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1.

Objective

To determine if carriers of the allelic expression of the G variant of the human mu opioid receptor (OPRM1) A118G polymorphism have greater increases in striatal dopamine (DA) release after tobacco smoking.

Methods

Nineteen of 20 genotyped male tobacco smokers, after overnight abstinence, smoked denicotinized (denic) and average nicotine (nic) containing tobacco cigarettes in a PET brain imaging study using [11C]raclopride.

Results

The right striatum had more free D2 receptors than the left striatum pre- and post-tobacco smoking. After smoking the nic cigarettes, mean decreased DA binding was observed in the left dorsal caudate (− 14 6 11; t = 3.77), left and right ventral putamen (− 26 3–8; t = 4.27; 28 2 1; t = 4.25, respectively), and right caudate (17 18 1; t = 3.92). The effects of A118G genotype on the binding potentials for these four regions were then analyzed. Carriers of the G allele had larger magnitudes of DA release in response to nic smoking than those homozygous for the more prevalent AA allele in the right caudate and right ventral pallidum (t = 3.03; p = 0.008 and t = 3.91; p = 0.001). A voxel by voxel whole brain SPM analysis using an independent samples t test did not reveal any other differences between genotype groups. In addition, the venous plasma cortisol levels of the volunteers from 8:30 a.m. to 12:40 p.m. were lower in the AG/GG allele carriers. Nic smoking increased plasma cortisol in both groups, but they were higher in the AA group.

Conclusion

This preliminary study indicates a difference in both brain striatal DA release and plasma cortisol in A118G polymorphic male tobacco smokers.  相似文献   

2.

Purpose

High cortisol plasma concentrations have been shown to be associated with increases in homocysteine levels. Here we studied whether decreases in cortisol concentration, induced by an acute oral dose of a benzodiazepine, could decrease homocysteine, and if changes were similar in both genders.

Methods

This was a double-blind, cross-over design study of acute oral flunitrazepam (1.2 mg) and placebo in young, healthy, male and female (n = 21) volunteers. Blood samples were collected 3 h after ingestion (after peak-plasma concentration of flunitrazepam was reached). Various biochemical parameters were analysed, such as plasma homocysteine, cysteine, folate, vitamins B6, B12, and sexual hormones.

Results

Flunitrazepam reduced cortisol (p = 0.0011), cysteine (p = 0.014) and homocysteine (p = 0.028) concentrations, irrespective of gender. No correlations were found between cortisol and other biochemical markers (all r's < 0.03). Concentration of cysteine and homocysteine were negatively correlated with plasma flunitrazepam concentration, suggesting that changes in these amino acids might be related to the metabolism of this benzodiazepine.

Conclusion

Acute administration of flunitrazepam decreases plasma homocysteine and cysteine by mechanisms that seem unrelated to changes in cortisol. Given the importance of homocysteine as a marker of life-threatening disorders, the mechanisms involved in the decrease of these amino acids are potential targets for clinical application.  相似文献   

3.

Objective

Our objective was to examine the cortisol release during a mental challenge in severe mental disorders versus healthy controls (HC), analyzing effects of sex, clinical characteristics and medication, and comparing Bipolar Disorder (BD) to Schizophrenia (SCZ).

Methods

Patients with BD and SCZ (n = 151) were recruited from a catchment area. HC (n = 98) were randomly selected from the same area. Salivary samples were collected before and after a mental challenge and cortisol levels determined.

Results

During the challenge there was an interaction between group and sex (P = 0.015) with male patients having a blunted cortisol release compared to male HC (P = 0.037). Cortisol change did not differ significantly between BD and SCZ. In all patients, the cortisol change correlated with number of psychotic episodes (r = − 0.23, P = 0.025), and in females patients, with number of depressive episodes (r = − 0.33, P = 0.015). Patients using antidepressants had a greater cortisol release during challenge than those not using antidepressants (P = 0.043).

Conclusions

Male patients with severe mental disorders seem to have a uniform abnormal cortisol release during mental challenges which associates with clinical course, and with beneficial effects of antidepressants.  相似文献   

4.

Background

Norepinephrine (NE) plays a central role in post-traumatic stress disorder (PTSD). Dopamine β-hydroxylase (DβH) converts dopamine (DA) to NE and its activity varies widely across individuals. Mustapic et al. (2007) reported a PTSD-associated deficit in serum DβH activity in a genotype-controlled analysis of combat veterans. We tested whether such a deficit would occur in a sample of civilians.

