Classification Models for Neurocognitive Impairment in HIV Infection Based on Demographic and Clinical Variables

Objective

We used demographic and clinical data to design practical classification models for prediction of neurocognitive impairment (NCI) in people with HIV infection.

Methods

The study population comprised 331 HIV-infected patients with available demographic, clinical, and neurocognitive data collected using a comprehensive battery of neuropsychological tests. Classification and regression trees (CART) were developed to obtain detailed and reliable models to predict NCI. Following a practical clinical approach, NCI was considered the main variable for study outcomes, and analyses were performed separately in treatment-naïve and treatment-experienced patients.

Results

The study sample comprised 52 treatment-naïve and 279 experienced patients. In the first group, the variables identified as better predictors of NCI were CD4 cell count and age (correct classification [CC]: 79.6%, 3 final nodes). In treatment-experienced patients, the variables most closely related to NCI were years of education, nadir CD4 cell count, central nervous system penetration-effectiveness score, age, employment status, and confounding comorbidities (CC: 82.1%, 7 final nodes). In patients with an undetectable viral load and no comorbidities, we obtained a fairly accurate model in which the main variables were nadir CD4 cell count, current CD4 cell count, time on current treatment, and past highest viral load (CC: 88%, 6 final nodes).

Conclusion

Practical classification models to predict NCI in HIV infection can be obtained using demographic and clinical variables. An approach based on CART analyses may facilitate screening for HIV-associated neurocognitive disorders and complement clinical information about risk and protective factors for NCI in HIV-infected patients.     

Contextual Social Cognition Impairments in Schizophrenia and Bipolar Disorder

Background

The ability to integrate contextual information with social cues to generate social meaning is a key aspect of social cognition. It is widely accepted that patients with schizophrenia and bipolar disorders have deficits in social cognition; however, previous studies on these disorders did not use tasks that replicate everyday situations.

Methodology/Principal Findings

This study evaluates the performance of patients with schizophrenia and bipolar disorders on social cognition tasks (emotional processing, empathy, and social norms knowledge) that incorporate different levels of contextual dependence and involvement of real-life scenarios. Furthermore, we explored the association between social cognition measures, clinical symptoms and executive functions. Using a logistic regression analysis, we explored whether the involvement of more basic skills in emotional processing predicted performance on empathy tasks. The results showed that both patient groups exhibited deficits in social cognition tasks with greater context sensitivity and involvement of real-life scenarios. These deficits were more severe in schizophrenic than in bipolar patients. Patients did not differ from controls in tasks involving explicit knowledge. Moreover, schizophrenic patients’ depression levels were negatively correlated with performance on empathy tasks.

Conclusions/Significance

Overall performance on emotion recognition predicted performance on intentionality attribution during the more ambiguous situations of the empathy task. These results suggest that social cognition deficits could be related to a general impairment in the capacity to implicitly integrate contextual cues. Important implications for the assessment and treatment of individuals with schizophrenia and bipolar disorders, as well as for neurocognitive models of these pathologies are discussed.     

Neurological Soft Signs and Their Relationships to Neurocognitive Functions: A Re-Visit with the Structural Equation Modeling Design

Background

Neurological soft signs and neurocognitive impairments have long been considered important features of schizophrenia. Previous correlational studies have suggested that there is a significant relationship between neurological soft signs and neurocognitive functions. The purpose of the current study was to examine the underlying relationships between these two distinct constructs with structural equation modeling (SEM).

Methods

118 patients with schizophrenia and 160 healthy controls were recruited for the current study. The abridged version of the Cambridge Neurological Inventory (CNI) and a set of neurocognitive function tests were administered to all participants. SEM was then conducted independently in these two samples to examine the relationships between neurological soft signs and neurocognitive functions.

Results

Both the measurement and structural models showed that the models fit well to the data in both patients and healthy controls. The structural equations also showed that there were modest to moderate associations among neurological soft signs, executive attention, verbal memory, and visual memory, while the healthy controls showed more limited associations.

Conclusions

The current findings indicate that motor coordination, sensory integration, and disinhibition contribute to the latent construct of neurological soft signs, whereas the subset of neurocognitive function tests contribute to the latent constructs of executive attention, verbal memory, and visual memory in the present sample. Greater evidence of neurological soft signs is associated with more severe impairment of executive attention and memory functions. Clinical and theoretical implications of the model findings are discussed.     

