Sex-specific cortisol levels in bipolar disorder and schizophrenia during mental challenge--relationship to clinical characteristics and medication

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.     

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study

Objectives

We evaluated the efficacy of bimodal repetitive transcranial magnetic stimulation (rTMS) in treating pharmacologically non-responsive patients with schizophrenia.

Methods

Ten patients with DSM-IV schizophrenia, unresponsive to pharmacological treatment, underwent treatment with 15 rTMS sessions, as an adjunctive therapy, for three weeks. Each session comprised 40 trains, beginning every 30 s: 20 trains of 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC) with a 3-s duration and 20 trains of 1 Hz rTMS to the left temporoparietal cortex (TPC) with a 30-s duration. We assessed patients via the Positive and Negative Syndrome Scale (PANSS) and Korean Version of the Calgary Depression Scale for Schizophrenia (K-CDSS), at five time points: baseline, Days 8, 15, and 22, and 1 week after final treatment (Day 29). Patients who agreed to take neurocognitive tests underwent neurocognitive function evaluations at baseline and 1 week after final treatment.

Results

At Day 29, all PANSS subscale scores in had decreased significantly compared to baseline (Z = − 2.214, p = 0.027, positive; Z = − 2.132, p = 0.033, negative; Z = − 2.023, p = 0.043, general pathology; Z = − 2.371, p = 0.018, total). Effect over time was significant for the PANSS positive and negative subscale scores and total score (χ² = 13.35, p = 0.010; χ² = 10.27, p = 0.036; and χ² = 16.50, p = 0.002, respectively) but not for the general pathology subscale. Among the neurocognitive tests, the fourth and fifth trials and total K-AVLT scores showed significant increases (Z = − 2.041, p = 0.041; Z = − 2.251, p = 0.024; and Z = − 2.201, p = 0.028, respectively), suggesting improvement in short-term auditory verbal memory.

Conclusions

Bimodal rTMS stimulation of left DLPFC and left TPC induced clinical improvement in pharmacologically non-responsive schizophrenia patients and may have improved their short-term verbal memories.     

Subcortical brain volumes relate to neurocognition in schizophrenia and bipolar disorder and healthy controls

Background

Similar patterns of subcortical brain abnormalities and neurocognitive dysfunction have been demonstrated in schizophrenia and bipolar disorder, with more extensive findings in schizophrenia. It is unknown whether relationships between subcortical volumes and neurocognitive performance are similar or different between schizophrenia and bipolar disorder.

Methods

MRI scans and neuropsychological test performance were obtained from 117 schizophrenia or 121 bipolar spectrum disorder patients and 192 healthy control subjects. Using the FreeSurfer software, volumes of 18 selected subcortical structures were automatically segmented and analyzed for relationships with results from 7 neurocognitive tests.

Results

In schizophrenia, larger left ventricular volumes were related to poorer motor speed, and bilateral putamen volumes were related to poorer verbal learning, executive functioning and working memory performance. In bipolar disorder, larger left ventricular volumes were related to poorer motor speed and executive functioning. The relationship between left putamen volume and working memory was specific to schizophrenia. The relationships between left inferior lateral ventricles and motor speed and between right putamen volumes and executive functioning were similar in schizophrenia and bipolar disorder, and different from healthy controls. The results remained significant after corrections for use of antipsychotic medication. Significant structure-function relationships were also found when all subjects were combined into one group.

Conclusion

The present findings suggest that there are differences as well as similarities in subcortical structure/function relationships between patients with schizophrenia or bipolar disorder and healthy individuals. The observed differences further suggest that ventricular and putamen volume sizes may reflect severity of cognitive dysfunction in these disorders.     

Influence of TAAR6 polymorphisms on response to aripiprazole

Background

There is some evidence suggesting a role of TAAR6 in schizophrenia. The aim of the present study is to investigate possible influences of a panel of markers in TAAR6 (rs8192625, rs4305745, rs4305746, rs6903874, rs6937506) on clinical outcomes and side effects in a sample of Korean schizophrenic aripiprazole treated patients.

