Biomedical subjects

Gerard Sanacora

Publications and source records attributed to Gerard Sanacora.

23 records · Page 2Linked to original sources

PubMed2003

Increased cortical GABA concentrations in depressed patients receiving ECT.

OBJECTIVE: Reduced gamma-aminobutyric acid (GABA) concentrations have been reported in the plasma, CSF, and cortex of depressed subjects. Of interest is that ECT, one of the most effective treatments for severe refractory depression, produces considerable anticonvulsant effects that may be related to increased GABAergic transmission. The purpose of this study was to determine if cortical GABA concentrations increase following a course of ECT. METHOD: Occipital cortex GABA concentrations in eight depressed patients were measured by using proton magnetic resonance spectroscopy before and after a course of ECT. RESULTS: A significant increase in occipital cortex GABA concentrations was seen following ECT treatment of depression. CONCLUSIONS: Occipital cortex GABA concentrations increase two-fold following ECT. This suggests possible GABAergic involvement in ECT's mechanism of anticonvulsant and antidepressant actions.

Anticonvulsants↗

PubMed2003

Clinical studies implementing glutamate neurotransmission in mood disorders.

Emerging evidence suggests that the amino acid neurotransmitter systems are associated with the pathophysiology and treatment of mood disorders. Recent advances in the areas of molecular neurobiology, pharmacology, and magnetic resonance spectroscopy (MRS) now provide better tools to probe the function of the amino acid neurotransmitter systems and are affording us the opportunity to better investigate the relationship of these systems to mood disorders. Here we review the available literature in the field and suggest a possible pathophysiological model that may account for the many of the findings.

Animals↗

PubMed2002

Monoamine depletion in unmedicated depressed subjects.

BACKGROUND: Although significant evidence suggests that diminished monoamine function is associated with clinical depression, catecholamine or indoleamine depletion alone has not been associated with significant mood changes in unmedicated depressed subjects or never-depressed control subjects. This study assesses the integrated role of these monoamine systems in depressed patients. METHODS: Unmedicated depressed subjects underwent a 2-week, double-blind, random-ordered crossover study consisting of the following active and control conditions respectively: indoleamine (via tryptophan depletion) plus catecholamine (via alpha-methyl-paratyrosine administration) depletion and, separately, indoleamine plus sham (via diphenhydramine administration) catecholamine depletion. Ten subjects completed both conditions; two subjects were withdrawn after active testing and one after control testing. RESULTS: Mean Hamilton Depression Rating Scale (HDRS) scores decreased progressively throughout the study days (baseline 26.7 points +/- 1.7 SEM and termination 20.0 +/- 2.4, active depletion; baseline 26.1 points +/- 2.3 SEM and termination 23.2 +/- 2.6, control testing) but did not differ between groups. Only three patients demonstrated 20% or greater increases from baseline HDRS at any point during the observation days. CONCLUSIONS: Overall, results show that simultaneous disruptions of indoleamine and catecholamine function do not exacerbate symptoms in unmedicated depressed subjects, thus lending further support to the notion that monoamines regulate mood in actively depressed patients via indirect mechanisms.

Adult↗

PubMed2002

Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression.

BACKGROUND: Plasma activity of dopamine beta-hydroxylase (DbetaH), the enzyme that converts dopamine to norepinephrine, is reportedly lower in patients with unipolar major depression with psychotic features (UDPF) than in those with nonpsychotic unipolar major depression (UD). Plasma DbetaH is under genetic control by the structural locus encoding DbetaH protein, DBH. This study tested the hypothesis that diagnosis-specific allelic variation at DBH accounts for lower plasma DbetaH in UDPF. METHODS: Plasma DbetaH activity was measured in samples from patients with UDPF (n = 33) and UD (n = 45). Genotypes were determined at several functional DBH polymorphisms, including C-1021T, a single nucleotide polymorphism (SNP) in the proximal 5' region that associates with variation in plasma DbetaH activity. RESULTS: Mean plasma DbetaH activity was significantly lower in UDPF than in UD. Genotyping at DBH did not reveal genetic associations distinguishing UDPF from UD. A two-way analysis of variance showed significant effects of genotype and diagnostic group but no significant interaction. CONCLUSIONS: Although the effects of the diagnosis of UDPF, and of DBH allele status, on plasma DbetaH activity were replicated, the lower plasma DbetaH in patients with UDPF was not accounted for by DBH genotype. Several explanations for this result are possible. First, other variants at DBH, or at other loci, could account for the findings. Second, nongenetic factors could account for the differences in plasma DbetaH. In this regard, we hypothesize that abnormal regulation of hypothalamic-pituitary-adrenal function in UDPF lowers expression of DbetaH protein, which could in turn alter the ratio of dopamine and norepinephrine in noradrenergic neurons, thereby promoting development of psychotic symptoms.

Adult↗

PubMed2002

Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors.

OBJECTIVE: Studies have demonstrated low concentrations of gamma-aminobutyric acid (GABA) in the plasma and CSF of individuals with major depression, and low GABA concentrations have also been found in the occipital cortex of depressed subjects. The goal of this study was to determine whether these occipital cortex GABA concentrations are altered after administration of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. METHOD: By means of proton magnetic resonance spectroscopy, occipital cortex GABA concentrations were measured in 11 medication-free depressed patients before initiation of treatment with SSRI medications and after an average of 2 months of treatment. RESULTS: A significant increase in occipital cortex GABA concentrations was seen after SSRI treatment. CONCLUSIONS: SSRI treatment of major depression is associated with increased occipital cortex GABA concentrations. This appears to result in a normalization of low pretreatment GABA concentrations, an effect that may contribute to a common mechanism of antidepressant action.

Adult↗