Emotion-Related Visual Mismatch Responses in Schizophrenia: Impairments and Correlations with Emotion Recognition

Background and Objectives

Mismatch negativity (MMN) is an event-related potential (ERP) measure of preattentional sensory processing. While deficits in the auditory MMN are robust electrophysiological findings in schizophrenia, little is known about visual mismatch response and its association with social cognitive functions such as emotion recognition in schizophrenia. Our aim was to study the potential deficit in the visual mismatch response to unexpected facial emotions in schizophrenia and its association with emotion recognition impairments, and to localize the sources of the mismatch signals.

Experimental Design

The sample comprised 24 patients with schizophrenia and 24 healthy control subjects. Controls were matched individually to patients by gender, age, and education. ERPs were recorded using a high-density 128-channel BioSemi amplifier. Mismatch responses to happy and fearful faces were determined in 2 time windows over six regions of interest (ROIs). Emotion recognition performance and its association with the mismatch response were also investigated.

Principal Observations

Mismatch signals to both emotional conditions were significantly attenuated in patients compared to controls in central and temporal ROIs. Controls recognized emotions significantly better than patients. The association between overall emotion recognition performance and mismatch response to the happy condition was significant in the 250–360 ms time window in the central ROI. The estimated sources of the mismatch responses for both emotional conditions were localized in frontal regions, where patients showed significantly lower activity.

Conclusions

Impaired generation of mismatch signals indicate insufficient automatic processing of emotions in patients with schizophrenia, which correlates strongly with decreased emotion recognition.     

Friends and Symptom Dimensions in Patients with Psychosis: A Pooled Analysis

Background

Having friends is associated with more favourable clinical outcomes and a higher quality of life in mental disorders. Patients with schizophrenia have fewer friends than other mentally ill patients. No large scale studies have evaluated so far what symptom dimensions of schizophrenia are associated with the lack of friendships.

Methods

Data from four multi-centre studies on outpatients with schizophrenia and related disorders (ICD F20-29) were included in a pooled analysis (N = 1396). We established whether patients had close friends and contact with friends by using the equivalent items on friendships of the Manchester Short Assessment of Quality of Life or of the Lancashire Quality of Life Profile. Symptoms were measured by the Brief Psychiatric Rating Scale or by the identical items included in the Positive and Negative Syndrome Scale.

Results

Seven hundred and sixty-nine patients (55.1%) had seen a friend in the previous week and 917 (65.7%) had someone they regarded as a close friend. Low levels of negative symptoms and hostility were significantly associated with having a close friend and contact with a friend. Overall, almost twice as many patients with absent or mild negative symptoms had met a friend in the last week, compared with those with moderate negative symptoms.

Conclusions

Higher levels of negative symptoms and hostility are specifically associated with the lack of friendships in patients with psychotic disorders. These findings suggest the importance of developing effective treatments for negative symptoms and hostility in order to improve the probability of patients with schizophrenia to have friends.     

A Genetic Deconstruction of Neurocognitive Traits in Schizophrenia and Bipolar Disorder

Background

Impairments in cognitive functions are common in patients suffering from psychiatric disorders, such as schizophrenia and bipolar disorder. Cognitive traits have been proposed as useful for understanding the biological and genetic mechanisms implicated in cognitive function in healthy individuals and in the dysfunction observed in psychiatric disorders.

Methods

Sets of genes associated with a range of cognitive functions often impaired in schizophrenia and bipolar disorder were generated from a genome-wide association study (GWAS) on a sample comprising 670 healthy Norwegian adults who were phenotyped for a broad battery of cognitive tests. These gene sets were then tested for enrichment of association in GWASs of schizophrenia and bipolar disorder. The GWAS data was derived from three independent single-centre schizophrenia samples, three independent single-centre bipolar disorder samples, and the multi-centre schizophrenia and bipolar disorder samples from the Psychiatric Genomics Consortium.

Results

The strongest enrichments were observed for visuospatial attention and verbal abilities sets in bipolar disorder. Delayed verbal memory was also enriched in one sample of bipolar disorder. For schizophrenia, the strongest evidence of enrichment was observed for the sets of genes associated with performance in a colour-word interference test and for sets associated with memory learning slope.

Conclusions

Our results are consistent with the increasing evidence that cognitive functions share genetic factors with schizophrenia and bipolar disorder. Our data provides evidence that genetic studies using polygenic and pleiotropic models can be used to link specific cognitive functions with psychiatric disorders.     