Methods

Efficacy was assessed at baseline and weeks 1, 2, 4, 6, 8 using CGI-S, CGI-I, BPRS and SANS. Side effects were evaluated through SAS, BAS and AIMS. Multivariate analysis of covariance (MANCOVA) was used to test possible influences of single SNPs on clinical and safety scores. Tests for associations using multi-marker haplotypes were performed using the statistics environment “R”.

Results

A significant time per genotype interaction was found between rs4305746 in repeated measures of ANOVA on BPRS scores (F = 2.45, df = 10,365, p = 0.008). In particular G/A and A/A genotype patients were more likely to improve over time as compared to carriers of the G/G genotype. Permutation analysis confirmed a significant effect of rs4305746 on course of BPRS scores over time (p = 0.007). Haplotype analysis did not reveal any significant association with clinical and safety scores at any time.

Conclusion

A possible association could exist between some genotypes in TAAR6 and response to aripiprazole. However, several limitations characterize the present work, such as small sample size, the finding related to a single scale and the possibility of false positive findings, thus further investigation is required.     

Acetyl-l-Carnitine in the treatment of anhedonia, melancholic and negative symptoms in alcohol dependent subjects

Objective

Aim of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of Acetyl-l-Carnitine (ALC), at different dosages, on specific anhedonic symptoms in detoxified alcohol dependent subjects. Secondary endpoints were the effect of ALC on melancholic and negative symptoms.

Method

Sixty-four anhedonic alcohol dependent patients with minor or absent withdrawal symptoms were randomized: 23 received ALC at a dosage of 3 g/day, 21 received ALC at a dosage of 1 g/day, and 20 were given placebo. ALC was given intravenously for 10 days, followed by 80 days of oral treatment plus a follow-up period of 45 days. The presence of anhedonic symptoms was determined by the SHAPS (Snaith-Hamilton Pleasure Scale) and the VASa (Visual Analogue Scale for Anhedonia); negative and melancholic symptoms were evaluated by the SANS (Scale for the Assessment of Negative Symptoms), and the BRMS (Bech-Rafaelsen Melancholia Scale).

Results

The natural course of anhedonia in the placebo group showed a decline until day 30 and remains stable for the rest of the study. Intravenously ALC accelerated the improvement of anhedonia reaching constant low levels early, on day 10. At this step levels of anhedonia (SHAPS, VASa) and melancholic symptoms (BRMES) resulted significantly reduced (p < 0.05) in both the ALC 3 g and ALC 1 g groups with respect to placebo; SANS scores significantly reduced only in the ALC 1 g respect to placebo (p = 0.014). During oral treatment with ALC, anhedonia scores did not differ from placebo.

Conclusion

Intravenously ALC was effective in accelerating the abstinence-associated improvement of anhedonia, melancholic and negative symptoms, whereas oral ALC treatment starting on day 10 showed no further improvements. Accordingly, in alcohol dependent subjects, ALC may be considered as a new potentially useful drug for the treatment of anhedonia.     

Improvements in both psychosis and motor signs in Parkinson's disease, and changes in regional cerebral blood flow after electroconvulsive therapy

Purpose

Psychotic symptoms in Parkinson's disease (PD) are relatively common and, in addition to creating a disturbance in patients' daily lives, have consistently been shown to be associated with poor outcome. The use of anti-PD medications has been the most widely identified risk factor for PD psychosis (PDP). However, the pathophysiology of PDP remains unclear. Although the efficacy of electroconvulsive therapy (ECT) for PD had been pointed out, only one study has demonstrated the effectiveness of ECT on both psychotic symptoms and motor symptoms. The aim of this study was to examine the acute effectiveness of ECT on PD and to identify the brain areas associated with PDP.

