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Biomedical subjects

G L Kramer

Publications and source records attributed to G L Kramer.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1996

Low plasma gamma-aminobutyric acid levels during the late luteal phase of women with premenstrual dysphoric disorder.

OBJECTIVE: Plasma gamma-aminobutyric acid (GABA) levels have been reported to be low in some patients with major depressive disorder. Premenstrual dysphoric disorder is often associated with major depressive disorder. Therefore, the authors sought to determine whether women with premenstrual dysphoric disorder with or without prior major depressive disorder also had low plasma GABA levels. METHOD: Plasma GABA levels were measured in 27 women with premenstrual dysphoric disorder and 21 comparison women during the the mid-follicular and late luteal phases of the menstrual cycle. RESULTS: In comparison women, plasma GABA levels increased from the mid-follicular to the late luteal phase. Women with premenstrual dysphoric disorder and a past history of major depressive disorder had low plasma GABA levels during both phases. In women with premenstrual dysphoric disorder but no past major depressive disorder, plasma GABA levels decreased from the nonsymptomatic, mid-follicular phase to the symptomatic, late luteal phase. CONCLUSIONS: Decreased GABA function may represent a common biological link between subtypes of depressive and premenstrual dysphoric disorders. A trait in major depressive disorder and a state-dependent decrease in premenstrual dysphoric disorder might imply a possible continuum between the two disorders.

Adult↗
PubMed1996

Serotonin dysfunction disorders: a behavioral neurochemistry perspective.

The spectrum of efficacy of the serotonin selective reuptake inhibitor (SSRI) antidepressant drugs continues to expand. In fact, no psychiatric syndrome seems to worsen with these agents, and few studies fail to demonstrate clinical improvement in some patients, regardless of any nosologic nicety, such as precise DSM diagnosis. This suggests that the biological rubric of psychopathology is dimensional rather than categorical. New research using in vivo microdialysis shows differences in neurochemistry among SSRIs, wherein fluoxetine blocks reuptake of dopamine and norepinephrine, as well as serotonin, in medial prefrontal cortex, and fluvoxamine has a relatively more selective neurochemical profile. In the animal model of learned helplessness, which is a biobehavioral model for stress-induced anxiety causing depression, the SSRIs including fluvoxamine prevent helplessness. From these and other data, a neurotransmitter balance theory of biopsychopathology is formulated. In this hypothetical construct, dopamine, norepinephrine, and GABA modulate thought, anxiety, and mood, respectively. Serotonin is a stabilizing agent, which assists in returning the mind to its homeostatic setpoint.

Animals↗
PubMed1996

Valproate as an antidepressant in major depressive disorder.

Thirty-three outpatients who met DSM-IV criteria for major depressive disorder (MDD) with no history of manic or hypomanic symptomatology were enrolled in an 8-week open trial of valproate. By Week 4, 15 of the 28 completers (54%) demonstrated a significant clinical response as defined by a score reduction of 50 percent or more or a total score of 9 or lower on the Hamilton Rating Scale for Depression (HRSD). Mean HRSD scores of the completers decreased 48.8 percent at Week 4 (p < .0001). At Week 8, 19 of the 22 completers (86%) showed a significant response. Mean HRSD scores decreased from 22 +/- 5 at baseline to 7 +/- 4 at Week 8 (p < .0001). With the intent-to-treat analysis at Week 8, 66 percent were responders, and total group mean HRSD scores decreased 55 percent (p < .0001). The data suggest that valproate may be an effective treatment for MDD. Double-blind, placebo-controlled trials are needed to further document its efficacy in the treatment of MDD.

Adult↗
PubMed1995

Levels of gamma-aminobutyric acid in cerebrospinal fluid and plasma during alcohol withdrawal.

Aminobutyric acid (GABA) is implicated in the biochemical pathophysiology of alcohol intoxication, dependence and withdrawal. We therefore measured GABA in both cerebrospinal fluid (CSF) and plasma from 14 male alcohol-dependent patients during acute alcohol withdrawal (day 1) and again after 21 days of inpatient treatment (day 21). Plasma GABA levels on admission correlated with indices of liver function. When corrected for differences in liver function, plasma levels of GABA levels on day 1 were significantly higher than on day 21. CSF GABA concentrations were also significantly higher during withdrawal compared with concentrations after 3 weeks of abstinence. The change in plasma GABA levels correlated significantly with the change in CSF GABA levels, although there was no correlation between plasma and CSF levels at either time. These findings demonstrate that changes in CSF GABA may be reflected in plasma GABA, and they highlight the potential importance of the GABA system in alcohol dependence and withdrawal.

Adult↗
PubMed1995

Stability of plasma GABA at four-year follow-up in patients with primary unipolar depression.

The biology of mood disorders involves gamma-aminobutyric acid (GABA), a neurotransmitter whose levels in plasma likely reflect brain GABA activity. Previous research has shown that a subset of patients with primary unipolar major depression have low plasma GABA levels, which parallels findings from studies of cerebrospinal fluid. We have completed a 4-year follow-up on 46 male patients with primary unipolar depression. Plasma levels of GABA were stable over this time. For the group, mean plasma GABA levels on follow-up did not change significantly from entry levels. Plasma GABA levels measured on follow-up were significantly (p < .001) correlated with entry levels. Patients with low plasma GABA levels (< 100 pmol/ml) on entry into the study were likely to remain low on follow-up, and patients with plasma GABA levels in the control range (> or = 100 pmol/ml) at entry similarly remained in this category (chi 2 = 7.23, p = .007). This was true whether or not the patient had recovered from depression on follow-up. Levels of plasma GABA did not significantly correlate with severity of depression at either entry (p = .40) or follow-up (p = .52), nor was there a significant correlation between change in plasma GABA and change in the 17-item Hamilton Depression Rating Scale score from entry to follow-up (p = .89). These data are consistent with the notion that plasma GABA is independent of clinical state in patients with primary unipolar depression. Low plasma GABA may be a trait marker of illness in a subset of patients with mood disorder.

Adult↗
PubMed1994

In vivo biogenic amine efflux in medial prefrontal cortex with imipramine, fluoxetine, and fluvoxamine.

In vivo brain microdialysis was used to determine the effects of the standard tricyclic antidepressant imipramine and the two selective serotonin reuptake inhibitors (SSRIs) antidepressants, fluoxetine and fluvoxamine, on extracellular levels of norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat medial prefrontal cortex. When given intraperitoneally (IP), imipramine increased NE in the microdialysis perfusate, and elevated DA and 5-HT to a lesser extent. Similar dose-dependent increases in DA and 5-HT were detected after IP fluoxetine, although NE was less affected. In contrast, IP fluvoxamine produced no change in basal NE nor DA, although a large increase in 5-HT occurred at an intermediate dose. When administered directly into cortex, all three antidepressants increased 5-HT by the same amount in a dose-dependent fashion. Intracortical imipramine and fluoxetine increased NE, and fluoxetine and fluvoxamine both increased DA, with fluoxetine doing so at a lower concentration. These data suggest that the SSRIs are not entirely selective for serotonin in vivo.

Animals↗