Stability of positive and negative symptom constructs during neuroleptic treatment in schizophrenia.

To assess the structural stability of positive and negative symptom ratings, we rated 40 schizophrenic inpatients on the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS) at medication-free baseline and after 4 weeks of neuroleptic treatment. Positive symptom variables consisted of six BPRS items, and the negative symptom variables consisted of the five SANS subscale global scores. On principal components analysis, a three-factor, oblique-rotated solution resulted, with a negative symptom factor, a positive symptom factor, and an unstable behavioral agitation factor. The pre- and posttreatment factor loading patterns were similar. The findings suggest that BPRS-positive symptom items and the SANS measure distinct clinical dimensions and that the construct is stable, as demonstrated by minimal structural change with time.     

Distinguishing depression and negative symptoms in unmedicated patients with schizophrenia

Depression can occur in schizophrenia but can be difficult to distinguish from negative symptoms of the illness. To evaluate whether concurrent use of the Hamilton Rating Scale for Depression (HRSD) and the Brief Psychiatric Rating Scale (BPRS) could successfully separate depression and negative symptoms, we examined ratings on 69 unmedicated schizophrenic inpatients. A classical BPRS depression subscale score correlated highly (rho = 0.80) with the HRSD total score. The classical BPRS "negative symptom" subscale score was unrelated to both the BPRS and HRSD depression summary measures. Among individual HRSD items, negative symptoms correlated only with work/activities and retardation. The findings suggest that negative and depressive symptoms may be assessed independently.     

Depression in Kraepelinian schizophrenia

In order to improve our understanding of depression in chronic schizophrenia, depressive symptoms were assessed in institutionalized, so called Kraepelinian, patients with schizophrenia (N = 43). The patients had been ill and dependent on others for at least 5 years. Depressive symptoms as measured by the Hamilton Depression (HAM-D) scale were less prevalent in this population compared to published data on non-Kraepelinian patients. Only 5% of our Kraepelinian patients had a HAM-D score >/= 16. There was also a low prevalence of core depressive symptoms (depressed mood, suicidal ideation, and guilt). The relationship of depression to other dimensions of schizophrenia was explored. Depression had a modest positive correlation (r = 0.44) with general psychopathology as measured by the Brief Psychiatric Rating Scale (BPRS), but not with positive symptoms as measured by BPRS positive subscale or negative symptoms as measured by the Scale for the Assessment of Negative Symptoms (SANS). Depression also showed a modest positive correlation (r =.48) using the Simpson-Angus Rating Scale (SAS) for extrapyramidal symptoms (EPS). These results indicate that in Kraepelinian schizophrenia, depression is not prevalent, even though patients are severely ill both in symptom and functioning domains. The results of our analysis support that Kraepelinian schizophrenia is a distinct subtype, and raise questions regarding the boundary between schizoaffective disorder and non-Kraepelinian schizophrenia. Finally, the low rate of depression observed revives the notion that preservation of core functional abilities is important for a depressive reaction to evolve in schizophrenia.     

首发精神分裂症病人的抑郁症状

目的探讨首发精神分裂症病人抑郁症状的发生率、特征及相关因素。方法于入院、治疗3、6、9、12月时用汉密尔顿抑郁量表(HAMD)、简明精神病评定量表(BPRS)、阴性症状量表中文版(SANS-CV)、临床总体印象量表(CGI)及功能总体评定量表(GAF)对164例首发精神分裂症患者进行评定。结果急性期首发精神分裂症病人轻度或以上程度抑郁症状的发生率为71%,但在缓解期降至12%。急性期突出的抑郁表现为认知障碍与迟缓(因子分各占HAMD总分的35%和29%)。抑郁症状随着精神病性症状的缓解而减轻,与性别、发病年龄、受教育时间、病程及前驱期长短无关。HAMD总分在急性期仅与BPRS的焦虑抑郁因子分有关,但在缓解期与阴阳性症状、临床总体印象以及总体功能均有密切的相关性;急性期以及治疗3个月时的抑郁症状与随后的阴阳性症状、总体功能的变化无关。结论首发精神分裂症急性期的抑郁症状可能是一个独立的症状群,抑郁程度不能作为预测首发精神分裂症病人预后的指标。     

Negative and depressive symptoms in suicidal schizophrenics

The aim of this study was to determine the value of positive, negative and depressive symptoms, and of the dexamethasone suppression test (DST), in differentiating schizophrenics with and without a history of suicide. Fifty-seven hospitalized patients with schizophrenia were assessed at the end of a neuroleptic free interval with the Brief Psychiatric Rating Scale (BPRS), the Hamilton Rating Scale for Depression (HRSD), and with a dexamethasone challenge. Suicide attempters were significantly more likely to meet criteria for major depression than nonattempters. Scores on the HRSD differentiated the two groups whereas the sums of positive and negative symptom items from the BPRS did not. DST a.m. and p.m. cortisol values differentiated suicide attempters from nonattempters and HRSD scores correlated significantly with cortisol levels. This study confirms the importance of depressive symptoms in schizophrenic patients with a history of suicide. Assessment of the hypothalamic-pituitary-adrenal axis in schizophrenia may also provide useful information.     

