Prevalence, predictors, and patterns of mechanical restraint use for inpatients with dual diagnosis.

Purpose: This study examined the prevalence, predictors, and patterns of mechanical restraint in an inpatient dual diagnosis population.

Design And Methods: Data were longitudinally collected from patients affected by severe mental illness and comorbid substance abuse that were hospitalized in three large wards from 2006 to 2012.

Findings: In a sample of 1698 hospitalizations, the use of mechanical restraint ranged between 1% and 4% per year.

Association of the leucine-7 to proline-7 variation in the signal sequence of neuropeptide Y with major depression.

Objective: There is clear evidence of a genetic component in major depression, and several studies indicate that neuropeptide Y (NPY) could play an important role in the pathophysiology of the disease. A well-known polymorphism encoding the substitution of leucine to proline in the signal peptide sequence of NPY (Leu7Pro variation) was previously found to protect against depression. Our study aimed at replicating this association in a large Danish population with major depression.

Treating panic symptoms within everyday clinical settings: the feasibility of a group cognitive behavioural intervention.

Panic disorder is a common and debilitating disorder that has a prevalence rate of 3-5% in the general population. Cognitive-behavioural interventions have been shown to be an efficacious treatment for panic, although a limited number of studies have examined the effectiveness of such interventions implemented in everyday clinical settings. The aim of the following pilot study was to examine the feasibility of a brief group cognitive-behavioural intervention carried out in a clinical setting.

Validity of the BPRS, the BDI and the BAI in dual diagnosis patients.

Aim: The psychometric properties of the Brief Psychiatric Rating Scale, the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI) were tested in a sample of 134 patients with a substance use disorder and a non-substance related psychiatric disorder in a special inpatient dual diagnosis treatment unit.

Methods: Subjects were assessed at baseline. At discharge on average 6 months post-intake, 78% of patients were re-assessed using the same instruments.

Aberrant behavioral effects of a dopamine D1 receptor antagonist and agonist in monkeys: evidence of uncharted dopamine D1 receptor actions.

Background: Basic research indicates a role for dopamine (DA) D1 antagonism in the treatment of schizophrenia. Clinical trials have not confirmed any role. Besides the defining second messenger (adenylyl cyclase [AC]), DA D1 receptors are linked to other effectors (e.

Honokiol and magnolol selectively interact with GABAA receptor subtypes in vitro.

Honokiol and magnolol have been identified as modulators of the GABAA receptors in vitro. Our previous study suggested a possible selectivity of honokiol and magnolol on GABAA receptor subtypes. This possibility was examined in the current study by 3H-muscimol and 3H-flunitrazepam binding assays on various rat brain membrane preparations and human recombinant GABA(A) receptor subunit combinations expressed by the Sf-9/baculovirus system.

Two conserved arginines in the extracellular N-terminal domain of the GABA(A) receptor alpha(5) subunit are crucial for receptor function.

The gamma-aminobutyric acid (GABA) binding pocket within the GABA(A) receptor complex has been suggested to contain arginine residues. The aim of this study was to test this hypothesis by mutating arginine residues potentially contributing to the formation of a GABA binding pocket. Thus, six arginines conserved in human GABA(A) receptor alpha subunits (arginine 34, 70, 77, 123, 135, and 224) as well as two nonconserved arginines (79 and 190), all located in the extracellular N-terminal segment of the alpha(5) subunit, were substituted by lysines.

Identification and cloning of a gamma 3 subunit splice variant of the human GABA(A) receptor.

cDNA sequences encoding two forms of the GABA(A) gamma 3 receptor subunit were cloned from human hippocampus. The nucleotide sequences differ by the absence (gamma 3S) or presence (gamma 3L) of 18 bp located in the presumed intracellular loop between transmembrane region (TM) III and IV. The extra 18 bp in the gamma 3L subunit generates a consensus site for phosphorylation by protein kinase C (PKC).

The continuing problem of extrapyramidal symptoms: strategies for avoidance and effective treatment.

Antipsychotic agents remain the most effective treatment for both acute and chronic schizophrenia. However, conventional antipsychotic agents are frequently associated with significant side effects including, perhaps most notably, extrapyramidal symptoms (EPS). The emergence of EPS can significantly compromise patient compliance with treatment and can have profound effects on long-term treatment outcomes.

New and old antipsychotics versus clozapine in a monkey model: adverse effects and antiamphetamine effects.

