Correlates of lateral ventricular size in chronic schizophrenia, I: Behavioral and treatment response measures

The ventricle-brain ratio (VBR) of 28 drug-free male schizophrenic inpatients was significantly higher than that of 21 matched normal control subjects and was not related to severity of positive or negative symptoms. Response to haloperidol in an open 6-week trial using a fixed-dose schedule was not predicted by severity of positive or negative symptoms or by VBR. The nine severely deteriorated patients with chronic "Kraepelinian" schizophrenia had left lateral ventricles 28% larger than their right, whereas the control subjects and other schizophrenic patients did not show ventricular asymmetry.     

Blood monoamine oxidases and CT scans in subgroups of chronic schizophrenics

An assay method for monoamine oxidase (MAO) employing whole blood samples is described. With this method, whole blood samples collected from three subgroups of chronic schizophrenic patients were assayed directly for MAO_b activity without the need for prior isolation of platelets. Our results support previous findings from assays with platelets that chronic paranoid schizophrenics have decreased blood MAO_b activity compared to chronic non-paranoid schizophrenics or normal controls. The level of MAO_b activity in the blood of the non-paranoid schizophrenics was also linearly correlated with ventricular size (i.e. ventricular brain ratio, VBR) as determined by CT scan analysis. This correlation was not true for the paranoid group. The MAO_b data in conjunction with the VBR data were sufficient to divide without overlap our schizophrenic patient population into two clinically defined subgroups.     

Platelet monoamine oxidase activity in schizophrenia: Relationship to family history of the illness and neuroleptic treatment

Platelet monoamine oxidase (MAO) activity was determined in a large population of drug-free and haloperidol-treated schizophrenic patients and healthy controls and, in a second study, in a sample of schizophrenics after a wash-out period and at different times during treatment with haloperidol. Enzyme activity was significantly decreased in both acute and chronic haloperidol-treated schizophrenics, but not in drug-free schizophrenics, compared with normal controls. No significant difference was observed between drug-free schizophrenics with a family history of the illness and those without such history, and between healthy relatives of schizophrenic patients and normal controls without a family history of schizophrenia.MAO activity was significantly reduced after 14 and 21 days of haloperidol treatment, and such reduction did not correlate with response to treatment. These data strongly support the idea that neuroleptic intake may, at least in part, explain low MAO values repeatedly reported in schizophrenics.     

Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: a double-blind, randomized, placebo-controlled study

BACKGROUND: Previous studies suggest that the serotonin-3 (5-HT3) receptor antagonist ondansetron possesses the therapeutic potential for schizophrenia. This study was designed to determine whether ondansetron as an adjunct to haloperidol could enhance the clinical efficacy and reduce the adverse side effects in chronic treatment-resistant schizophrenia. METHODS: Under double-blind, randomized conditions, 121 treatment-resistant inpatients with chronic DSM-IV-diagnosed schizophrenia received haloperidol (4-30 mg/day) combined with either placebo (N=63) or a fixed dose of 8 mg/day of ondansetron (N=58) for 12 weeks. Efficacy was defined as the change from baseline to endpoint in score on overall scale and subscales of the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). Side effects were evaluated using the Treatment Emergent Symptom Scale and Extrapyramidal Symptom Rating Scale. RESULTS: Ondansetron combined with haloperidol produced a significantly greater improvement on PANSS overall scale and subscales for negative symptoms, general psychopathology, and cognition at endpoint compared to placebo with haloperidol, but no between-treatment group difference was observed on the subscale for positive symptoms and CGI-S. The ondansetron-treated group had a significantly higher proportion of patients with a 30% or greater baseline-to-endpoint reduction in PANSS total score than placebo. Patients in adjunctive ondansetron therapy also experienced significantly lower incidence and severity of parkinsonism and akathisia as well as fewer behavioral hyperactivity, cardiac, and gastrointestinal side effects. CONCLUSIONS: Ondansetron is an effective adjunctive agent in enhancing the effectiveness and reducing some adverse side effects of antipsychotic therapy for chronic, treatment-resistant schizophrenia, particularly for negative and cognitive symptoms.     

A computerized tomographic study in patients with depressive disorder: a comparison with schizophrenic patients and controls

Using computed tomography, Ventricular Brain Ratio (VBR) was assessed in a sample of 42 depressive patients, 36 schizophrenic patients and 37 controls. The values of affective patients laid between, but did not differ significantly from those of schizophrenic patients on the one hand and controls on the other. The schizophrenic patients showed VBR increase when compared to controls. Possible implications of VBR measurement, in patients with affective illness are discussed.     

