Plasma Gamma-aminobutyric Acid Levels Research Articles

Interactive Effect of Dietary Gamma-Aminobutyric Acid (GABA) and Water Temperature on Growth Performance, Blood Plasma Indices, Heat Shock Proteins and GABAergic Gene Expression in Juvenile Olive Flounder Paralichthys olivaceus.

Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system of living organisms and has the ability to reduce the magnitude of stress in humans and animals. In this study, we evaluated the supplemental effects of GABA on normal and high water temperature based on growth, blood plasma composition as well as heat shock proteins and GABA-related gene expression in juvenile olive flounder. For this, a 2 × 2 factorial design of experiment was employed to investigate the dietary effects of GABA at 0 mg/kg of diet (GABA0 diet) and 200 mg/kg of diet (GABA200 diet) in water temperatures of 20 ± 1 °C (normal temperature) and 27 ± 1 °C (high temperature) for 28 days. A total of 180 fish with an average initial weight of 40.1 ± 0.4 g (mean ± SD) were distributed into 12 tanks, of which, each tank contained 15 fish based on the 4 dietary treatment groups in triplicate. At the end of the feeding trial, the results demonstrated that both temperature and GABA had significant effects on the growth performance of the fish. However, fish fed the GABA200 diet had a significantly higher final body weight, weight gain and specific growth rate as well as a significantly lower feed conversion ratio than the fish fed the GABA0 diet at the high water temperature. A significant interactive effect of water temperature and GABA was observed on the growth performance of olive flounder based on the two-way analysis of variance. The plasma GABA levels in fish were increased in a dose-dependent manner at normal or high water temperatures, whereas cortisol and glucose levels were decreased in fish fed GABA-supplemented diets under temperature stress. The GABA-related mRNA expression in the brains of the fish such as GABA type A receptor-associated protein (Gabarap), GABA type B receptor 1 (Gabbr1) and glutamate decarboxylase 1 (Gad1) were not significantly affected by GABA-supplemented diets under normal or temperature stressed conditions. On the other hand, the mRNA expression of heat shock proteins (hsp) in the livers of the fish, such as hsp70 and hsp90, were unchanged in fish fed the GABA diets compared to the control diet at the high water temperature. Collectively, the present study showed that dietary supplementation with GABA could enhance growth performance, and improve the feed utilization, plasma biochemical parameters and heat shock proteins and GABA-related gene expression under the stress of high water temperatures in juvenile olive flounder.

Aldehyde dehydrogenase 2-associated changes in pharmacokinetics, locomotor function and peripheral glutamic acid and gamma-aminobutyric acid levels during acute alcohol intoxication in male mice.

The insufficiency of human aldehyde dehydrogenase 2 (ALDH2) has been consistently associated with high blood acetaldehyde levels and impaired locomotor function during acute alcohol intoxication. The ALDH2-associated change in peripheral glutamic acid (Glu) and gamma-aminobutyric acid (GABA) levels and its correlation with pharmacokinetics and psychomotor function remain unclear. In this study, ALDH2*2 mice were used to build an acute alcohol intoxication model after intraperitoneal administration. The blood ethanol and acetaldehyde concentrations were analyzed to generate concentration-time curves at two doses of alcohol (2.0 and 4.0 g/kg). The dose of 4.0 g/kg was selected in accordance with the preliminary behavioral evaluation result to perform the following behavioral tests (e.g. the rotarod test, the open field test, and the Y-maze test), so as to assess locomotor activity, anxiety and cognitive ability. Plasma Glu and GABA levels were determined through enzyme-linked immunosorbent assays. The results suggested that the ALDH2*2 mice had highly accumulated acetaldehyde levels, impaired locomotor activity and anxiety-like emotion but unimpaired cognitive function, compared to the wild type (WT) mice. The plasma Glu level and the ratio of Glu/GABA in the alcohol-treated WT and ALDH2*2 groups decreased from 2 to 5 h after intraperitoneal administration, whereas the GABA level did not change significantly. The blood alcohol concentration in the WT and ALDH2*2 mice was positively correlated with plasma Glu level, whereas the blood acetaldehyde level was found as the opposite. We speculate that the decline degree of Glu/GABA ratio could be associated with psychomotor retardation and needs to be further investigated.

