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.     

Effects of haloperidol and risperidone on cerebrohemodynamics in drug-naive schizophrenic patients

Background

Use of antipsychotics may be associated with cerebrovascular adverse events in psychotic patients. In this study, the effects of haloperidol and risperidone on the cerebral hemodynamics and the possible relationships between antipsychotics and cerebrovascular risks tendency were evaluated by Transcranial Doppler ultrasonography (TCD).

Methods

Twenty drug-na?¨ve schizophrenic patients and 20 normal control subjects were included. The patients were divided into haloperidol- and risperidone-treated groups and received treatment for 8 weeks double-blindly. The subjects’ cerebral blood flow mean velocities (MV) and pulsatility index (PI) were measured weekly by TCD. The Positive and Negative Syndrome Scale for schizophrenia (PANSS) was used to assess the patients’ psychopathological symptoms.

Results

Increased MV and decreased PI were found significantly in drug-na?¨ve schizophrenic patients than normal subjects before treatment (p < 0.01). The decreased PI could be normalized after 8 weeks of antipsychotic treatment, while the increased MV could not. Treatment with haloperidol could significantly increase the PI than the treatment with risperidone (p < 0.01) throughout the treatment course. The PANSS scores of both groups were significantly improved (p < 0.05) at the endpoints of treatment.

Conclusions

Our findings indicate that haloperidol may affect the cerebral hemodynamics in drug-na?¨ve schizophrenics more prominently than that of risperidone via TCD monitoring.     

Antipsychotic dose and diminished neural modulation: a multi-site fMRI study

Background

The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.

Methods

Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.

Results

Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho = − 0.32, P = 0.0039), motor/caudate (rho = − 0.22, P = 0.046), posterior default mode (rho = 0.26, P = 0.020), and anterior default mode networks (rho = 0.24, P = 0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t₇₇ = 2.01, P = 0.048).

Conclusion

The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia.     

Weight gain and ghrelin level after olanzapine monotherapy

Background

The present study aimed to explore the association between weight gain and ghrelin among schizophrenic patients under olanzapine treatment. The relationships among weight gain and adiponectin, fasting glucose, and lipid profile were also investigated.

Methods

This case-control study recruited 66 schizophrenic patients from the Chung Shan Medical University Hospital in central Taiwan. All of them were undergoing olanzapine monotherapy and were categorized into weight gain (WG) and non-weight gain (NWG) groups. Subjects in the control group (CG) were recruited from a healthy community population based on a health survey (n = 119). Multivariate logistic regression was used to explore the association of ghrelin with weight gain.

Results

The 66 schizophrenic patients had a mean age of 36.3 ± 9.6 years, with 50% females. They received olanzapine treatment for a mean period of 8.3 ± 7.5 years. The control group had a mean age of 38.9 ± 9.3 years and 52.9% were females. Comparing fasting serum ghrelin levels, the WG group had the lowest mean value (822.3 ± 253.1 pg/ml) while the control group had the highest mean value (1261.2 ± 1639.7 pg/ml), with a significant difference between the two (p = 0.01). In contrast, there was no difference in adiponectin levels among the three groups. The WG and NWG groups had higher diastolic blood pressure than the control group, but systolic blood pressure was the same in all three groups. There was no difference in the total cholesterol level although the WG and NWG groups had higher triglyceride (TG) and glucose levels than the control group.

Conclusions

Weight gain after olanzapine treatment is associated with lower ghrelin level. Olanzapine is linked to elevated diastolic pressure, TG, and glucose, regardless of the weight gain.     

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.     

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.     

High plasma nesfatin-1 level in patients with major depressive disorder

Aim

In the present study, our aim was to determine the changes in the plasma concentrations of a recently discovered peptide hormone nesfatin-1 in patients with major depressive disorder and then to make a comparison with the control group.

Method

Subjects in the patient group were randomly selected from Mustafa Kemal University, Medical School, Research and Training Hospital, Psychiatry Department, Outpatient Clinic and subjects in the control group were selected from healthy volunteers. Healthy control subjects were matched in terms of weight and body mass index. Hamilton Depression Rating Scale (HAM-D) was applied to both groups. ELISA method was used for measurement of plasma nesfatin-1 levels.

Results

The average nesfatin-1 level was statistically higher in patients with major depressive disorder than in the control group (p < 0.001). A positive correlation was observed between plasma nesfatin-1 levels and HAM-D scores both in the patient group (r = 0.59, p < 0.001) and in the control group (r = 0.58, p < 0.001).