Methods

The severity of current adult PTSD symptoms and current DSM-IV diagnosis of PTSD were determined by the PTSD Symptom Scale (PSS). Adulthood trauma exposure was assessed using the Traumatic Experience Inventory (TEI). Serum DβH activity (sDβH) was assayed by HPLC with electrochemical detection and genotypes were determined using the Taqman® platform.

Results

Two hundred and twenty seven African American (AA) subjects were enrolled in this study, with a mean age (± SD) of 42.9 (± 12.9) years. We found a strong association between rs1611115 genotype and sDβH (p < 0.0001). After controlling for adulthood trauma exposure, there were no significant differences of sDβH between subjects who met a PTSD diagnosis and those who did not (p > 0.05) in any genotype group. No significant correlations were found between sDβH and PTSD severity, but sDβH significantly associated with the status of comorbid depression based on the cutoff of HAMD (p = 0.014) in subjects with PTSD.

Conclusions

We have replicated in this sample the prior finding that DBH rs1611115 genotype strongly associates with sDβH. No associations between sDβH and PTSD diagnosis or symptom severity were found in this civilian sample.  相似文献   

5.

Background

Various formal thought disorders are presented as symptoms by manic patients including pressure of speech, flight of ideas, and more complex speech with strong emotional components. N400 is the event-related potential, in which amplitude is suggested to be a general index of efforts to retrieve stored semantic context, which depends on the stored representation itself and the retrieval cue stimuli. The present study examines N400 components induced by a word-matching task in manic patients, and compare these responses to those induced by the task in schizophrenia and healthy controls.

Methods

Twenty manic patients, twenty schizophrenic patients, and twenty healthy controls performed the word-matching task, in which they were presented with 120 (60 congruent and 60 incongruent) word pairs, they were instructed to discriminate whether each word pair was congruent or incongruent. During the task, we recorded the electroencephalogram.

Results

Reaction time analysis revealed a main effect for priming, in which reaction times were longer in response to incongruent words than to congruent words in all three participant groups (F = 43.1, p < 0.001) with no group effects (F = 2.3, p = 0.11). N400 analysis showed the main effect for priming (F = 30.2, p < 0.001), for group (F = 5.0, p = 0.01), and the interaction of priming × group (F = 4.6, p = 0.02). Post-hoc analysis of this interaction revealed larger N400 amplitudes to congruent words in manic patients (F = 4.0, p = 0.02) and smaller N400 to incongruent words in schizophrenic patients than in other groups (F = 6.1, p = 0.004). No correlations were found between N400 and symptom severity within patient groups.

Conclusions

These findings suggest that priming effects of contextually related word pairs are decreased in patients with bipolar mania, whereas priming N400 responses of contextually unrelated word pairs are increased in schizophrenia. This may be the neurophysiological evidence of abnormal automatic semantic processing in patients with bipolar mania, and it also reflects a qualitative difference in thought and speech disorders between bipolar manic and schizophrenia.  相似文献   

6.

Objective

Accumulating data indicate the involvement of the serotonergic system in adolescent aggression. The aim of this study was to examine the platelet-poor plasma (PPP) serotonin (5-HT) levels among delinquent adolescent boys with conduct disorder (CD) in comparison with normal controls.

Method

PPP 5-HT levels were measured in 16 male delinquent CD adolescents from a correctional facility and in 14 normal male adolescent controls. Severity of aggressive behavior was assessed by the Child Behavior Checklist (CBCL) and the Overt Aggression Scale (OAS).

Results

Delinquent CD adolescents had higher PPP 5-HT levels (about 3-fold) than the normal controls (27.68 ± 32.29 vs. 7.76 ± 4.23 ng/ml, respectively, p = 0.027). In the delinquent CD adolescents a significant correlation was found between the PPP 5-HT levels and the CBCL and OAS aggressive scores (r = 0.68, p = 0.0034 and r = 0.59, p = 0.016, respectively).

Conclusions

Juvenile delinquency is associated with high PPP 5-HT levels. Modulation of 5-HT neurotransmission may have a role in the symptomatology and treatment of severe adolescent CD.  相似文献   

7.

Background

The effect of antipsychotic drugs on brain morphology is under debate. Here we investigate the effects of risperidone, olanzapine and low doses of haloperidol on cortical and subcortical morphometry in first episode drug naïve patients with non-affective psychosis.

Methods

Morphological variables were measured in three treatment groups (haloperidol = 18; risperidone = 16; olanzapine = 18) and in healthy subjects (N = 38) at baseline and after one year. The relationship between brain morphometric changes and changes in clinical scores was also assessed.