Plasma gamma-aminobutyric acid (GABA) levels and posttraumatic stress disorder symptoms in trauma-exposed women: a preliminary report.

Aberrations in the stress response are associated with posttraumatic stress disorder (PTSD) symptom development, maintenance, and severity. Gamma-aminobutyric acid (GABA), the brain's primary inhibitory neurotransmitter, may play a key role in stress recovery. In this preliminary study, we examined whether plasma GABA levels differed between women with PTSD and trauma-exposed healthy controls. Thirty participants provided plasma samples during two phases of the menstrual cycle: the early follicular phase and the mid-luteal phase. During each phase, blood was drawn after 45 min of rest, and after mild and moderately stressful psychophysiological tasks. Plasma GABA levels were measured using HPLC-mass spectrometry (LC-MS/MS). In analyses using PTSD diagnosis as a categorical group variable, women with and without a diagnosis of PTSD did not differ in plasma GABA levels (ps > .18). However, in analyses examining PTSD symptom severity as a continuous variable, there was a trend-level positive association between more severe PTSD symptoms and higher plasma GABA levels across the four blood draws (p = .06). In analyses examining DSM-IV PTSD symptom clusters separately, dysphoria symptoms were positively and significantly associated with plasma GABA levels (p = .03). Similarly, there was a trend-level positive association between avoidance cluster symptoms and plasma GABA levels (p = .06). Plasma GABA levels were not modulated by experimentally induced stress or menstrual cycle phase. Dysregulation in GABA may be a neurobiological marker and/or potential treatment target for women with PTSD symptom profiles characterized by prominent dysphoria and avoidance cluster symptoms.

Polymeric nanoencapsulation of zaleplon into PLGA nanoparticles for enhanced pharmacokinetics and pharmacological activity.

Zaleplon (ZP) is a sedative and hypnotic drug used for the treatment of insomnia. Despite its potent anticonvulsant activity, ZP is not commonly used for the treatment of convulsion since ZP is characterized by its low oral bioavailability as a result of poor solubility and extensive liver metabolism. The following study aimed to formulate specifically controlled release nano‐vehicles for oral and parenteral delivery of ZP to enhance its oral bioavailability and biological activity. A modified single emulsification–solvent evaporation method of sonication force was adopted to optimize the inclusion of ZP into biodegradable nanoparticles (NPs) using poly (dl‐lactic‐co‐glycolic acid) (PLGA). The impacts of various formulation variables on the physicochemical characteristics of the ZP‐PLGA‐NPs and drug release profiles were investigated. Pharmacokinetics and pharmacological activity of ZP‐PLGA‐NPs were studied using experimental animals and were compared with generic ZP tablets. Assessment of gamma‐aminobutyric acid (GABA) level in plasma after oral administration was conducted using enzyme‐linked immunosorbent assay. The maximal electroshock‐induced seizures model evaluated anticonvulsant activity after the parenteral administration of ZP‐loaded NPs. The prepared ZP‐PLGA NPs were negatively charged spherical particles with an average size of 120–300 nm. Optimized ZP‐PLGA NPs showed higher plasma GABA levels, longer sedative, hypnotic effects, and a 3.42‐fold augmentation in oral drug bioavailability in comparison to ZP‐marketed products. Moreover, parenteral administration of ZP‐NPs showed higher anticonvulsant activity compared to free drug. Oral administration of ZP‐PLGA NPs achieved a significant improvement in the drug bioavailability, and parenteral administration showed a pronounced anticonvulsant activity.

Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high-fat diet.