Negative symptomatology in schizophrenic outpatients.

This study examines the prevalence of negative symptoms, and assesses the convergence of negative and depressive symptoms in 60 chronically ill schizophrenic outpatients. Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms and the negative symptom cluster of the Brief Psychiatric Rating Scale (BPRS). Depressive symptoms were assessed with the depression subscale of the Brief Symptom Inventory and the depressive symptom cluster of the BPRS. A majority of patients in this group of relatively stable, schizophrenic outpatients demonstrated mild to moderate degrees of both negative and depressive symptoms. Correlations were not significant between negative symptom and depressive symptom measures, which suggests that the symptom constructs are relatively independent. Comparisons between a subgroup with prominent negative symptoms (N = 18) and a subgroup with minimal negative symptoms (N = 32) also revealed no significant group differences in variables that characterize clinical course (i.e., age of onset and frequency and duration of hospitalization) or in the severity of depressive symptoms. This lack of any significant differences on the clinical course variables may be partially explained by the heterogeneity of negative symptoms. The constellation of negative symptoms may differ not only in etiology but also in their temporal relationships to other aspects of the patient's clinical course. Longitudinal studies will be needed to track the long-term outcome of negative and depressive symptoms.     

Preliminary experiences and results with the Munich version of the Andreasen Scale. Assessment of productive and negative symptoms in chronic schizophrenic patients

The Andreasen Scale (SANS), an instrument for evaluating negative symptoms in schizophrenic patients, was translated at the Psychiatric Hospital of Munich and tested on 35 chronic schizophrenic inpatients at the Regensburg State Mental Hospital. In addition, psychopathology was evaluated with the BPRS, sociodemographic data were collected, and cognitive performance was evaluated by the MMS. Also, VBR was determined on the basis of CAT scans. Our results suggest that the SANS is a reliable instrument for measuring negative symptoms; however, the symptom complexes are affected by age, duration of illness and hospitalization, thus making a clear distinction between negative symptoms per se and the effects of hospitalization questionable.     

The predictive value of P300-amplitudes in the course of schizophrenic disorders

Summary Auditory P300-amplitudes have been found to be correlated with the social functioning and with the impairment in daily life by negative symptoms in cross-sectional studies. In this prospective longitudinal study, the correlation of auditory P300-amplitudes registrated at the index examination was investigated with the clinical outcome after an average of 2.4 years. Based on previous studies, only schizophrenic patients who were in a stabilized residual state were included in the study. Reference-independent P300-parameters of the index examination were correlated with axis V of DSM-III-R (GAP), with the Brief Psychiatric Rating Scale (BPRS) and with the Scale for Assessment of Negative Symptoms (SANS) assessed at the follow-up examination. The correlation of index P300-amplitude with social functioning at follow-up was significant. No correlations of index P300 with the current symptomatology at follow-up, as expressed by BPRS and SANS was found, however. The results indicate a predictive value of the P300-amplitude on the clinical outcome in terms of social functioning of schizophrenic patients.     

Sertraline as monotherapy in the treatment of psychotic and nonpsychotic depression

BACKGROUND: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) are effective when used alone in the treatment of unipolar depression with psychotic features. The purpose of the present study was to examine the response to sertraline for patients with and without psychotic features using standard criteria such as recovery and remission. METHOD: An 8-week open-label trial of sertraline in depressed inpatients was conducted. Twenty-five subjects had DSM-IV major depressive disorder with psychotic features, and 25 had DSM-IV major depressive disorder without psychotic features. After a 1-week open washout, all subjects were rated using the Hamilton Rating Scale for Depression (HAM-D) and Brief Psychiatric Rating Scale (BPRS) at baseline. The HAM-D was administered weekly, and the BPRS was administered again only at the end of the 8-week trial. Medication dosage was started at 50 mg/day, increased to 100 mg/day after 1 week, and then increased up to 200 mg/day if subjects had not remitted. RESULTS: Depressed patients without psychosis responded significantly better than did depressed patients with psychosis using the criteria of remission (HAM-D score - 7; p =.001), response (HAM-D score - 50% of baseline score; p =.011), referral for electroconvulsive therapy (HAM-D score >/= 15; p =.011), or change in HAM-D scores (p =.016). Baseline HAM-D score and psychosis independently predicted response, whereas baseline BPRS scores did not, regardless of whether psychotic status was entered into the analyses. CONCLUSION: Psychotic depression responds more poorly than depression without psychosis to sertraline alone. Psychosis was a predictor of response independent of degree of depression and general psychopathology. Limitations due to an open-label design are discussed, as are differences between this study and others using SSRIs for psychotic depression.     

