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Biomedical subjects

A J Rush

Publications and source records attributed to A J Rush.

At least 73 records · Page 4Linked to original sources

Toward a redefinition of psychiatric emergency.

OBJECTIVE: To compare three methods for rating legitimate use of psychiatric emergency services (PES) in order to develop criteria that can differentiate appropriate from inappropriate PES service requests. METHOD: Ratings of PES visits by treating physicians and ratings of the same visits made during review of medical records. STUDY DESIGN: Two previously used methods of identifying justified PES service use were compared with the treating physician's rating of the same: (1) hospitalization as visit outcome and (2) retrospective chart ratings of visit characteristics using traditional medico-surgical criteria for "emergent" illness episodes. DATA EXTRACTION METHODS: Data were extracted through use of a physician questionnaire, and medical and administrative record review. PRINCIPAL FINDINGS: Agreement between the methods ranged from 47.1 percent to 74.1 percent. A total of 21.7 percent of visits were rated as true health "emergencies" by the traditional definition, while 70.4 percent of visits were rated as "necessary" by treating physicians, and 21.0 percent resulted in hospitalization. Acuteness of behavioral dyscontrol and imminent dangerousness at the time of the visit were common characteristics of appropriate use by most combinations of the three methods of rating visits. CONCLUSIONS: The rating systems employed in similar recent studies produce widely varying percentages of visits so classified. However, it does appear likely that a minimum of 25-30 percent of visits are nonemergent and could be triaged to other, less costly treatment providers. Proposed criteria by which to identify "legitimate" psychiatric emergency room treatment requests includes only patient presentations with (a) acute behavioral dyscontrol or (b) imminent dangerousness to self or others.

Adolescent↗

Platelet alpha2A-adrenoceptor function in major depression: Gi coupling, effects of imipramine and relationship to treatment outcome.

Studies suggest alpha2A-adrenoceptors (alpha(2A)AR) dysregulation in major depressive disorder (MDD). Platelet alpha(2A)ARs exist in high- and low-conformational states that are regulated by Gi protein. Although alpha(2A)AR coupling to Gi protein plays an important role in signal transduction and is modulated by antidepressants, it has not been previously investigated. Alpha2AR density in the high- and low-conformational states, agonist affinity and coupling efficiency were investigated in 27 healthy control subjects, 23 drug-free MDD patients and 16 patients after imipramine treatment using [3H]yohimbine saturation and norepinephrine displacement of [3H]yohimbine binding experiments. Coupling measures were derived from NE-displacement experiments. Patients had significantly higher alpha(2A)AR density, particularly in the high-conformational state, than control subjects. Coupling indices were normal in patients. High pre-treatment agonist affinity to the receptor in the high-conformational state and normal coupling predicted positive treatment outcome. Decreased coupling to Gi predicted a negative treatment outcome. Imipramine induced uncoupling (-11%) and redistribution of receptor density in treatment responders only, but had no effect on alpha(2A)AR coupling or density in treatment non-responders. Increased alpha(2A)AR density may represent a trait marker in MDD. The results provide indirect evidence for abnormal protein kinase A (PKA) and protein kinase C (PKC) in MDD which may be pursued in future investigations.

Adrenergic Uptake Inhibitors↗

Neutrophil beta(2)-adrenoceptor function in major depression: G(s) coupling, effects of imipramine and relationship to treatment outcome.

Abnormal beta(2)-adrenoceptor density and beta(2)-adrenoceptor-mediated cyclic adenosine monophosphate (cAMP) responses were inconsistently reported in major depressive disorder. Tricyclic antidepressants downregulate beta-adrenoceptor density and decrease coupling to G(s) protein. Abnormal beta-adrenoceptor coupling may exist in major depressive disorder and may relate to treatment response. We investigated beta(2)-adrenoceptor coupling to G(s) protein in 25 controls, 23 major depressive disorder drug-free patients and 16 major depressive disorder patients after chronic imipramine treatment using agonist displacement experiments. Pretreatment beta(2)-adrenoceptor coupling and density were normal in patients as a whole. Chronic imipramine induced beta(2)-adrenoceptor uncoupling. This effect was observed in treatment responders who had increased beta(2)-adrenoceptor density in the high-conformational state and supercoupling prior to treatment. Beta(2)-adrenoceptor density decreased after imipramine treatment. Treatment non-responders had seemingly normal pretreatment beta(2)-adrenoceptor function, which was not changed by imipramine. Differences in beta(2)-adrenoceptor regulation in major depressive disorder may underlie treatment response. The results indirectly implicate abnormal agonist-mediated beta(2)-adrenoceptor gene expression, protein kinase A, and protein kinase C in major depressive disorder.

