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Updated: Jul 4, 2026

Closed-Loop Neurostimulation for Biomarker-Driven, Personalized Treatment of Major Depressive Disorder
Published on: July 7, 2023
Evidence for separate diseases?: Stages of one disease or different combinations of symptom dimensions?
Heinz Häfner1, Wolfram an der Heiden, Kurt Maurer
1Schizophrenia Research Unit, Central Institute of Mental Health, J5, 68159, Mannheim, Germany. heinz.haefner@zi-mannheim.de
Objective:
We tested Kraepelin's dichotomy model by studying the separability of schizophrenia and depression on the basis of symptoms and illness course.
Materials And Methods:
Matched untreated patients with schizophrenia and depression (n = 130 each) and 130 "healthy" controls were assessed from onset to first admission. In a second study the same variables were studied in 107 patients with schizophrenia over a homogenised follow-up of 134 months (11.2 years).
Results:
The symptom most frequently marking the onset of both schizophrenia and depression was depressive mood. Both disorders exhibited the same prodromal core syndrome. It was not until the emergence of positive symptoms that the disorders became separable by the international classification systems. Depression remained the most frequent syndrome over the entire course of schizophrenia.
Conclusion:
Depression does not represent comorbidity, but an integral part of psychosis. A dimensional disease model based on successively emerging hierarchical symptom patterns, not unknown to the later Kraepelin, is offered as an explanation.
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