Conclusion

Our findings suggest a possible relationship between major depressive disorder and high plasma nesfatin-1 level.     

Sunshine-exposure variation of human striatal dopamine D2/D3 receptor availability in healthy volunteers

Background

In addition to the serotonergic system, the central dopaminergic system has been reported to be correlated with seasonality. The aim of this study was to explore the difference in striatal dopamine D₂/D₃ receptor availability between healthy volunteers who had a high-sunshine exposure and those who had a low exposure.

Methods

Sixty-eight participants were enrolled, and those in the upper and lower quartiles in terms of sunshine exposure were categorized into high- (n = 17) and low-sunshine-exposure (n = 18) subgroups. Single photon emission computed tomography with [¹²³I] iodo-benzamide was used to measure striatal dopamine D₂/D₃ receptor availability.

Results

Striatal dopamine D₂/D₃ receptor availability was significantly greater in the subjects with high-sunshine exposure than in those with low-sunshine exposure (F = 7.97, p = 0.01) after controlling for age, sex, and smoking status.

Limitations

Different subjects were examined at different time points in our study. In addition, the sex and tobacco use distributions differed between groups.

Conclusion

The central dopaminergic system may play a role in the neurobiological characteristics of sunshine-exposure variation.     

Visual naming performance after ATL resection: Impact of atypical language dominance

Purpose

To characterize the interaction between language dominance and lateralization of the epileptic focus for pre- and postoperative Boston Naming Test (BNT) performance in patients undergoing anterior temporal lobectomy (ATL).

Methods

Analysis of pre- and postoperative BNT scores depending on lateralization of language as measured by the intracarotid amobarbital procedure (IAP) versus lateralization of the temporal lobe epileptic focus.

Results

Changes between pre- and postoperative BNT performance depended on epilepsy lateralization (effect size = 0.189) with significant decrease in patients undergoing left ATL. Subgroup analysis in these showed that postoperative decline in BNT scores was significant in patients with atypical (n = 14; p < 0.05), but did not reach statistical significance in patients with left language dominance (n = 36; p = 0.09). Chi-square test revealed a trend of higher proportions of patients experiencing significant postsurgical deterioration in naming performance in atypical (57.1%) as compared to left language dominance (30.6%; p = 0.082). Surgical failure was also associated with greater decline of BNT scores and was more common in atypical than in left language dominant patients (χ² (1, n = 98) = 4.62, p = 0.032). Age of onset, duration of epilepsy, and seizure frequency had no impact on changes in BNT performance.

Conclusion

Atypical language dominance is a predictor of change in visual naming performance after left ATL and may also impact postsurgical seizure control. This should be considered when counseling surgical candidates.     

Impaired ability to shift weight onto the non-paretic leg in right-cortical brain-damaged patients

Background

: Stroke patients experience postural instability that can impede functional improvements in their gait. However, the precise functions of the dominant and non-dominant hemispheres in controlling static standing posture and weight-bearing remain unclear.

Objective

: To investigate differences in balancing ability between right-handed patients with right and left hemispheric lesions.

Methods

: Weight shifting was quantitatively evaluated to determine the ability of patients to control their balance in a static posture and during conscious weight shifting onto the paretic or non-paretic leg. Participants were enrolled from a consecutive series of stroke patients attending a rehabilitation program (n = 49; 31 male, 18 female; mean age 69.3 ± 9.4 years). Age-matched normal controls were recruited as volunteers (n = 12; 4 male, 8 female; mean age 67.9 ± 4.9 years).

Results

: Patients with cortical lesions in the right hemisphere were able to shift less weight onto the non-paretic leg than patients with cortical lesions in the left hemisphere (p < 0.05). There were no correlations between the existence of unilateral spatial neglect and the percentage of weight shifted onto the non-paretic leg, static standing posture (r = 0.27, p = 0.40) or dynamic standing posture (r = −0.37, p = 0.24). In contrast, there was a significant correlation between the percentage of weight consciously shifted onto the non-paretic leg and the existence of anosognosia (r = 0.74, p = 0.006), but not between static standing posture and anosognosia (r = −0.15, p = 0.63).

Conclusion

: Patients with right cortical hemispheric lesions were able to shift less body weight onto their non-paretic leg. These patients should be encouraged to practice shifting their weight towards their non-paretic leg to improve their balance.     