Increased levels of plasma free amino acids (pFAAs) can disturb the blood glucose levels in patients with obesity, diabetes mellitus and metabolic syndrome (MS) and are associated with enhanced protein oxidation. Oxidation of proteins, especially in the muscles, can promote protein degradation and elevate the levels of pFAAs. Gamma-aminobutyric acid (GABA), a food additive, can reduce high-fat diet (HFD)-induced hyperglycaemia; however, the mechanisms remain unclear. The aim of this study was to evaluate the effects of GABA on protein oxidation and pFAAs changes. One hundred male C57BL/6 mice were randomly divided into five groups that were fed with control diet, HFD and HFD supplied with 0.2%, 0.12% and 0.06% GABA in drinking water for 20 weeks respectively. HFD feeding led to muscular oxidative stress, protein oxidation, pFAA disorders, hyperglycaemia and augmented plasma GABA levels. Treatment with GABA restored normally fasting blood glucose level and dose-dependently inhibited body weight gains, muscular oxidation and protein degradation. While medium and low doses of GABA mitigated HFD-induced pFAA disorders, the high dose of GABA deteriorated the pFAA disorders. Medium dose of GABA increased the levels of GABA, but high dose of GABA reduced the levels of plasma GABA and increased the activity of succinic semialdehyde dehydrogenase in the liver. Therefore, treatment with GABA mitigated HFD-induced hyperglycaemia probably by repairing HFD-induced muscular oxidative stress and pFAA disorders in mice. Our data also suggest that an optimal dose of GABA is crucial for the prevention of excess GABA-related decrease in the levels of pFAA and GABA as well as obesity.

Decreased Hepatocyte Growth Factor (HGF) and Gamma Aminobutyric Acid (GABA) in Individuals with Obsessive-Compulsive Disorder (OCD)

IntroductionThere is support for the role of gamma aminobutyric acid (GABA) in the etiology of mood disorders. Recent research has shown that hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility. This study was designed to determine and correlate plasma levels of HGF and GABA as well as symptom severity in individuals with obsessive-compulsive disorder (OCD).Subjects and methodsPlasma from 15 individuals with OCD (9 males, 6 females;, mean age 38.7 years) and 17 neurotypical controls (10 males, 7 females; mean age 35.2 years) was assessed for HGF, GABA, urokinase plasminogen activator (uPA), and urokinase plasminogen activator receptor (uPAR) concentration using enzyme-linked immunosorbest assays ELISAs. Symptom severity was assessed in these OCD individuals and compared with HGF and GABA concentrations.ResultsIn this preliminary study, individuals with OCD had significantly decreased HGF levels, decreased plasma levels of GABA and decreased uPA. We found that both uPA and uPAR levels correlate with HGF. Both low uPA and low uPAR levels correlate with high symptom severity in individuals with OCD. Low GABA levels in OCD individuals also correlate with high symptom severity.DiscussionThese results demonstrate a preliminary association between HGF, GABA, uPA levels, and OCD and suggest that plasma GABA and uPA levels are related to symptom severity in individuals with OCD.

Correlation between Hepatocyte Growth Factor (HGF) and Gamma-Aminobutyric Acid (GABA) Plasma Levels in Autistic Children

There is much support for the role of Gamma-Aminobutyric acid (GABA) in the etiology of autism. Recent research has shown that hepatocyte growth factor (HGF) modulates GABAergic inhibition and seizure susceptibility. This study was designed to determine and correlate plasma levels of HGF, GABA, as well as symptom severity, in autistic children and neurotypical controls. Plasma from 48 autistic children and 29 neurotypical controls was assessed for HGF and GABA concentration using ELISAs. Symptom severity was assessed in these autistic individuals and compared to HGF and GABA concentrations. We previously reported that autistic children had significantly decreased levels of HGF. In this study, the same autistic children had significantly increased plasma levels of GABA (P = 0.002) and decreased HGF levels correlated with these increased GABA levels (r = 0.3; P = 0.05). High GABA levels correlated with increasing hyperactivity (r = 0.6; P = 0.0007) and impulsivity severity (r = 0.5; P = 0.007), tip toeing severity (r = 0.35; P = 0.03), light sensitivity (r = 0.4; P = 0.02), and tactile sensitivity (r = 0.4; P = 0.01). HGF levels did not correlate significantly with any symptom severity. These results suggest an association between HGF and GABA levels and suggest that plasma GABA levels are related to symptom severity in autistic children.

