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Updated: May 8, 2026

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Published on: May 2, 2025
Depression with psychotic features is influenced by the polymorphism of the serotonin transporter gene
T J Stamm1, J Stingl2, K Wiethoff1
1Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Introduction:
Current diagnostic classifications regard psychotic symptoms during depressive episodes as indicators of depression severity. However, growing evidence suggests that depression with psychotic symptoms (MDP) may represent a distinct subtype of depression. In the course of the search for discriminating factors we tested the hypothesis that the serotonin transporter gene (5-HTTLPR) may interact with the manifestation of psychotic symptoms in acute depression.
Methods:
112 inpatients (61 female) with a depressive episode (16 bipolar, 86 unipolar) at admission were genotyped for 5-HTTLPR variants. Psychotic symptoms und general psychopathology were evaluated comprehensively using the Manual of the Association for Methodology and Documentation in Psychiatry (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie, 1981). For statistical analysis a chi-square test and a logistic regression model was used.
Results:
16 (14.3%) out of 112 patients were currently presenting with psychotic symptoms. The primary finding of our study was the higher prevalence of the s-allele of the 5-HTTLPR within the group of MDP patients (Pearson χ²=7.87; df=2; p<0.03). Secondly, in a logistic regression model, 5-HTTLPR was found to significantly contribute to the diagnosis of MDP (χ²=6.5; df=1; p=0.01). This effect was even more pronounced upon comparing only severely depressed patients with MDP patients. From a psychopathological perspective, MDP patients showed higher AMDP hostility and apathy scores but equal AMDP depression scores.
Discussion:
This is the first study to show an influence of 5-HTTLPR on psychotic symptoms in acutely depressed patients.
Limitations:
The lack of a control group and the relatively small sample size limits the present study's findings, thus replication in a larger sample is necessary.
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