# Thalamic GABA+ levels are negatively associated with neuropsychiatric symptoms in patients with insomnia

**Authors:** Mingyuan Dai, Huande Hong, Yumeng Mao, Rui Wang, Yanlong Jia, Dongyuan Xu, Gen Yan

PMC · DOI: 10.3389/fnhum.2026.1750271 · Frontiers in Human Neuroscience · 2026-02-05

## TL;DR

This study found that lower GABA+ levels in the thalamus are linked to worse fatigue and anxiety in people with insomnia.

## Contribution

The study provides new neurochemical evidence linking thalamic GABA+ levels to neuropsychiatric symptoms in insomnia.

## Key findings

- GABA+ levels were significantly lower in insomnia patients compared to healthy controls.
- Lower GABA+ levels were negatively correlated with fatigue and anxiety in insomnia patients.
- GPC and Cr+PCr levels were significantly higher in insomnia patients.

## Abstract

Insomnia is the most common type of sleep disorder; however, the neurobiological causes and correlates of hyperarousal in insomnia remain to be fully determined, and the levels of cerebral metabolites in patients with insomnia remain unclear. This study aimed to quantify changes in cerebral metabolite levels in patients with insomnia and to explore their relationship with fatigue, anxiety, and subjective sleepiness.

Twenty unmedicated patients with insomnia disorder and 21 age- and sex-matched healthy volunteers were included. The concentrations of metabolites including γ-aminobutyric acid (GABA+), glutamate (Glu), glycerophosphocholine (GPC), creatine (Cr), and phosphocreatine (PCr) were obtained by magnetic resonance spectroscopy, and the differences in metabolites between the two groups were compared. Sleep quality, sleepiness, anxiety, and fatigue were assessed using the Pittsburgh Sleep Quality Index (PSQI), Karolinska Sleepiness Scale (KSS), Beck Anxiety Inventory (BAI), and Fatigue Severity Scale (FSS), respectively. Correlations between the changes in GABA+, Glu, and GPC levels and the PSQI, KSS, FSS, and BAI scores were evaluated in patients with insomnia.

GABA+ levels were significantly lower in patients with insomnia than in healthy controls (p = 0.027), whereas GPC and Cr+PCr levels were significantly higher (p < 0.001 and p = 0.003, respectively). However, Glu levels were comparable between the groups (p = 0.962). Furthermore, GABA+ levels were significantly negatively correlated with FSS (r = −0.656, p = 0.003) and BAI (r = −0.467, p = 0.038) scores; a trend-level negative association with KSS was also observed (r = −0.419, p = 0.066).

Our results revealed alterations in the levels of GABA+ and GPC in the thalamus of patients with insomnia. These findings provide objective neurochemical evidence for the pathophysiological mechanisms of insomnia.

## Linked entities

- **Chemicals:** γ-aminobutyric acid (PubChem CID 119), glutamate (PubChem CID 611), glycerophosphocholine (PubChem CID 11234), creatine (PubChem CID 586), phosphocreatine (PubChem CID 9548602)
- **Diseases:** insomnia (MONDO:0013600)

## Full-text entities

- **Genes:** GYPC (glycophorin C (Gerbich blood group)) [NCBI Gene 2995] {aka CD236, CD236R, GE, GPC, GPD, GYPD}
- **Diseases:** daytime functional impairment (MESH:D003072), social and occupational functioning (MESH:D060051), sleep deprivation (MESH:D012892), infarction (MESH:D007238), depressants (MESH:D003866), cardiovascular disease (MESH:D002318), brain abnormalities (MESH:D001927), daytime tiredness (MESH:D006970), anxiety disorders (MESH:D001008), difficulty (MESH:D051346), Sleepiness (MESH:D000077260), chronic fatigue (MESH:D015673), Fatigue (MESH:D005221), obesity (MESH:D009765), hemorrhage (MESH:D006470), Anxiety (MESH:D001007), intracranial lesions (MESH:D020765), neurological, endocrine, or psychiatric disorders (MESH:D001523), substance abuse (MESH:D019966), Insomnia (MESH:D007319), diabetes (MESH:D003920), tumors (MESH:D009369), Sleep Disorders (MESH:D012893), alcohol (MESH:D000437), ID (MESH:C537985)
- **Chemicals:** phosphocholine (MESH:D010767), myo-inositol (MESH:D007294), Ins (MESH:D007204), lipids (MESH:D008055), Gln (MESH:D005973), N-acetylaspartylglutamate (MESH:C027172), Cr (MESH:D003401), PCr (MESH:D010725), N-acetylaspartate (MESH:C000179), Benzodiazepines (MESH:D001569), caffeine (MESH:D002110), 31P (-), GABA (MESH:D005680), Glu (MESH:D018698), acetylcholine (MESH:D000109), Water (MESH:D014867), phospholipid (MESH:D010743), choline (MESH:D002794), GPC (MESH:D005997)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12916559/full.md

## References

47 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916559/full.md

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Source: https://tomesphere.com/paper/PMC12916559