Improving Quality of Emergency Care Through Integration of Mental Health.

The goal of this study was to better integrate emergency medical and psychiatric care at a large urban public hospital, identify impact on quality improvement metrics, and reduce healthcare cost. A psychiatric fast track service was implemented as a quality improvement initiative. Data on disposition from the emergency department from January 2011 to May 2012 for patients impacted by the pilot were analyzed.

The pharmacologic treatment of anxiety and depression in African Americans. Considerations for the general practitioner.

A growing pool of recent research points to the importance of ethnicity in psychopharmacologic management of depression and anxiety disorders, with sometimes profound implications for efficacy and safety. Such research has provided provocative findings that illustrate important interethnic pharmacogenetic, pharmacokinetic, and pharmacodynamic differences, especially for African Americans. We did a systematic literature review of psychopharmacologic treatment considerations among African Americans with anxiety and mood disturbance seen by primary care physicians, who provide most psychopharmacologic treatment.

Regulation of signal transduction pathways by mood-stabilizing agents: implications for the delayed onset of therapeutic efficacy.

A series of investigations were performed to elucidate the mechanisms of action of lithium, valproate, and carbamazepine. We have found that lithium exerts major effects on G proteins, most likely via a posttranslational process stabilizing the inactive heterotrimeric (alpha beta gamma) form of the protein. We also find that chronic lithium and valproate exert major, very similar effects on the PKC signaling pathway, with both drugs decreasing the levels of membrane-associated PKC alpha and epsilon, and have similar effects on the DNA binding activity of the transcription factor, AP-1.

Ethnic considerations in the pharmacotherapy of mood disorders.

In the past several years, there has been an increased appreciation for the importance of including cultural and ethnic factors in the evaluation and treatment of patients in psychiatry. Most of the focus has been on understanding the patients' psychosocial milieu and how these factors contribute to the patient's overall clinical presentation. Few studies have addressed the significance of pharmacogenetic heterogeneity among various cultural, ethnic, and racial groups.

Regulation of corticotropin-releasing factor secretion and synthesis in the human neuroblastoma clones- BE(2)-M17 and BE(2)-C.

The BE(2)-M17 and BE(2)-C human neuroblastoma cell lines have been shown to synthesize and secrete corticotropin-releasing factor (CRF) following retinoic acid treatment. It has been demonstrated that CRF secretion and intracellular synthesis increases in response to forskolin treatment. In this report, we have further characterized these cells in response to protein kinase C activators, dexamethasone, interleukin-1 alpha, as well as various neurotransmitters and peptides.

Clozapine-induced EEG abnormalities and clinical response to clozapine.

The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures.

Natural killer cell activity in schizophrenia and schizoaffective disorder: a pilot study.

Natural killer cell activity was prospectively studied in 15 patients with chronic schizophrenia and in seven patients with schizoaffective disorder, depressed type. These patients were compared to individually matched normal controls. No mean differences in natural killer cell activity between the patient groups and their controls were observed.

Limbic-hypothalamic-pituitary-adrenal axis activity and ventricular-to-brain ratio studies in affective illness and schizophrenia.

Some investigators have speculated that structural brain alterations observed in some psychiatric patients might be related to increased limbic-hypothalamic-pituitary-adrenal axis (LHPA) activity. To explore this hypothesis, we prospectively studied 166 research volunteers (19 patients with research diagnostic criteria (RDC) major depression, 9 patients with RDC bipolar depression, 45 patients with RDC schizophrenia, and 94 RDC normal controls), examining the relationship between magnetic resonance image-determined ventricular-to-brain ratio (VBR) and indices of LHPA axis function (cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF), CSF adrenocorticotropic hormone (ACTH), and 24-hour urinary-free cortisol secretion). We observed no significant differences in mean VBR among the three patient groups and the normal control volunteers.

ECT treatment does not enhance neuroendocrine responses to serotonergic challenge.

We prospectively investigated the effects of a course of electroconvulsive therapy (ECT) on neuroendocrine responses to serotonergic challenge in five depressed patients. Low dose intravenous chlorimipramine (CMI) challenge produced a modest release of prolactin and significant increases in plasma adrenocorticotrophic hormone (ACTH) and cortisol. Interestingly, ECT did not alter the neuroendocrine responses to serotonergic challenge despite clinical response in four of the five patients.

Lithium administration modulates platelet Gi in humans.

Platelet G proteins were assessed in 7 normal volunteers before and after 14 days of lithium administration at therapeutic plasma levels. Cholera and pertussis toxin catalyzed ADP-ribosylation of platelet membrane proteins were measured by SDS-PAGE. Immunoblotting with specific antibodies was used to measure platelet membrane alpha i content.

Cognitive deficits in delirium: assessment over time.

Delirium is commonly defined as a transient organic brain syndrome characterized by concurrent disorders of attention, perception, thinking, memory, psychomotor behavior, and the sleep-wake cycle. One of the difficulties in studying delirium is that symptoms tend to fluctuate over the course of the day. Pre-existing organic brain disease appears to be a significant risk factor for the development of delirium, and numerous studies have shown a high rate of delirium in patients with cerebrovascular disease, Parkinson's disease, and Alzheimer's disease.