Methods

The study was conducted at Juntendo University Hospital in Tokyo. Eight patients with L-DOPA- or dopamine (DA) agonist-induced PDP, who were resistant to quetiapine treatment, were enrolled. Severity of PD was evaluated using the Hoehn and Yahr stage. Psychotic symptoms were evaluated using multiple measures from the Scale for the Assessment of Positive Symptoms (SAPS). Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc ECD SPECT) was used to assess regional cerebral blood flow (rCBF) before and after a course of ECT. A voxel-by-voxel group analysis was performed using Statistical Parametric Mapping (SPM5).

Results

Our study clearly demonstrated that PDP was significantly less severe after ECT than before ECT, as indicated by change in mean SAPS total domain score (t = 7.2, P = 0.0002). Furthermore, the patients showed significant improvement in Hoehn and Yahr stage after ECT (t = 11.7, P < 0.0001). A further notable observation was significant increase in rCBF in the right middle frontal gyrus after ECT.

Conclusion

We conclude that a course of ECT produced notable improvements not only in PDP but also in the severity of PD. The findings of change in rCBF suggest implications for dysfunction in the middle frontal region for patients with PDP.     

Verbal learning contributes to cognitive insight in schizophrenia independently of affective and psychotic symptoms

Objective

Patients with schizophrenia exhibit distorted beliefs and experiences, and their own evaluation of this is labeled cognitive insight. We examined the relationship between cognitive insight and neurocognition, as well as the contribution of neurocognition in explaining cognitive insight.

Method

Clinically characterized patients with schizophrenia (n = 102) were assessed with a measure of cognitive insight, Beck Cognitive Insight Scale (BCIS) and a neuropsychological test battery. The contribution of neurocognition to the explained variance in BCIS components self-reflectiveness (i.e. objectivity and reflectiveness) and self-certainty (i.e. overconfidence in own beliefs) was examined controlling for current affective and psychotic symptoms.

Results

A significant negative correlation was found between self-certainty and verbal learning, whereas no associations were found between self-reflectiveness and any of the neuropsychological tests. Verbal learning was added significantly to the explained variance in self-certainty after controlling for potential confounders.

Conclusion

High self-certainty was associated with poor verbal learning. This suggests that overconfidence in own beliefs is associated with cognitive dysfunction in schizophrenia.     

Effects of discontinuation of long-term biperiden use on cognitive function and quality of life in schizophrenia

Background

The high use of long-term antiparkinsonian anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual discontinuation of biperiden, an anticholinergic drug, on cognitive function and quality of life (QOL) in schizophrenia.

Methods

Thirty-four schizophrenic patients who had received a second-generation antipsychotic (SGA) with concomitant biperiden for at least 3 months were enrolled. Before and 4 weeks after discontinuation of biperiden, the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J) and the Schizophrenia Quality of Life Scale (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare the practice effect on BACS-J, 10 chronic patients with schizophrenia were assessed without tapering biperiden.

Results

Biperiden was discontinued safely in most patients, and no emergent extrapyramidal symptoms were observed. Significant improvements were shown in attention, processing speed, and composite score, as measured by the BACS-J without practice effect. In addition, the psychosocial condition score on the SQLS-J and the general psychopathology score on the PANSS significantly improved after biperiden discontinuation.

Conclusion

Discontinuation of long-term biperiden use may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects.     

Suicidality in temporal lobe epilepsy: measuring the weight of impulsivity and depression

Objective

The aim of the work described here was to measure the role of psychopathological features, specifically impulsivity and depression, in suicidality in patients with temporal lobe epilepsy (TLE).

Methods

Neuropsychiatric evaluation of 66 outpatients with TLE was performed with the following instruments: a structured clinical interview (Mini International Neuropsychiatric Interview Plus), the Barratt Impulsiveness Scale, the Hamilton Anxiety Scale, the Beck Depression Inventory, and the Brief Psychiatric Rating Scale.

