Using a brief intervention to improve decisional capacity in schizophrenia research

Studies have shown that individuals with psychiatric or general medical illness can benefit from interventions designed to enhance decisional capacity for research informed consent. In some cases, interventions have been rather lengthy or complex. The current study was designed to determine whether a brief intervention could improve decisional capacity in people with schizophrenia. Thirty individuals with schizophrenia and 30 healthy comparison participants were presented with a hypothetical research scenario. Decisional capacity was assessed with the MacArthur Competence Assessment Tool-Clinical Research version. Those with schizophrenia received a brief intervention aimed at improving understanding of the research protocol, after which decisional capacity was reassessed. A neuropsychological battery and symptom rating scales were also administered. At baseline, the schizophrenia group earned significantly lower scores than the comparison group on 2 aspects of decisional capacity (understanding, appreciation). At follow-up, the schizophrenia group had improved significantly on understanding and was no longer significantly different from the comparison group on any of the 4 dimensions of decisional capacity. Follow-up analyses also showed a significant effect of the intervention on a subset of the schizophrenia group who had performed most poorly at baseline. Participants with schizophrenia earned significantly lower scores than those in the comparison group across multiple neuropsychological domains. These findings add to the existing literature indicating that brief interventions can improve decisional capacity in individuals with schizophrenia, despite the fact that the illness typically causes significant cognitive dysfunction. The use of such interventions will enable a larger number of people with schizophrenia to make informed decisions regarding research participation.     

Telomerase levels in schizophrenia: a preliminary study

We previously demonstrated that telomere length was markedly reduced in peripheral blood lymphocytes from individuals with schizophrenia. Since reduced telomere length can be caused by decreased telomerase activity, we quantitated basal telomerase activity in peripheral blood lymphocytes derived from individuals with schizophrenia (n=53), unaffected relatives (n=31) and unrelated controls (n=59). Telomerase activity varied greatly among individuals, suggesting that this enzymatic activity is affected by various factors. We observed a nominally significant decrease in telomerase activity among individuals with schizophrenia compared to unaffected individuals (unaffected relatives and unrelated controls). Further studies are needed to investigate the role of telomerase in schizophrenia.     

Prevalence and correlates of adequate performance on a measure of abilities related to decisional capacity: differences among three standards for the MacCAT-CR in patients with schizophrenia

Despite the availability of structured decision-making capacity assessment tools, insufficient guidance exists for applying their results. Investigators often use cutpoints on these instruments to identify potential subjects in need of further assessment or education. Yet, information is lacking regarding the effects of different cutpoints on the proportion and characteristics of individuals categorized as possessing adequate or impaired decisional abilities for consent to research. To demonstrate the potential impact of different standards, we informed 91 individuals, aged 50 or older with a diagnosis of schizophrenia or schizoaffective disorder, about a hypothetical clinical trial, and assessed their decisional abilities with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Three published MacCAT-CR-based standards were applied to participants' scores to examine the rates and correlates of categorical determinations of adequate performance. The three standards ranged in stringency: the most stringent incorporated cutpoints on all three of the major MacCAT-CR subscales (Understanding, Appreciation, and Reasoning); the other two standards required threshold performance only on the Understanding subscale. The most stringent standard resulted in a 57% rate of impaired performance; the intermediate standard, 19%; and the least stringent standard, 8%. Nearly half of the participants (n=45) were classified as having performed adequately by the least stringent standard yet inadequately by the most stringent. The majority of these 45 were impaired on the Appreciation subscale (n=9), Reasoning (n=15), or both (n=18). Cognitive functioning was correlated with performance status for the more stringent standards. These findings underscore the need for refinement of capacity assessment procedures and for improvements in the use of capacity assessment tools for screening purposes and to assist in categorical capacity determinations.     

FMRI of response to nicotine during a smooth pursuit eye movement task in schizophrenia

OBJECTIVE: Nicotine temporarily normalizes smooth pursuit eye movement deficits in schizophrenia. This study used functional magnetic resonance imaging (fMRI) to examine changes in brain hemodynamic response associated with nicotine administration during a smooth pursuit eye movement task in subjects with schizophrenia. METHOD: Nine subjects with schizophrenia performed the eye movement task while undergoing fMRI. Subjects then were given nicotine or placebo and repeated the task while being scanned. Subjects repeated the procedure the following week, receiving the counterbalanced condition. RESULTS: Compared with placebo, nicotine was associated with greater activity in the anterior and posterior cingulate gyri, precuneus, and area MT/MST and less activity in the hippocampus and parietal eye fields. CONCLUSIONS: Changes in area MT/MST and the cingulate gyrus are consistent with an improvement in perception and attention to moving stimuli. The most important observed difference between nicotine and placebo--less activation of the hippocampus after nicotine than after placebo administration--is consistent with nicotinic receptor mediation of inhibitory neuronal dysfunction in schizophrenia.     