Effects of antipsychotics on cognitive performance in drug-naive schizophrenic patients

It has been reported that antipsychotics may improve cognitive function in the treatment of schizophrenia. The present study examined the effect of haloperidol and risperidone on cognitive performance in schizophrenic patients. 95 healthy subjects and 68 schizophrenic patients were recruited for comparison of cognitive function. As 20 of the 68 schizophrenic patients were drug-naive, they were randomly divided into two groups and double-blinded for treatment with either haloperidol or risperidone for an 8-week period. Each subject received Wisconsin Card Sorting Test (WCST) and Maze paradigms for cognitive function performance. For schizophrenic patients, the Positive and Negative Syndrome Scale (PANSS) was used for evaluation of clinical symptoms. Results demonstrated that in both WCST and Maze paradigms the 68 schizophrenic patients had worse cognitive performance compared with healthy subjects. Of the 20 drug-naive schizophrenic patients from the 68 in-patients, both haloperidol and risperidone improved the clinical symptoms. Maze tasks performance was improved progressively after haloperidol and risperidone treatment, although improvement was greatest with risperidone. Both haloperidol and risperidone had no evident effect on WCST performance. Our findings suggest that Maze paradigms may be an ideal tool for evaluation of pharmacological treatment effects on cognitive function in schizophrenic patients. Furthermore, risperidone may have more treatment benefits than haloperidol on cognitive performance in drug-naive schizophrenic patients.     

Psychometric properties of French version of the Calgary depression scale for schizophrenics (CDSS)

The Calgary Depression scale for schizophrenia (CDSS) is a 9 items scale, simple, quick and easy to use. It allows a quantitative approach of the subjective (or cognitive) dimension of the depression, and was developed by Addington et al. (1-5). In this work, we studied the psychometric properties of the CDSS in a population of 95 schizophrenic patients, and 41 non schizophrenic depressed patients. The CDSS was compared with commonly used hetero-questionnaires as the Hamilton Depression Scale (HDRS), the Montgomery-Asberg Depression Scale (MADRS), the Widl?cher depressive slowness scale (ERD), and auto-questionnaires as the Beck Depression Inventory (BDI), and the Beck Hopelessness scale (H). In the schizophrenic group, psychotic symptoms were evaluated with the Positive and Negative Symptoms Scale (PANSS), and the extrapyramidal symptoms with the Extrapyramidal symptoms scale (EPRS). In the two populations, the CDSS has similar psychometric properties. The principal component analyses accounts for a unifactorial structure in both groups. In schizophrenics the total score of the CDSS is strongly correlated with the total scores of the HDRS, the MADRS, the ERD, and the G6 item of the PANSS. In non schizophrenic depressed patients, the total score of the CDSS is highly correlated to the total scores of the HDRS, the MADRS and the BDI, with a weaker correlation with the ERD and the H total scores. In these patients, a cut-point strictly superior to 13 may be proposed as a severity criterion for depression in these patients. The internal consistency is satisfactory in both groups, with a Cronbach's alpha of 0.82 in schizophrenics and 0.59 in non schizophrenic depressed subjects. In schizophrenics, items C4 (guilty ideas of reference) and C7 (early awakening) are not necessary to the constitution of the scale. In depressed patients, the deletion of item C6 (morning depression) might increase the internal consistency. Inte-raters agreement is high, with weighted kappas all superior to 0.75 in schizophrenics and to 0.61 in depressed patients. Stability over time is good, and the 72 hours test-retest total score of the CDSS is independent from negative and extrapyramidal symptoms. On the other hand, the positive sub-score and the positive factor of the PANSS are correlated to the CDSS total score. The validation of the CDSS is still not complete: sensitivity to change and stability of the factorial structure remain to be explored. Nevertheless, the CDSS is an interesting tool for a quantitative approach of the subjective dimension of depression in both schizophrenic and non schizophrenic patients.     

Lack of a bimodal distribution of ventricular size in schizophrenia: a Gaussian mixture analysis of 1056 cases and controls.

The finding of clinical and laboratory differences between schizophrenic patients with large and small cerebral ventricles has led to the widespread assumption that large ventricles are a marker that characterizes a subgroup of patients with schizophrenia. We reviewed all published English language ventricle-to-brain ratio (VBR) studies in which individual data points were available (schizophrenics: n = 691, medical controls; n = 205, normal volunteers: n = 160). Using a univariate normal mixture model to examine the distribution of ventricular size in each group, we found no evidence of a mixture of Gaussian distributions (i.e., "bimodality") within any of the three groups. The same analysis was then performed on the combined sample of schizophrenic patients and normal and medical controls, respectively. In each case the improvement in fit of a mixture of normal distributions compared to a single component normal distribution was significant. The data do not support the notion that ventricular enlargement is a discontinuous marker of a subtype of schizophrenia.     