万拉法新与氯丙咪嗪治疗精神分裂症后抑郁对照研究

目的 验证万拉法新治疗精神分裂症后抑郁的疗效及安全性。方法 对65例精神分裂症后抑郁患者随机入组,分别以万拉法新与氯丙咪嗪治疗6周。采用汉密尔顿抑郁量表(HAMD)、简明精神病量表(BPRS)、阴性症状量表(SANS)评定临床疗效,采用副反应量表(TESS)评定副反应。结果 万拉法新组与氯丙咪嗪组治疗前后HAMD、BRPS、SANS评分及减分率比较均无显著性差异(P>0.05)。万拉法新组的副反应较氯丙咪嗪组少而轻,但各有1例精神病症状恶化。结论 万拉法新治疗精神分裂症后抑郁的疗效确切,但极个别病例精神病症状恶化。     

Missing Peaks in Auditory Brainstem Responses and Negative Symptoms in Schizophrenia

Abstract: Auditory brainstem responses (ABRs) were examined in 30 schizophrenic patients and 29 normal subjects. The psychotic symptoms were assessed by the Brief Psychiatric Rating Scale (BPRS) and the Scale for Assessment of Negative Symptoms (SANS) in the patients. At least one of the waves I, II or III was found missing on either side at 80 dBHL (hearing level) in 8 (27%) of the patients but in only one (3%) of the normal subjects. There was a significant association between the missing peaks and the BPRS negative symptom cluster or the total score of the SANS. These results suggest that some schizophrenics, especially those with negative symptoms, have an abnormality of input processing of auditory information in the lower brainstem.     

A subscale for negative symptoms from the Comprehensive Psychopathological Rating Scale (CPRS): a comparison with the Schedule for Assessment of Negative Symptoms (SANS)

The Comprehensive Psychopathological Rating Scale (CPRS) was used to determine symptomatology in 145 schizophrenic patients. In 40 of these patients the Schedule for Assessment of Negative Symptoms (SANS) was also applied in order to determine which items in the CPRS represent negative schizophrenic symptoms. Of the patients, 115 were drug-free and 30 were treated with major transquilizers at the time of the rating. A principal component analysis with oblique solution and Varimax rotation grouped the items from CPRS into ten factors. These factors were subsequently correlated to the total scores of the SANS. When a factor showed a positive correlation with the SANS, the individual items within the factor were examined for correlation to both the subscales and the total SANS scores. Of the 33 items, 5 used in the CPRS showed a positive correlation with the SANS and were therefore considered to represent negative symptomatology in schizophrenia. These items were withdrawal, reduced speech, lack of appropriate emotions, slowness of movements and indecision. The items were grouped as a negative symptom subscale in the CPRS.     

Correlations between standard auditory evoked potentials and symptomatology in a group of 50 schizophrenic patients

Standard auditory evoked potentials (AEP) were recorded in 50 schizophrenic patients and 47 normal controls. All patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS), and the Positive and Negative Syndrome Scale (PANSS), and were classified in three groups (positive-type [n = 10], negative-type [n = 23]and mixed-type [n = 17]patients) according to the normative criteria suggested by Kay. The mean latencies of AEP components (N1, P2, N2) and mean peak-to-peak amplitudes (N1P2, P2N2) did not correlate with age, duration of illness, length of hospitalisation or neuroleptic dosage. The evoked response did not differ between the three groups of patients (positive, negative and mixed). There was only a trend (P = 0.075) to a longer N1 latency in the negative-type group and a shorter one in the positive-type group than in the mixed-type and the control groups. The latency of N1 component correlated significantly with negative symptoms of schizophrenia (SANS scores). This correlation was related to the severity of a depressive dimension of the disorder reflected by the “depressive factor” of BPRS or “affective flattening” and “avolition” subscales of SANS.     