Assessing the infrequent oral supplementation of olanzapine long-acting injection in the treatment of schizophrenia

Objective

Adding another antipsychotic to a treatment regimen was previously used in evaluating the medication's efficacy. Supplementation of depot antipsychotics with oral antipsychotics is particularly meaningful because depot formulations are typically chosen for patients struggling with adherence to oral antipsychotics. This post-hoc analysis assessed supplementation of olanzapine long-acting injection (olanzapine-LAI) with oral olanzapine.

Subjects and methods

We used 12 months of data from an open-label, single-arm extension study of patients with schizophrenia or schizoaffective disorder (N = 931) treated with olanzapine-LAI. The prevalence, duration, time to first supplementation, and best predictors of oral supplementation were assessed.

Results

Oral supplementation occurred in 21% of patients for a median of 31 days with mean modal dose of 10.8 mg/day. Mean time to first supplementation was shorter for patients who were at least moderately ill at baseline compared to less ill patients (47 vs. 97 days, p < 0.001). Best predictors of oral supplementation included a more severe illness profile at baseline, lower olanzapine-LAI dose prior to oral supplementation, supervised living arrangements, and being African-American.

Conclusion

Supplementation of olanzapine-LAI appears to be infrequent, of relatively short duration, and reserved for more severely ill patients who may require a targeted rescue medication due to signs of impending relapse.     

Efficacy and safety of noradrenalin reuptake inhibitor augmentation therapy for schizophrenia: A meta-analysis of double-blind randomized placebo-controlled trials

Background

We performed an updated meta-analysis of noradrenalin reuptake inhibitor (NRI) augmentation therapy in patients with schizophrenia treated with antipsychotics based on a previous meta-analysis (Singh et al.).

Methods

PubMed, Cochrane Library databases, and PsycINFO citations were searched from their inception to June 10, 2013 without language restrictions. We conducted a systematic review and meta-analysis of individual patient data from randomized controlled trials comparing NRI augmentation therapy with placebo. The outcome measure for efficacy was the psychopathology of schizophrenia and the measures for safety were discontinuation rate and several side effects. We used standardized mean differences (SMD) to estimate treatment effects for continuous variables, and risk ratios (RR) for dichotomous variables, with their 95% confidence intervals (CIs). A random-effects model was used.

Results

Nine studies (4 atomoxetine studies, 3 reboxetine studies, 1 reboxetine–betahistine combination study and 1 mazindol study, total n = 298) were identified. No statistically significant effects of NRI augmentation therapy on overall (p = 0.90), positive (p = 0.81), and negative (p = 0.89) symptoms were found. NRI augmentation therapy was marginally superior to placebo for efficacy of depressive symptoms (SMD = −1.08, p = 0.05). Dropout due to all-cause (p = 0.70), inefficacy (p = 0.64), or adverse events (p = 0.18) was similar in both groups. NRI augmentation therapy showed a significantly lower increase or larger reduction in body weight than placebo (SMD = −0.47, p = 0.03). Reboxetine augmentation was associated with less weight gain that placebo in antipsychotic treated schizophrenia patients (SMD = −0.78, p = 0.0001).

Conclusion

NRIs may exert an effect on depressive symptoms, and seem to be well-tolerated treatments.     

Sleep deprivation and accidental fall risk in children

Objectives

To look for an association between sleep deprivation and risk of accidental falls (AF) in children.

Methods

A questionnaire was applied to two groups of children aged 1-14 years, encompassing children observed in an emergency room for AF (G1) and children attending health care visits (HV) (G2). Collected data included demographic characteristics, medical history, previous week’s sleep pattern (PWSP), sleep duration and sleep pattern in the preceding 24 h, mechanism of fall, and injury severity. Exclusion criteria: acute or chronic disease or exposure to drugs interfering with sleep. Statistical analyses included Fisher’s exact test, Pearson Chi-square, Fisher-Freeman-Halton test, T and Mann-Whitney tests for independent samples, and multivariate logistic regression (α = 5%).

Results

We obtained 1756 questionnaires in G1 and 277 in G2. Of those, 834 in G1 and 267 in G2 were analyzed. We found an increased risk of AF in boys (OR 1.6; 95% CI 1.2-2.4). After controlling for age, gender, summer holidays, parental education and profession, lack of naps and PWSP were associated with increased risk (OR 2.1; 95% CI 1.3-3.3 and OR 2.7; 95% CI 1.2-6.1). In 3-5 year-old children there was an association between AF and a shorter than usual sleep duration in the previous 24 h (p = 0.02).

