# Beyond vertebrates: Drosophila melanogaster as a model to study negative symptoms of schizophrenia

**Authors:** Maximiliano Elgueta-Reyes, Sergio Hidalgo, Jorge M. Campusano

PMC · DOI: 10.3389/fpsyt.2025.1622281 · 2025-07-23

## TL;DR

This paper explores using fruit flies to study negative symptoms of schizophrenia, like social withdrawal and apathy, by examining genetic and behavioral models.

## Contribution

The paper introduces Drosophila melanogaster as a novel model for studying schizophrenia's negative symptoms through conserved neurochemical pathways and genetic tools.

## Key findings

- Mutations in genes like dysb1, Rim, and Neuroligins in Drosophila are linked to behaviors resembling schizophrenia's negative symptoms.
- Behavioral paradigms in fruit flies are being developed to assess social interaction and motivation deficits.
- Drosophila enables precise investigation of neural circuits and molecular pathways related to schizophrenia.

## Abstract

Schizophrenia is a complex neuropsychiatric disorder characterized by positive, negative, and cognitive symptoms. While positive symptoms have been extensively studied, negative symptoms—such as anhedonia, social withdrawal, and apathy—remain challenging to model and treat. Vertebrate animal models for schizophrenia have provided insights into some of the underlying mechanisms associated with this disorder. Recently, Drosophila melanogaster has emerged as a valuable model due to its genetic tractability, conserved neurochemical pathways as compared to vertebrates, and suitability for high-throughput behavioral analyses. Mutations in genes such as dysb1, Rim, and Neuroligins have been linked to behaviors in flies resembling negative symptoms of schizophrenia, supporting the relevance of this animal model in psychiatric research. Moreover, behavioral paradigms aimed at assessing social interaction, motivation, and anhedonia in Drosophila are being refined to better capture schizophrenia-related deficits. The use of Drosophila enables precise investigation of neural circuits and molecular pathways underlying negative symptoms of schizophrenia, research that has the potential to lead to novel therapeutic targets.

## Linked entities

- **Genes:** RBBP8 (RB binding protein 8, endonuclease) [NCBI Gene 5932]
- **Diseases:** schizophrenia (MONDO:0005090)
- **Species:** Drosophila melanogaster (taxon 7227)

## Full-text entities

- **Genes:** Rim (Rab3 interacting molecule) [NCBI Gene 42150] {aka CG33547, CG7301, CG7305, CG7321, DRIM, DmRIM}
- **Diseases:** Schizophrenia (MESH:D012559), neuropsychiatric disorder (MESH:D001523), anhedonia (MESH:D059445)
- **Species:** Drosophila melanogaster (fruit fly, species) [taxon 7227]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12329227/full.md

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Source: https://tomesphere.com/paper/PMC12329227