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Background <p>Bipolar disorder (BD) is a mood disorder affecting approximately 1–2% of the population. It is treated primarily with mood stabilizers, which have variable efficacy and tolerability. Omega-3 polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA), have emerged as potential adjunctive treatments, though clinical findings and underlying mechanisms remain inconsistent. Given that <i>myo</i>-inositol depletion is proposed as a common mechanism for conventional mood stabilizers, we hypothesized that DHA, which modulates components of the phosphatidylinositol pathway, would alter intracellular <i>myo</i>-inositol and thus modulate <i>myo</i>-inositol homeostasis. The aim of this study was to determine the effect of DHA on intracellular <i>myo</i>-inositol and the expression of key genes involved in its biosynthesis.</p> Methods <p>Using an enzymatic assay, intracellular <i>myo</i>-inositol levels were measured in the extracts of cells grown in the presence of DHA. The effect of DHA on the expression of the <i>myo</i>-inositol biosynthetic genes <i>INO1</i> (inositol-1-phosphate synthase) and <i>INM1</i> (inositol monophosphatase) was assessed by RT-qPCR.</p> Results <p>DHA altered intracellular <i>myo</i>-inositol in a concentration-dependent manner, with low concentrations decreasing levels and higher concentrations producing increases relative to untreated controls. RT-qPCR analysis showed corresponding modulation of <i>INO1</i> and <i>INM1</i> expression, consistent with changes in <i>myo</i>-inositol homeostasis. While some group differences reached statistical significance, particularly in comparisons with valproate (VPA)-treated controls, most contrasts among DHA-treated groups were not significant.</p> Conclusion <p>These findings provide preliminary evidence that DHA modulates intracellular <i>myo</i>-inositol levels and the expression of key biosynthetic genes in yeast. The biphasic response observed suggests a dose-sensitive effect that may help explain inconsistencies in clinical outcomes. While the results support the idea that omega-3 fatty acids influence inositol homeostasis, they should be considered hypothesis-generating and warrant confirmation in mammalian models and clinical settings.</p> Clinical trial number <p>Not applicable.</p>

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Docosahexaenoic acid modulates myo-inositol and myo-inositol biosynthetic genes expression: implications for bipolar disorder

  • 期刊论文

  • 发表日期：

    2026年1月5日

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  • Marlene Murray,
  • Haley Kang,
  • Taejun Ok,
  • Kimberly Park,
  • Joanne Jee Yeon Lee,
  • Bomi Kim,
  • Hyukje Sung,
  • Talisa Tait,
  • Daniel Colon Hidalgo,
  • Yudy Guzman

摘要

Background

Bipolar disorder (BD) is a mood disorder affecting approximately 1–2% of the population. It is treated primarily with mood stabilizers, which have variable efficacy and tolerability. Omega-3 polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA), have emerged as potential adjunctive treatments, though clinical findings and underlying mechanisms remain inconsistent. Given that myo-inositol depletion is proposed as a common mechanism for conventional mood stabilizers, we hypothesized that DHA, which modulates components of the phosphatidylinositol pathway, would alter intracellular myo-inositol and thus modulate myo-inositol homeostasis. The aim of this study was to determine the effect of DHA on intracellular myo-inositol and the expression of key genes involved in its biosynthesis.

Methods

Using an enzymatic assay, intracellular myo-inositol levels were measured in the extracts of cells grown in the presence of DHA. The effect of DHA on the expression of the myo-inositol biosynthetic genes INO1 (inositol-1-phosphate synthase) and INM1 (inositol monophosphatase) was assessed by RT-qPCR.

Results

DHA altered intracellular myo-inositol in a concentration-dependent manner, with low concentrations decreasing levels and higher concentrations producing increases relative to untreated controls. RT-qPCR analysis showed corresponding modulation of INO1 and INM1 expression, consistent with changes in myo-inositol homeostasis. While some group differences reached statistical significance, particularly in comparisons with valproate (VPA)-treated controls, most contrasts among DHA-treated groups were not significant.

Conclusion

These findings provide preliminary evidence that DHA modulates intracellular myo-inositol levels and the expression of key biosynthetic genes in yeast. The biphasic response observed suggests a dose-sensitive effect that may help explain inconsistencies in clinical outcomes. While the results support the idea that omega-3 fatty acids influence inositol homeostasis, they should be considered hypothesis-generating and warrant confirmation in mammalian models and clinical settings.

Clinical trial number

Not applicable.