The change in plasma GABA, glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression

The aim of this study was to investigate the relationship between plasma glutamate, glutamine and gamma-aminobutyric acid (GABA) levels in female patients with major depression treated with S-citalopram or fluoxetine. The patients were assigned into S-citalopram (10 mg/day) or fluoxetine (20 mg/day) groups (n = 15 per group). The Hamilton and Beck Depression Inventory Scales were performed on all study participants, and blood samples were collected. The same procedures were repeated 10 days following the onset of therapy. Fifteen female healthy volunteers were also included in the study for the evaluation of normal plasma levels. The plasma GABA levels of the healthy volunteers were higher whereas those for glutamate and glutamine were lower than the day zero samples of the patients. An increase in plasma GABA levels and a decrease in glutamate and glutamine levels were observed on the 10th day of treatment. No difference was detected between the drug treatments. Our findings may suggest that GABA, glutamate and glutamine play a role in depression and that plasma GABA may be used as a biomarker for treatment control.

Is There a Role for Valproic Acid in the Treatment of Catatonia?

Back to table of contents Previous article Next article LETTERFull AccessIs There a Role for Valproic Acid in the Treatment of Catatonia?Richard Bowers D.O.Sarbjot Singh Ajit M.D,Richard Bowers D.O.Search for more papers by this authorSarbjot Singh Ajit M.DSearch for more papers by this author,Published Online:1 Apr 2007AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail SIR: Catatonia is a complex neuropsychiatric disorder, with various medical and psychiatric etiologies, that presents with autism, rigidity, motor immobility (motor signs of catatonia), as well as uncontrollable anxieties, emotional lability, and compulsive emotions (affective signs of catatonia). 1 Catatonia has been treated successfully with GABAergic agents, such as lorazepam and ECT. Research shows that several treatments with ECT in rats increase gamma-aminobutyric acid (GABA) levels in the CNS. 2 We present a case where valproic acid was used successfully in the treatment of catatonia. Case Report“Ms. G” was a 46-year-old woman with a history of alcohol dependence who possibly suffered from a mood disorder for years based on her biopsychosocial history; however, she was never treated for her mood disorder. She presented with motor as well as affective signs of catatonia on multiple admissions to various hospitals within a span of 4 months. She was treated with benzodiazepines with improvement in catatonic motor signs. Ms. G was placed on various antipsychotics for her catatonic affective symptoms, which failed to improve, with her motor signs invariably returning. She was transferred to our institution for further evaluation and after several weeks with no improvement was placed on a regimen of valproic acid, 1000 mg, and within 3 to 4 days her catatonic symptoms dissipated. The patient was discharged on this regimen with no subsequent catatonic episodes.Comment Case reports using valproic acid in the treatment of catatonia successfully have documented neuroimaging studies showing a GABA-A receptor density reduction in the brains of catatonic patients. 2 These data further support a GABAergic deficit in catatonic patients. The relationship between catatonia and mood disorders is well established, where approximately a quarter to half the patients with catatonia also meet criteria for a mood disorder. 3 Plasma GABA levels have also been noted to be low in approximately 40% of patients with mood disorders, which further supports the hypothesis of a GABAergic deficit in catatonia and bipolar disorder. 4 Extrapolating from the above, we suggest that GABA modulation may be a significant factor involved in illness ranging from mood disorders to catatonia. The number of patients with catatonic schizophrenia has declined, yet the number of patients with catatonia associated with mood disorders has remained stable. 3 This may, in part, be due to use of antipsychotics and involvement of a GABAergic mechanism (animal studies have shown GABA modulation of GABA receptors in animals treated on antipsychotics for a period of time). 5 This may support a greater preponderance for GABAergic deficit in mood disorder patients then in schizophrenia patients. The mechanism is not clear on how valproic acid works, but it is clear that it increases CNS GABA. Studies have shown that valproic acid enhances GABA level and neuronal GABA responsiveness. The use of valproic acid should be considered an option for treatment of catatonic patients, particularly those with mood disorders. Department of Psychiatry, University of Missouri, Columbia, Mo.