Rationale: Neuroleptic primed Cebus apella monkeys have proven reliable in screening antipsychotics for extrapyramidal side effect (EPS) potential in humans, and the ratio EPS liability/antiamphetamine efficacy ["therapeutic index" (TI)] has fit well with clinical results.

Objectives: 1) To find the TIs of one new (quetiapine), three potential [NNC 756 (dopamine (DA) D1 antagonist), NNC 22-0031 (alpha-1 adrenergic/5-HT2 serotonergic/DA D1 and D2 antagonist) and DOD 647 (DA D1 and D2 antagonist)] and three old antipsychotics (haloperidol, melperone and clozapine), 2) to test the model further and 3) to gain more insight as to clozapine's neuropharmacology.

Methods: Seven monkeys received haloperidol daily for 2 years; all were sensitized to dystonia.

Subjective experience and mental side-effects of antipsychotic treatment.

Many schizophrenic patients have a negative attitude towards antipsychotic drugs. This attitude is not only due to lack of insight into the disease, lack of recognition of the beneficial effects of the drugs, and to objective side-effects. The negative attitude is to a high degree due to mental side-effects and a sceptical opinion about antipsychotic medication in general.

MK-801-induced dystonia in cebus monkeys.

MK-801 (dizocilpine), a noncompetitive N-methyl-D-aspartate antagonist, induces dystonia in monkeys at doses of 0.08 mg/kg. This syndrome was tested with the dopamine D1 receptor antagonist NNC 756, the DA D2 receptor antagonist raclopride, the atypical antipsychotic clozapine, the dopamine D1 receptor agonist SKF 81297, the dopamine D2/D3 receptor agonist quinpirole, the anticholinergic biperiden, amphetamine, and the benzodiazepine midazolam in 7 Cebus apella monkeys previously treated with dopaminergic agents.

Differential changes in induced seizures after hippocampal treatment of rats with an antisense oligodeoxynucleotide to the GABA(A) receptor gamma2 subunit.

Gamma-aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. Impairment of GABAergic neurotransmission may be involved in the pathogenesis of epileptic phenomena. We have previously characterized biochemical and histological changes following unilateral intrahippocampal infusion of a phosphorothioate antisense oligodeoxynucleotide to the GABA(A) receptor gamma2 subunit in rats in vivo.

The use of in vivo antisense oligonucleotide technology for the investigation of brain GABA receptors.

Antisense oligodeoxynucleotides (ODN) can be used as selective inhibitors of in vivo gene expression in the central nervous system (CNS) of experimental animals. The gamma-aminobutyric acid type A (GABAA) receptor is a member of the ligand-gated ion channel superfamily of neurotransmitter receptors. GABAA receptor function is allosterically modulated by several clinically important compounds, e.

Diazepam protects against rat hippocampal neuronal cell death induced by antisense oligodeoxynucleotide to GABA(A) receptor gamma2 subunit.

Antisense oligodeoxynucleotides (ODNs) are used for the selective inhibition of gene expression. Antisense ODNs are promising tools for the investigation of physiological implications of proteins in the central nervous system of rodents in vivo. We have previously demonstrated that a phosphorothioate antisense ODN to the GABA(A) receptor gamma2 subunit, but not sense or mismatch control ODNs, induces a decrease in ex vivo benzodiazepine receptor radioligand binding in rat hippocampus when infused into the hippocampus in vivo [Karle et al.

Effects of 5-(4-piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) receptor partial agonist, on recombinant human GABA(A) receptors.

gamma-Aminobutyric acidA (GABA(A)) gated chloride ion channels were expressed from human recombinant cDNA using the baculovirus/Sf-9 insect cell expression system. The electrophysiological effects in whole-cell currents of 5-(4-piperidyl) isoxazol-3-ol (4-PIOL), a GABA(A) receptor partial agonist, were investigated on GABA(A) receptor complexes of alpha1beta2gamma2S subunits as well as a slightly modified construct of alpha1(valine 121)beta2gamma2S subunits. Here we report that (1)4-PIOL induces an inward whole-cell current in a concentration-dependent manner in both alpha1(val 121)beta2gamma2S and alpha1(ile 121)beta2gamma2S receptor subunit combinations.

A clinical trial of dextromethorphan in amyotrophic lateral sclerosis.

Introduction: Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, excitotoxicity mediated by glutamate has been implicated. Dextromethorphan is a NMDA-glutamate receptor antagonist with neuroprotective properties.