Neural correlates of formal thought disorder in schizophrenia: preliminary findings from a functional magnetic resonance imaging study

BACKGROUND: Formal thought disorder (FTD) is a core symptom of schizophrenia, but its pathophysiology is little understood. We examined the neural correlates of FTD using functional magnetic resonance imaging. METHODS: Blood oxygenation level-dependent contrast was measured using functional magnetic resonance imaging while 6 patients with schizophrenia and 6 control subjects spoke about 7 Rorschach inkblots for 3 minutes each. In patients, varying degrees of thought-disordered speech were elicited during each "run." In a within-subject design, the severity of positive FTD was correlated with the level of blood oxygenation level-dependent contrast in the 2 runs that showed the highest variance of FTD in each patient. RESULTS: The severity of positive FTD in patients was negatively correlated (P<.001) with signal changes in the left superior and middle temporal gyri. Positive correlations were evident in the cerebellar vermis, the right caudate body, and the precentral gyrus. CONCLUSIONS: The severity of positive FTD was inversely correlated with the level of activity in the Wernicke area, a region implicated in the production of coherent speech. Reduced activity in this area might contribute to the articulation of incoherent speech. Because of the small sample size, these findings should be considered preliminary.     

Reduced cerebellar inhibition in schizophrenia: a preliminary study

OBJECTIVE: Postmortem and structural imaging studies suggest that patients with schizophrenia have disrupted cerebellar activity. It has been speculated that these abnormalities mediate disorganized thought processes and psychosis. The authors' goal was to use transcranial magnetic stimulation to measure cerebellar inhibition, a proxy of cerebellar activity, as the principal output of the cerebellum is inhibitory. METHOD: Cerebellar inhibition was accomplished by delivering a magnetic cerebellar conditioning stimulus 5-15 msec before a magnetic test stimulus to the motor cortex. The cerebellar conditioning stimulus inhibits the size of the motor evoked potential produced by the test stimulus by approximately 50%. Ten patients with schizophrenia and 10 healthy comparison subjects completed the cerebellar inhibition protocol. RESULTS: Patients with schizophrenia demonstrated significant deficits in cerebellar inhibition compared with healthy subjects. CONCLUSIONS: The authors conclude that deficits in cerebellar inhibitory activity in schizophrenia may be the result of an abnormality in the cerebellum or disrupted cerebellar-thalamic-cortical connectivity.     

Nuclear magnetic resonance in schizophrenia: a preliminary study

Nuclear magnetic resonance (NMR) scans were performed in nine patients with schizophrenia and five control subjects. NMR scans allowed multiple-plane views of the brains of schizophrenic patients and demonstrated much greater detail of morphological structure than computed tomographic (CT) scans. This small sample of subjects, however, showed no significant differences in several quantitative measurements between schizophrenic patients and control subjects. Problems in the interpretation of image intensity measures of NMR scans are discussed.     

Magnitude of impairment in decisional capacity in people with schizophrenia compared to normal subjects: an overview

The capacity of individuals with schizophrenia to make decisions related to research participation or clinical treatment has received increasing empirical attention. A number of studies have compared patients with schizophrenia to nonpsychiatric comparison subjects (NPCs) on structured measures of decision-making capacity. In this review, we evaluated the magnitude of the difference between schizophrenia and NPC groups reported across these studies, as well as the influence of sample characteristics on observed effect sizes. We also computed the effect sizes of group differences in psychopathology and cognitive deficits. Twelve studies met the search criteria; a majority of them reported data using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) or for Treatment (MacCAT-T). The mean effect size (evaluated in terms of Cohen's d) for group differences on the Understanding subscale of the MacCAT instruments was 0.88 (SD = 0.40); it was twice as high among inpatient samples as among outpatients. Similar differences were observed in terms of Appreciation and Reasoning subscales, but the effect sizes for Expression of Choice were small (mean d = 0.29, SD = 0.24). Notably, these observed effect sizes were generally smaller than those for differences between schizophrenia and NPC groups in psychopathology (mean d = 2.06, SD = 1.03) and cognition (mean d = 1.01, SD = 0.61). The published studies demonstrate a substantial heterogeneity in decision-making capacity among people with schizophrenia, as well as among NPCs, suggesting that the presence of schizophrenia does not necessarily mean the patient has impairment in capacity.     