Adrenergic Uptake Inhibitors↗

Characteristics of norepinephrine and clonidine displacement of [3H]yohimbine binding to platelet alpha2-adrenoreceptors in healthy volunteers.

Clonidine's estimates of platelet alpha2-adrenoreceptor (alpha2AR) density are substantially lower than yohimbine's. This discrepancy could have contributed to inconsistent results from studies on the role of alpha2AR in depression. Furthermore, few studies have investigated the relative distribution of alpha2AR between the high- and low-affinity states or their Gi protein coupling. [3H]yohimbine saturable binding to platelet alpha2AR, its displacement by norepinephrine and clonidine, and the effects of Gpp(NH)p on agonist displacement curves were investigated in 11 healthy volunteers. Clonidine estimates of alpha2AR density were close to norepinephrine estimates, and both were strongly correlated. Clonidine's K(L)/K(H) ratio was lower than norepinephrine's, consistent with its partial agonist nature. Norepinephrine and clonidine displacement curves revealed two affinity states. Gpp(NH)p induced a significant rightward shift to a single low-affinity state. When used in combination with a specific antagonist, clonidine's estimates of alpha2AR density were similar to those of norepinephrine's, and both were higher than previously reported, when clonidine was used alone. Re-evaluation of previous studies on alpha2AR in depression using clonidine is needed. The combined use of antagonist-saturation and agonist-displacement experiments to examine possible dysregulation in alpha2AR coupling to Gi protein in psychiatric disorders is recommended.

Adult↗

Platelet alpha2-adrenergic receptor coupling efficiency to Gi protein in subjects with post-traumatic stress disorder and normal controls.

Low platelet membrane alpha2-adrenergic receptor (alpha2AR) density and low basal and forskolin-stimulated cyclic adenosine monophosphate responses, which have been reported in post-traumatic stress disorder (PTSD), suggest either abnormal alpha2AR coupling to G(i) protein or dysregulation in post-receptor signal transduction mechanisms. alpha2AR density in the high- and low-conformational states, agonist affinity in both states and coupling to G(i) protein were investigated in 23 drug-free combat PTSD patients and 25 normal controls. alpha2AR coupling measures were not different between PTSD patients and controls. Total alpha2AR density was higher in PTSD patients than controls, due to a higher density of the receptor in the high-conformational state. There were no differences in agonist affinity to the receptor in either conformational state. Results rule out dysregulation in alpha2AR coupling to G(i) protein. Studies of post-receptor signal transduction mechanisms are warranted.

Adult↗

Neutrophil beta2-adrenergic receptor coupling efficiency to Gs protein in subjects with post-traumatic stress disorder and normal controls.

The symptomatology of post-traumatic stress disorder (PTSD) involves sympathetic hyperarousal. Several of these sympathetic symptoms are mediated through end-organ beta2-adrenergic receptors (beta2AR). Increased sympathetic activity in PTSD could therefore be due to increased betaAR function. This study investigated betaAR function in 30 healthy controls and 20 drug-free PTSD patients. BetaAR binding studies were conducted using antagonist-saturation and agonist-displacement experiments. Measures of beta2AR coupling to Gs protein were derived from agonist-displacement experiments. PTSD patients had significantly higher beta2AR density particularly in the high-conformational state and higher beta2AR coupling than controls, as reflected in a higher percentage of receptors in the high conformational state and a higher ratio of the agonist dissociaton constant from the receptor in the low/high-conformational state. Increased betaAR function in PTSD is consistent with the symptomatology of this disorder. Increased betaAR density and coupling may be consistent with downregulation of betaAR density and uncoupling by antidepressants and may underlie their partial efficacy in PTSD. Dysregulation in Gs protein function is postulated and, agonist-mediated regulation of betaAR expression and/or betaAR kinase activity in PTSD should be investigated in future studies.

Adult↗

Clinical and economic impact of newer versus older antipsychotic medications in a community mental health center.