Conclusions

To our knowledge, our study is the largest so far to assess the association between sleep deprivation and childhood injury. It evidences a protective effect of naps in children. Sleep duration of less than 8 h increases risk of AF. Pre-schoolers may be particularly susceptible to sleep deprivation.     

Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain

Background

Antipsychotic-induced weight gain (AIWG) is a serious side-effect of antipsychotic medication leading to metabolic syndrome and increased cardiovascular morbidity. Unfortunately, there are still no valid predictors to assess an individual's risk to gain weight. Previous studies have indicated an impact of genetic variation in the genes encoding leptin, LEP, and leptin receptor, LEPR, on AIWG, but results have not been conclusive. Thus, we investigated polymorphisms in both genes for an association with AIWG.

Methods

A total of 181 schizophrenic and schizoaffective patients treated with various antipsychotics were included. In a small subset of patients, leptin plasma levels were additionally obtained. Five polymorphisms in LEP and LEPR (LEP: rs7799039 (-2548G/A polymorphism), rs10954173, rs3828942; LEPR: rs1327120, rs1137101 (Q223R polymorphism) were genotyped using TaqMan assays. Statistical association with % weight change from baseline weight was performed using ANCOVA with baseline weight as covariate.

Results

ANCOVA showed a non-significant trend for genotype association of the rs7799039 marker (p = .068). No significant association of the other LEP and LEPR SNPs with AIWG was detected. However, we found a significant association between a haplotype of LEP rs7799039G–rs10954173G–rs3828942G (p = .035) and AIWG. The rs7799039 G-allele (p = .042) and G-allele of rs3828942 (p = .032) were associated with higher weight gain.

Conclusion

Our study supports the hypothesis of an impact of LEP gene variation on AIWG. Limitations of our study include heterogeneous samples, short treatment duration and multiple comparisons. Our findings were compared to previous studies in detail in order to provide the readers with a more conclusive picture. However, further studies are warranted including more gene variants and interaction analyses with other genes of the leptin–melanocortin pathway.     

Insulin resistance and metabolic profile in antipsychotic naïve schizophrenia patients

Objectives

Several studies have suggested insulin resistance related to dyslipidemia and body weight in drug treated schizophrenia patients. Although, insulin resistance or impaired glucose tolerance is also reported in antipsychotic naïve schizophrenia patients, their relationship with dyslipidemic changes and body weight is not well established. The present study was undertaken to examine insulin resistance in antipsychotic naïve schizophrenia patients of this region and to evaluate any association between lipid parameters and body weight with their insulin resistance, if any.

Method

Plasma glucose, total serum cholesterol and its LDL, HDL fractions, and serum insulin levels were measured from fasting blood samples of newly diagnosed, antipsychotic naïve schizophrenia patients (n = 30) and matched control group (n = 25) in a hospital based case control study. Homoeostatic model assessment (HOMA) was done to evaluate insulin resistance.

Results

Means of plasma glucose, total serum cholesterol and its LDL, HDL fractions did not vary significantly (p > 0.05) between cases and control. Insulin resistance was significantly increased (p < 0.05) in drug naïve cases. Multiple linear regression analyses did not show any association (p > 0.05) between insulin resistance and lipid parameters.

Conclusions

Newly diagnosed schizophrenia patients were more prone to insulin resistance in our study population. This was not associated with any dyslipidemic changes as the lipid parameters were not elevated in them compared to the healthy controls. It was not dyslipidemia, but some other common genetic or risk factors that might be responsible for the increased insulin resistance in antipsychotic naïve schizophrenia patients in our study population.     

Open adjunctive ziprasidone associated with weight loss in obese and overweight bipolar disorder patients

Objective

To assess effectiveness and tolerability of open adjunctive ziprasidone for weight loss in obese/overweight patients with bipolar disorders (BD) in diverse mood states, taking weight gain-implicated psychotropic medications.

Method

22 obese and three overweight BD patients (20 female; 10 BD-I, 14 BD-II, 1 BD-NOS) with mean ± SD baseline body mass index (BMI) of 31.8 ± 2.5 kg/m² received ZIP (mean final dose 190 ± 92 mg/day) for mean of 79.2 ± 23.2 days. Weight was assessed at six weekly and three biweekly visits. Subjects entered the study in diverse mood states. At baseline, 21 were taking second-generation antipsychotics, 7 lithium, and 1 valproate, which could be reduced/discontinued at investigators’ discretion.