慢性精神分裂症患者的抑郁症状研究

目的:了解慢性精神分裂症患者的抑郁症状及其相关的影响因素。方法:对180名住院慢性精神分裂症患者测试卡尔加里精神分裂症抑郁量表(CDSS)、阳性症状量表(SAPS)、阴性症状量表(SANS)、治疗中出现的症状量表(TESS)及自编的相关因素调查表。结果:慢性精神分裂症患者的抑郁症状发生率为40.6%;有无抑郁发生的两组比较,在总病程、住院次数、文化程度、家庭经济水平、社会支持、自知力恢复及药物种类、剂量、时间及不良反应、阳性阴性症状和合并躯体疾病等方面差异有显著性。Logistic回归分析显示,精神分裂症患者出现抑郁症状的相关影响因素依次为:阴性症状、合并躯体疾病、抗精神病药的种类、社会支持、自知力及药物不良反应。结论:慢性精神分裂症患者抑郁症状发生率高、影响因素多,需从多方面对精神分裂症患者的抑郁进行预防和治疗。     

Negative symptoms in depressed and schizophrenic patients: how do they differ?

BACKGROUND: The present study evaluated differences in negative symptoms between schizophrenic and depressive patients and investigated whether a consideration of the nature of negative symptoms (enduring vs. nonenduring) can help to improve their specificity for schizophrenia. METHOD: Patients enrolled in the study were consecutively hospitalized with an acute exacerbation of schizophrenia (N = 33) or major depressive disorder (N = 43) (DSM-IV). Negative and depressive symptoms were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and the Montgomery-Asberg Depression Rating Scale, respectively. Duration of negative symptoms was assessed through a semistructured interview with the patients and their closest relatives. On the basis of the assessed duration of symptoms, negative symptoms were categorized as enduring or nonenduring. RESULTS: Analyses revealed high SANS ratings for both diagnostic groups. Negative symptoms in depressive patients (p =.01), but not in schizophrenic patients, were significantly associated with the presence or the emergence of depressive symptoms. The prevalence of enduring negative symptoms was significantly higher in schizophrenic patients than in depressive patients (p <.01). A consideration of enduring negative symptoms significantly increased the discriminative power of negative symptoms for schizophrenia (p =.02). CONCLUSION: The present findings suggest that negative symptoms in most depressive patients are just an epiphenomenon of depressive symptoms and can be distinguished from schizophrenic negative symptoms.     

Depressive symptoms in stable chronic schizophrenia: prevalence and relationship to psychopathology and treatment

The prevalence and correlates of the depressive syndrome were explored in a population of 120 patients with stable, chronic schizophrenia living in the community. The presence of clinically significant depressive symptoms was defined by a score of 17 or greater on the Beck Depression Inventory. Patients were examined to assess severity of schizophrenic symptoms and medication side-effects. Sixteen of the 120 patients (13.3%) had significant depressive symptoms. Depressive symptoms were significantly correlated with the hostility/suspiciousness (P<0.0001), the positive symptom (P=0.0009) factor of the BPRS and with scores on the Significant Others Scale, a measure of patients' perceived lack of social support (P=0.0004). The association between depression and akathisia approached significance (P=0.007). There was no correlation with demographic variables, alcohol intake, antipsychotic dosage or anticholinergic dosage. Using a scale that rates the subjective aspects of the depressive syndrome, we found no evidence of a relationship between depression and negative symptoms in this population. These results indicate that persistent depressive symptoms in stable patients in the community are related to the degree of persistent positive psychotic symptoms, patient perceptions of social support and, weakly, to the degree of akathisia but not other aspects of antipsychotic treatment.     

Correlations between the MMPI and the Brief Psychiatric Rating Scale in schizophrenic and schizoaffective patients

Though self-report measures and clinician-based ratings are extensively used to document psychopathology, there has been little work examining the relationship between these different types of measurement techniques. The current work examined the relationship between the Minnesota Multiphasic Personality Inventory (MMPI) and the Brief Psychiatric Rating Scale (BPRS) in patients with schizophrenia and schizoaffective disorder. Correlations were calculated in an initial exploratory sample, and a set of relationships was selected for confirmation in a second sample. The BPRS items of hallucinatory behavior and tension significantly correlated with MMPI measures of psychoticism. BPRS measures of hostility correlated with scale 4 (Psychopathic Deviate) of the MMPI. BPRS and MMPI measures of depression also were related. In contrast, BPRS and MMPI measures thought to reflect negative symptoms were uncorrelated. These results offer behavioral validity for the use of the MMPI in schizophrenic samples and suggest that the two measures tap similar as well as separable symptom constructs thought to be common in schizophrenia.     