Relationship Between Posttrauma GABA Plasma Levels and PTSD at 1-Year Follow-Up

Gamma-aminobutyric acid (GABA) exerts a prominent effect on central adrenergic stress responses in times of high stress and has been associated with acute posttraumatic stress disorder (PTSD). The authors examined the association between low posttrauma plasma GABA levels and long-term PTSD. Plasma GABA levels were measured in 78 victims of road traffic accidents who met criteria for trauma exposure on arrival at a trauma department and were admitted for at least 3 days. Patients were assessed for PTSD and major depressive disorder at 6-week and 1-year follow-ups. At 6 weeks and at 1 year, mean posttrauma GABA levels were significantly lower among subjects who met all or nearly all criteria for PTSD than among those who did not. Among patients who met all or nearly all criteria for PTSD at 6 weeks, 75% of those with posttrauma GABA levels above 0.20 mmol/ml no longer met criteria at 1 year. By contrast, among patients whose GABA levels were below 0.20 mmol/ml, 80% met all or nearly all criteria for PTSD at 1 year. Two-thirds of patients who met all or nearly all criteria for PTSD at 1 year also met criteria for major depressive disorder. A plasma GABA level above 0.20 mmol/ml may protect against chronic PTSD and may represent a marker of recovery from trauma.

Relationship Between Posttrauma GABA Plasma Levels and PTSD at 1-Year Follow-Up

Gamma-aminobutyric acid (GABA) exerts a prominent effect on central adrenergic stress responses in times of high stress and has been associated with acute posttraumatic stress disorder (PTSD). The authors examined the association between low posttrauma plasma GABA levels and long-term PTSD.Plasma GABA levels were measured in 78 victims of road traffic accidents who met criteria for trauma exposure on arrival at a trauma department and were admitted for at least 3 days. Patients were assessed for PTSD and major depressive disorder at 6-week and 1-year follow-ups.At 6 weeks and at 1 year, mean posttrauma GABA levels were significantly lower among subjects who met all or nearly all criteria for PTSD than among those who did not. Among patients who met all or nearly all criteria for PTSD at 6 weeks, 75% of those with posttrauma GABA levels above 0.20 mmol/ml no longer met criteria at 1 year. By contrast, among patients whose GABA levels were below 0.20 mmol/ml, 80% met all or nearly all criteria for PTSD at 1 year. Two-thirds of patients who met all or nearly all criteria for PTSD at 1 year also met criteria for major depressive disorder.A plasma GABA level above 0.20 mmol/ml may protect against chronic PTSD and may represent a marker of recovery from trauma.

Behavioral correlates of GABAergic disruption in Alzheimer's disease

Losses of gamma-aminobutyric acid (GABA) have been variably demonstrated in Alzheimer's disease (AD) and may be related to the presence of behavioral and psychological symptoms of dementia (BPSD) in AD. Our objective was to assess the relationship between plasma GABA (pGABA) levels and specific BPSD in patients with severe AD. pGABA levels and BPSD were measured in 14 institutionalized AD patients (8M/6F, mean age +/- S.D. = 85.6 +/- 4.5 years) with severe cognitive impairment (Mini-mental State Examination score = 4.5 +/- 4.6) and prominent behavioral disturbances (Neuropsychiatric Inventory (NPI) score = 33.4 +/- 23.6). pGABA was positively correlated with depression and apathy scores on the NPI and negatively correlated with age. Apathy and age were independent predictors of pGABA levels. The final stages of AD are associated with GABAergic changes, which may contribute to depression and apathy in AD.