Analysis of Visual Cognitive Impairments in Schizophrenia at the Early Stages of the Disease and Their Correction by Interactive Virtual Environment

The paper describes the results of studies aimed at evaluating the effect of interactive virtual environments on the visual system, including the magno-and parvo-systems. Analysis was conducted in patients diagnosed with paranoid schizophrenia diagnosed from one to five years ago. Comparative analysis of visual evoked potentials during the perception of images that differed in their semantic (animate/inanimate) and physical characteristics (filtration images at high/low spatial frequencies) was used for the assessment of the impact of virtual environments. The images of objects were filtered via digital filtration for selective effect on the magno-and parvo-channels of the visual system. To evaluate the function of visual perception, the measurement of contrast sensitivity using Gabor elements was used. At the early stages of schizophrenia, the patients exhibited a decrease in the amplitudes of the components of cognitive visual evoked potentials to stimuli filtered at high spatial frequencies and reduced contrast sensitivity at high spatial frequencies. The effect of virtual environments on the visual system resulted in a significant increase in the amplitude of the cognitive components of visual evoked potentials in the paradigm of presentation of images filtered at the high spatial frequencies, which allows the conclusion about a stimulating effect of the virtual environment on the parvo-system functioning. The activation of the magno-system occurred to a lesser extent. The present study represents the findings obtained by the studies of cognitive impairments in schizophrenia and the methods of their correction conducted at the Laboratory of Physiology of Vision of the Pavlov Institute of Physiology of the Russian Academy of Sciences and at the Laboratory of Neurobiology of Action Programming of the Bechtereva Institute of the Human Brain of the Russian Academy of Sciences.     

Harnessing Clinical Psychiatric Data with an Electronic Assessment Tool (OPCRIT+): The Utility of Symptom Dimensions

Progress in personalised psychiatry is dependent on researchers having access to systematic and accurately acquired symptom data across clinical diagnoses. We have developed a structured psychiatric assessment tool, OPCRIT+, that is being introduced into the electronic medical records system of the South London and Maudsley NHS Foundation Trust which can help to achieve this. In this report we examine the utility of the symptom data being collected with the tool. Cross-sectional mental state data from a mixed-diagnostic cohort of 876 inpatients was subjected to a principal components analysis (PCA). Six components, explaining 46% of the variance in recorded symptoms, were extracted. The components represented dimensions of mania, depression, positive symptoms, anxiety, negative symptoms and disorganization. As indicated by component scores, different clinical diagnoses demonstrated distinct symptom profiles characterized by wide-ranging levels of severity. When comparing the predictive value of symptoms against diagnosis for a variety of clinical outcome measures (e.g. ‘Overactive, aggressive behaviour’), symptoms proved superior in five instances (R² range: 0.06–0.28) whereas diagnosis was best just once (R²∶0.25). This report demonstrates that symptom data being routinely gathered in an NHS trust, when documented on the appropriate tool, have considerable potential for onward use in a variety of clinical and research applications via representation as dimensions of psychopathology.     

Haplotypes of the D-Amino Acid Oxidase Gene Are Significantly Associated with Schizophrenia and Its Neurocognitive Deficits

D-amino acid oxidase (DAO) has been reported to be associated with schizophrenia. This study aimed to search for genetic variants associated with this gene. The genomic regions of all exons, highly conserved regions of introns, and promoters of this gene were sequenced. Potentially meaningful single-nucleotide polymorphisms (SNPs) obtained from direct sequencing were selected for genotyping in 600 controls and 912 patients with schizophrenia and in a replicated sample consisting of 388 patients with schizophrenia. Genetic associations were examined using single-locus and haplotype association analyses. In single-locus analyses, the frequency of the C allele of a novel SNP rs55944529 located at intron 8 was found to be significantly higher in the original large patient sample (p = 0.016). This allele was associated with a higher level of DAO mRNA expression in the Epstein-Barr virus-transformed lymphocytes. The haplotype distribution of a haplotype block composed of rs11114083-rs2070586-rs2070587-rs55944529 across intron 1 and intron 8 was significantly different between the patients and controls and the haplotype frequencies of AAGC were significantly higher in patients, in both the original (corrected p < 0.0001) and replicated samples (corrected p = 0.0003). The CGTC haplotype was specifically associated with the subgroup with deficits in sustained attention and executive function and the AAGC haplotype was associated with the subgroup without such deficits. The DAO gene was a susceptibility gene for schizophrenia and the genomic region between intron 1 and intron 8 may harbor functional genetic variants, which may influence the mRNA expression of DAO and neurocognitive functions in schizophrenia.     

