Body mass index in male Caucasian veterans with or without posttraumatic stress disorder

Obesity (defined as body mass index (BMI) higher than 30), is a serious and global public health problem, associated with increased morbidity and mortality and it represents a risk factor for developing various somatic and psychiatric disorders. Combat-related posttraumatic stress disorder (PTSD) is frequently associated with increased BMI which leads to overweight and obesity. We therefore evaluated BMI in the ethnically uniform Croatian male participants of the Caucasian origin, combat exposed veterans with or without PTSD, controlled for the effect of trauma, age, smoking, alcohol consumption, physical activity and comorbid psychiatric disorders, and in age matched healthy control subjects. BMI did not differ significantly between veterans with or without PTSD and healthy control subjects, or when participants were subdivided according to the age groups, BMI categories, or the presence of psychiatric disorders. Limitation of the study might be a small number of veterans with or without PTSD. Similar BMI was found in Croatian male veterans with or without PTSD, and age matched healthy control subjects. The data provided evidence of overweight and obesity in large number of veterans but also in healthy control subjects, and indicated that public health organizations should develop more effective strategies to prevent overweight and obesity.     

A randomized double-blind clinical trial on analgesic efficacy of fluoxetine for persistent somatoform pain disorder

Objectives

To verify the efficacy and safety of fluoxetine in treating patients with persistent somatoform pain disorder (PSPD).

Methods

In this 8-week, randomized double-blind placebo-controlled study, 80 patients with an ICD-10 diagnosis of PSPD were randomly assigned to receive 20 mg fluoxetine or a placebo. Several psychological scales including Medical Outcomes Study Pain Measures (MOSPM), Hamilton Depression Scale-17 items (HAMD₁₇) and Treatment Emergent Symptom Scale (TESS) were used to assess analgesic efficacy and safety of fluoxetine, and the possible analgesic mechanism of fluoxetine was preliminarily analyzed. All data were analyzed by SPSS11.5 with t-test, one-way ANOVA and a mixed-effects model repeated measures analysis. Intent-to-treat (ITT) analysis was performed and the last observation carry forward (LOCF) was used for missing values.

Results

There was a significant difference of MOSPM total score between the fluoxetine and placebo group after 2 weeks of treatment. The analgesic effect of fluoxetine was related with treatment time, and depressive patients showed a better analgesic effect than non-depressive patients. An adverse effect of fluoxetine was scarcely found.

Conclusions

Fluoxetine has a better analgesic effect than a placebo in treating persistent somatoform pain disorder, and is considered a safe treatment; its analgesic effect may be related to an antidepressant effect.     

Diagnostic specificity of the insular cortex abnormalities in first-episode psychotic disorders

Volume reductions of the insular cortex have been described in schizophrenia, but it remains unclear whether other psychotic disorders such as affective psychosis also exhibit insular cortex abnormalities. In this study, we used magnetic resonance imaging to investigate the gray matter volume of the anterior (short) and posterior (long) insular cortices in 162 first-episode patients with various psychotic disorders (46 schizophrenia, 57 schizophreniform disorder, 34 affective psychosis, and 25 other psychoses) and 62 age- and gender-matched healthy comparison subjects. Patients with schizophrenia showed bilateral volume reduction of the anterior and posterior insular cortices compared with controls, but the remaining first-episode psychosis subgroups had normal insular volumes. The volumes of these insular subregions were significantly smaller in schizophrenia patients than in patients with schizophreniform disorder or affective psychoses. There was no association between the insular cortex volume and daily dosage or type of antipsychotic medication in any patient group. These findings suggest that the widespread volume reduction of the insular cortex is specific to established schizophrenia, implicating its role in the neurobiology of clinical characteristics associated with schizophrenia.     

A highly sensitive automated complex running wheel test to detect latent motor deficits in the mouse MPTP model of Parkinson's disease

The subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) paradigm is one of the most widely used in vivo models of Parkinson's disease (PD). However, particularly in the mouse model it has remained difficult to reliably detect behavioural correlates for PD. In the present study we apply a novel murine motor test, the motor skill sequence (MOSS) based on computerized recording of voluntary running wheel activity, and found latent motor skill deficits in the subchronic MPTP mouse model. Mice are first subjected to a 2-week training phase. The animals then receive either MPTP injections according to the standard subchronic MPTP paradigm (30 mg/kg) or vehicle injections for 5 consecutive days. Running performance transiently fell during the injection phase but returned to baseline within few days. The animals were then exposed to complex wheels with irregularly spaced crossbars demanding high central motor coordination abilities. Though both groups showed clear improvement of running performance in the learning phase on the complex wheel, MPTP animals displayed clear central motor deficits on the complex wheels, as indicated by a reduced maximum speed and running distance, despite unchanged running motivation. Our results demonstrate latent motor deficits in MPTP-treated mice, which can be unmasked by MOSS. MOSS is thus capable of detecting and quantifying central motor deficits in this widely used model of PD with high sensitivity. The automated full time data collection of several different running parameters makes it also a suitable test for efficient in vivo screening of potential therapeutic compounds in this model for PD.     

Cystic fibrosis heterozygotes do not have increased platelet activation

INTRODUCTION: We have previously demonstrated platelet hyperreactivity in cystic fibrosis (CF) patients. Carriers of one CF mutation (heterozygotes) have been shown to have abnormalities related to the presence of only one-half the normal amount of CF transmembrane conductance regulator protein. Platelet hyperreactivity in CF heterozygotes would be an important cardiovascular risk factor, since approximately 1 in 25 Caucasians is a CF carrier. MATERIALS AND METHODS: We used highly sensitive assays of platelet activation to assess the difference between 16 CF heterozygotes and 16 age- and sex-matched healthy controls without CF mutations. RESULTS: We found no difference in platelet activation between CF heterozygotes and controls. CONCLUSIONS: The 50% reduction in the CF transmembrane conductance regulator protein in heterozygotes is insufficient to cause platelet activation.     

The effects of olanzapine and fluphenazine on plasma cortisol, prolactin and muscle rigidity in schizophrenic patients: a double blind study

Pharmacotherapy of schizophrenia is associated with the stressful side effects. Muscle rigidity causes distress, discomfort and poor compliance. The aim of the study was to determine the relationship between plasma hormones (cortisol and prolactin/PRL) and muscle rigidity in female schizophrenic patients treated with olanzapine or fluphenazine. In a randomized, double-blind 22-weeks study, 12 patients were treated with olanzapine (5-20 mg/day) and 10 patients received fluphenazine (6-21 mg/day). Treatment with olanzapine moderately decreased, while treatment with fluphenazine significantly increased plasma cortisol levels and muscle rigidity. The marked and moderate increase in plasma PRL levels were found in patients treated with fluphenazine and olanzapine, respectively. The results suggested that olanzapine induced moderate neuroendocrine effects and a reduction in rigidity as compared to fluphenazine treatment.     

Basilar artery blood flow velocity changes in patients with panic disorder following 35% carbon dioxide challenge

PURPOSE: We compared the mean basilar artery blood flow velocity (BABFV) between patients with panic disorder and healthy subjects both at rest and immediately following carbon dioxide (CO(2)) challenge, and examined the effects of treatment on BABFV. METHODS: Twenty four patients with panic disorder with or without agoraphobia and 12 healthy comparison subjects were studied. Visual Analog Anxiety Scale was used to evaluate the anxiogenic effect of 35% CO(2) inhalation. Mean BABFV was monitored using transcranial Doppler ultrasonography at rest and 10, 20, 30, 60, 90, 120 s after 35% CO(2) challenge both before and after four weeks treatment with paroxetine. RESULTS: The hemodynamic response pattern of basilar artery to CO(2) inhalation was significantly different between two groups. CO(2) rapidly triggered blood flow velocity in basilar artery amongst panic patients but not in healthy comparisons. The mean time to normalization of BABFV was significantly longer in panic patients. Four weeks of treatment with paroxetine led to a significantly reduced mean BABFV after 35% CO(2) inhalation in comparison with pretreatment. CONCLUSIONS: Patients with panic disorder had impaired cerebral regulatory mechanisms observed as a change in response characteristics in BABFV in response to CO(2) inhalation. Treatment with paroxetine reduced the increase of BABFV seen in patients after the CO(2) challenge.     