Results

At one year, the three antipsychotics had had an equal effect on the gray matter cortical structure, overall and lobes (all p's > 0.121.). A significant time-by-group interaction was found in lateral ventricle volume (F2,47 = 5.65; p = 0.006). Post-hoc comparisons revealed a significant increase in lateral ventricles in patients treated with risperidone (p = 0.009).Patients exposed to atypicals (olanzapine and risperidone) exhibited a decrease in caudate nucleus volume (p = 0.001). In general, brain changes did not account in any significant manner for clinical changes over time in any treatment group.

Conclusions

We conclude that low doses of haloperidol, risperidone and olanzapine seem to have an equal effect on the gray matter cortical structure after 1 year of treatment. In contrast to typical antipsychotics, atypicals have differential effects on lateral ventricle and caudate nucleus volumes.  相似文献   

8.

Introduction

Plasminogen activator inhibitor (PAI-1) may have an independent prognostic value in breast cancer (BC). PAI-1 4G/5G polymorphism may have significance for antigen expression. Thus, we analyzed the possible associations between PAI-1 4G/5G polymorphism, plasma PAI-1 levels, and clinicopathological features of breast cancer (BC) patients.

Patients and Methods

PAI-1 4G/5G polymorphism (both on germinal and tumor DNA) and plasma PAI-1 levels were investigated in 99 BC patients and 50 unrelated healthy women similar for age and menopausal status.

Results

No association was found between allele frequencies and clinicopathological features of BC or plasma antigen levels. Plasma PAI-1 levels were higher in BC compared to controls (p = 0.002), particularly in patients with large tumors (p < 0.001). 5-year follow-up was achieved in 79 patients: 30% had relapsing disease, 63% with positive compared to 37% with negative PAI-1 levels (p < 0.05). 5-year relapse-free survival rate of positive PAI-1 was 46% vs., 77% of negative patients (p = 0.02).

Conclusions

We may conclude that plasma PAI-1 levels in BC patients could represent a useful prognostic variable for relapse, although PAI-1 polymorphism might not represent a genetic susceptibility factor.  相似文献   

9.

Objective

Refinement of endoscopic pituitary surgery requires an understanding of the impact of demographic and surgical variables on outcomes.

Methods

Multivariate logistic regression and ANOVA models were used to explore variables for association with outcomes in a consecutive series of 57 patients undergoing endoscopic pituitary surgery.

Results

The mean duration of surgery was 177 min and was longer in patients with larger tumor size (p = 0.03) and presentation with visual symptoms (p = 0.02) in univariate analyses. The median duration of hospitalization was 3 days and was longer in patients with larger tumors (p = 0.0005). Gross tumor removal was achieved in 89%. Tumor size correlated with extent of tumor removal with an almost 3-fold decrease in complete tumor removal for every 1 cm increase in tumor size (p = 0.047). High rates of hormonal control (90%) and improvement in visual symptoms (92%) were noted.

Conclusions

High rates of gross tumor removal, hormonal cure and visual field improvement were noted in this series. Markers including tumor size and visual symptoms may be used to stratify patients.  相似文献   

10.

Background

Despite of a high comorbidity of depressive and/or anxiety disorders with fibromyalgia, information on the clinical implications of this comorbidity is limited but antidepressants are commonly prescribed to treat fibromyalgia in clinical practice. We investigated whether a history of depressive and/or anxiety disorders was associated with response to paroxetine controlled release (CR) in the treatment of fibromyalgia.

Methods

One hundred sixteen (116) fibromyalgia subjects were randomized to receive paroxetine CR or placebo for 12 weeks. The primary outcome was treatment response defined as ≥ 25% reduction in the Fibromyalgia Impact Questionnaire (FIQ) score. In multivariate logistic regression, we determined if a history of depression and/or anxiety disorders was an independent predictor of response to paroxetine CR.

Results

In logistic regression, the history of depression and/or anxiety did not predict treatment response as measured by ≥ 25% reduction in Fibromyalgia Impact Questionnaire (FIQ) score (OR = 0.66, 95% CI = .29–1.49, Wald = 0.97, p = 0.32), while the drug status (paroxetine CR) was significantly associated with treatment response (OR = 2.57, CI = 1.2–5.61, Wald = 5.5, p = 0.02).

Conclusion

A significant proportion of patients with fibromyalgia had a history of anxiety and or depressive disorders. However response to treatment of fibromyalgia symptoms with paroxetine CR was not associated with a history of depressive and/or anxiety disorders. Our findings need to be confirmed in more adequately-powered and well-designed subsequent studies.  相似文献   

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