Material And Methods: The effect of treatment with dextromethorphan (150 mg daily) in ALS patients was evaluated in a randomized, double-blind, placebo-controlled study.

Decreased agonist sensitivity of human GABA(A) receptors by an amino acid variant, isoleucine to valine, in the alpha1 subunit.

Recombinant human GABA(A) receptors were investigated in vitro by coexpression of cDNAs coding for alpha1, beta2, and gamma2 subunits in the baculovirus/Sf-9 insect cell system. We report that a single amino acid exchange (isoleucine 121 to valine 121) in the N-terminal, extracellular part of the alpha1 subunit induces a marked decrease in agonist GABA(A) receptor ligand sensitivity. The potency of muscimol and GABA to inhibit the binding of the GABA(A) receptor antagonist [3H]SR 95531 (2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide) was higher in receptor complexes of alpha1(ile 121) beta2gamma2 than in those of alpha1(val 121) beta2gamma2 (IC50 values were 32-fold and 26-fold lower for muscimol and GABA, respectively).

Quantification of brain metabolites in amyotrophic lateral sclerosis by localized proton magnetic resonance spectroscopy.

We performed proton magnetic resonance spectroscopy (1H-MRS) in patients with motor neuron disease (MND) to determine the absolute in vivo concentrations in the brain of the metabolites N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr/PCr). We examined the spectra acquired from a 20 x 20 x 20-mm3 voxel placed in the motor cortex and in the cerebellum from seven patients with clinically probable or definite amyotrophic lateral sclerosis (ALS) according to the El Escorial criteria, from three patients with suspected ALS (progressive muscular atrophy), and from eight normal control subjects. We estimated the concentrations of the metabolites using the water signal as an internal standard.

Characterisation of the furanocoumarin phellopterin as a rat brain benzodiazepine receptor partial agonist in vitro.

Phellopterin, a naturally occurring furanocoumarin found in the roots of Angelica dahurica, inhibits [3H]diazepam and ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4] benzodiazepine-3-carboxylate ([3H]Ro 15-1788) binding to the benzodiazepine site of the rat brain gamma-aminobutyric acidA (GABAA) receptor in vitro with IC50 values of 400 and 680 nM, respectively. Two other naturally occurring furanocoumarins, byakangelicol and imperatorin were significantly less potent, with IC50 values for inhibition of [3H]diazepam binding of 8.0 and 12.

Muscarinic, N-methyl-D-aspartate (NMDA) and benzodiazepine receptor binding sites in cortical membranes from amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder causing marked pathology in the motoneuron system. The pathophysiology of the selective degeneration of motor neurons in the disease is as yet unknown, but evidence suggests that excitotoxic mechanisms might be involved. The present study was undertaken to determine whether defects in neurotransmitter receptors are involved in the disease, analyzing uniformly sampled specimens from neocortex and motorcortex.

Unsaturated free fatty acids increase benzodiazepine receptor agonist binding depending on the subunit composition of the GABAA receptor complex.

It has been shown previously that unsaturated free fatty acids (FFAs) strongly enhance the binding of agonist benzodiazepine receptor ligands and GABAA receptor ligands in the CNS in vitro. To investigate the selectivity of this effect, recombinant human GABAA/benzodiazepine receptor complexes formed by different subunit compositions (alpha x beta y gamma 2, x = 1, 2, 3, and 5; y = 1, 2, and 3) were expressed using the baculovirus-transfected Sf9 insect cell system. At 10(-4) M, unsaturated FFAs, particularly arachidonic (20:4) and docosahexaenoic (22:6) acids, strongly stimulated (> 200% of control values) the binding of [3H]flunitrazepam ([3H]FNM) to the alpha 3 beta 2 gamma 2 receptor combination in whole cell preparations.

Cerebrospinal fluid from amyotrophic lateral sclerosis has no effect on intracellular free calcium in cultured cortical neurons.

The data from the literature regarding the presence of a neurotoxic factor in amyotrophic lateral sclerosis (ALS) plasma or cerebrospinal fluid (CSF) remain controversial. As a new approach to this question, we have studied the effect of CSF from ALS patients on the temporal dynamics of the intracellular free calcium concentration ([Ca2+]i) of murine cortical neurons in cultures using Fura-2 fluorescence videomicroscopy and single-cell imaging. CSF from seven ALS patients and controls was added at dilutions up to 20% to cortical neuronal cultures.