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Biomedical subjects

G L Kramer

Publications and source records attributed to G L Kramer.

At least 19 recordsLinked to original sources
PubMed1999

D-fenfluramine challenge in posttraumatic stress disorder.

BACKGROUND: Much progress has been made in understanding the role of catecholamines in the pathophysiology of posttraumatic stress disorder (PTSD). Recent research has broadened the scope of neuroregulation of PTSD to include serotonin. METHODS: We used the serotonin-releasing agent and reuptake inhibitor, d-fenfluramine, to assess the integrity of the serotonin-mediated prolactin release in 8 men with combat-induced PTSD and 8 healthy men. RESULTS: The veterans with PTSD had a significantly lower prolactin response to d-fenfluramine as compared to healthy control subjects. The prolactin response to d-fenfluramine was inversely correlated with the patient's level of PTSD symptomatology and measures of aggression. CONCLUSIONS: This study demonstrates a central serotonin dysfunction, as reflected in a lower prolactin response to d-fenfluramine, in patients with PTSD.

Analysis of Variance↗
PubMed1999

Decrease in stress-induced c-Fos-like immunoreactivity in the lateral septal nucleus of learned helpless rats.

Inescapable stress can induce learned helplessness in many species of animals. Learned helplessness is a phenomenon which has some behavioral and neurotransmitter analogies with human clinical depression. Stress can also induce the expression of immediate early genes, including c-fos in many areas of the central nervous system. We examined stress-induced c-Fos-like immunoreactivity (FLI) using the learned helplessness paradigm. Naive rats showed significantly higher FLI than the tested groups in all the amygdaloid regions and in the hypothalamic paraventricular nucleus. However, in the lateral septal nucleus, helpless animals showed significantly reduced FLI in response to stress, compared to the other groups. These, and other previous data, highlight the importance of the septal area in mediating behavioral responses to inescapable stress.

Animals↗
PubMed1998

GABA and brain abnormalities in schizophrenia.

Some recent autopsy studies indicate that gamma-aminobutyric acid (GABA) function is decreased in brain areas that involve some of the well-described structural changes observed in schizophrenia. The current study examined the relationship between CSF and plasma GABA levels and brain structural measures in schizophrenia. Sixty-two drug-free, physically healthy male patients with schizophrenia (DSM-IIIR) were evaluated for plasma and CSF GABA, as well as brain structural measures on CT scans. Plasma levels of GABA were associated with prefrontal sulcal widening and VBRs, but not global sulcal widening in the schizophrenic patients. CSF GABA measures were not associated with brain structural measures, but were associated with age and age of onset. The significant relationship between plasma GABA, but not CSF GABA, and specific brain morphology measures in schizophrenic patients suggests that if GABA transmission is impaired in schizophrenia, it is a local, but not global, phenomenon.

Adult↗
PubMed1997

Learned helplessness increases 5-hydroxytryptamine1B receptor mRNA levels in the rat dorsal raphe nucleus.

Learned helplessness is a behavioral condition induced by exposure to inescapable stress that models aspects of stress-related disorders including depression and posttraumatic stress disorder, and has been associated with diminished serotonin release in the rat frontal cortex. Our hypothesis was that presynaptic 5-hydroxytryptamine1B (5-HT1B) receptors, which inhibit the synthesis and release of serotonin in nerve terminals, may be increased in learned helplessness. Postsynaptic 5-HT1B mRNA hybridization levels in the hippocampus or frontal cortex were unchanged following induction of learned helplessness; however, presynaptic 5-HT1B mRNA hybridization signal in the dorsal raphe nucleus of helpless rats was 25% higher than control values. There was no change in dorsal raphe serotonin transporter mRNA level. The detection of increased 5-HT1B mRNA levels in the dorsal raphe nucleus suggests an increased capacity to synthesize presynaptic 5-HT1B receptors and could account for diminished serotonin neurotransmission in learned helplessness.

Animals↗
PubMed1997

Plasma gamma-aminobutyric acid (GABA) predicts outcome in patients with alcohol dependence.

1. Previous studies have suggested that low plasma GABA levels (< or = 100 pmol/ml) may characterize a subset of patients with alcohol dependence. 2. In order to assess the clinical relevance of this biologic finding, the authors followed 49 alcohol dependent patients for up to 18 months following inpatient treatment. Treatment outcome was assessed by continuous abstinence and continued contact with research personnel. 3. Alcohol dependent patients with low plasma GABA had significantly better outcome than patients with plasma GABA in the normal control range (101-150 pmol/ml). 4. These findings suggest that plasma GABA measures may prove to be clinically useful in identifying alcohol dependent patients at risk for relapse.

Alcoholism↗
PubMed1997

Growth hormone response to the GABAB agonist baclofen in major depressive disorder.

Growth hormone (GH) response to the gamma-aminobutyric acid B receptor agonist, baclofen, was measured in 16 male patients with major depressive disorder and in 16 age-matched healthy male controls. No significant differences were found in the GH response to baclofen between the depressed patients and controls. On repeat testing, the GH response to baclofen showed significant retest reliability in both groups. There was no significant correlation between serum baclofen levels and the GH response to baclofen. Age significantly correlated with GH response, with older subjects having lower GH response to baclofen. These data do not suggest that a blunted GH response to baclofen. represents a specific neuroendocrine feature of major depression.

