Plasma Gamma-aminobutyric Acid Concentrations Research Articles

Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers.

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined whether levels of immunological protein markers changed with depression, age, or the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). An analysis of plasma samples from patients with a major depressive episode and control blood donors (CBD) revealed the expression of 67 inflammatory markers. Thirteen of these markers displayed augmented levels in patients compared to CBD. Twenty-one markers correlated with the age of the patients, whereas 10 markers correlated with the age of CBD. Interestingly, CST5 and CDCP1 showed the strongest correlation with age in the patients and CBD, respectively. IL-18 was the only marker that correlated with the MADRS-S scores of the patients. Neuronal growth factors (NGFs) were significantly enhanced in plasma from the patients, as was the average plasma GABA concentration. GABA modulated the release of seven cytokines in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) from the patients. The study reveals significant changes in the plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.

Is plasma GABA level a biomarker of Post-Traumatic Stress Disorder (PTSD) severity? A preliminary study

ObjectivesAn increased reactivity to the environment is observed in Post-Traumatic Stress Disorder (PTSD). It would be related to impairment of the Gamma Amino Butyric Acid (GABA) neurotransmission. The study aimed to evaluate plasma GABA concentration as a candidate for PTSD severity biomarker. MethodsThis hypothesis was studied in 17 PTSD patients and 17 healthy Controls using classic and emotional Stroop paradigms. Plasma GABA concentrations were assessed before and after both Stroop tests to evaluate GABA basal tone and GABA reactivity (change in GABAp), respectively. ResultsDuring baseline, PTSD had lower plasma GABA concentrations than the Controls. After the Stroop conflicts GABA reactivity was also lower in PTSD than in the Controls. The GABA baseline tone was negatively correlated with the severity of the PTSD symptoms. This relation was only marginally observed for GABA reactivity. The results produced a trend due to the small size of the sample compared to the number of statistical results given. ConclusionAltogether, the reduced GABA concentration observed in PTSD could be considered as a possible biomarker for PTSD severity.

Plasma GABA levels correlate with aggressiveness in relatives of patients with unipolar depressive disorder

Plasma gamma-aminobutyric acid (GABA) levels are decreased in some patients with depression, mania and alcoholism. Medications which increase plasma GABA improve symptoms of mood disorders and can decrease aggression. We examined the relationship between plasma GABA and aggressiveness on the Buss-Durkee Hostility Inventory in 77 psychiatrically healthy adults. In subjects selected for having a first-degree relative with primary unipolar depressive disorder (FH+, n=33), plasma GABA was negatively correlated with aggressiveness (beta=−0.338, P=0.036), as was age (beta=−0.483, P=0.005). A relationship between plasma GABA levels and aggressiveness was not observed in subjects with no such family history (FH−, n=44). Moreover, FH+ subjects had significantly lower plasma GABA concentrations than FH− subjects. These data suggest that low GABA levels may correlate with some aspects of aggressiveness and may be genetically regulated.

An alteration in the gamma-aminobutyric acid receptor system in experimentally induced septic shock in rats.

To investigate the role of the brain gamma-aminobutyric acid receptor system in septic shock. Prospective, controlled study. Animal laboratory. Twenty-one male Wistar rats (7 wks old) were randomized to three groups: group 1 (n = 7, control); group 2 (n = 7, sham-operated); group 3 (n = 7, cecal ligation and puncture group). Under light ether anesthesia, the rats were treated as described above. Twenty-four hours after treatment, the rats were killed by decapitation. Plasma amino acid concentrations were measured using the collected blood. The brain was excised as rapidly as possible, and separated into forebrain, cerebellum, and brain stem. The brain gamma-aminobutyric acid concentration was measured at each of the three regions. Using 3H-musimol, which is a gamma-aminobutyric acid receptor agonist, as a radioligand, the gamma-aminobutyric receptor densities were measured in these three regions by a radio-receptor assay. The concentrations of the branch-chain amino acids (leucine, isoleucine, valine) were lower in the cecal ligation and puncture group than in the control and sham operated groups. The concentrations of the sulfur-containing amino acids (cysteine and taurine) were increased in the cecal ligation and puncture group compared with the other two groups, but the methionine concentration was increased in the sham-operated and the cecal ligation and puncture groups compared with the control group (p < .05). The plasma gamma-aminobutyric acid concentration was not detectable in any of the three groups. The ammonia concentration was greater in the cecal ligation and puncture group than in the other two groups. There was no significant difference in the brain gamma-aminobutyric acid concentration among the three groups. The maximum number of binding sites in the forebrain of the cecal ligation and puncture group was higher than in the other two groups at both high- and low-affinity sites (control group: high-affinity sites 0.34 +/- 0.03, low-affinity sites 2.93 +/- 0.28; sham-operated group: high-affinity sites 0.35 +/- 0.03, low-affinity sites 2.73 +/- 0.18; cecal ligation and puncture group: high-affinity sites 0.59 +/- 0.13, low-affinity sites 3.53 +/- 0.21; mean +/- SEM pmol/mg protein) (p < .05). There were no significant differences observed in other regions of the brain (cerebellum and brain stem) in the three groups. The dissociation constants for 3H-musimol were almost unchanged in the three groups. An increase in the gamma-aminobutyric acid-A receptor density was observed in the forebrain of the cecal ligation and puncture model rats. This alteration may be closely related to the pathogenesis of brain dysfunction during septic shock.

