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Biomedical subjects

F Petty

Publications and source records attributed to F Petty.

At least 19 recordsLinked to original sources
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↗
PubMed1999

Adrenergic receptor function in panic disorder. I. Platelet alpha 2 receptors: Gi protein coupling, effects of imipramine, and relationship to treatment outcome.

Various studies suggest alpha 2-adrenergic receptor (alpha 2AR) dysregulation in panic disorder (PD). Platelet alpha 2-AR exist in high- and low-conformational states as a function of their coupling to Gi protein. alpha 2AR coupling is important in signal transduction and is modulated by antidepressants. alpha 2AR density in the high- and low-conformational states, agonist affinity, and coupling efficiency were investigated in 21 healthy controls, 21 drug-free PD patients, and eight imipramine-treated patients using norepinephrine displacement of 3H-yohimbine binding. Percentage of receptors in the high-conformational state (%RH) and the ratio of the agonist dissociation constant to the receptor in the low-/high-conformational state (KL/KH), calculated from displacement experiments, were used as coupling indices. Patients had high alpha 2AR density in both conformational states. %RH and KL/KH ratio were significantly different, particularly in patients with Hamilton scale for depression (HAMD) scores > or = 15. Imipramine treatment (29 weeks) had no effect on alpha 2AR density or coupling, despite improvement in anxiety ratings. High pretreatment alpha 2AR density and coupling predicted low severity of anxiety after treatment. Increased alpha 2AR density and abnormal coupling may represent an adaptive mechanism or trait marker in PD.

Adult↗
PubMed1999

Clinical practice guidelines for bipolar disorder from the Department of Veterans Affairs.

BACKGROUND: For the last several years, the Department of Veterans Affairs (VA) has been involved in the development of practice guidelines for major medical, surgical, and mental disorders. This article describes the development and content of the VA-Clinical Practice Guidelines for Bipolar Disorder, which are available in their entirety on the Journal Web site (http://www. psychiatrist.com). METHOD: A multidisciplinary work group composed of content experts in the field of bipolar disorder and practitioners in general clinical practice was convened by the VA's Office of Performance and Quality and the Mental Health Strategic Health Group. The work group was instructed in algorithm development and methods of evidence evaluation. Draft guidelines were developed over the course of 6 months of meetings and conference calls, and that draft was then sent to nationally prominent content experts for final critique. RESULTS: The Bipolar Guidelines are part of the family of the VA Clinical Guidelines for Management of Persons with Psychosis and consist of explicit algorithms supplemented by annotations that explain the specific decision points and their basis in the scientific literature. The guidelines are organized into 5 modules: a Core Module for diagnosis and assignment to mood state plus 4 treatment modules (Manic/Hypomanic/Mixed Episode, Bipolar Depressive Episode, Rapid Cycling, and Bipolar Disorder With Psychotic Features). The modules specify particular diagnostic and treatment tasks at each step, including both somatotherapeutic and psychotherapeutic interventions. CONCLUSION: The VA Bipolar Guidelines are designed for easy clinical reference in decision making with individual patients, as well as for use as a scholarly reference tool. They also have utility in training activities and quality improvement programs.

American Heart Association↗
PubMed1998

Nicotinic receptor desensitization and sensory gating deficits in schizophrenia.

BACKGROUND: Nicotinic receptor dysfunction is a possible mechanism of the abnormal sensory gating observed in schizophrenia with the P50 auditory event-related potential. Although nicotinic receptors normally desensitize after activation by acetylcholine or nicotine, pathologically increased desensitization might cause receptor dysfunction in schizophrenia. To examine this possibility, central cholinergic neuronal activity was diminished by allowing schizophrenic patients to sleep briefly, after which they experienced a transient period of normal P50 gating, consistent with receptor resensitization during the absence of cholinergic stimulation. A critical test of the mechanism is whether this resensitization is blocked by concurrent administration of nicotine, which would provide continuous receptor stimulation. METHODS: Six schizophrenic patients repeated the sleep experiment during nicotine exposure from a dermal patch, in a double-blind, placebo-controlled design. RESULTS: The normalization of P50 gating immediately postsleep was replicated in the placebo arm, but this effect was decreased in all six patients during exposure to nicotine. CONCLUSIONS: The results suggest that nicotinic receptor desensitization is responsible for the loss of P50 gating in schizophrenia.

Acoustic Stimulation↗
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↗
PubMed1998

Extrapyramidal adverse effects associated with sertraline.

1. Extrapyramidal adverse effects have been reported with the selective serotonin re-uptake inhibitor (SSRI) antidepressants, particularly fluoxetine and paroxetine. 2. Recently, the SSRI sertraline has also been associated with treatment-emergent extrapyramidal syndrome (EPS) side effects. A review of the literature identified thirteen published cases of sertraline-induced EPS, several of which were confounded by the presence of concomitant medications, and few reported quantitative data using rating scales. 3. We present another case of EPS associated with sertraline in which daily ratings were obtained using the Abnormal Involuntary Movement Scale. 4. This review and case report add to the small but growing literature suggesting that sertraline, like the other SSRI's may cause significant extrapyramidal side-effects. These movement disorders presumably occur through an interaction between serotonergic and dopaminergic pathways, providing an important clinical correlation of interactions between these neurotransmitter systems.

Akathisia, Drug-Induced↗
PubMed1998

A survey of sexual trauma treatment provided by VA medical centers.

