CSF GABA in depressed patients and normal controls
ABSTRACT The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has been implicated in the pathophysiology of depression. Therefore, we examined cerebrospinal fluid (CSF) levels of GABA in depressed patients (N = 25) and normal controls (N = 20). There was no significant difference between the groups. However, among the depressed patients the subgroup of unipolar melancholic patients (N = 13) had significantly lower CSF levels of GABA than the rest of the depressed patients (N = 12). There was no significant difference for CSF levels of GABA between depressed patients who were (N = 14) or were not (N = 11) cortisol non-suppressors. It was of interest that among the controls there was a significant negative correlation between CSF levels of GABA and CSF levels of norepinephrine.
- SourceAvailable from: Shang-Feng Gao
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- "• 17 MDD patients ( Petty and Schlesser 1981 ) • 23 euthymic medication - free BPD patients ( Berrettini and others 1983 ) • 58 MDD patients ( Petty and Sherman 1984 ) • 133 patients with MDD , BPD , and mania ( Petty and others 1990 ) • 77 male patients with MDD ( Petty and others 1992 ) • BPD patients in manic ( n = 24 ) and in depressed states ( n = 33 ) ( Petty and others 1993a ) • 46 male patients with MDD ( Petty and others 1995 ) Decreased CSF GABA Levels • 17 depressed patients including 10 MDD and 5 BPD ( Gold and others 1980 ) • 6 treated patients with depressive syndromes ( Zimmer and others 1980 ) • 26 depressed patients ( Gerner and Hare 1981 ) • 13 depressed patients with MDD ( n = 10 ) and BPD ( n = 3 ) ( Kasa and others 1982 ) • 9 euthymic medication - free MDD and BPD patients ( Berret - tini and others 1983 ) • 41 depressed patients with 1 MDD ( n = 10 ) and BPD ( n = 30 ) ( Gerner and others 1984 ) Unaltered CSF GABA Levels • 25 longer recovered euthymic BPD patients ( Berrettini and others 1986 ) • 25 depressed patients , 13 were melancholic ( Roy and others 1991 ) "
ABSTRACT: Stress response and depression have a significant impact on modern society. Although the symptoms are well characterized, the molecular mechanisms underlying depression are largely unknown. The monoamine hypothesis, which postulates dysfunctional noradrenergic and serotonergic systems as the underlying primary cause of depression, has been valuable for the development of conventional antidepressants, which can reverse these dysfunctional states to some degree. However, recent data from various neuroscience disciplines have questioned the major role of amines in the pathogenesis of depression. A considerable amount of evidence has accumulated that suggests that normalization of the hypothalamo-pituitary-adrenal (HPA) system might be the final step necessary for a remission of depression. In addition, an increasing body of clinical and postmortem evidence is pointing to a role played by γ-aminobutyric acid (GABA) and glutamate in the etiology of depression. This review examines the evidence, mainly obtained from clinical studies or from postmortem brain material, for a major role of the HPA axis, glutamatergic, and GABAergic systems in the pathogenesis of major and bipolar depression. The authors hope that these insights will stimulate further studies with the final aim of developing new types of antidepressants that combine increased efficacy with a shorter delay of the onset of action and reduced side-effect profiles.The Neuroscientist 03/2010; 17(1):124-44. DOI:10.1177/1073858410361780 · 7.62 Impact Factor
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- "Therefore, our findings of positive correlations between KYN and 3-HAA and striatal tCho suggest that pathways involved in cellular survival may be more relevant to the pathogenesis of melancholic adolescent MDD compared to other subtypes of MDD. This notion is supported by findings from adult MDD studies documenting reductions of γaminobutyric acid (GABA) concentrations in the plasma (Petty et al., 1992), the CSF (Roy et al., 1991), and the occipital lobe (Sanacora et al., 2004) as well as increased glutamate brain concentrations (Sanacora et al., 2004), which were more pronounced in melancholic MDD patients compared to controls. "
ABSTRACT: Cytokine induction of the enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in the development of major depressive disorder (MDD). IDO metabolizes tryptophan (TRP) into kynurenine (KYN), thereby decreasing TRP availability to the brain. KYN is further metabolized into several neurotoxins. The aims of this pilot were to examine possible relationships between plasma TRP, KYN, and 3-hydroxyanthranilic acid (3-HAA, neurotoxic metabolite) and striatal total choline (tCho, cell membrane turnover biomarker) in adolescents with MDD. We hypothesized that MDD adolescents would exhibit: i) positive correlations between KYN and 3-HAA and striatal tCho and a negative correlation between TRP and striatal tCho; and, ii) the anticipated correlations would be more pronounced in the melancholic subtype group. Fourteen adolescents with MDD (seven with melancholic features) and six healthy controls were enrolled. Minimums of 6 weeks MDD duration and a severity score of 40 on the Children's Depression Rating Scale-Revised were required. All were scanned at 3T with MRI, multi-voxel 3-dimensional, high, 0.75 cm(3), spatial resolution proton magnetic resonance spectroscopic imaging. Striatal tCho concentrations were assessed using phantom replacement. Spearman correlation coefficients were Bonferroni-corrected. Positive correlations were found only in the melancholic group, between KYN and 3-HAA and tCho in the right caudate (r=0.93, p=0.03) and the left putamen (r=0.96, p=.006), respectively. These preliminary findings suggest a possible role of the KYN pathway in adolescent melancholic MDD. Larger studies should follow.Progress in Neuro-Psychopharmacology and Biological Psychiatry 09/2009; 34(1):37-44. DOI:10.1016/j.pnpbp.2009.09.015 · 4.03 Impact Factor
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- "Anticonvulsants that elevate GABA in humans have antidepressant as well as mood stabilizing and anxiolytic properties (Calabrese et al 1999). Moreover, GABA levels have been reported as decreased in the cerebrospinal fluid of patients with melancholic subtype of depression in some but not in all studies (Gold et al 1980; Roy et al 1991). Consistent with these findings, brain imaging studies using proton magnetic resonance spectroscopy demonstrated lower GABA concentrations in depressed patients than in healthy subjects (Sanacora et al 1999, 2004). "
ABSTRACT: Several lines of evidence suggest that central cortical inhibitory mechanisms, especially associated with gamma-aminobutyric acid (GABA) neurotransmission, may play a role in the pathophysiology of major depression. Transcranial magnetic stimulation is a useful tool for investigating central cortical inhibitory mechanisms associated with GABAergic neurotransmission in psychiatric and neurological disorders. By means of transcranial magnetic stimulation, different parameters of cortical excitability, including motor threshold, the cortical silent period, and intracortical inhibition/facilitation, were investigated in 20 medication-free depressed patients and 20 age- and gender-matched healthy volunteers. Silent period and intracortical inhibition were reduced in depressed patients, consistent with a reduced GABAergic tone. Moreover, patients showed a significant hemispheric asymmetry in motor threshold. This study provides evidence of reduced GABAergic tone and motor threshold asymmetry in patients with major depression.Biological Psychiatry 04/2006; 59(5):395-400. DOI:10.1016/j.biopsych.2005.07.036 · 10.25 Impact Factor