Adult↗
PubMed1997

Benzodiazepine prevention of swim stress-induced sensitization of cortical biogenic amines: an in vivo microdialysis study.

In vivo microdialysis was used to determine the effect of diazepam, flumazenil and FG-7142 upon the biogenic amine response to acute and repeated swim stress in the medial prefrontal cortex of the rat. Acute swim stress increased norepinephrine levels, although dopamine and serotonin levels remained stable. Upon re-exposure to swim stress twenty-four hours later, sustained increases (200-300% of baseline) in all three biogenic amines were detected. This enhanced response to re-stress was not seen in rats pretreated with either a benzodiazepine: agonist (diazepam, 2 mg/kg), an antagonist (flumazenil, 10 mg/kg), or an inverse agonist (FG-7142, 10 mg/kg) given prior to the first swim stress. Therefore, the sensitization of biogenic amine response to re-stress may be prevented by compounds which differ in their activity at the benzodiazepine receptor.

Animals↗
PubMed1997

Plasma GABA in children and adolescents with mood, behavior, and comorbid mood and behavior disorders: a preliminary study.

Plasma GABA concentrations (pGABA) were measured in 115 inpatients (aged 7-17) with child psychiatric disorders. Group mean pGABAs were compared for 38 patients with mood disorders only (MOOD), 29 with behavior disorders only (BEH), 48 with comorbid mood and behavior disorders (MOOD + BEH), and 14 normal controls (CON, aged 14-17). The BEH group was characterized by (a) high mean pGABAs (157 vs. 133 pmol/ml), (b) lower mean pGABAs in BEH subjects who had been receiving pharmacotherapy with SSRIs or other medications (p < 0.026), and (c) decreased pGABA with increasing age (p = 0.019). These features were not found in controls or in groups of patients with mood disorders (MOOD or MOOD + BEH). Elevated mean pGABA in the BEH group appeared specifically in patients with comorbid CD and ADHD, not in patients with ADHD or CD alone (p = 0.004). No patient in BEH (or CON) had pGABA below 100 pmol/ml, but low pGABAs were found in 15% of MOOD patients (who had no behavior disorder) and in 16% of MOOD + BEH patients. Pharmacotherapy did not change pGABAs in the MOOD or the MOOD + BEH groups. No pGABA differences were found among the anxiety disorders, either alone or with mood or behavior comorbidity. The finding that plasma GABA levels are elevated in nonmedicated behavior disorders that present in the absence of mood disorders, and appear to lower following medication treatments, merits increased attention to the pharmacological study of nonaffective behavior disorders.

Adolescent↗
PubMed1996

Whole-blood serotonin in children and adolescents with mood and behavior disorders.

Whole-blood serotonin (5-hydroxytryptamine, 5-HT) levels were measured in 118 children and adolescents with DSM-III-R mood disorders (n = 30) or behavior disorders (n = 27), a mixed group who met criteria for both mood and behavior disorders (n = 47), and a small sample of normal control subjects (n = 14). The patients were selected from consecutive admissions to an inpatient state hospital setting and the control subjects were recruited from a local high school. Levels of whole-blood 5-HT were significantly higher in the behavior disorder group (193 +/- 120) than in the mood disorder (122 +/- 83) or mixed mood and behavior (137 +/- 95) patient groups, but did not differ from control levels (170 +/- 48). A subsample of patients irrespective of diagnostic classification who had been on a selective serotonin reuptake inhibitor (SSRI) before admission had significantly lower whole-blood 5-HT concentrations (97.8 +/- 78.4) than those in patients who had been receiving some other type of psychotropic medication at admission (159.8 +/- 109.2) and from those in unmedicated patients (161.9 +/- 101.4). The 5-HT concentrations for patients receiving non-SSRI psychotropic medications did not differ from those of unmedicated patients. The frequency analysis of 5-HT concentration by psychiatric disorder group suggests that patients with mood disorders have the lowest values (below 100 ng/ml) and patients with behavior disorders have the highest values (above 300 ng/ml). Levels in the limited sample of normal subjects were all between 100 and 300 ng/ml. These findings were not accounted for by age, sex, gender, race, or season and lend support to accumulating research on simple neurobiological indicators in blood that help to distinguish these child/adolescent psychiatric disorders from each other and from individuals without these disorders.

Adolescent↗
PubMed1996

Effect of benzodiazepines on plasma levels of homovanillic acid in anxious patients and control subjects.

The effects of four logarithmically increasing doses of intravenous diazepam or placebo on plasma homovanillic acid (HVA) were determined in benzodiazepine-naive patients with panic disorder (PD) or generalized anxiety disorder (GAD), and in healthy controls. Plasma HVA was measured at baseline and 3 min after the first and fourth doses of diazepam/placebo. Mean baseline plasma HVA levels were significantly lower in PD patients compared with GAD patients and controls. Although plasma HVA levels decreased significantly with time in all groups, there was no diazepam effect. This study suggests that low dopaminergic activity may occur in a subset of anxious patients (PD), and that diazepam does not significantly affect dopaminergic activity as measured by plasma HVA in humans.