This pilot study was conducted to compare both the clinical effectiveness and the treatment costs of newer (atypical) antipsychotic medications (clozapine and risperidone) with those of older (classic) neuroleptic medications (chlorpromazine and haloperidol) for psychosis in a community mental health care setting. The study used a retrospective, uncontrolled, open, nonrandomized, within-subjects design and relied on medical records as a data source for 37 clients. All clients received older antipsychotics for at least 1 year, newer antipsychotics for a transition period of 3 months, and the newer agents for at least an additional year. The newer antipsychotic medications were more effective and less costly (total cost of care, $3000 less per client per year [1997 dollars]) than the older medications. Effect-size estimates for the measured variables provide a guide for future research into the cost-effectiveness of these newer medications within the community mental health care setting. These findings can provide policy makers with guidance on treating people with major mental disorders in the most effective and efficient manner. Because of limited budgets, community mental health centers making the investment in newer, more expensive medications to improve client outcomes have to maintain the same or lower total cost of care. Results of the current study suggest that short-term investment in the newer medications by community mental health centers offers superior clinical effectiveness and lower long-term overall cost of care.

Adult↗

Prediction of response to fluoxetine and placebo in children and adolescents with major depression: a hypothesis generating study.

BACKGROUND: The results of multivariate analyses to identify potential predictors of response to fluoxetine or placebo separately in 96 child and adolescent outpatients with major depressive disorder from a recent controlled trial are presented. METHODS: A variety of clinical, demographic and laboratory factors were examined as possible predictors of response to fluoxetine or placebo using logistic regression models. RESULTS: No single variable or combination of variables strongly predicted response to fluoxetine. For the placebo group, a younger age, a shorter duration of depressive episode, and a lower socioeconomic status predicted response with an overall predictive power of 81%. CONCLUSIONS: This study is limited by the small sample size and should be considered hypothesis generating rather than confirming.

Adolescent↗

Age of onset in chronic major depression: relation to demographic and clinical variables, family history, and treatment response.

BACKGROUND: The clinical and etiological significance of the early-late onset distinction in chronic major depressive disorder was explored. METHOD: Subjects were 289 outpatients with DSM-III-R chronic major depression drawn from a multi-site study comparing the efficacy of sertraline and imipramine in the acute and long-term treatment of chronic depression. Patients received comprehensive evaluations using semi-structured interviews and rating scales. RESULTS: Early-onset chronic major depression was associated with a longer index major depressive episode and higher rates of recurrent major depressive episodes, comorbid personality disorders, lifetime substance use disorders, depressive personality traits, and a history of psychiatric hospitalization. In addition, more early-onset patients tended to have a family history of mood disorders. The early-late onset distinction was not associated with differences in symptom severity, functional impairment, or treatment response. LIMITATIONS: Family members were not interviewed directly; there were a large number of statistical comparisons; and interrater reliability of the assessments was not evaluated. CONCLUSIONS: Early-onset chronic major depression has a more malignant course and is associated with greater comorbidity than late-onset chronic major depression.

Adult↗

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↗

Effects of fluoxetine on the polysomnogram in outpatients with major depression.

This study investigated the effects of open-label fluoxetine (20 mg/d) on the polysomnogram (PSG) in depressed outpatients (n = 58) who were treated for 5 weeks, after which dose escalation was available (< or = 40 mg/d), based on clinical judgment. Thirty-six patients completed all 10 weeks of acute phase treatment and responded (HRS-D < or = 10). PSG assessments were conducted and subjective sleep evaluations were gathered at baseline and at weeks 1, 5, and 10. Of the 36 subjects who completed the acute phase, 17 were reevaluated after 30 weeks on continuation phase treatment and 13 after approximately 7 weeks (range 6-8 weeks) following medication discontinuation. Acute phase treatment in responders was associated with significant increases in REM latency, Stage 1 sleep, and REM density, as well as significant decreases in sleep efficiency, total REM sleep, and Stage 2 sleep. Conversely, subjective measures of sleep indicated a steady improvement during acute phase treatment. After fluoxetine was discontinued, total REM sleep and sleep efficiency were found to be increased as compared to baseline.

Adolescent↗

Hippocampal remodeling and damage by corticosteroids: implications for mood disorders.

Mood disorders are common, recurrent and disabling illnesses which are frequently associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation and memory loss. The hippocampus provides negative feedback to the HPA axis and has an important role in key aspects of spatial and declarative memory. Thus, hippocampal dysfunction could account for both the memory impairment and neuroendocrine abnormalities found in mood disorders. The critical role of the hippocampus in declarative memory, emotional processing, and vulnerability to stress has been demonstrated in both animal and human studies. Cellular processes in the hippocampus including long-term potentiation, neurogenesis, and dendritic remodeling are currently areas of intense study. Human studies report cognitive impairment consistent with hippocampal dysfunction in depression, bipolar disorder, Cushing's disease, and in those individuals receiving exogenous corticosteroids. This review examines data on the role of corticosteroids in hippocampal remodeling and atrophy in patients with mood disorders. Interventions to prevent or reverse the damaging effects of corticosteroids on the hippocampus are discussed.

