6 weeks of monotherapy with the relatively selective D2receptor antagonist, amisulpride (280.3±159 mg per day). A reduced principal component space based on 19 electrophysiological variables and 26 cognitive variables was used as input for a Gaussian mixture model to identify subgroups of patients. With support vector machines, we explored the relation between PANSS subscores and the identified subgroups. We identified two statistically distinct subgroups of patients. We found no significant baseline psychopathological differences between these subgroups, but the effect of treatment in the groups was predicted with an accuracy of 74.3% (P=0.003). In conclusion, electrophysiology and cognition data may be used to classify subgroups of schizophrenia patients. The two distinct subgroups, which we identified, were psychopathologically inseparable before treatment, yet their response to dopaminergic blockade was predicted with significant accuracy. This proof of principle encourages further endeavors to apply data-driven, multivariate and multimodal models to facilitate progress from symptom-based psychiatry toward individualized treatment regimens.
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Services Glostrup, University of Copenhagen, Copenhagen, Denmark.|Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Glostrup, University of Copenhagen, Copenhagen, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Bak
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Services Glostrup, University of Copenhagen, Copenhagen, Denmark.|Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Glostrup, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B H
authors.initials: BH
authors.lastname: Ebdrup
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Services Glostrup, University of Copenhagen, Copenhagen, Denmark.|Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Glostrup, University of Copenhagen, Copenhagen, Denmark.|Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.|Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Oranje
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Services Glostrup, University of Copenhagen, Copenhagen, Denmark.|Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Glostrup, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Fagerlund
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Services Glostrup, University of Copenhagen, Copenhagen, Denmark.|Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Glostrup, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M H
authors.initials: MH
authors.lastname: Jensen
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Services Glostrup, University of Copenhagen, Copenhagen, Denmark.|Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Glostrup, University of Copenhagen, Copenhagen, Denmark.
authors.forename: S W
authors.initials: SW
authors.lastname: Düring
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Services Glostrup, University of Copenhagen, Copenhagen, Denmark.|Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Glostrup, University of Copenhagen, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M Ø
authors.initials: MØ
authors.lastname: Nielsen
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, Mental Health Services Glostrup, University of Copenhagen, Copenhagen, Denmark.|Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Glostrup, University of Copenhagen, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B Y
authors.initials: BY
authors.lastname: Glenthøj
authors.affiliation: Cognitive Systems, DTU Compute, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark.
authors.forename: L K
authors.initials: LK
authors.lastname: Hansen
mesh_terms: D000328:Adult; D000465:Algorithms; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D003072:Cognition Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology* / Q000523:psychology*; D004569:Electroencephalography / Q000187:drug effects; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069550:Machine Learning; D008297:Male; D008606:Mental Processes / Q000187:drug effects / Q000502:physiology*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D016011:Normal Distribution; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011594:Psychometrics; D012016:Reference Values; D012559:Schizophrenia / Q000145:classification* / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D013469:Sulpiride / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D013469:Sulpiride; D000077582:Amisulpride