Adult↗
PubMed1996

Plasma levels of gamma-aminobutyric acid and panic disorder.

Low levels of gamma-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.

Adult↗
PubMed1996

Growth hormone response to baclofen: a comparison of 10-mg and 20-mg doses in healthy men.

Growth hormone (GH) response and baclofen levels were measured in seven healthy adult men following a 10-mg and a 20-mg dose of oral baclofen (gamma-aminobutyric acidB agonist) to determine the preferred dose in baclofen challenge studies. Multivariate analysis of variance (ANOVA) with repeated measures revealed no differences between the doses. However, when a univariate ANOVA with repeated measures was performed for each dose, the 10-mg dose showed no significant GH response over time, whereas the 20-mg dose showed a significant GH response over time. The average delta GH (change in GH from baseline) was 7.84 ng/ml (SD = 10.17) for the 10-mg dose and 3.34 ng/ml (SD = 3.64) for the 20-mg dose. The variability in the delta GH response to the 10-mg dose was significantly greater than the response to the 20-mg dose of baclofen. This variance in GH response was not explained by the differences in serum baclofen levels. Thus, a 20-mg baclofen dose appears to be preferable to a 10 mg-dose in baclofen challenge studies.

Adult↗
PubMed1996

Plasma GABA predicts acute response to divalproex in mania.

Bipolar I, manic phase inpatients were treated with divalproex sodium, lithium, or placebo in a previously reported parallel group multicenter, double-blind, randomized, controlled acute phase treatment trial. Plasma concentrations of gamma aminobutyric acid (GABA) were measured before and after treatment. Higher pretreatment plasma GABA levels were significantly (p = .04) related to a better clinical response to divalproex (n = 19). Pretreatment plasma GABA levels did not correlate with response to either lithium (n = 13) or placebo (n = 31). Following treatment with divalproex sodium, plasma GABA levels decreased significantly (p < .05), compared to placebo. Pretreatment plasma GABA levels were not related to overall severity of manic symptoms. Plasma GABA may predict response to pharmacologic agents acting on the GABA system.

Adult↗
PubMed1996

Effect of diazepam on plasma gamma-aminobutyric acid in sons of alcoholic fathers.

A subgroup of abstinent alcoholics, display low levels of plasma gamma-aminobutyric acid (GABA). Two previous studies of plasma GABA in sons of alcoholic fathers (SOAs) have yielded conflicting results. The aim of the current study was to measure plasma GABA both at baseline and after challenge with diazepam, a GABAA receptor agonist, in a group of SOAs already shown to display decreased eye movement, memory, and sedative effects of diazepam. Twenty-seven SOAs and 23 male control subjects received four logarithmically increasing doses of diazepam or placebo in randomized order on 2 days at least 1 week apart. Plasma GABA was measured at baseline and after the last dose. There were no significant differences between SOAs and controls in baseline plasma GABA levels. In the whole sample, there were significant correlations between baseline plasma GABA and both high novelty-seeking and low-harm avoidance scores on the Tridimensional Personality Questionnaire. Both SOAs and controls displayed decreases in plasma GABA over time on both testing days, but there was no effect of diazepam on plasma GABA and no significant difference between groups in plasma GABA response to diazepam. These results suggest that neither low plasma GABA at baseline nor altered plasma GABA response to diazepam is associated with increased genetic risk for alcoholism.

Adolescent↗
PubMed1996

Excitatory amino acid concentrations in the spinal dorsal horn of cats during muscle contraction.

In anesthetized cats, static hindlimb muscle contraction reflexly increases mean arterial pressure (MAP) and heart rate (HR). Pharmacological and immunohistochemical evidence suggests that excitatory amino acids are involved in the spinal transmission of this reflex. Using microdialysis and high-performance liquid chromatography technology, we tested the hypothesis that static contraction of the triceps surae muscle increases the extracellular concentration of glutamate (Glu) and aspartate (Asp) at the L7 level of the dorsal horn of the spinal cord. With the exception of the L7 dorsal root, the L5-S2 dorsal and ventral roots were cut ipsilateral to the contracting muscle. After the insertion of microdialysis probes and a 3-h recovery period, a 2-min static contraction was electrically evoked. MAP and HR increased by 53 +/- 8 mmHg and 20 +/- 4 beats/min. The concentration of Glu increased from 324 +/- 59 to 857 +/- 80 nM, whereas Asp increased from 199 +/- 57 to 499 +/- 113 nM. These results were repeatable, in that Glu and Asp rose by similar amounts in two subsequent contractions. In both of these latter contractions, MAP and HR were also significantly increased. By contrast, in a subset of cats whose L7 dorsal roots were cut after the first contraction, neither MAP, HR, Glu, nor Asp was significantly increased over baseline levels. These data demonstrate that static contraction of the hindlimb increases the extracellular concentration of Glu and Asp in the dorsal horn. In summary, the results from this study are in agreement with previous findings suggesting that excitatory amino acids are involved in the spinal transmission of sensory information from the hindlimb muscle.

Animals↗