In 1992 Congress mandated the Department of Veterans Affairs to provide treatment to veterans traumatized by sexual assault experienced during active military duty. A 1995 survey of how VA medical centers had responded to this mandate indicated that 51 percent of 136 centers had established a sexual trauma treatment team. Teams treated a mean+/-SD of 5.5+/-10 patients a week, and newly referred veterans waited a mean of 3.3+/-4 days for evaluation. Teams varied in the discipline mix of providers, training, organizational structure, services offered, and caseload. Medical centers without dedicated treatment teams offered nonspecialized services to sexually traumatized veterans or offered community referrals for sexual trauma treatment services.

Crisis Intervention↗
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

Static muscle contraction elicits a baroreflex-dependent increase in glutamate concentration in the ventrolateral medulla.

In anesthetized cats, static contraction of the hindlimb reflexly increases mean arterial pressure (MAP). This cardiovascular adjustment is reduced by the arterial baroreflex. Both of these reflex responses are mediated through activation of ventrolateral medullary (VLM) regions. We tested the hypothesis that the concentration of glutamate (Glu) increases in the caudal ventrolateral medulla (cVLM) during static hindlimb contractions in anesthetized cats, and that barodenervation reduces this elevation in Glu levels. Static contractions of the triceps surae muscle of one hindlimb were evoked by electrical stimulation of the peripheral ends of cut L7 and S1 ventral roots. After the insertion of the microdialysis probes and a 3-h recovery period, a 2-min static contraction increased MAP by 47 +/- 7 mmHg. The concentration of Glu increased from 606 +/- 189 to 1042 +/- 228 nM. These results were repeatable in that Glu, as well as MAP, rose by a similar amount in two subsequent contractions. By contrast, in a subset of cats paralyzed prior to the third contraction, neither MAP nor Glu were significantly increased over baseline levels during the third stimulation period. In a third group of cats, hindlimb contraction increased MAP and Glu levels. However, the Glu release was attenuated in subsequent contractions after these cats were barodenervated. During the same periods of stimulation, the denervation accentuated the rise in MAP. These data demonstrate that static contraction of the hindlimb increases the extracellular concentration of Glu in the cVLM. Further, our study implicates this neurotransmitter in the baroreflex mediated reduction of the pressor reflex response to static muscle contraction.

Animals↗
PubMed1997

Depression during mania. Treatment response to lithium or divalproex.

BACKGROUND: Little information exists from controlled studies about clinical characteristics that predict treatment response in mania. The presence of depressive symptoms during manic episodes may be associated with poor response to psychopharmacological treatments. This is an investigation of the relation between depressive symptoms and treatment response in acute manic episodes. METHODS AND DESIGN: In a parallel-group, double-blind study, 179 patients hospitalized for acute manic episodes were randomized to receive divalproex sodium, lithium carbonate, or placebo (ratio, 2:1:2). The study was carried out at 9 academic medical centers. Patients had comprehensive evaluations of behavior and symptoms before and during 3 weeks of treatment. The primary outcome measure, change in mania factor scores derived from the Schedule for Affective Disorders and Schizophrenia: Change Version, was compared in patients with and without depressive symptoms at baseline according to nurse- or physician-rated scales. RESULTS: Depressive symptoms were associated with poor antimanic response to lithium and with better response to divalproex. This was not due to differences in overall severity of illness, substance abuse, gender, age, or history. CONCLUSIONS: These data suggest that even a modest level of pretreatment depression-related symptoms is a robust predictor of lithium nonresponse, and is associated with better response to divalproex. Although their overall efficacy in acute mania is similar, lithium and divalproex may be most effective in clinically and biologically distinct groups of patients.

Adult↗
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↗
PubMed1997

Post-traumatic stress disorder and serotonin: new directions for research and treatment.

The overlap in clinical phenomenology and morbidity between post-traumatic stress disorder (PTSD) and such conditions as major depression, anxiety disorders and aggression, in which a serotonin dysfunction is implicated, suggests a role for serotonin in the pathophysiology of PTSD. In this paper, we review current knowledge concerning the role of serotonergic mechanisms and interventions in PTSD. Since there is no clearly effective pharmacologic intervention for this disorder, the underlying neurochemical dysfunction needs to be carefully defined so that more effective treatment can be developed. Preclinical and clinical studies of the serotonergic mechanisms in the pathophysiology of PTSD and treatment trials involving serotonergic agents are limited, but indicate considerable promise. Further investigation of a serotonergic dysfunction in PTSD and of its treatment with serotonergic agents is warranted.

Humans↗
PubMed1997

Maintenance clinical trials in bipolar disorder: design implications of the divalproex-lithium-placebo study.

Maintenance studies in bipolar disorder have received increased attention in recent years. The interest is driven by apparent contradictions between results of early placebo-controlled trials of lithium and recent open studies, as well as interest in a new group of drugs with mood-stabilizing properties. The multiple outcome indices that require attention in prophylactic bipolar disorder studies add a dimension not present in acute studies of bipolar disorder. We present the methodology of a recently completed randomized, double-blind, placebo-controlled, parallel-group comparison of divalproex and lithium. We examine the consequences of salient design features, along with their implications for future studies. A fundamental conclusion is that such maintenance studies should be designed and executed to emphasize enrollment of patients with relatively active, severe forms of the illness. This goal is not achieved simply, as inherent features of long-term, placebo-controlled studies drive recruitment and enrollment in the direction of patients with milder forms of bipolar disorder. Attention to the frequency of both manic and depressive episodes and the severity of an index manic episode may aid in the selection of patients most suitable for studies designed to achieve adequate statistical power.

Adult↗