Normal Prefrontal Gamma-Aminobutyric Acid Levels in Remitted Depressed Subjects Determined by Proton Magnetic Resonance Spectroscopy

There is growing evidence that the brain gamma-aminobutyric acid (GABA) system is involved in depression. Lowered plasma GABA levels were identified as a traitlike abnormality found in patients with remitted unipolar depression and in healthy first-degree relatives of patients with unipolar depression. Major depressive disorder has been associated with neuroimaging and neuropathological abnormalities in the prefrontal cortex by various types of evidence. As a result, the current study investigates whether GABA levels in the prefrontal cortex differ between unmedicated subjects with remitted major depressive disorder (rMDD) and healthy control subjects. Sixteen rMDD subjects and 15 healthy control subjects underwent magnetic resonance spectroscopy. We used a 3 Tesla GE whole body scanner with a homogeneous resonator coil providing a homogenous radiofrequency field and capability of obtaining measurement from the prefrontal cortex. Gamma-aminobutyric acid levels were measured in the ventromedial prefrontal cortex and dorsolateral/anterior medial prefrontal cortex. There was no difference in GABA concentrations between rMDD subjects and healthy control subjects in the ventromedial prefrontal cortex and dorsolateral/anterior medial prefrontal cortex. Secondary analyses provided preliminary evidence for a negative relationship between the glutamate/glutamine (Glx)/GABA ratio and age of onset of major depression in the ventromedial prefrontal cortex. This result suggests that GABA levels in the prefrontal cortex, if found to be reduced in symptomatic depression, do not represent a persistent characteristic of major depression. Further research is needed to determine brain GABA levels in different brain regions, in different stages of depressive illness, and in different depressive subtypes.

Low posttrauma GABA plasma levels as a predictive factor in the development of acute posttraumatic stress disorder

Background Gamma amino-butyric acid (GABA) regulates the intensity and the duration of the central hyperadrenergic response in times of high stress and has been negatively associated with anxiety, depression, and sleep problems. We hypothesized that individuals with low plasma GABA levels may be more prone to develop posttraumatic stress disorder (PTSD) in the aftermath of trauma exposure. Methods To test this hypothesis, we measured plasma GABA levels in a population of 108 road traffic accident victims on arrival at a traumatology department and assessed them for PTSD 6 weeks later. Results The mean GABA level (nmol/mL) in the PTSD group ( n = 55; M = .20; SD = .08) was significantly lower compared with members of the trauma-exposed group who did not develop PTSD [n = 17; M = .30; SD = .09), t(70) = 3.94, p = .0002]. Conclusions Provided that GABA levels in the brain are genetically predetermined, our results would suggest that individuals with low plasma GABA levels are premorbidly more vulnerable to stress-related disorders such as acute PTSD. If replicated, plasma GABA levels measured in the aftermath of trauma exposure might help to identify individuals at high risk for developing PTSD.

GABAergic dysfunction in mood disorders.

The authors review the available literature on the preclinical and clinical studies involving GABAergic neurotransmission in mood disorders. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter present almost exclusively in the central nervous system (CNS), distributed across almost all brain regions, and expressed in interneurons modulating local circuits. The role of GABAergic dysfunction in mood disorders was first proposed 20 years ago. Preclinical studies have suggested that GABA levels may be decreased in animal models of depression, and clinical studies reported low plasma and CSF GABA levels in mood disorder patients. Also, antidepressants, mood stabilizers, electroconvulsive therapy, and GABA agonists have been shown to reverse the depression-like behavior in animal models and to be effective in unipolar and bipolar patients by increasing brain GABAergic activity. The hypothesis of reduced GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these disorders. However, low GABAergic cortical function may probably be a feature of a subset of mood disorder patients, representing a genetic susceptibility. In this paper, we discuss the status of GABAergic hypothesis of mood disorders and suggest possible directions for future preclinical and clinical research in this area.

