# Arginine metabolism and neurocognitive impairment in offspring of bipolar parents: a high-risk case-control study

**Authors:** Gökçeçiçek Arıcı Sağlıyan, Fatih Hilmi Çetin, Fikret Akyürek, Oğuzhan Tok, Özlem Çiçek Zekey, Mustafa Esad Tezcan, Bilal Sağlıyan, Serhat Türkoğlu, Halit Necmi Uçar, Bahadır Öztürk, Kürşat Altınbaş

PMC · DOI: 10.3389/fpsyt.2025.1511397 · Frontiers in Psychiatry · 2025-02-17

## TL;DR

This study found that children of parents with bipolar disorder have altered arginine metabolism and worse neurocognitive function, suggesting a possible link to future risk.

## Contribution

The study identifies specific arginine metabolites as potential endophenotypes for bipolar disorder in high-risk offspring.

## Key findings

- High-risk children had higher ADMA, SDMA, and ornithine levels compared to controls.
- Citrulline and NOS activity were significantly lower in the high-risk group.
- Neurocognitive impairments in high-risk children correlated with arginine metabolite levels.

## Abstract

The aim of this study is to investigate whether arginine and its metabolites can be an endophenotype for bipolar disorder (BD) and to evaluate the role of arginine metabolites and neurocognitive function levels in unaffected healthy children of parents diagnosed with BD in cognitive impairment.

The study included 37 healthy children of parents diagnosed with BD Type I as the high-risk group and 36 healthy children of parents without any psychiatric disorders as the control group. The arginine, n-monomethyl-l-arginine acetate (L-NMMA), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), citrulline, homoarginine, ornithine serum levels, and nitric oxide synthase (NOS) activity level of both groups were compared.

The study found that in the high-risk group, ADMA, SDMA, and ornithine levels were significantly higher compared to the controls, while citrulline and NOS activity level were significantly lower in the high-risk group compared to the controls. All neurocognitive performances of the high-risk group were considered statistically significantly worse compared to controls. The impairment in neurocognitive functions in the high-risk group was found to be correlated with ADMA, L-NMMA, citrulline, homoarginine, ornithine levels, and NOS activity level.

These findings highlight a potential link between arginine metabolism and executive dysfunction in individuals at high risk for BD. Further longitudinal studies are essential to fully understand the complex interactions between these factors.

## Linked entities

- **Chemicals:** arginine (PubChem CID 232), n-monomethyl-l-arginine acetate (PubChem CID 22853172), asymmetric dimethylarginine (PubChem CID 123831), symmetric dimethylarginine (PubChem CID 169148), citrulline (PubChem CID 833), homoarginine (PubChem CID 9085), ornithine (PubChem CID 389)
- **Diseases:** bipolar disorder (MONDO:0004985)

## Full-text entities

- **Genes:** NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}
- **Diseases:** cognitive impairment (MESH:D003072), executive dysfunction (MESH:D006331), impairment in neurocognitive functions (MESH:D019965), psychiatric disorders (MESH:D001523), BD (MESH:D001714)
- **Chemicals:** n-monomethyl-l-arginine acetate (-), Arginine (MESH:D001120), SDMA (MESH:C024917), ADMA (MESH:C018524), citrulline (MESH:D002956), ornithine (MESH:D009952), homoarginine (MESH:D006709), L-NMMA (MESH:D019323)

## Full text

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## Figures

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## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC11872899/full.md

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Source: https://tomesphere.com/paper/PMC11872899