The assessment of decisional capacity

The physician must explain the treatment or procedure in detail including risks, benefits, and alternative options; the patient's choice must be voluntary; the patient must demonstrate his or her ability to understand the risks and benefits of their choice; and the patient must be able to manipulate information in a logical way. These criteria must be met in order for the process of informed consent to be valid.     

Working memory capacity in schizophrenia: a parametric fMRI study

Impaired working memory (WM) function in schizophrenia has been associated with abnormal activation of the dorsolateral prefrontal cortex (DLPFC). It is, however, not clear whether abnormal activation is a sign of DLPFC pathology, or a correlate of poor performance. We address this question by examining activity in the WM brain system at different levels of task difficulty. A parametric fMRI paradigm is used to examine how the WM system responds to increasing load. A parametric fMRI design with four levels of a spatial N-back task was used to examine the relationships between working memory load, functional output (performance) and brain activity in 10 schizophrenic patients on atypical antipsychotic medication and to compare these to 10 healthy controls. In spite of increasingly poor performance in schizophrenic patients, activity increased normally in DLPFC and inferior parietal cortex bilaterally and in anterior cingulate, with increasing load. At 3-back, activity dropped in DLPFC in comparison with controls, but not in the other regions. The results indicate that peak activation of the WM-system is reached at a lower processing load in schizophrenic patients than in healthy controls. As a decline of DLPFC activity at high processing loads in itself is not abnormal, WM dysfunction in schizophrenia appears to be the result of an impaired functional output of the whole WM system, causing elevation of the effective burden imposed by WM tasks.     

Symmetry of callosal information transfer in schizophrenia: a preliminary study

OBJECTIVE: While there is much evidence to suggest left hemisphere dysfunction and interhemispheric transfer deficits in schizophrenia, the right hemisphere is rarely implicated. This study uses 128-channel EEG to assess whether asymmetry of interhemispheric transfer found in normal individuals is present in those with schizophrenia, and whether this might point to a right-hemisphere dysfunction. METHODS: Simple reaction time (RT) was recorded to stimuli presented to the left visual field (LVF), right visual field (RVF) or bilaterally (BVF) in 13 males with schizophrenia and 13 controls. 128-Channel EEG was simultaneously recorded. Interhemispheric transfer time (IHTT) in each direction was calculated by comparing the latencies of N160 EP components in the hemispheres contralateral and ipsilateral to stimulation. RESULTS: While controls showed faster information transfer from the right-to-left hemisphere, this asymmetry was not present in the schizophrenia group who also exhibited a concomitant decrease in the amplitude of the N160 in the right hemisphere. CONCLUSIONS: Results are interpreted with reference to a loss of rapidly conducting myelinated axons in the right hemisphere in schizophrenia.     

Nutritional assessment of patients with schizophrenia: a preliminary study

The prevalence of obesity in the United States population is increasing, and similar trends can be observed among schizophrenia patients. No thorough examination of the actual nutritional composition of the diet of schizophrenia patients in the United States has been carried out. We therefore employed a 24-hour diet recall in 146 schizophrenia outpatients to gather information on different nutritional variables, such as total caloric intake and total fat, protein, carbohydrate, cholesterol, and fiber content. Data were subsequently compared to data for the general population collected in the Third National Health and Nutrition Examination Survey (NHANES III). Schizophrenia patients as a group ate more food when compared to NHANES III subjects, but the relative percentages of calories derived from fat, protein, and carbohydrates were not found to be different. Therefore, it is unlikely that schizophrenia patients make dietary choices different from those of people in the general population. Instead, schizophrenia patients seem to eat more of the same food.     

FMRI indices of auditory attention in schizophrenia

The present study sought to identify abnormalities in activation in several brain regions in response to an auditory attention task in patients with schizophrenia. Ten patients and twenty healthy control participants were examined using Functional Magnetic Resonance Imaging (FMRI) measures acquired during an auditory attention task. Region of interest analyses of activation of targeted regions implicated in attention included: anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, parahippocampal gyrus (PHG), and superior temporal gyrus (STG). The results indicated over-activation in patients with schizophrenia. While the control group showed notable coherence in activation within and across hemispheres the schizophrenia group showed relatively less coherence overall that was only present in the right hemisphere. These findings suggest that patients with schizophrenia show both an over-engagement of brain regions during attention task as well as a lack of communication among neural regions involved.     

