Hospital comorbidity bias and the concept of schizophrenia

Background The comorbidity bias predicts that if disease definition is based on observations of patients in the hospital, spurious comorbidity of psychopathological dimensions that increase the probability of hospital admission will be included in the disease concept, whereas comorbid dimensions that are not associated with admission will be excluded. The direction of any dimensional comorbidity bias in psychotic illness was assessed in a longitudinal analysis of the psychopathology of patients assessed both inside and outside the hospital. Method Four hundred and eighty patients with broadly defined psychotic disorders were assessed between one and nine times (median two times) over a 5-year period with, amongst others, the Brief Psychiatric Rating Scale. Dimensional comorbidities between positive symptoms, negative symptoms, depression/anxiety, and manic excitement were compared, in addition to their associations with current and future admission status. Results Higher levels of psychopathology in all symptom domains were associated with both current and future hospital admissions. Associations between the positive, negative, and manic symptom domains were higher for patients in the hospital than for patients outside the hospital, in particular, between positive symptoms and manic excitement (β=0.28, p<0.001). However, associations between depression and other symptom domains were higher in out-patients as compared to in-patients (positive symptoms and depression, β=−0.26; p<0.002). Conclusion The current analyses suggest that, to the extent that disease concepts of psychosis do not take into account effects of dimensional comorbidity biases occasioned by differential psychopathology according to treatment setting, “florid” psychotic psychopathology may be overrepresented, whereas depressive symptoms may be spuriously excluded. Bak and Drukker shared first authorship     

Diagnostic value of the DSM and ICD categories of psychosis: an evidence-based approach

Background: It is generally assumed that the distinction between affective and non-affective psychosis occasioned by modern diagnostic criteria provides a useful symptomatic contrast. Method: In a sample of 708 patients with chronic psychosis, the distinction of lifetime DSM-III-R and ICD-10 diagnoses of affective versus non-affective psychosis was used as a diagnostic test to detect lifetime presence of depressive, manic, positive, negative and disorganisation symptoms. Results: A manic or depressive affective diagnosis was a perfect test to diagnose the presence of manic and depressive symptoms, as evidenced by very high diagnostic likelihood ratios. However, this test result was based solely on the inclusion criterion that patients with affective psychosis must have affective symptoms (guaranteeing high specificity and high likelihood ratios), and ignored the fact that patients with non-affective psychosis also had high affective symptom scores (low sensitivity). Furthermore, a non-affective psychotic diagnosis was a very poor test to diagnose correctly the presence of positive, negative and disorganisation symptoms in comparison with an affective psychotic diagnosis. In general, the DSM-III-R categories performed somewhat better as a diagnostic test than those of ICD-10. Conclusion: The evidence for true diagnostic value of the distinction between affective and non-affective psychotic diagnoses is weak. Rather, the distinction appears to obscure natural overlap between the symptom dimensions of the different diagnostic categories.     

Depressive,positive, negative and parkinsonian symptomsin schizophrenia

OBJECTIVE: Depressive symptoms are common in schizophrenia but their relationship to the positive and negative symptoms of the disorder and to extrapyramidal side-effects remains unclear.Considerable overlap exists between these symptom clusters when rated with traditional clinical rating scales. The aim of this study was to investigate the relationship of depressive to positive, negative and parkinsonian symptoms using the recent adaptation of the Positive and Negative Syndrome Scale (PANSS). METHOD: The study involved the cross-sectional measurement of symptoms in a sample of community-treated and hospitalized patients with schizophrenia. Structured assessment included thePANSS, Montgomery-Asberg Depression Rating Scale (MADRS) and the Extrapyramidal Side Effects Rating Scale (ESRS). RESULTS: Depressive symptoms were common and correlated with positive and negative symptoms. These correlations were of a similar magnitude using either the original PANSS factor structure or the newer pentagonal model. The overlap between depressive and negative symptoms was limited to certain items in the rating scales and there was a clear separation between these symptom clusters and the other items. Parkinsonian symptoms also correlated with negative symptoms rated with either PANSS model. CONCLUSION: Use of the pentagonal PANSS model does not improve its capacity to distinguish between depressive and negative symptoms. Positive, negative, parkinsonian and depressive symptoms overlap using common rating scales but there appears to be some separation between these symptom domains when rated with individual scale items rather than total scale scores.     