The Roles of Reward,Default, and Executive Control Networks in Set-Shifting Impairments in Schizophrenia

Patients with schizophrenia (SZ) show deficits on tasks of rapid reinforcement learning, like probabilistic reversal learning (PRL), but the neural bases for those impairments are not known. Recent evidence of relatively intact sensitivity to negative outcomes in the ventral striatum (VS) in many SZ patients suggests that PRL deficits may be largely attributable to processes downstream from feedback processing, involving both the activation of executive control task regions and deactivation of default mode network (DMN) components. We analyzed data from 29 chronic SZ patients and 21 matched normal controls (NCs) performing a PRL task in an MRI scanner. Subjects were presented with eight pairs of fractal stimuli, for 50 trials each. For each pair, subjects learned to choose the more frequently-rewarded (better) stimulus. Each time a criterion was reached, the better stimulus became the worse one, and the worse became the better. Responses to feedback events were assessed through whole-brain and regions-of-interest (ROI) analyses in DMN. We also assessed correlations between BOLD signal contrasts and clinical measures in SZs. Relative to NCs, SZ patients showed comparable deactivation of VS in response to negative feedback, but reduced deactivation of DMN components including medial prefrontal cortex (mPFC). The magnitudes of patients'' punishment-evoked deactivations in VS and ventromedial PFC correlated significantly with clinical ratings for avolition/anhedonia. These findings suggest that schizophrenia is associated with a reduced ability to deactivate components of default mode networks, following the presentation of informative feedback and that motivational deficits in SZ relate closely to feedback-evoked activity in reward circuit components. These results also confirm a role for ventrolateral and dorsomedial PFC in the execution of response-set shifts.     

Oscillatory Underpinnings of Mismatch Negativity and Their Relationship with Cognitive Function in Patients with Schizophrenia

Background

Impairments in mismatch negativity (MMN) generation have been consistently reported in patients with schizophrenia. However, underlying oscillatory activity of MMN deficits in schizophrenia and the relationship with cognitive impairments have not been investigated in detail. Time-frequency power and phase analyses can provide more detailed measures of brain dynamics of MMN deficits in schizophrenia.

Method

21 patients with schizophrenia and 21 healthy controls were tested with a roving frequency paradigm to generate MMN. Time-frequency domain power and phase-locking (PL) analysis was performed on all trials using short-time Fourier transforms with Hanning window tapering. A comprehensive battery (CANTAB) was used to assess neurocognitive functioning.

Results

Mean MMN amplitude was significantly lower in patients with schizophrenia (95% CI 0.18 - 0.77). Patients showed significantly lower EEG power (95% CI -1.02 - -0.014) in the ~4-7 Hz frequency range (theta band) between 170 and 210 ms. Patients with schizophrenia showed cognitive impairment in multiple domains of CANTAB. However, MMN impairments in amplitude and power were not correlated with clinical measures, medication dose, social functioning or neurocognitive performance.

Conclusion

The findings from this study suggested that while MMN may be a useful marker to probe NMDA receptor mediated mechanisms and associated impairments in gain control and perceptual changes, it may not be a useful marker in association with clinical or cognitive changes. Trial-by-trial EEG power analysis can be used as a measure of brain dynamics underlying MMN deficits which also can have implications for the use of MMN as a biomarker for drug discovery.     

The DAO Gene Is Associated with Schizophrenia and Interacts with Other Genes in the Taiwan Han Chinese Population

Background

Schizophrenia is a highly heritable disease with a polygenic mode of inheritance. Many studies have contributed to our understanding of the genetic underpinnings of schizophrenia, but little is known about how interactions among genes affect the risk of schizophrenia. This study aimed to assess the associations and interactions among genes that confer vulnerability to schizophrenia and to examine the moderating effect of neuropsychological impairment.

Methods

We analyzed 99 SNPs from 10 candidate genes in 1,512 subject samples. The permutation-based single-locus, multi-locus association tests, and a gene-based multifactorial dimension reduction procedure were used to examine genetic associations and interactions to schizophrenia.

Results

We found that no single SNP was significantly associated with schizophrenia. However, a risk haplotype, namely A-T-C of the SNP triplet rsDAO7-rsDAO8-rsDAO13 of the DAO gene, was strongly associated with schizophrenia. Interaction analyses identified multiple between-gene and within-gene interactions. Between-gene interactions including DAO*DISC1 , DAO*NRG1 and DAO*RASD2 and a within-gene interaction for CACNG2 were found among schizophrenia subjects with severe sustained attention deficits, suggesting a modifying effect of impaired neuropsychological functioning. Other interactions such as the within-gene interaction of DAO and the between-gene interaction of DAO and PTK2B were consistently identified regardless of stratification by neuropsychological dysfunction. Importantly, except for the within-gene interaction of CACNG2, all of the identified risk haplotypes and interactions involved SNPs from DAO.