精神分裂症患者认知功能损害与氧化应激关系的初步研究

目的：探讨精神分裂症患者认知功能缺损与氧化应激的关系。方法：对39例精神分裂症患者（患者组），36名健康对照者（对照组）进行神经心理测验和氧化应激指标的检测.结果：（1）在神经心理测验中，患者组与对照组在总测验数、总错误数、持续错误数、语言流畅、领悟、相似和联想学习的差异有非常显著性（P＜0．01），数字广度的差异有显著性（P＜0．05）；（2）患者组后的一氧化氮（NO）浓度与WCST的总错误数呈显著正相关，与相似测验呈显著性负相关，超氧化物歧化酶（SOD）活性与相似性测验、数字广度测验呈显著性负相关（r分别为0．409，－0．404，－0．432，－0．420，P＜0．05）。结论：（1）精神分裂症认知功能缺损的生物学基础可能与氧化应激有关；（2）SOD和NO可能是与认知功能密切相关的氧化应激指标。     

慢性精神分裂症患者结对康复模式的探讨

目的　探讨结对康复模式对慢性精神分裂症患者的疗效和可行性。方法　将 2 30例慢性精神分裂症患者随机分为研究组 (结对康复 )和对照组 (一般康复 ) ,每组各 115例。研究组分三个层次结成对子 ,一是工作人员带患者 ,二是患者带患者 ,三是患者再带患者。康复措施内容包括开放管理 ;活动小组 ;行为、技能训练并开展竞赛 ;心理康复和健康教育 ;娱乐活动 ;体育治疗 ;建立病友园地 ;药物治疗。康复治疗第 10 0天时评定住院用护士观察量表、阴性症状量表、日常生活能力量表、社会功能筛选量表、临床疗效总评量表及自制的健康教育评价量表 ;随访两年观察其复发率。结果( 1)治疗第 10 0天时 ,研究组和对照组各量表的评分均优于治疗前 ,差异有非常显著性 (P <0 0 1) ,其中研究组的疗效优于对照组 (P <0 0 1) ;( 2 )研究组康复治疗的有效率 ( 81 7% )高于对照组 ( 5 7 4 % ;P <0 0 1) ;( 3)研究组两年的复发率 ( 37 4 % )低于对照组 ( 6 4 3% ;P <0 0 1)。结论　研究组结对模式康复疗效满意 ,是一种可行的康复治疗措施     

Brain metabolic correlates of fatigue in Parkinson's disease: a PET study

Purpose: The neural bases of fatigue in Parkinson's disease (PD) remain uncertain. We aimed to assess the brain metabolic correlates of fatigue in patients with PD.

Patients and methods: Twenty-seven PD patients without clinically relevant depression (17-item Hamilton Depression Rating Scale (HAMD) score ≥ 14), apathy (Apathy Scale (AS) score ≥ 14) and excessive daytime somnolence (Epworth Sleepiness Scale (ESS) score ≥ 10) were evaluated with Fatigue Severity Scale (FSS). Each patient had an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale motor part. Levodopa equivalent daily dose for each patient was also calculated. The PET images were analyzed using statistical parametric mapping software. We introduced the age, educational level, HAMD scores, AS scores and ESS scores as covariates.

Results: High FSS scores were associated with brain hypermetabolism in areas including the right middle temporal gyrus (Brodmann area (BA) 37) and left middle occipital gyrus (BA 19). Increased FSS scores correlated with hypometabolism in regions such as the right precuneus (BA 23), left inferior frontal gyrus (BA 45) and left superior frontal gyrus (orbital part, BA 11).

Conclusion: This study demonstrates that brain areas including frontal, temporal and parietal regions indicative of emotion, motivation and cognitive functions are involved in fatigue in PD patients.     

Brain correlates of pro-social personality traits: a voxel-based morphometry study

Of the five personality dimensions described by the Big Five Personality Model (Costa and McCrae 1992), Extraversion and Agreeableness are the traits most commonly associated with a pro-social orientation. In this study we tested whether a pro-social orientation, as expressed in terms of Extraversion and Agreeableness, is associated with a specific grey matter phenotype. Fifty-two healthy participants underwent magnetic resonance imaging (MRI) and completed the NEO-Five Factor Inventory (NEO-FFI), a self-report measure of the Big Five personality traits. Voxel-based morphometry (VBM) was used to investigate the correlation between brain structure and the personality traits of Agreeableness and Extraversion. We found that Extraversion was negatively correlated with grey matter density in the middle frontal and orbitofrontal gyri while Agreeableness was negatively correlated with grey matter density in the inferior parietal, middle occipital and posterior cingulate gyri. No positive correlations were found. These results suggest that pro-social personality traits seem to be associated with decreases in grey matter density in more frontal regions for Extraversion, and more posterior regions for Agreeableness.     