The relationship of clozapine and haloperidol treatment response to prefrontal,hippocampal, and caudate brain volumes

OBJECTIVE: The study was designed to assess the predictive relationship between brain structure volume and positive and negative symptom response to clozapine and haloperidol. METHOD: Partially responsive outpatients with schizophrenia who participated in a 10-week, parallel-group, double-blind comparison of clozapine and haloperidol and who had an available magnetic resonance imaging scan were included in the current study. Prefrontal gray and white matter, hippocampal, and caudate volumes were manually measured. The Scale for the Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS) were used to assess symptom changes. The Simpson-Angus Rating Scale was used to assess extrapyramidal symptoms. RESULTS: Twenty-two patients randomly assigned to clozapine and 23 patients assigned to haloperidol met study entry criteria. There were significant interactions between treatment and right prefrontal gray matter volume for BPRS total score and SANS total score. There were no significant treatment-by-brain structure interactions for BPRS positive symptom items. Right prefrontal gray matter volume was also related to differential treatment effects for the BPRS subscales of anxiety/depression and hostility and the Simpson-Angus Rating Scale akathisia item. CONCLUSIONS: These results suggest that there is a differential interaction among clozapine and haloperidol, brain structure, and treatment response. Partially responsive patients with larger brain volumes may be more likely to experience the benefits of clozapine treatment, but they may be more vulnerable to side effects and experience a subsequent worsening of their symptoms when treated with haloperidol.     

An 8-week open-label trial of a 6-day course of mifepristone for the treatment of psychotic depression

OBJECTIVE: Several investigations suggest that mifepristone leads to the rapid amelioration of psychotic depression. However, these studies were of short duration (1 week or less) and included subjects who were taking other psychotropic medications. The goals of this study were to extend these findings by conducting an 8-week trial of mifepristone for subjects with psychotic depression who were taking no concomitant psychiatric medications. METHOD: Twenty subjects with a DSM-IV major depressive episode with psychotic features (for convenience we use the term psychotic depression) taking no psychotropic medications were given a 6-day course of mifepristone and followed as inpatients for a total of 8 weeks. Nonblinded ratings using the Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions scale (CGI) were performed at baseline and at the end of weeks 1, 4, and 8. The Brief Psychiatric Rating Scale (BPRS) was also administered at baseline and after weeks 4 and 8. Subjects were recruited between February 2003 and December 2003. RESULTS: Significant improvements in HAM-D and CGI scores were shown after 1 week and between weeks 1 and 4 but not between weeks 4 and 8. BPRS scores improved significantly after week 4, while the improvement in BPRS scores between weeks 4 and 8 was of borderline significance. CONCLUSION: Mifepristone appears to be a useful intervention for psychotic depression, leading to significant improvements even after a 1-week course of administration. Issues related to its optimal dosing and to prediction of response are discussed, as are the implications of lack of a placebo group and the use of nonblinded ratings in the present study.     

Depression in schizophrenia: comparison of first- and second-generation antipsychotic drugs

The aim of this study was to compare the effects of different antipsychotics on depressive symptoms in schizophrenic patients. The data were drawn from a retrospective, naturalistic, observational study in which 222 subjects diagnosed as being affected by schizophrenia during a re-exacerbation phase received 6 weeks of monotherapy with fluphenazine decanoate, haloperidol decanoate, haloperidol, clozapine, olanzapine, quetiapine, risperidone or l-sulpiride. The Brief Psychiatric Rating Scale (BPRS), Extrapyramidal Side Effects Rating Scale (EPSE) and Anticholinergic Rating Scale (ACS) were administered at baseline and six weeks after the beginning of the study; depressive symptoms were evaluated using the BPRS items "depressive mood" and "guilt feelings". All of the antipsychotic drugs led to improvements in the depressive dimension, but this was statistically significant only in the case of fluphenazine decanoate, haloperidol, olanzapine, risperidone and l-sulpiride. A clinical improvement in the depressive dimension significantly correlated with the severity of the psychotic picture and its amelioration. Female patients were significantly more likely to show an improvement in depressive symptoms. In conclusion, our findings suggest that atypical antipsychotics as a class do not seem to be more effective on the depressive dimension during the course of schizophrenia than typical ones, at least as far as the collected BPRS data are concerned. The only factor that seemed to influence the improvement in depressive symptoms during our study was gender, as females were significantly more likely to improve although there were no between-gender differences in the baseline severity of the clinical picture.