Lateral ventricle-brain ratio and balance between CSF HVA and 5-HIAA in schizophrenia.

Objective: Lateral ventricle enlargement in schizophrenia has been positively correlated with poor premorbid competence, negative symptoms, and poor treatment response and negatively correlated with concentrations of homovanillic acid (HVA), a dopaminergic metabolite. The authors provide further evidence of a reciprocal relationship between lateral ventricle size and dopaminergic activity in schizophrenia.

Method: They assessed the relationship between lateral ventricle enlargement (ventricle-brain ratio, VBR) and CSF neurotransmitter metabolite concentrations (HVA and 5-hydroxyindoleacetic acid [5-HIAA]) in 45 patients with schizophrenia, 28 with affective disorders (19 patients with major depression and nine with bipolar disorder), and 91 normal comparison subjects.

The mechanisms of action of lithium. II. Effects on adenylate cyclase activity and beta-adrenergic receptor binding in normal subjects.

As part of a study of the effects of lithium carbonate on neurochemical function in man, platelet and lymphocyte adenylate cyclase activity and lymphocyte beta-adrenergic receptor binding characteristics were determined before and after 2 weeks of lithium treatment in 10 normal volunteers. Lithium had differential effects on platelet and lymphocyte adenylate cyclase activity. In platelets, basal and stimulated (guanyl imidodiphosphate [Gpp[NH]p] or cesium fluoride) adenylate cyclase activity was significantly augmented by lithium treatment.

The mechanisms of action of lithium. I. Effects on serotoninergic and noradrenergic systems in normal subjects.

The effects of 2 weeks of lithium carbonate administration at therapeutic plasma levels were examined in 11 normal volunteers. Serotoninergic function before and after lithium administration was assessed using low-dose intravenous clomipramine hydrochloride challenge, while urinary and plasma metabolites of norepinephrine (NE) were used to assess noradrenergic systems. Long-term lithium administration in normal subjects did not significantly or consistently enhance serotonin-mediated neuroendocrine responses but did increase measures related to neuronal release of NE.

Hypothalamic--pituitary--adrenal axis and monoamine transmitter activity in depression: a pilot study of central and peripheral effects of electroconvulsive therapy.

Central and peripheral measures of hypothalamic--pituitary--adrenal (HPA) axis and monoamine neurotransmitter activity were assessed in 8 depressed patients during a medication-free period and again after completion of a course of electroconvulsive therapy (ECT). Seven patients responded fully to ECT. At baseline there was corresponding activation of the HPA and noradrenergic systems, with apparent elevation in cerebrospinal fluid (CSF) concentrations of corticotropin-releasing hormone (CRH) in some patients.

Signal transduction modulation by lithium: cell culture, cerebral microdialysis and human studies.

Considerable evidence suggests that signal transduction pathways are targets of lithium (Li) action. A number of investigators have reported that Li attenuates both adenylate cyclase (AC) activity and phosphoinositide (PI) turnover in rodents and in humans, thus "dampening" these systems. We have studied selected components of these second-messenger systems in a series of clinical and preclinical investigations.

Intravenous alprazolam challenge in normal subjects. Biochemical, cardiovascular, and behavioral effects.

Alprazolam, a novel benzodiazepine derivative is thought to be effective in the treatment of anxiety, panic, and depressive disorders. There is considerable interest in alprazolam's mechanism of action, particularly whether its profile of actions might resemble that of the alpha 2 adrenoreceptor agonist, clonidine. The present study assessed the biochemical, cardiovascular, and behavioral responses of healthy volunteers to acute intravenous infusions of alprazolam and placebo.

Antidepressants reduce whole-body norepinephrine turnover while enhancing 6-hydroxymelatonin output.

The effects of antidepressant treatment on noradrenergic function were studied in 27 patients with a major affective disorder. Twenty-four-hour urinary excretion of 6-hydroxymelatonin and "whole-body norepinephrine (NE) turnover," ie, 24-hour urinary output of NE and its major metabolites 3-methoxy-4-hydroxyphenylglycol, vanillylmandelic acid, and normetanephrine, were measured before and after treatment with the tricyclic desipramine hydrochloride, the aminoketone bupropion hydrochloride, the nonselective monoamine oxidase (MAO) inhibitor tranylcypromine sulfate, and the specific MAO type A inhibitor clorgiline. 6-Hydroxymelatonin excretion increased following antidepressant treatment, while at the same time whole-body NE turnover was reduced.

Disparate Biochemical Actions of Electroconvulsive Therapy and Antidepressant Drugs.

Electroconvulsive therapy (ECT) effects on monoamine transmitter metabolites in the cerebrospinal fluid (CSF) were evaluated in three patients after completion of a course of bilateral or unilateral ECT. Each patient had earlier undergone an unsuccessful trial with an antidepressant drug. Despite the disparate nature of the basic pharmacology of the antidepressant drugs used, common chronic effects were observed in the CSF, with reductions in 3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in all patients despite lack of therapeutic response.