2026 ECNP Congress

PS01-1173

Peripheral amino acid neurotransmitter dynamics during pregnancy and its implications on gestational diabetes mellitus and depression

Pooja Ghosh — D. Mohan, R.M. Anjana, U. Ram, V. Mohan, P. Saravanan, K. Gokulakrishnan, B.N. Srikumar · National Institute of Mental Health and Neuro Sciences, Neurophysiology, Bengaluru, India

2026 ECNP Congress

Introduction

The global prevalence of depression during pregnancy and the postpartum period is estimated at 10–15%, while anxiety disorders affect approximately 8–10% of women [1]. While neurotransmitters are essential regulators of mood, behaviour, and emotional processes, the interaction between classical amino acid neurotransmitter systems and maternal behaviour across pregnancy and postpartum is not well understood. Given the interconnected pathophysiology of depression and gestational diabetes mellitus (GDM) [2], the interaction between neurotransmitter levels, mood disorders, and GDM may be bidirectional, highlighting the importance of understanding their combined impact during pregnancy. These complex interactions may influence both maternal metabolic adaptations and neuropsychological outcomes, potentially contributing to adverse pregnancy trajectories. However, longitudinal studies examining these interactions across gestation remains limited. This study therefore aimed to profile amino acid neurotransmitters during early and mid-pregnancy in a nested cohort of women enrolled in the STRiDE study. Women with normal fasting glucose levels and no depressive symptoms during early pregnancy (<16 weeks) were included in the study.

Methods

During the OGTT visit at 24-28 weeks, a 75 g OGTT and PHQ-9 assessment were performed. Women were categorized into four groups (n=30-54, each): Normal glucose tolerance without development of depressive symptoms (NGT), NGT subjects who developed depressive symptoms (NGT+DS), Pregnant women who developed GDM but not depressive symptoms (GDM), and subjects who developed both GDM and depressive symptoms (GDM+DS). The plasma levels of amino acid neurotransmitters such as Aspartate, Glutamate, Serine, Glutamine, Glycine, Taurine, GABA from 1st and 2nd trimester pregnancy were measured using reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with fluorescence detection. Paired t test was done to check statistical significance during the normal pregnancy and two-way ANOVA was done to for assessing the influence of depression and GDM on early and mid-pregnancy neurotransmitter levels.

Results

Significant trimester-specific alterations in amino acid neurotransmitters were observed across study groups. In normal pregnancy, the second trimester was characterized by a significant reduction in aspartate, serine, and glycine levels (p<0.0001, p<0.001, and p<0.05, respectively), alongside a marked increase in GABA (p<0.0001). In the first trimester, glutamine and GABA exhibited notable changes, with glutamine levels significantly elevated in both the depression groups (p<0.01). GABA levels were also significantly increased, particularly in the GDM with depression group (p<0.0001). In contrast, during the second trimester, glutamine levels were significantly reduced, most prominently in the GDM with depression group (p<0.01), suggesting potential disruptions in amino acid transport and neurotransmitter metabolism associated with insulin resistance.

Conclusions

The findings showed that gestational diabetes and antenatal depression are associated with altered longitudinal patterns of plasma amino acid neurotransmitters during pregnancy. The differential regulation of glutamine and GABA across trimesters suggests a potential interaction between metabolic dysfunction and neurochemical pathways. This study provides novel longitudinal evidence addressing a gap in understanding peripheral neurochemical adaptations in pregnancy. These results may have implications for identifying biomarkers of metabolic and mental health risk during gestation.

Acknowledgement

Indian Council of Medical Research (ICMR) (EMDR/SG/13/2023-2234)

References

  1. Sharma R, Bansal P, Saini L, Sharma N and Dhingra R 2024. Zuranolone, a neuroactive drug, used in the treatment of postpartum depression by modulation of GABAA receptors Pharmacol. Biochem. Behav. 238 173734.
  2. Thirumoorthy C, Rekha R P, Deepa M, Ram U, Shalu D, Venkatesan U, Srikumar B N, Anjana R M, Balasubramanyam M, Mohan V, Saravanan P, Govindaraj P and Gokulakrishnan K 2025. Association of early pregnancy telomere length and mitochondrial copy number with gestational diabetes mellitus and depressive symptoms Psychoneuroendocrinology 176 107431.