# Conserved NT5C2 links context-specific behaviors with psychiatric and metabolic risk

## TL;DR

This study shows that the NT5C2 enzyme connects behaviors related to energy and mood, linking risks for psychiatric and metabolic disorders.

## Contribution

The paper demonstrates that NT5C2 is a conserved regulator linking neuro-metabolic pathways to specific behaviors.

## Key findings

- Reduced NT5C2 function in fruit flies alters activity and food intake during satiation.
- Mouse studies show NT5C2 knockout affects locomotion, anxiety, and sensorimotor gating.
- Human data links NT5C2 variants to psychiatric and metabolic traits like schizophrenia and BMI.

## Abstract

The cytosolic 5′-nucleotidase II (NT5C2) enzyme has been implicated in both psychiatric disorders and metabolic traits, but whether these associations reflect a shared biological basis remains unclear. Here we combined cross-species approaches to investigate how reduced NT5C2 function shapes behavior.

In Drosophila melanogaster, neuronal knockdown of the ortholog dNT5B increased activity around light-dark transitions, reduced sleep fragmentation, and selectively suppressed food intake under satiated conditions. Moreover, analysis of mouse phenotyping data revealed that whole-body Nt5c2 knockout alters locomotor activity, sensorimotor gating, and anxiety-related behaviors. Finally, human variant-trait associations showed reproducible enrichment in both metabolic domains, including body composition and BMI, and neuro-psychiatric outcomes such as schizophrenia, smoking, and anxiety.

Together, these phenotypic findings indicate that NT5C2 is a conserved neuro-metabolic regulator, linking energy-related pathways to specific behavioral dimensions that may underlie its pleiotropic impact on psychiatric and metabolic risk.