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.     

Depression in first episode psychosis: The role of subordination and shame

Depression in early psychosis is linked to poor outcome, relapse and risk of suicide, yet remains poorly understood. This article aims to examine the development of depression in acute and post psychotic phases of first episode psychosis (FEP), and its relationship to persecutors, voices, insight, and recovery. Data were gathered on 92 patients with acute FEP on depression course, severity and experience of positive symptoms, insight and appraisals of illness using validated semi-structured interviews and questionnaires. Measures were repeated at 12 months. Malevolent voices, use of safety behaviours and subordination to persecutors were associated with depression and suicidal behaviour in acute FEP. Loss, Shame, low level continuing positive symptoms and longer duration of untreated psychosis were associated with post psychotic depression. Negative appraisals remained stable despite recovery in other symptom domains. Thus, depression and risk in early psychosis may be propagated by the personal significance and content of positive symptoms experienced. When in recovery, low level symptoms, longer period of illness and negative appraisals are significant factors.     

Psychopathology and cognition in schizophrenia spectrum disorders: the role of depressive symptoms.

The cognitive correlates of five symptom dimensions based on PANSS ratings were examined in a group of 50 recent onset psychotic patients, using both objective and subjective cognitive measures. We were particularly interested in the depression dimension, since it has not been studied extensively thus far. The depression dimension showed a high number of correlations with both objective and subjective cognitive measures, such as problems with simple and divided attention, psychomotor slowing and subjectively experienced distractibility, overload and diminished attentional control. The other dimensions, including negative symptoms, have less cognitive correlates. It is possible that previous studies based on a three-dimensional model confounded correlates of negative symptoms with correlates of depressive symptoms. The results of this study suggest the need for more research into the mechanisms underlying the relationship between depressive symptoms and cognitive functioning in schizophrenia, and that patients with depressive symptoms are less efficient in information processing, but can compensate by investing more mental effort. Because subjective cognitive measures were related to mental effort in previous research, they can be a useful tool in future research.     

Longitudinal assessment of negative symptoms in schizophrenia/schizoaffective patients, other psychotic patients, and depressed patients

This study assessed differences in negative symptom presentation between schizophrenia/schizoaffective, other psychotic, and depressed patients over a 10-year followup period. One hundred fifty individuals with schizophrenia or schizoaffective disorders (SZ/SZAF), other psychotic disorders (OP), and depressed patients (DP) were assessed at index hospitalization, then reassessed at 4.5-year, 7.5-year, and 10-year followups. SZ/SZAF patients significantly differed from DP patients in frequency and persistence of negative symptoms but were not significantly different from the OP group. Negative symptoms were not associated with depression in any diagnostic group. Dosage, but not simple use, of conventional antipsychotic medications was related to severity of symptoms in the SZ/SZAF group. Although negative symptoms were typically most severe and most common in the SZ/SZAF subjects in comparison to the DP patients, there were few statistically significant differences in the phenomenology of negative symptoms between the OP and SZ/SZAF groups. The data are consistent with a model that identifies negative symptoms as common to mental illnesses generally, with particularly high rates in psychotic illnesses.     

Dimensionality of depression in acute schizophrenia: a methodological study using the Bech-Rafaelsen Melancholia Scale (BRMES)

Despite the great clinical importance of depressive symptoms in schizophrenia there is a lack of studies on the assessment and evaluation of depression in acutely psychotic patients. For the Bech-Rafaelsen Melancholia Scale (BRMES), among other advantages, the concept of unidimensionality was confirmed in patients with major depression by different methodological approaches including Rasch analysis. The present evaluation was designed to investigate the scale properties of the BRMES in acutely schizophrenic patients with particular emphasis on the dimensionality of the scale. Three different statistical approaches were used: principal component analysis in combination with computer simulation, polytomous Rasch analysis using advanced latent trait and latent class models and confirmatory factor analysis (CFA) by means of linear structure model approaches. The statistical methods were applied to BRMES baseline data of 132 acutely schizophrenic patients with predominantly positive symptoms participating in a multi-center pharmacological trial. The different methodological approaches revealed converging results indicating: (1) a substantial proportion of acutely ill schizophrenic patients showed depressive symptoms; (2) the hypothesis of unidimensionality of the BRMES had to be rejected for the sample of acutely schizophrenic patients and (3) a three-factorial model of depressive symptoms as measured by the BRMES (retardation, depressive core symptoms, unspecific depressive symptoms) yielded the best fit of the present data. Depression in acutely psychotic patients has to be considered rather as a heterogeneous construct than as a well-defined syndrome. The differentiation of depressive symptomatology should facilitate treatment evaluation and help to clarify relationships between different symptom classes in further studies.     