Results

Weight and BMI decreased from baseline to endpoint by 4.5 ± 3.4 kg and 1.6 ± 1.2 kg/m², respectively, at weekly rates of 0.37 kg and 0.13 kg/m², respectively (all p < 0.00001). 48% of patients had at least 5% weight loss. Obesity rate decreased from 88% to 35% (p < 0.0001). Waist circumference decreased 1.6 inches (p = 0.0001). Overall, mood did not change. Patients with at least moderate baseline mood symptoms experienced significant mood improvement, despite 72% patients decreasing/discontinuing weight gain-implicated psychotropic medications. Seven patients discontinued ZIP early: 3 for weight loss inefficacy, and 1 each for viral gastroenteritis, loss of consciousness, pneumonia with hypomania, and lost to follow up.

Conclusion

Open adjunctive ziprasidone may be effective for weight loss in obese/overweight BD patients taking weight gain-implicated psychotropic medications. These preliminary data should be considered with caution due to the open uncontrolled design, small sample size, and brief duration.     

Poor creativity in frontotemporal dementia: A window into the neural bases of the creative mind

Background

The prefrontal cortex (PFC) supports functions critical for creative thinking. Damage to the PFC is expected to impair creativity. Yet, previous works suggested the emergence of artistic talent in patients with frontotemporal lobar degeneration (FTLD), which was interpreted as increased creativity.

Objective

We designed a study in patients with frontal variant (fv) of FTLD in order to verify whether: (1) creativity is impaired after frontal degeneration, (2) poor creativity is associated with frontal dysfunctions, and (3) poor creativity is related to hypoperfusion in specific PFC regions.

Materials and methods

Three groups of subjects were enrolled in the study: fvFTLD patients (n = 17), non-demented Parkinson's disease (PD) patients (n = 12) and healthy controls (n = 17). Participants performed a standardized test of creativity, the Torrance Test of Creative Thinking (TTCT) and tests assessing frontal functions. Brain perfusion was correlated to fvFTLD patients’ performance in the TTCT.

Results

Patients with fvFTLD were strongly impaired in all dimensions of the TTCT, compared to PD patients and controls. Disinhibited and perseverative responses were observed only in fvFTLD patients, leading to “pseudo-creative” responses. Poor creativity was positively correlated with several frontal tests. Poor creativity was also correlated with prefrontal hypoperfusion, particularly in the frontal pole.

Conclusions

Poor creativity is associated with fvFTLD. The results also suggest that the integrity of the PFC (in particular frontopolar) is strongly associated with creative thinking. The emergence of artistic talent in patients with fvFTLD is explained by the release of involuntary behaviors, rather than by the development of creative thinking.     

Clinical predictors of recurrent venous thromboembolism: a single institute experience in Korea

Introduction

Racial disparities in incidence rate as well as risk factors for venous thromboembolism (VTE) exist between Asian and Western populations. Moreover, predictors for recurrent VTE were not identified in Asians. Thus, this study was undertaken to investigate risk factors for recurrent VTE events in Korean people.

Materials and Methods

Three hundred-three patients newly diagnosed as VTE were enrolled from Seoul National University Hospital. Recurrence rate based on risk factors for VTE were investigated. Cumulative incidence of recurrent VTE was calculated by the Kaplan and Meier method. Independent predictors for VTE were determined using Cox proportional hazards model.

Results

After a median follow-up of 44 months, 24 (8%) of 303 patients relapsed for a total observation time of 1,217 patient-year. Cumulative incidences of recurrent VTE were 3% at 1 year, 10% at 5 years, and 18% at 8 years. Independent predictors for recurrent VTE were presence of residual thrombosis (hazard ratio [HR] = 3.1, 95% confidence interval [CI] 1.0-9.3; p = 0.044), antiphospholipid syndrome (APS) (HR = 4.3, 95% CI 1.0-19.0; p = 0.052), and age 50 years or younger (HR = 2.5, 95% CI 1.0-6.6; p = 0.053) by multivariate analysis. Residual thrombosis and APS remained predictive of recurrence by the anticoagulation-period stratified analysis.

Conclusions

In contrast to Western populations, Korean patients with VTE had the lower recurrent rate. Extended anticoagulation is necessary for Korean patients with residual thrombosis or APS.     

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.     

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.