Adrenal Cortex Hormones↗

Biological rhythm disturbance in depression: temporal coherence of ultradian sleep EEG rhythms.

BACKGROUND: Recent studies have suggested that major depressive disorders are associated with a breakdown in the organization of ultradian rhythm in sleep EEG. The present study used cross-spectral analysis of sleep EEG to confirm this finding, in a larger-scale study, evaluating the influence of gender and age on ultradian rhythms in depression. METHODS: Temporal coherence of ultradian (80-120 min) rhythms in beta, theta and delta, recorded from central and parietal sites, were compared in 120 symptomatic, unmedicated, depressed outpatients and 59 healthy normal controls. RESULTS: Few macro-architectural differences were noted between patients and controls. However, interhemispheric beta and theta coherence and intrahemispheric coherence between beta and delta rhythms were significantly lower in depressed patients. Coherence measures were lowest in women with depression and highest in men in the control group, but were not strongly influenced by age. Over 65% of depressed patients were > or = 2 standard deviations below normal on at least one coherence measure, in sharp contrast to less than 10% of patients on macro-architectural variables. CONCLUSIONS: It was concluded that dysregulation of ultradian rhythms characterizes the majority of depressed out-patients, primarily women, even when macro-architecture did not differentiate groups. The outcome of this study supports the view that the pathophysiology of depression is strongly influenced by gender. It was suggested that low temporal coherence in depression reflects a breakdown in the organization of sleep EEG rhythms within and between the two hemispheres.

Activity Cycles↗

Evidence for the segregation of a major gene for human plasma GABA levels.

Gamma-aminobutryic acid (GABA) is a major neurotransmitter in the central nervous system, and plasma levels of GABA may reflect brain GABA activity. In 35-40% of patients with mood disorders, plasma GABA levels are low compared to psychiatrically normal controls. Low plasma GABA in this subgroup of patients has characteristics of a biological trait marker for mood disorders. Low plasma GABA is also found in a subset of patients with alcohol dependence, but not in schizophrenia, anxiety, or eating disorders, suggesting some diagnostic specificity. Previous data from a small study of monozygotic twins are consistent with the hypothesis that plasma GABA levels are under genetic control. To better understand these mechanisms, we conducted a segregation analysis of plasma GABA levels in a sample of 157 individuals from 50 nuclear families. Analysis using the Class D regressive model indicated that the familial transmission of plasma GABA levels is compatible with the segregation of a recessive major gene. Our results suggest that plasma GABA levels are under single gene control. Future research should address the precise mechanisms which may account for the abnormality in GABA levels seen in a subset of patients with mood disorders.

Adolescent↗

The Texas Children's Medication Algorithm Project: report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Major Depressive Disorder.

OBJECTIVES: To develop consensus guidelines for medication treatment algorithms for childhood major depressive disorder (MDD) based on scientific evidence and clinical opinion when science is lacking. The ultimate goal of this approach is to synthesize research and clinical experience for the practitioner and to increase the uniformity of preferred treatment for childhood MDD. A final goal is to develop an approach that can be tested as to whether it improves clinical outcomes for children and adolescents with MDD. METHOD: A consensus conference was held. Participants included academic clinicians and researchers, practicing clinicians, administrators, consumers, and families. The focus was to review and use clinical evidence to recommend specific pharmacological approaches for treatment of MDD in children and adolescents. After a series of presentations of current research evidence and panel discussion, the consensus panel met, agreed on assumptions, and drafted the algorithms. The process initially addressed strategies of treatment and then tactics to implement the strategies. RESULTS: Consensually agreed-upon algorithms for major depressions (with and without psychosis) and comorbid attention deficit disorders were developed. Treatment strategies emphasized the use of selective serotonin reuptake inhibitors. The algorithm consists of systematic strategies for treatment interventions and recommended tactics for implementation of the strategies, including medication augmentation and medication combinations. Participants recommended prospective evaluation of the algorithms in various public sector settings, and many volunteered as sites for such an evaluation. CONCLUSIONS: Using scientific and clinical experience, consensus-derived algorithms for children and adolescents with MDD can be developed.