Results

A current Axis I psychiatric diagnosis, mainly mood and anxiety disorders, was assigned to 37 subjects (56.1%) Presence of suicide risk was identified in 19 patients (28.8%), and 14 (21.2%) had attempted suicide. Frequency of seizures (P = 0.012), current major depression (P = 0.001), and motor impulsivity (P = 0.005) were associated with suicide risk on univariate analysis. Logistic regression stressed the main relevance of major depression (OR = 12.82, 95% CI = 2.58-63.76, P = 0.002) and motor impulsivity (OR = 1.21, 95% CI = 1.06-1.38, P = 0.005) to suicide risk.

Conclusion

Depression has a major influence on suicidality in epilepsy. Motor impulsivity is also relevant and may be an important component of depression in TLE associated with suicide risk.     

Mirtazapine augmentation enhances cognitive and reduces negative symptoms in schizophrenia patients treated with risperidone: a randomized controlled trial

This preliminary study aimed to determine if adding mirtazapine to risperidone might improve negative and cognitive symptoms in schizophrenia. In an 8-week, double-blind clinical trial, we randomly assigned 21 stabilized outpatients with schizophrenia undergoing risperidone treatment to adjunctive treatment with either mirtazapine or a placebo. The mirtazapine group exhibited a statistically significant improvement in cognitive function, including vocabulary and immediate memory, and negative symptoms (as measured by negative symptom scales) and showed an adverse effect of 5.83 kg mean weight gain. This study suggests augmenting risperidone with mirtazapine can effectively improve both negative and some cognitive symptoms of schizophrenia.

Research highlights

? Mirtazapine enhances some cognitive symptoms of schizophrenia. ? Mirtazapine reduces negative symptoms of schizophrenia.     

Hopelessness, a potential endophenotpye for suicidal behavior, is influenced by TPH2 gene variants

Objectives

Hopelessness is one of the strongest risk factors for suicidal behavior but relevant genetic studies are poorly available. Tryptophan hydroxylase (TPH) is widely considered to be a good candidate for genetic association studies on depression and suicide, however, investigations on these complex, multifactorial phenotypes have resulted in conflicting data. We hypothesized that hopelessness could be a mediating phenotype between TPH2 gene, depression and suicidal behavior.

Methods

Depressive phenotype and suicidal risk were investigated of 760 individuals from general population by Zung Self Rating Depression Scale (ZDS), Beck's Hopelessness Scale (BHS) and a detailed background questionnaire. All participants' DNA samples were genotyped for 7 tag SNPs in TPH2 gene. Generalized linear models were performed for single marker association studies and p-values were corrected by Bonferroni criteria. In haplotype analyses score tests were used and permutated p-values were computed.

Results

Four SNPs of TPH2 gene showed association with hopelessness but only rs6582078 had a significant effect on the BHS scores after Bonferroni's correction; GG individuals had significantly higher BHS scores, while GT and TT had intermediate and lower BHS scores respectively (p = 0.0047). Compared with other genotypes, homozygous GG individuals also had almost three times greater estimated suicidal risk, as did carriers of the AA genotype of rs6582078 (OR = 2.87; p = 0.005) and also of rs1352250 (OR = 2.86; p = 0.006). A risk and a protective haplotype of TPH2 gene were also identified in association with hopelessness. ZDS scores have not shown any association with TPH2 gene.

Conclusions

We found that hopelessness, with its allied increased suicidal risk was strongly associated with TPH2 gene variants in multiple tests. These findings suggest that TPH2 gene confers risk for suicidal behavior while hopelessness can be a potential endophenotype for suicidal vulnerability.     

Baseline platelet size is increased in patients with acute coronary syndromes developing early stent thrombosis and predicts future residual platelet reactivity. A case-control study

Introduction

Pre-procedural predictors of early stent thrombosis (ST) and future response to platelet inhibitors are in demand. We sought to evaluate the impact of baseline platelet indices on the occurrence of early ST and future residual platelet reactivity.