Plasma gamma-amino-butyric acid (GABA) levels in cholecystokinine-tetrapeptide (CCK-4) induced anxiety.

Dysregulation of the GABA system is supposed to play an important role in the pathophysiology of panic disorder. Moreover, prior investigations revealed an association between GABA plasma levels and experimental induced panic with lactate. To evaluate a possible relationship between plasma GABA and CCK-4 induced panic plasma GABA levels in healthy volunteers were investigated. 12 healthy subjects were challenged with 50 micro g CCK-4. Blood samples for determination of plasma GABA were drawn at baseline, 5 and 10 minutes after CCK-4 injection. Plasma GABA levels did not change significantly during the CCK-4 challenge as revealed by ANOVA for repeated measurements. There was no correlation between baseline GABA levels and anxiogenic response to CCK-4. In contrast to previous findings with lactate our study does not suggest a possible relationship between plasma GABA levels and experimental induced panic with CCK-4.

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.

Divalproex sodium increases plasma GABA levels in healthy volunteers.

The purpose of this study was to ascertain the effects of divalproex sodium (DVP), an anticonvulsant and mood stabilizer, on plasma gamma-aminobutyric acid (GABA) levels in healthy humans. Twenty healthy volunteers with no lifetime history of psychiatric illness or family history in first-degree relatives were recruited. Each subject received DVP 1000 mg per day for 1 week. Blood samples for assay of plasma levels of GABA were taken from each subject before and after the administration of DVP. GABA concentrations were analysed using high pressure liquid chromatography with fluorescence detection after derivatization with o-phthaldialdehyde. It was found that DVP administration for 1 week resulted in a small, but significant, increase in plasma levels of GABA. Our results suggest that DVP enhances GABA activity in humans. Further treatment studies of DVP on GABA function in patients with psychiatric disorders are needed to explore the significance of the enhancing effect of DVP on GABA activity.

516. Plasma GABA is inversely correlated with self-reported hostility: a preliminary report

Decreased concentrations of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in brain, cerebrospinal fluid and plasma have been detected in patients with affective disorders, who often display aggressive behavior. In addition, preliminary reports indicate that psychopharmacological agents which elevate GABA show clinical efficacy in reducing aggression. In order to directly examine the relationship between plasma GABA (pGABA) and aggression, pGABA was measured and related to Buss-Durkee Hostility Inventory (BDHI) total scores in a mixed sample of adults (n = 82): those meeting DMS-III-R criteria for primary unipolar depression, bipolar disorder, or no axis I disorders. Overall, pGABA showed a negative correlation with hostility. First, BDHI scores were significantly higher in the subset of subjects whose pGABA levels were below a previously established normal range cutoff value of 100 pmol/mL. Second, plasma GABA levels showed a statistically significant negative relationship with BDHI scores, even after controlling for age, gender, liver enzymes, and DSM-III-R mood disorder. Finally, pGABA also showed a direct negative correlation with BDHI scores in persons not meeting DSM-III-R criteria for any Axis I disorder (Pearson r = −.390, p = .024). These preliminary data suggest that lower plasma GABA levels may be a trait characteristic of aggressiveness.

Plasma levels of gamma-aminobutyric acid and panic disorder

Low levels of γ-aminobutyric acid (GABA) in plasma have been associated with the presence of mood disorders in patients with major depressive disorder. We examined plasma GABA in patients with panic disorder, a disorder that is often comorbid with major depression, and in a group of control subjects. Patients with panic disorder had plasma GABA levels that did not differ significantly from levels in controls subjects. These data support the specificity of low plasma GABA as a marker for mood disorders.