Adolescent↗

Structured diagnostic assessment and depot fluphenazine treatment of multiple suicide attempters in the emergency department.

The aim of this study was to compare the efficacy of two doses of monthly intramuscular (i.m.) injections of fluphenazine decanoate in reducing self-harm behaviours in outpatients with histories of multiple suicide attempts. Fifty-eight patients who presented to a psychiatric emergency service after an attempted suicide and who had histories of multiple suicide attempts, were randomized to receive monthly i.m. injections of fluphenazine decanoate. Thirty patients received monthly 12.5 mg ('low' dose), and 28 patients received monthly 1.5 mg ('ultra low' dose) under double-blind conditions. DSM-III-R diagnoses were obtained on all patients using the Structured Clinical Interview for DSM-III-R-Patient Version (SCID-P) and SCID for DSM-III-R Personality Disorders (SCID-II). Outcomes were assessed by the Parasuicide History Inventory and the Abnormal Involuntary Movement Scale, collected monthly for 6 months. Patients had an average of six current Axis I and 2.6 Axis II diagnoses, with borderline personality (85%) and alcohol dependence (58%) occurring most frequently in the sample. Both the low dose and ultra-low dose groups showed a marked reduction in self-harm behaviours. For 'serious' self-harm behaviours, there was a trend for a greater effect of the low dose over the ultra-low dose group, however, the differences did not reach statistical significance. A survival analysis indicated that the presence of 'acute' stressors at baseline and female sex were risk factors for continuing (post-randomization) 'serious' self-harm behaviours, while younger age and the absence of concurrent general medical conditions were risk factors for all self-harm behaviours.

Adult↗

Clinical outcome in a randomized 1-year trial of clozapine versus treatment as usual for patients with treatment-resistant illness and a history of mania.

OBJECTIVE: Case series and follow-up studies suggest that clozapine may have mood-stabilizing properties in addition to antipsychotic action in patients with schizoaffective disorder, bipolar type, and bipolar I disorder, but the generalizability of these findings is limited. This article describes a randomized, open study of clozapine add-on therapy versus treatment as usual for patients with treatment-resistant illness and a history of mania. METHOD: Thirty-eight patients meeting the DSM-IV criteria for schizoaffective or bipolar disorder that was deemed treatment-resistant were randomly assigned to clozapine add-on treatment (N = 19) or treatment as usual (no clozapine) (N = 19) and followed up for 1 year. Patients received monthly ratings on the Brief Psychiatric Rating Scale, Clinical Global Impression scale, Bech-Rafaelsen Mania Scale, Hamilton Depression Rating Scale, Scale for the Assessment of Positive Symptoms, Scale for the Assessment of Negative Symptoms, Abnormal Involuntary Movement Scale, and a 40-item side effect checklist. Differences between treatment groups were assessed according to a pattern-mix random-regression model. An additional analysis compared group differences in rating scale scores against relative time in the study. RESULTS: Significant between-group differences were found in scores on all rating scales except the Hamilton depression scale. Total medication use over 1 year significantly decreased in the clozapine group. No significant differences between groups in somatic complaints were noted. The subjects with nonpsychotic bipolar I disorder who received clozapine showed a degree of improvement similar to that of the entire clozapine-treated group. Clozapine dose was significantly higher for the patients with schizoaffective illness than for those with bipolar disorder. CONCLUSIONS: The results of this study support clozapine's independent mood-stabilizing property. They demonstrate that clozapine use was associated with significant clinical improvement relative to treatment as usual.

Adult↗

The Texas Medication Algorithm Project: development and implementation of the schizophrenia algorithm.

The Texas Medication Algorithm Project is a program designed to improve the quality of care of persons with serious mental disorders across sites in the Texas public mental health system and to create a uniform clinical environment from which cost estimates can be made. This paper describes the process of developing a pharmacological treatment algorithm for schizophrenia that addresses use of antipsychotics as well as other medications for side effects and co-existing symptoms. Input from clinicians, consultants, and consumers informed development of the algorithm, which was based on existing expert consensus guidelines. Information about the project can be found on the Internet at www.mhmr.state.tx.us/meds/tmap.htm. The authors present and describe the original and current versions of the algorithm, outline the feedback process by which it will be refined, and discuss how new medications will be incorporated as they enter the market.

Algorithms↗