Brain anatomy of symptom stratification in schizophrenia: a voxel-based morphometry study

Background: Although some Magnetic Resonance Imaging (MRI) studies have investigated the relationship between clinical severity and neuroanatomical alterations in patients with schizophrenia (SCZ), the biological signature associated with illness severity in schizophrenia is still uncertain. Therefore, this study aims to investigate structural brain abnormalities in SCZ, with particular regards to the identification of potential deficits associated with the severity of illness.

Methods: In total, 1.5T MRI data were acquired for 61 subjects with SCZ and 59 matched healthy controls (HC). The patient group was divided in two sub-groups based on clinical severity, one composed of 34 mild-to-moderately ill patients, and the other of 27 severely ill patients, and compared with matched HC.

Results: The whole group of patients with SCZ had significantly reduced grey matter (GM) volumes in the left inferior and middle temporal gyrus compared to HC (p?p?Conclusion: The results showed significant GM volume reductions in temporal regions in patients with SCZ compared to matched HC, confirming the role of these regions in the pathophysiology of SCZ. Furthermore, specific cerebellar grey matter volume reductions were identified in patients with severe illness, which may contribute to stratifying patients with SCZ according to their clinical phenotype expression, ultimately helping in guiding targeted therapeutic/rehabilitation interventions.     

MRI changes in schizophrenia in late life: a preliminary controlled study

The aim of this pilot study was to compare cerebral changes on magnetic resonance imaging (MRI) scans in elderly schizophrenic subjects with those in psychiatric and normal control subjects. We compared the MRIs of 19 subjects with schizophrenia, 19 age- and gender-matched subjects with recurrent major depression, and 19 age- and gender-matched nonpsychiatric control subjects. Deep white matter hyperintensities (DWMH) in right posterior regions were significantly more prominent in the schizophrenic group than in the two comparison groups. Total ratings of MRI abnormalities were significantly related to age in both the normal control and schizophrenic groups, but not in the depressive group. Age of onset was positively associated with total ratings in the depressive group, but not in the schizophrenic group. Thus, a subset of elderly patients with schizophrenia appear to have cerebral white matter abnormalities; such abnormalities may not be confined to lage-onset schizophrenia. Systematic MRI studies of early- and late-onset schizophrenia in late life are needed to resolve this question.     

Brain anatomy in adults with velocardiofacial syndrome with and without schizophrenia: preliminary results of a structural magnetic resonance imaging study

CONTEXT: Velocardiofacial syndrome is associated with interstitial deletions of chromosome 22q11, mild to borderline learning disability, characteristic dysmorphology, and a high prevalence of schizophrenia. The biological basis for this increased risk for schizophrenia is unknown, but people with velocardiofacial syndrome may have genetically determined differences in brain anatomy that predispose to the development of schizophrenia. OBJECTIVE: To determine whether there are differences in brain structure between subjects with velocardiofacial syndrome with and without schizophrenia. DESIGN: A cross-sectional quantitative structural magnetic resonance imaging study in 39 adult subjects. SETTING: Referrals were made through medical genetics clinics and psychiatric services throughout the United Kingdom. PARTICIPANTS: Thirteen subjects with velocardiofacial syndrome and schizophrenia, 12 with velocardiofacial syndrome without history of a psychosis, and 14 healthy controls volunteered to participate after screening for eligibility. MAIN OUTCOME MEASURES: Total and regional brain volumes were analyzed by means of manual tracing, and gray- and white-matter densities were obtained by computerized voxel-based methods. RESULTS: People with velocardiofacial syndrome and schizophrenia, compared with both controls and nonschizophrenic patients with velocardiofacial syndrome, had a significant (P<.05) reduction in volume of whole-brain (white + gray) matter and whole-brain white matter, and an increase in total and sulcal cerebrospinal fluid volume. Both velocardiofacial syndrome groups had a reduced cerebellar volume compared with controls. CONCLUSIONS: Within velocardiofacial syndrome, schizophrenia is associated with generalized differences in brain anatomy, but white matter may be particularly implicated. Studies with larger samples are needed to replicate our findings.