Association between major Multidrug Resistance 1 (MDR1) gene polymorphisms and plasma concentration of prolactin during risperidone treatment in schizophrenic patients

An in vitro study has suggested that risperidone is a substrate of P-glycoprotein, which is coded by MDR1gene. The rate of P-glycoprotein efflux transport can mediate brain penetration of lipophilic drugs. We therefore studied the effects of major polymorphisms of MDR1 gene on plasma concentrations of prolactin. Subjects included 175 schizophrenic patients (68 males, 107 females) who were receiving 3 mg of risperidone twice daily for at least 4 weeks. Sample collections were conducted 12 h after the bedtime dosing. The plasma concentrations of prolactin in females were significantly higher than in males (54.3+/-27.2 versus 126.8+/-70.2 ng/ml, p<0.001). There was no difference in mean (+/-SD) plasma concentration of prolactin between C3435T genotypes [C/C, C/T, T/T; 62.3+/-33.3, 49.4+/-15.6, 53.2+/-33.2 ng/ml, ns] or G2677T/A genotypes [G/G, G/T or A, T or A/T or A; 58.0+/-27.7, 58.5+/-35.0, 46.1+/-20.7 ng/ml, ns] in males nor between C3435T genotypes (123.6+/-65.0, 127.8+/-79.2, 130.4+/-49.7 ng/ml, ns) or G2677T/A genotypes (123.3+/-67.0, 97.7+/-71.2, 144.9+/-69.9 ng/ml, ns) in females. Multiple regression analyses including plasma drug concentration and age revealed that plasma concentration of prolactin correlated with gender (standardized beta=0.540, p<0.001) and negatively with age (standardized beta=-0.183, p<0.01). No correlations were found between prolactin concentration and MDR1 genotypes. These findings suggest that prolactin concentrations in females are much higher than in males but the major MDR1 variants are not associated with the plasma concentration of prolactin.     

Single prolonged stress increases contextual freezing and the expression of glycine transporter 1 and vesicle-associated membrane protein 2 mRNA in the hippocampus of rats

Rats subjected to single prolonged stress (SPS) show enhanced HPA negative feedback, exaggerated acoustic startle response, and enhanced contextual freezing 7 days after SPS, and accordingly, SPS is an animal model of PTSD. To elucidate the influence of contextual fear on gene expression in the hippocampus of SPS rats, we used cDNA microarray followed by real-time quantitative PCR analyses to compare the hippocampal gene expression profiles between rats that were or were not subjected to SPS during exposure to contextual fear. In the behavioral experiments, spontaneous locomotor activity was measured 7 days after SPS. Twenty-four hours after footshock conditioning (7 days after SPS), freezing behavior was measured during re-exposure to the chamber in which footshock was delivered. Based on the behavioral analysis, rats subjected to SPS exhibited a significant enhancement of contextual freezing compared to rats not subjected to SPS, without any changes in locomotor activity. Analyses using cDNA microarray and RT-PCR showed that the hippocampal levels of glycine transporter 1 (Gly-T1) and vesicle-associated membrane protein 2 (VAMP2) mRNA in rats subjected to SPS were significantly increased relative to sham-treated rats. Administration of SPS alone did not affect the expression of these 2 genes. These findings suggest that the upregulation of Gly-T1 and VAMP2 in the hippocampus may be, at least in part, involved in the enhanced susceptibility to contextual fear in rats subjected to SPS.     

Antidepressant-like effect of the extract from leaves of Schinus molle L. in mice: evidence for the involvement of the monoaminergic system

Schinus molle L. (Anacardiaceae), among other uses, is popularly employed for the treatment of depression. In this study, the antidepressant-like effect of the hexanic extract from leaves of S. molle was investigated in the mouse tail suspension test (TST), a predictive model of depression. The immobility time in the TST was significantly reduced by the extract (dose range 30-600 mg/kg, p.o.), without accompanying changes in ambulation when assessed in an open-field test. The efficacy of extract was found to be comparable to that of fluoxetine (10 mg/kg, p.o.). The anti-immobility effect of the extract (100 mg/kg, p.o.) was prevented by pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), NAN-190 (0.5 mg/kg, i.p., a 5-HT(1A) receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist), ketanserin (5 mg/kg, i.p., a 5-HT(2A/2C) receptor antagonist), MDL72222 (0.1 mg/kg, i.p., a 5-HT(3) receptor antagonist), prazosin (1 mg/kg, i.p., an alpha(1)-adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist), SCH23390 (0.05 mg/kg, s.c., a D(1) receptor antagonist) or sulpiride (50 mg/kg, i.p., a D(2) receptor antagonist). It may be concluded that the hexanic extract of S. molle produces an antidepressant-like effect that seems to be dependent on its interaction with the serotonergic, noradrenergic and dopaminergic systems. These results provide evidence that the extract from S. molle shares with established antidepressants some pharmacological effects, at least at a preclinical level.