Conclusions

These results suggest that DAO, which is involved in the N-methyl-d-aspartate receptor regulation, signaling and glutamate metabolism, is the master gene of the genetic associations and interactions underlying schizophrenia. Besides, the interaction between DAO and RASD2 has provided an insight in integrating the glutamate and dopamine hypotheses of schizophrenia.     

天津滨海滩涂湿地鸟类丰富度与环境因子的关系研究

由于湿地生态系统的重要性、脆弱性和复杂性,湿地生态系统的保护与修复是当今世界的热点与难点问题之一。本研究选取天津滨海新区的3处湿地生态系统作为参考场地,1处湿地生态系统作为验证场地,通过量化4处场地不同类型栖息地的7个环境因素,综合鸟类对各类型栖息地的使用情况,并采用逐步回归分析,结果表明植被覆盖率、植物水平斑块丰富度及人为干扰程度与鸟类物种丰富度呈显著相关,并建立模型1;植物香农－威纳指数、植物水平斑块丰富度及人为干扰程度与鸟类共位群丰富度呈显著相关关系,并建立模型2。最后,利用验证场地的数据进行模型验证,得出所建立的模型能够较为准确地对栖息地内的鸟类丰富度进行预测。该研究构架了1种利用栖息地类型预测场地鸟类丰富度的方法,以期供相关研究或实际规划设计工作参考。     

裸盖菇属的真菌鉴定及分子系统学初探

裸盖菇属(Psilocybe)的许多真菌含有神经致幻型毒素,这些毒素被中国卫生部列为A类管制药品。在药检时,这些真菌样品通常是粉末。因此,仅依靠形态分类鉴定该类真菌非常困难。研究采用ITS序列分析的方法鉴定该类真菌并初步探讨了该属种间的系统发育关系。由系统发育树推断Psilocybe属可能是多源进化的。通过序列分析可以鉴定真菌样品为Psilocybe属。     

上海农耕区鸟类群落特征及与几种生境因子的关系

2000-2002年冬季和夏季,采用固定样带法在上海郊区所有区县选择了17条样带,对农耕区鸟类做了4次抽样调查。记录了鸟类的组成、数量、出现频率及生境因子特征。根据调查数据,计算鸟类密度、多样性、均匀度、优势度、生物量、相对重要值等群落特征参数。调查共记录到鸟类76种,隶属13目26科。平均密度为5．19只／hm^2,多样性指数为1．8742。优势种为麻雀、家燕、白头鹎、棕背伯劳和白鹊鸰。鸟类组成中水鸟(夜鹭、白鹭等)较多,占了总数的1／3;与上海其他区域相比,鸟类密度较高,但种类相对较少,数量集中在少数几个物种(麻雀、家燕、白头鹎、棕背伯劳等)。鸟类物种丰富度与荒地面积呈显著正相关,与环境污染程度呈显著负相关,与林地面积、人口密度、水体面积等相关不显著。提示荒地对鸟类多样性非常重要。     

Hemocyanins Relationships in Their Structure, Function and Assembly

Hemocyanins are high molecular weight oxygen-carrying proteinsthat occur in the molluscs and arthropods. The oxygen-bindingsite in these proteins is a pair of copper atoms bound directlyto ammo acid side chains. The biscopper sites of these proteinsbind single molecules of dioxygen or carbon monoxide. In arthropodsthere are two copper atoms per approximately 70 000 daltonsof protein. This corresponds to the molecular weight of theminimum polypeptide chain. In molluscs however there are twocopper atoms per 50,000 daltons of protein. This does not correspondto the minimum polypeptide chain although it does correspondto the minimal functional unit. The minimal polypeptide chainin molluscan hemocyanins is approximately 400,000 daltons andappears to be composed of eight or more 50 000 dalton unitslinked together like a string of pearls. In the molluscs, thenative hemocyanins found in the hemolymph generally occur asgiant cylindrical molecules 350 Å in diameter, 380 Ålong, with molecular weights of 9 000,000. These large moleculesare composed of approximately 20 polypeptide chains. In thehemolymph of the arthropods depending upon the species, hemocyaminsoccur as hexamers dodecamers 24-mers and 48-mers. The molecularweight of the 48-mers is about 3 600,000. The respiratory functionsof hemocyamns show a wide range of allosteric properties. Thelarge molecules commonly show cooperativity in oxygen binding.The number of interacting subunits is in some cases dependentupon external conditions of pH and ionic composition. The oxygenaffinity is usually sensitive to pH and to low molecular weightcofactors like chloride, calcium and magnesium ions. The intrinsicoxygen binding properties of an organism s hemocyanin and itsallosteric control by modulators allow organisms possessingthese giant molecules to adapt to their environmental conditions.     