Differentiating primary from secondary negative symptoms in schizophrenia: a study of neuroleptic-naive patients before and after treatment

OBJECTIVE: The study examined the primary versus secondary character of negative symptoms in a group of first-episode, neuroleptic-naive psychotic patients before and after they started neuroleptic treatment. METHOD: Forty-seven inpatients with a first episode of schizophrenia or related psychotic disorders were examined for the presence of negative symptoms, psychosis, depression, and parkinsonism at admission to an inpatient psychiatric unit, before receiving neuroleptics, and at discharge an average 3.3 weeks later, after starting neuroleptic treatment. RESULTS: Although patients' mean scores on measures of positive, negative, and depressive symptoms decreased significantly over the treatment period, the mean rating of nonakinetic parkinsonism worsened. The mean rating of akinetic parkinsonism did not change significantly over the treatment period. Negative symptoms at admission were not predicted by positive or depressive symptoms at admission. Residual negative symptoms at discharge were mainly predicted by negative symptoms at admission (i.e., primary symptoms) and to a negligible degree by residual positive and depressive symptoms. Change in negative symptoms over the observation period was predicted to a marginal degree by change in depressive symptoms. CONCLUSIONS: Negative symptoms rated during a first psychotic episode before and after starting antipsychotic treatment are mainly primary in character and should be considered as a direct manifestation of the basic dysfunctions of schizophrenia.     

Depressive symptom profiles and severity patterns in outpatients with psychotic vs nonpsychotic major depression

Background

Previous research suggests that patients with psychotic major depression (PMD) may differ from those with nonpsychotic major depression (NMD) not only in psychotic features but also in their depressive symptom presentation. The present study contrasted the rates and severity of depressive symptoms in outpatients diagnosed with PMD vs NMD.

Method

The sample consisted of 1112 patients diagnosed with major depression, of which 60 (5.3%) exhibited psychotic features. Depressive symptoms were assessed by trained diagnosticians at intake using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and supplemented by severity items from the Schedule for Affective Disorders and Schizophrenia.

Results

Patients with PMD were more likely to endorse the presence of weight loss, insomnia, psychomotor agitation, indecisiveness, and suicidality compared with NMD patients. Furthermore, PMD patients showed higher levels of severity on several depressive symptoms, including depressed mood, appetite loss, insomnia, psychomotor disturbances (agitation and retardation), fatigue, worthlessness, guilt, cognitive disturbances (concentration and indecisiveness), hopelessness, and suicidal ideation. The presence of psychomotor disturbance, insomnia, indecisiveness, and suicidal ideation was predictive of diagnostic status even after controlling for the effects of demographic characteristics and other symptoms.

Conclusions

These findings are consistent with past research suggesting that PMD is characterized by a unique depressive symptom profile in addition to psychotic features and higher levels of overall depression severity. The identification of specific depressive symptoms in addition to delusions/hallucinations that can differentiate PMD vs NMD patients can aid in the early detection of the disorder. These investigations also provide insights into potential treatment targets for this high-risk population.     

The effects of neuroticism, extraversion, and positive and negative life events on a one-year course of depressive symptoms in euthymic previously depressed patients versus healthy controls

We investigated a) the concurrent impact of positive and negative life events on the course of depressive symptoms in persons remitted from depression and healthy controls, b) whether the impact of life events on symptom course is moderated by the history of depression and the personality traits of neuroticism and extraversion, and c) whether life events mediate possible relationships of history of depression and personality traits with symptom course. Using data from the Netherlands Study of Depression and Anxiety, we examined 239 euthymic participants with a previous depressive disorder based on DSM-IV and 450 healthy controls who completed a) baseline assessments of personality dimensions (NEO Five-Factor Inventory) and depression severity (Inventory of Depressive Symptoms [IDS]) and b) 1-year follow-up assessments of depression severity and the occurrence of positive and negative life events during the follow-up period (List of Threatening Events Questionnaire). Remitted persons reported higher IDS scores at 1-year follow-up than did the controls. Extraversion and positive and negative life events independently predicted the course of depressive symptoms. The impact of life events on symptom course was not moderated by history of depression or personality traits. The effect of extraversion on symptom course was partly caused by differential engagement in positive life events.     