Materials and methods

Hundred and eight patients with acute coronary syndromes (ACS) in whom stents were implanted were included: 36 consecutive ST cases and 72 matched controls. Platelet indices assessed with flow cytometry before stent implantation were retrieved from the department's data base. Residual platelet reactivity specific to aspirin (aspirin reaction units-ARU) and clopidogrel (P2Y12 reaction units-PRU) was assessed prospectively with VerifyNow^® under dual antiplatelet treatment.

Results

Platelet size reported as mean platelet volume (MPV) or proportion of large platelets (LPLT) was significantly higher in ST cases compared with controls (10.4, 95% confidence intervals [CI], 10.1-10.8 vs. 9.7, CI, 9.5-9.9, P = 0.0004 and 35.8, CI, 34.2-37.3 vs. 33.3, CI, 32.2-34.3, P = 0.007, respectively). Dual aspirin and clopidogrel poor-responsiveness was diagnosed significantly more often in ST cases than in controls (19.6% vs. 1.4%, P = 0.004), whereas no difference was observed for single aspirin or clopidogrel poor-responsiveness. A strong correlation was found between MPV and both, ARU (r = 0.66, P < 0.0001) and PRU (r = 0.55, P < 0.0001). Similarly, higher LPLT was associated with higher ARU (r = 0.47, P < 0.0001) and PRU (r = 0.38, P = 0.0001).

Conclusions

Baseline platelet size is increased in patients with ACS developing early ST and correlates with future residual platelet reactivity under aspirin and clopidogrel therapy. Dual but not isolated aspirin or clopidogrel poor-responsiveness appears to be associated with early ST.     

A pilot study of antipsychotic prescribing decisions for acutely-Ill hospitalized patients

Background

Evidence on antipsychotic prescribing decisions is limited. This pilot study quantified factors considered in choosing an antipsychotic and evaluated the influence of metabolic status on treatment decisions.

Methods

Prescribing decisions by 4 psychiatrists were examined based on 80 adult patients initiated on antipsychotic medication diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder by DSM-IV criteria, who were admitted to an acute inpatient psychiatric program of an urban Veterans Affairs Medical Center. The primary analysis examined the association between antipsychotic treatment choice and predictions of symptom control and metabolic risk. Secondary analyses included comparison of the chosen and next best treatments in predicted symptom control and metabolic risk, the frequency of reasons cited for drug choice, and the association between treatment choice and patients' baseline metabolic parameters. Mean differences and odds-ratios (OR) with 95% confidence intervals were used to compare relationships between treatment choice, ratings of risk and metabolic data.

Results

Antipsychotic choice correlated significantly with ratings of predicted symptom control (OR = .92, p = 0.02) and metabolic risk (OR = .88, p = 0.01). Mean differences between the chosen and next best drugs were significant but small in predicted symptom control (F = 2.81, df = 3, 76; p < 0.05) compared with larger differences in anticipated metabolic risk (F = 14.80, df = 3, 76; p = 0.0001). Nevertheless, among 24 identified reasons influencing drug selection, anticipated metabolic risk of chosen antipsychotics was cited less often than efficacy measures. In contrast to psychiatrists' expectations of metabolic risk with selected treatments, we found that patients' actual baseline BMI, fasting glucose, blood pressure, and Framingham risk levels did not necessarily predict antipsychotic treatment choice independent of other factors.

Conclusion

In the context of an acute psychiatric hospitalization, pilot data suggest that predictions of symptom control and metabolic risk correlated significantly with antipsychotic choice, but study psychiatrists were willing to assume relative degrees of metabolic risk in favor of effective symptom control. However, prescribing decisions were influenced by numerous patient and treatment factors. These findings support the potential utility of the ATCQ questionnaire in quantifying antipsychotic prescribing decisions. Further validation studies of the ATCQ questionnaire could enhance translation of research findings and application of treatment guidelines.     