精神分裂症的强迫症状及临床特征的分析

目的 为探讨精神分裂症的强迫症状及其临床特征。方法 采用MMOCI、Y－BOCS、PANSS评定了符合CCMD－2－R中精神分裂症诊断标准的住院精神分裂症病人812例。并将其中合并有强迫症状者75例随机分为两组进行8周的对照治疗,同时进行Pearson相关分析。结果 精神分裂症的强迫症状发生率为9．24％,其中只有强迫思维者占64．0％,强迫思维与强迫行为均有者占36．0％。前者的PANSS、MMOCI、Y－BOCS评分、强迫症状所占的时间、对社会功能的影响,以及所带来的痛苦分都较低,而抵抗分较高,两组比较有显著差异。利培桐安慰剂组和利培酮合并氯丙咪嗪组的疗效都很明显,尤以后者较好。治疗前后强迫症状的评分都与PANSS、阳性症状及一般病理分呈显著的正相关,而与阴性症状分无关。结论 作者认为,强迫症状是精神分裂症的常见症状,可能是精神分裂症固有症状的成份之一。     

PANSS factors and scores in schizophrenic and bipolar disorders during an index acute episode: a further analysis of the cognitive component

To investigate the factor structure of psychotic symptoms, we compared the clinical characteristics of manic patients with those of schizophrenic patients evaluated with positive and negative syndrome scale (PANSS). The clinical symptoms of 148 bipolar patients and 86 schizophrenic patients hospitalized for an index psychotic episode were assessed. Schizophrenic patients showed more positive and cognitive symptoms than bipolars. The factor analysis of the two PANSS scores showed a three-factor solution with 'positive', 'negative' and 'mixed' depressive-activated factors for bipolars and 'positive', 'negative' and 'depressive' factors for schizophrenics. In both groups, the 'cognitive cluster' loaded on the first 'positive' factor while the 'lack of insight' (LOI) has a different meaning in the two groups, more related to the positive symptoms in the bipolar patients and more related to the negative symptoms in the schizophrenic patients. This finding suggests that LOI could be a non-unitary phenomenon in psychoses and it should be further explored to better elucidate differences in symptom structures between schizophrenic and bipolar disorders.     

Diagnostic issues in chronic schizophrenia: kraepelinian schizophrenia, undifferentiated schizophrenia, and state-independent negative symptoms

Data are presented concerning three recent clinical distinctions in schizophrenia: kraepelinian versus non-kraepelinian patients; mixed versus simple undifferentiated subtypes; and state-dependent versus state-independent negative symptoms. Schizophrenic patients who have been ill and dependent on others for the past 5 years ('kraepelinians') were compared to other chronic schizophrenics. The kraepelinian patients met the criteria for schizophrenia by more diagnostic systems than other patients, were less responsive to haloperidol, had more severe negative symptoms and formal thought disorder, and had similarly severe positive symptoms. They also had cerebral ventricles that demonstrated more left-to-right asymmetry and a greater family history of schizophrenia spectrum disorders. Mixed undifferentiated schizophrenic patients, who met criteria for more than one schizophrenic subtype, were compared to simple undifferentiated schizophrenic patients, who met criteria for no subtype. The mixed group was characterized by more severe positive and negative symptoms and formal thought disorder, worse social functioning, and a worse response to haloperidol. In a subgroup of patients who were studied once while in a state of exacerbation and once while in a state of relative remission, the negative symptoms of inattention and affective flattening were state-dependent, while anhedonia-asociality was state-independent.     

The relationship between haloperidol blood levels and clinical responses

Haloperidol blood levels in patients were determined to elucidate the relationship between blood levels and clinical effects. Determinations of haloperidol serum were performed by radioimmunoassay and the clinical status was estimated using BPRS. The relationship between haloperidol serum levels and BPRS total score was studied in 20 chronic schizophrenics currently receiving haloperidol treatment. The results did not show positive relationship between these two. Another 11 schizophrenic patients were treated with daily doses of average 6 mg of haloperidol. The patients were classified into improved and unchanged group according to the changes of BPRS total score. All 7 cases classified into the improved group had short duration of the illness less than one year. In this group, the levels were lower initially but gradually rised in paralled with the increase of extent of recovery on BPRS. Furthermore, improvement of psychopathology by means of decrease of BPRS total score was still found after haloperidol serum levels reached a plateau. The results did not support the view that high blood concentration of haloperidol might contribute to the clinical effects, but still suggested utility of measuring blood levels in acute or subacute patients being treated with haloperidol medications.     