The dexamethasone suppression test in affective illnesses and schizophrenia: relationship with psychotic symptoms

The authors studied the dexamethasone suppression test (DST) on a series of 112 inpatients including 65 patients with major depressive disorder (21 bipolars: 4 with, 17 without psychotic symptoms; 44 unipolars: 13 with, 31 without psychotic symptoms), 15 patients with depressive disorder, 10 schizoaffective and 22 schizophrenic patients. Using different diagnostic criteria, they confirm the best performances of the DST in depression for the diagnosis of a major depressive disorder, primarily endogenous. They also examined the potential influence of psychotic symptoms, suicidal behavior and family history of affective illness on the DST. The only significant difference found is in the cortisol plasma level at 4 p.m. in bipolar patients with psychotic symptoms. That fact and the high rate of abnormality of the DST in schizoaffective and schizophrenic patients indicate that psychotic symptoms per se may play a role in a dysregulation of the hypothalamo-pituitary adrenal axis.     

Depression, suicidal behavior and insight in adolescents with schizophrenia

OBJECTIVES: To investigate the interrelationships between depressive symptoms of adolescent schizophrenia, post-psychotic depression (PPD), negative signs, suicidal behavior and insights into the disease. METHODS: Three groups of 16 adolescent inpatients were assessed with regard to: Schizophrenia alone, schizophrenia with PPD and major depressive disorder (MDD). The following measures were used: DSM IV diagnostic criteria, the Calgary Depression Scale for Schizophrenia (CDSS), the PANSS (Positive and Negative Signs of Schizophrenia Scale), (BDI) Beck Depression Inventory, (CCL) Cognitive Check List, (HS) Hopelessness Scale, (SRS) Suicide Risk Scale, (CSPS) Child Suicide Potential Scale and the (SAUMD) Scale to Assess Unawareness of Mental Disorder. RESULTS: Compared with MDD adolescents, PPD adolescents showed few somatic and behavioral symptoms of depression but had equally severe cognitive and affective depressive symptomatology. Suicide risk scores and actual suicidal behavior was prominent in PPD adolescents. A positive and significant correlation was found between PPD symptoms, suicide risk and awareness of disease (insight). Negative symptoms of schizophrenia could be distinguished from PPD symptoms and there was a negative correlation between blunted affect and PPD scores. CONCLUSIONS: PPD can be diagnosed in adolescent schizophrenia. The symptom pattern is different from MDD, therefore, there may be cause to modify DSM IV provisional criteria for this condition. Adolescents with schizophrenia who have insight into their illness are at higher risk for suicidal behavior and the development of PPD.     

Rates and correlates of suicide attempts in first-admission psychotic patients

The relationship of attempted suicide to demographic characteristics, current and lifetime psychiatric diagnoses, clinical history, and current symptoms was assessed in a sample of 184 recently hospitalized psychotic patients. Forty-three patients (23%) had an attempt history, and 28 (15% of sample; 65% of attempters) made an attempt during the episode for which they were hospitalized. Demographic characteristics did not distinguish attempters from nonattempters. Variables significantly associated with having ever attempted suicide were current diagnosis of unipolar major depressive disorder but not bipolar; lifetime major depressive episode; a history characterized by a less acute onset, lower pre-admission psychosocial functioning, and episodes of physical violence; and a symptom picture characterized by greater depression, hopelessness, negative symptoms, hallucinations and less thought disorder. Those with a current attempt had significantly higher rates of lifetime history of major depression and less physical violence than those with past attempts only. The potential importance of the data for predicting future suicidal acts is discussed.     

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.     

Relationship between depressive symptoms and quality of life in Nigerian patients with schizophrenia

Purpose

Quality of life (QOL) in patients with schizophrenia is influenced by various factors such as depressive symptoms. This study assessed the relationship between depressive symptoms and QOL in outpatients with schizophrenia in Nigeria and evaluated the associated socio-demographic and clinical factors.