Root Pressure of Tropical Lianas and Their Relationships with Phylogeny and Environments

Lianas usually possess large vessels, which are vulnerable to cavitation. Root pressure may play an important role in embolism repair of vessels. However, little is known about the generality of root pressure in tropical lianas. To characterize root pressure of lianas in tropical rainforests, we used pressure transducers to measure root pressure in the rainy and dry seasons for a total of 32 lianas from 14 families common in Xishuangbanna. We further analyzed the associations of maximum root pressure with phylogeny and of transient root pressure with environmental factors. We found that all lianas we selected had root pressure, with maximum root pressure ranging from 2-138kPa. In the dry season, about 72% (23 species) of the lianas had relatively low root pressure (<15kPa) and maintained positive throughout the day. This may be important for water balance for roots and basal stems of lianas. There were three types of diurnal changes in liana root pressure. In Type I, root pressure had obvious diurnal variation in the dry and rainy seasons. In Type II, root pressure did not show obvious diurnal variation in the dry and rainy seasons. In Type III, either in the dry or in the rainy season, root pressure showed obvious diurnal variation. Root pressure varied substantially among lianas, with lianas from two families, Fabaceae and Vitaceae, usually having relatively higher root pressure, suggesting that phylogeny may influence root pressure. Transient root pressure closely responded to photosynthetically active radiation. In most cases, however, it was not related to rainfall and vapour pressure deficit. These results suggest that the associations of liana root pressure with environments need further investigation.     

Sequences of E/NS1 Gene Junction from Four Dengue-2 Viruses of Northeastern Thailand and Their Evolutionary Relationships with Other Dengue-2 Viruses

We determined the 240-nueleotide sequences of the E/NS1 gene junction of four dengue-2 viruses by the primer extension dideoxy chain termination method. These viruses were isolated from dengue patients with different clinical severities in Nakhon Phanom, Northeastern Thailand in 1993. The results were compared with the 52 published dengue-2 sequences of the same gene region. Sequence divergence of four new isolates varied from 4.17% to 5.42% compared with dengue-2 prototype New Guinea C strain whereas it varied from 5.42% to 6.67% and from 6.67% to 7.09% when compared with Jamaica 1409 strain and PR159/S1 strain, respectively. All nucleotide substitutions were found at the 3rd position of the codons which were silent mutations. All 56 isolates studied were classified into five genotypic groups by constructing the dendrogram. The results indicated that four new isolates from Northeastern Thailand belong to genotype II of dengue virus serotype 2, and were most closely related to prototype New Guinea C strain. We also observed the variation in nucleotide and amino acid sequences among clusters of isolates (Thailand-1980, Malaysia-1989 and Thailand-1993) which were obtained from the dengue patients with different clinical severities. The significance of these genetic differences have been discussed in terms of the possible correlation between genetic variability and virulence.     

Attitudes toward Placebo-Controlled Clinical Trials of Patients with Schizophrenia in Japan

Background

Although the use of placebo in clinical trials of schizophrenia patients is controversial because of medical and ethical concerns, placebo-controlled clinical trials are commonly used in the licensing of new drugs.

Aims

The objective of this study was to assess the attitudes toward placebo-controlled clinical trials among patients with schizophrenia in Japan.

Method

Using a cross-sectional design, we recruited patients (n = 251) aged 47.7±13.2 (mean±SD) with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to six psychiatric hospitals from December 2013 to March 2014. We employed a 14-item questionnaire specifically developed to survey patients'' attitudes toward placebo-controlled clinical trials.

Results

The results indicated that 33% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for improvement of disease, a guarantee of hospital treatment continuation, and encouragement by family or friends were associated with the willingness to participate in such trials, whereas a belief of additional time required for medical examinations was associated with non-participation.

Conclusions

Fewer than half of the respondents stated that they would be willing to participate in placebo-controlled clinical trials. Therefore, interpreting the results from placebo-controlled clinical trials could be negatively affected by selection bias.