Gender differences in the effects of peroxisome proliferator-activated receptor γ2 gene polymorphisms on metabolic adversity in patients with schizophrenia or schizoaffective disorder

Objective

Metabolic syndrome (MS) is a major health problem in schizophrenic patients. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is one of the candidate genes responsible for the liability to metabolic problems. In this study, we investigated the effect of the PPARγ2 gene Pro12Ala and C161T polymorphisms on metabolic adversities in patients with schizophrenia or schizoaffective disorder.

Methods

Metabolic profiles and PPARγ2 gene polymorphisms were determined in 600 patients (309 men and 291 women) with a clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic indices and components of MS were compared between patients with different Pro12Ala or C161T genotypes.

Results

In the whole population, the allele frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms had no significant effect on obesity or metabolic-related traits. However, following gender stratification of the data, we found female 12Ala allele carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI = 1.1-14.2, p = 0.04) and hypertension (OR = 2.9, 95% CI = 1.2-7.4, p = 0.02) than female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and systolic blood pressure (p = 0.01), and were at greater risk of developing hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed that PPARγ2 gene polymorphisms were significantly associated with HDL-C level in men and blood pressure in women.

Conclusions

We did not find an association of PPARγ2 gene polymorphisms with MS or obesity in our schizophrenia sample. But further analyses by gender stratification revealed gender-specific differences in the effect of different PPARγ2 genotypes on certain metabolic adversities in these patients.     

Soluble interleukin-2 receptor levels correlated with positive symptoms during quetiapine treatment in schizophrenia-spectrum disorders

Background

Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients. Thus far, the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor (sIL-2R) associated with clozapine treatment. Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology.

Methods

Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance use disorder (cannabis > alcohol > cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n = 24) was 466.6 mg ± 227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison purposes.

Results

On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, compared to controls. Plasma sIL-2R further increased after quetiapine treatment (p = 0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p < 0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r = − 0.524; p = 0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms.

Conclusion

These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related.     

Pain due to osteoarthritis may impair the early outcome of deep brain stimulation in Parkinson's disease

Objective

To analyse postoperative pain due to osteoarthritis in patients with Parkinson's disease submitted to bilateral subthalamic nucleus stimulation.

Methods

Fifty-three parkinsonian patients (mean age, 59.9 ± 8.3 years; mean disease duration, 11.5 ± 4.2 years) referred for subthalamic nucleus stimulation were enrolled. Patients were prospectively asked to refer and describe any pain due to osteoarthritis they experienced at any time during the preoperative period and within the 6 postoperative months. Pre-existing pain due to osteoarthritis, therapeutic changes, parkinsonian motor disability and weight gain were assessed as explanatory factors for occurrence pain due to osteoarthritis after surgery.

Results

After surgery, thirty patients (57%) complained of pain due to osteoarthritis whereas all demonstrated great functional improvement. Twenty (67%) among the 30 experienced similar pain sensation before surgery. Symptoms occurred rapidly, between 4 and 26 postoperative weeks. Multiple stepwise regression analysis showed that pre-existing pain due to osteoarthritis, 6-month postoperative UPDRS III motor score and axial sub-score improvements in the off-drug/on-stimulation condition were accurate independent predictors of pain due to osteoarthritis after surgery (F(8, 41) = 2.20, p < 0.047).

Conclusion

Our results highlight the high prevalence of pain due to osteoarthritis arising shortly after subthalamic implantation. An accurate pain and osteo-articular assessment should be performed preoperatively in parkinsonian candidates for subthalamic nucleus stimulation in order to limit occurrence of complications in the early postoperative period.     