Methods

One hundred patients with 10th edition of the International Classification of Diseases diagnosis of schizophrenia participated in this study. Socio-demographic and clinical factors such as depression were assessed with Zung Self-rating Depression Scale and symptoms of schizophrenia with the Positive and Negative Syndrome Scale of schizophrenia (PANSS). The level of functioning was assessed with the Global Assessment of Functioning Scale. QOL was assessed using the brief version of the World Health Organisation Quality of Life Scale.

Results

There were 27 (27.0 %) patients with depression. The depressed patients reported significant lower scores in all QOL domains when compared with the non-depressed group. All QOL domains were significantly negatively correlated with the total PANSS and all its subscales (except for psychological domain with total PANSS and social relationship and environmental domains with PANSS positive). Severity of depressive symptoms was significantly negatively correlated with all QOL domains. Functioning was significantly positively correlated with all QOL domains except in the environmental domain. Multiple regression analysis showed that depressive symptoms predicted all QOL domains except the social relationship domain while negative symptoms predicted social relationship and environmental domains.

Conclusion

Depression is a common occurrence during the course of schizophrenia. Depressive and negative symptoms have a significant impact on the QOL of patients with schizophrenia.     

Anhedonia in depression and schizophrenia: a reexamination.

The purpose of this study was to utilize factor analysis to help determine whether anhedonia is a symptom of both depression and schizophrenia. Measures of depression, positive and negative symptoms of schizophrenia, and anhedonia were administered to a group of schizophrenic patients (N = 54) and to a group of patients with major depressive disorder (N = 27). The correlation matrix among the various scales was subjected to an oblique exploratory factor analysis. Three factors were extracted, accounting for three quarters of the variance. The first measured depression, the second measured positive symptoms, and the third measured negative symptoms. Anhedonia loaded significantly on the first factor but not on the third, suggesting that it is a symptom of depression rather than schizophrenia. These results were corroborated by means of confirmatory factor analysis. We conclude that anhedonia is a symptom of depression and that it only appears to be a symptom of schizophrenia because it is a component of emotional blunting which is indeed a negative symptom of schizophrenia.     

Subtypes of depressive episodes according to ICD-10: prediction of risk of relapse and suicide

BACKGROUND: The long-term predictive ability of the ICD-10 subtypes of depression with melancholic syndrome and depression with psychosis has not been investigated. SAMPLING AND METHODS: All patients in Denmark who had a diagnosis of a single depressive episode at their first ever discharge during a period from 1994 to 1999 were identified. The risk of relapse leading to readmission and the risk of committing suicide were compared for patients discharged with an ICD-10 diagnosis of a single depressive episode with and without melancholic syndrome and for patients with and without psychotic symptoms, respectively. RESULTS: In all, 1,639 patients had a diagnosis of depressive episode without psychotic symptoms, 1,275 patients a diagnosis with psychotic symptoms, 293 a diagnosis without melancholic syndrome, and 248 a diagnosis with melancholic symptoms at first discharge. The risk of relapse leading to readmission was greater for patients with psychotic symptoms than for patients without, but no difference was found between the two groups in the risk of committing suicide during follow-up. No differences were found in the risk of relapse leading to readmission or suicide between patients with and without melancholic syndrome. CONCLUSIONS: The ICD-10 categorization into depression with and without psychotic symptoms seems to be clinically and prognostically useful, whereas the ICD-10 subtyping into melancholic and non-melancholic syndrome does not seem to have any long-term predictive value.     

Relationships between depression and psychotic symptoms of schizophrenia during an acute episode and stable period

The aim of the present study is to explore the relationship between depression and psychotic symptoms of schizophrenia over the course of illness. Sixty-eight patients meeting DSM-IV criteria for schizophrenia were enrolled, 27 in an acute episode, 41 when stable. Assessments were performed using the Calgary Depression Scale for Schizophrenia (CDSS) for depression and the Positive and Negative Syndrome Scale (PANSS) for psychotic symptoms. When considering patients in an acute episode (52% depressed), the CDSS score was correlated only with the PANSS positive sub-scale score. For patients in the stable period (38% depressed), the CDSS score was correlated with positive as well as negative and general psychopathology sub-scale scores. Hence, the relationship between depression and other symptoms of schizophrenia appear to differ during different stages of illness.