Plasma and cerebrospinal fluid gamma-aminobutyric acid in neurological disorders.

In 49 patients with various neurological disorders plasma and CSF gamma-aminobutyric acid (GABA) concentrations were determined by radioreceptor assay. The CSF GABA concentration of 127 +/- 47 pmol/ml (range: 65-275; n = 52) was independent of the age, the sex and the intake of various drugs including benzodiazepines, baclofen and antidepressants. Patients with diverse neurological disorders such as multiple sclerosis, ischaemic strokes, intracranial tumour and polyneuropathies had similar CSF GABA levels. The mean plasma GABA concentration was 309 +/- 79 pmol/ml (range: 179-498; n = 44). The correlation between the GABA concentrations of CSF and plasma was very poor (r = 0.18; n = 44). Therefore plasma GABA is not a suitable indicator for CSF GABA.

GABA in cerebrospinal fluid of children with febrile convulsions.

In 23 children with febrile convulsions the concentration of gamma-aminobutyric acid (GABA) in lumbar cerebrospinal fluid (CSF) was measured by a radioreceptor assay. The mean CSF GABA concentration of 134 (range, 73-294) pmoles/ml was significantly lower than that of 16 seizure-free children serving as controls, who had 210 (range, 117-475) pmoles/ml. The reduction in CSF GABA levels in patients with febrile convulsions was not reflected in plasma GABA concentrations. These data provide further evidence that impairment of GABA neurotransmission may contribute to an increased seizure propensity.

Role of central nervous system-derived or circulating gamma-aminobutyric acid on prolactin secretion in the rat.

To investigate the respective role in PRL secretion of gamma-aminobutyric acid (GABA), either derived from the central nervous system or circulating in plasma, experiments were performed using ethanolamine-O-sulfate (EOS), a specific inhibitor of GABA catabolism. Intracerebroventricular injection of EOS (2 mg/kg) induced in unanesthetized male rats 2-8 h post injection a clear-cut rise in hypothalamic, anterior pituitary (AP), and plasma GABA concentrations. Rises in GABA titers occurred earlier in the hypothalamus and AP (2 h) than in the plasma (4 h). Concomitant to alterations of GABA, there was a striking lowering of plasma PRL evident at 2 h and still present 24 h after EOS administration. In contrast, systemic administration of graded doses of EOS (200-400 mg/kg, iv) did not induce significant changes in plasma GABA concentrations 4 h post injection; only the 600 mg/kg dose of EOS increased GABA concentrations 4 h post injection in the hypothalamo-AP system and decreased plasma PRL concentrations. Finally, in hypophysectomized rats bearing ecotopic pituitaries, despite the occurrence of rises in the hypothalamic GABA after intracerebroventricular or systemic (600 mg/kg) administration of EOS, AP, plasma GABA, and plasma PRL concentrations were not altered. In all these findings indicate that: 1) changes in plasma PRL are best correlated to variations in the amino acid titers occurring in the hypothalamo-AP systems; and 2) circulating GABA does not play a functional role in the control of PRL secretion. Finally, since alterations in blood GABA levels after central or systemic administration of EOS appear to reflect primary changes occurring in the brain concentration of the amino acid, circulating GABA may be a reliable indicator of central nervous system GABAergic function.