Acute psychotic productivity in cerebral imaging

Regional cerebral blood flow (rCBF) was analysed in 24 neuroleptically never treated schizophrenics by 99m-Tc-HMPAO-SPECT. Psychopathological symptoms (PANSS) were correlated with rCBF-measures using multidimensional scaling (MDS). Highest degrees of correlation were found for ideas of grandiosity and formal thought disorders compared to different regions of interest (ROIs). An adynamic cluster was defined by basic symptoms which showed signs of deficiency. This cluster was by the highest degree correlated with a cluster defined by rCBF compared to four different clusters of basic symptoms. A fMRI-study was performed in schizophrenic patients with auditive hallucinations in comparison to healthy controls. We offered simple acoustic stimuli perceived as coming from the outside versus inside. For the outside condition, controls activated the medial temporal gyrus on the left side and the rightsided precuneus and postcentral gyrus which represent the auditive source locating and the stimulus processing systems, for inside, they activated the left insula. Hallucinating schizophrenic neither activated the one nor the other system. We discussed the findings as a possible explanation of the schizophrenics' tendency to misinterpret hallucinations as real perceptions.     

Ventricular enlargement in young chronic schizophrenics

The ventricular brain ratio (VBR) was measured in a group of 33 young in-patient schizophrenics and 25 controls. Results confirmed significant lateral ventricular enlargement in the schizophrenic patients, but could not demonstrate any association between the VBR and age or length of illness. Some aspects of the studied sample are discussed.     

Multivariate Analysis of Relationship between Childhood Trauma and Psychotic Symptoms in Patients with Schizophrenia

The aim of this study was to examine the relationship between childhood trauma and psychotic symptoms in schizophrenic patients after controlling for the possible confounding factors, such as depression and dissociative symptoms. Ninety-eight schizophrenic inpatients participated. Childhood trauma was examined using the Childhood Trauma Questionnaires (CTQ), which consists of physical abuse (PA), sexual abuse (SA), emotional abuse (EA), physical neglect (PN), and emotional neglect (EN). Positive and Negative Syndrome Scale (PANSS), Dissociative Experience Scale (DES), and Beck''s Depression Inventory (BDI) were also administered. Data were analyzed by partial correlation and general linear model. The total score of CTQ was positively correlated with positive, general, and total scores of PANSS. All five types of childhood trauma were associated with dissociative symptoms. EA and EN were positively correlated with depressive symptoms. Only SA significantly predicted positive symptoms of schizophrenia after controlling for age, sex, BDI, and DES scores, with a dose-response relationship between SA and positive symptoms.     

氯氮平联合美金刚治疗精神分裂症阴性症状对照研究

目的:探讨氯氮平联合美金刚治疗精神分裂症阴性症状的疗效及安全性. 方法:将64例以阴性症状为主的慢性精神分裂症患者随机分成两组,每组32例,两组在服用原有抗精神病药(氯氮平)的基础上,研究组联合美金刚治疗,对照组联合安慰剂治疗,观察12周.于治疗前、治疗8周及12周采用阳性与阴性症状量表(PANSS)、阴性症状量表(SANS)评定临床疗效. 结果:治疗8周及12周时研究组和对照组PANSS总分、阴性因子分及SANS总分较治疗前显著下降(P＜0.05或P＜0.01)),研究组较对照组下降更为显著(P＜0.05或P＜0.01). 结论:氯氮平联合美金刚治疗与单用氯氮平相比,可显著缓解精神分裂症患者的阴性症状.     

Perception of chimeric faces in schizophrenia and right hemispheric dysfunction

The aim of this study was the assessment of cerebral specialisation in perception of emotional chimeric drawings in 50 non-chronic schizophrenics (S), 50 chronic schizophrenics (CS), 30 right brain-damaged inpatients (P), and 50 normal controls. All were marked right handers. The assessment was performed after a four-week treatment. Structure and intensity of schizophrenia symptomatology were scored on the PANSS scale. Happy-sad chimeric face drawings (David 1989) were viewed twice in free vision. A perceiver bias towards left hemiface of chimeric drawings (LHF bias) and sad bias were scored in all subjects. Subjects rated their mood at the time of testing on a visual analogue scale. The schizophrenics and right brain-damaged inpatients showed significantly weaker LHF bias compared with healthy subjects, which may suggest right cerebral hemisphere dysfunction in perception of emotional chimeric drawings. Moreover, chronic schizophrenic patients revealed significantly weaker LHF bias and sad bias compared to non-chronic subjects. There was no correlation of left perceptual bias with clinical ratings: PANSS scale, MMSE, number of hospitalisations, neuroleptic dose, and current mood, which suggests stable properties of the perceptual deficit.     