Effects of risperidone on glucose metabolism in Chinese patients with schizophrenia: a prospective study

Background

While most of the second generation antipsychotic agents are associated with abnormal glucose metabolism, previous studies have shown that risperidone has relatively little effect upon blood glucose levels. This study aimed to explore the effect of risperidone on the glucose-regulating mechanism of patients with schizophrenia by using the oral glucose tolerance test (OGTT), measuring insulin and C-peptide levels.

Methods

Thirty inpatients with schizophrenia taking risperidone were studied. All the patients were given a simplified OGTT at baseline and six weeks after treatment. Plasma glucose, insulin, and C-peptide concentrations were measured at fasting, then 1 and 2 h after OGTT respectively. Other data, including demographic characteristics and plasma drug concentrations, were also recorded.

Results

(1) There was no significant increase in the proportion of patients demonstrating abnormal plasma glucose levels compared with baseline (p = 1.000, McNemar test); (2) risperidone was associated with elevated insulin concentrations (p = 0.013), C-peptide levels (p = 0.020), insulin/glucose ratio (p = 0.020) and BMI (p < 0.01); (3) no sex differences in glucose-related measures were observed.

Conclusion

Risperidone treatment may be associated with alterations in glucose-regulating mechanisms in patients with schizophrenia.     

Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: A prospective multicenter survey

Introduction

Although supplementation with antithrombin (AT) concentrates has been widely accepted for the treatment of disseminated intravascular coagulation (DIC) in Japan, the effects and adverse effects have not been investigated.

Materials and Methods

We conducted a nonrandomized multi-institutional survey. A total of 729 septic DIC patients with AT activity levels of 70% or lower, who had undergone AT substitution at either 1500 IU/day or 3000 IU/day for consecutive 3 days were analyzed. Of these, 650 and 79 patients had received 1500 IU/day (AT1500 group) and 3000 IU/day (AT3000 group), respectively.

Results

Bleeding events were observed in 6.52% of patients (severe bleeding, 1.71%). A significant decrease in initial AT level (below 50%) was observed in 69.6% of patients in AT3000 group and 48.2% in AT1500 group, and this difference was significant (P < 0.01). A logistic-regression analysis conducted using age, gender, body weight, initial AT activity, and supplemented AT dose, revealed that higher initial AT activity (odds ratio (OR), 1.032; P < 0.001), AT dose of 3000 IU/day (OR, 1.912; P = 0.026), and age (OR, 0.985; P = 0.023) were significant factors for improved survival.

Conclusion

The risk of severe bleeding is less than 2%, and concomitant administration of heparin did not increase the risk. The survival in AT1500 group was 65.2%, while that in AT3000 group was 74.7%.     

Genome-wide association study of blood pressure response to methylphenidate treatment of attention-deficit/hyperactivity disorder

Objective

We conducted a genome-wide association study of blood pressure in an open-label study of the methylphenidate transdermal system (MTS) for the treatment of attention-deficit/hyperactivity disorder (ADHD).

Method

Genotyping was conducted with the Affymetrix Genome-Wide Human SNP Array 6.0. Multivariate association analyses were conducted using the software package PLINK. After data cleaning and quality control we tested 316,934 SNPs in 140 children with ADHD.

Results

We observed no genome-wide statistically significant findings, but a SNP in a K⁺-dependent Na⁺/Ca²⁺ exchanger expressed in vascular smooth muscle (SLC24A3) was included in our top associations at p < 1E-04. Genetic enrichment analyses of genes with ≥ 1 SNP significant at p < 0.01, implicated several functional categories (FERM domain, p = 5.0E-07; immunoglobulin domain, p = 8.1E-06; the transmembrane region, p = 4.4E-05; channel activity, p = 2.0E-04; and type-III fibronectins, p = 2.7E-05) harboring genes previously associated with related cardiovascular phenotypes.

Conclusions

The hypothesis generating results from this study suggests that polymorphisms in several genes consistently associated with cardiovascular diseases may impact changes in blood pressure observed with methylphenidate pharmacotherapy in children with ADHD.