Negative symptoms of schizophrenia and the dexamethasone suppression test

The dexamethasone suppression test (DST) was administered to 30 inpatients who met the DSM-III-R criteria for chronic schizophrenia and shared similar environments. Four of them (13%) were DST nonsuppressors. The mean and maximum postdexamethasone cortisol levels were correlated with the patient's score on the scale for the Schedule for the Assessment of Negative Symptoms and with the score on the anergia subscale of the Brief Psychiatric Rating Scale. None of the correlations were statistically significant. Furthermore, the scores on the above scales were not significantly correlated with clinical variables such as duration of illness, number of admissions or length of hospitalization, nor were any significant correlations found between the postdexamethasone cortisol levels and the score on the Beck Depression Inventory. In addition, depressed and nondepressed schizophrenics did not differ regarding the rate of nonsuppression and the postdexamethasone cortisol levels. This study found that: 1) dexamethasone nonsuppression in schizophrenia was not related to the presence of negative symptoms; 2) there was no relationship between negative symptoms and illness variables; and 3) the depressed schizophrenics did not display increased nonsuppression compared with nondepressed schizophrenics.     

首发精神分裂症患者临床特征、认知功能的性别差异

目的比较住院男性及女性首发精神分裂症患者临床特征、认知功能等指标的差异。方法选择符合美国精神障碍诊断与统计手册第4版（DSM—IV）诊断标准的首发精神分裂症住院病人90例,其中男性48例,女性42例。收集临床资料,并使用阳性和阴性症状量表（PANSS）、汉密尔顿抑郁量表（HAMD）评定临床症状;威斯康星卡片分类测验（WCST）、重复性神经心理测查系统（RBANS）检测认知功能。结果男性患者比女性患者首次出现精神症状年龄要早2．8岁,首次住院男性患者年龄比女性患者早3．0岁,差异有统计学意义（P均〈0．05）;吸烟在男性患者中比例显著高于女性,差异有统计学意义（P〈0．001）;男性患者单身（未婚或离异）比例显著高于女性,差异有统计学意义（P〈0．05）。RBANS、WCST测查两性之间差异不显著,无统计学意义（P均〉0．05）;在精神症状方面,男性患者的夸大症状及情感交流障碍比女性更突出,差异具有统计学意义（P〈0．05）,但PANSS总分、各分量表分及HAMD评分在两者之间差异不显著,无统计学意义（P均〉0．05）。结论首发精神分裂症患者男性发病年龄要早于女性;在精神症状方面男性于女性之间存在着一定的差异;认知功能两者之间无差异;男性患者单身比例显著高于女性。     

探索性眼球活动与精神分裂症病情严重度的关系

目的通过与正常人群对照,研究探索性眼球活动（EEM）与精神分裂症病情的关系,并探索EEM是精神分裂症的特征性标志还是状态性标志。方法48名精神分裂症患者在入院初、治疗第4周末和第8周末,分别用三套EEM进行检查,并评定阳性与阴性症状量表（PANSS）。对42名正常对照者进行类似的三次EEM检查。比较两组PANSS得分以及EEM的凝视点数（NEF）、反应性探索（RSS）、判别值（D）。NEF、RSS、D越高,越正常。结果精神分裂症患者基线的NEF（27.2±7.0）低于正常对照组（30.9±4.9）,差异有统计学意义（t=-2.9,P=0.05）,基线RSS（4.7±1.9）也低于正常对照组（12.1±3.9）,差异有统计学意义（t=-11.7,P〈0.01）。患者组治疗第8周NEF（29.9±5.0）较基线增加（t=-2.2,P=0.03）,与对照组差异无统计学意义（t=-0.4,P=0.7）,而RSS（4.7±1.4）与基线相似（t=-0.2,P=0.9）,仍低于对照组（12.0±2.9）,差异有统计学意义意义（t=-8.3,P〈0.01）。结论EEM可作为精神分裂症的一种生物学标志,其NEF可能为状态性标志,而RSS则可能是特征性标志。