Natural history of schizophrenia subtypes. II. Positive and negative symptoms and long-term course.

The natural history and long-term course of schizophrenia divided by pervasiveness of positive and negative symptoms was explored among 187 schizophrenic patients from the Chestnut Lodge follow-up study. Schizophrenia with many negative symptoms was associated with poor premorbid functioning, insidious onset, partial or no remissions during the first several years of illness, and in most cases a progressive course leading to permanent disability. Schizophrenia with few negative symptoms was associated with good premorbid functioning, acute onset, intermittent early course, and a better prognosis. Positive symptoms predicted future hospitalizations but were less powerful and specific as indicators of differential illness history, course, and long-term functional incapacity. As predictors of long-term outcome, negative symptoms were of greater value measured at index admission several years after illness onset than at first hospital admission. Multivariate analyses indicated that two negative symptoms (anhedonia and affective flattening) contribute significantly to outcome variance independent of their association with premorbid functioning or positive symptoms. Patients with the poorest long-term outcome tended to show an increase in negative symptoms during the early years of their illness. Progressive negative symptoms early in the course of schizophrenia may thus reflect or signal a process leading to long-term functional disability.     

Self-efficacy and psychosocial functioning in schizophrenia: a mediational analysis

The construct of self-efficacy has been hypothesized to mediate the relationship between efforts at coping with psychiatric illness and functional outcome. This study examined whether self-efficacy mediated the relationships between psychosocial functioning and important predictors of functioning: premorbid functioning, negative symptoms, and cognitive functioning. Although self-efficacy was positively associated with psychosocial functioning, it did not mediate the relationships between functioning and the other established predictors. Rather, negative symptoms were the strongest predictor of functioning and mediated the relationship between self-efficacy and functioning. The findings suggest that negative symptoms, and not self-efficacy, are the most critical determinants of psychosocial functioning in schizophrenia, and that psychosocial treatment should focus on the amelioration of these symptoms.     

Premorbid adjustment as predictor of outcome in schizophrenia: results of a prospective study

Bailer J, Bräuer W, Rey E-R. Premorbid adjustment as predictor of outcome in schizophrenia: results of a prospective study. Acta Psychiatr Scand 1996: 93: 368–377. © Munksgaard 1996. The present prospective follow-up study of 163 schizophrenic patients admitted to hospital for the first time examined the relationship between premorbid adjustment and different measures of the 3-year course and outcome. The same instruments had been used in all phases of the study. The Premorbid Adjustment Scale was used to assess premorbid social functioning. Outcome measures were positive symptoms, negative symptoms, social disability and number of rehospitalizations. The results of the multiple regression analyses showed that premorbid adjustment was the strongest overall predictor of outcome. Premorbid adjustment was significantly associated with negative symptoms and social disability over the 3-year course of illness. In a further step, we examined the relationship between good, moderate and poor premorbid adjustment and the course of positive symptoms, negative symptoms and social disability within the first 3 years after index admission. The most important finding was that premorbid functioning showed a stronger correlation with the course of negative symptoms and social disability than with the course of positive symptoms. Poor premorbid social functioning implies a poor social course of the illness. Female subjects showed better premorbid functioning than male subjects. Good premorbid adjustment was strongly associated with an acute onset of the illness, and poor premorbid adjustment with an insidious onset.     

Deterioration in premorbid functioning in schizophrenia: a developmental model of negative symptoms in drug-free patients.

OBJECTIVE: The authors examined the relationship between negative symptoms and premorbid variables in drug-free schizophrenic patients. METHOD: The authors studied 63 clinically stable male schizophrenic inpatients who were not receiving any psychoactive medication. The patients were classified as having negative, positive, or mixed symptoms, and their premorbid functioning during childhood, early adolescence, and late adolescence was assessed by using the Premorbid Adjustment Scale. Correlational analyses were applied to the classification and developmental models. RESULTS: Patients with negative symptoms had significantly lower levels of premorbid functioning during late adolescence and significantly greater premorbid deterioration between childhood and early adolescence. Correlational analysis revealed significant positive relationships between premorbid variables and negative symptoms. CONCLUSIONS: The data suggest that a deterioration in social and intellectual functioning between childhood and adolescence is associated with the development of a negative symptom syndrome in schizophrenia. The premorbid deterioration appears to be an early prodrome of the disorder. Whether this residual negative symptom syndrome is in some way related to the deficit syndrome of schizophrenia awaits a prospective study.     

The relationship of premorbid functioning to illness course in schizophrenia and psychotic mood disorders during two years following first hospitalization

Studies suggest that better premorbid functioning is associated with better outcomes in chronic schizophrenia. Yet first admission studies, which are more appropriate to examine this, are less conclusive. Also, little attention has been given to whether these findings hold for other psychoses. We examined the relationship of premorbid functioning using the Premorbid Adjustment Scale and outcomes in first admission psychoses (schizophrenia, N = 177; bipolar disorder, N = 106; major depression, N = 68) in the Suffolk County-wide mental health project. Poor premorbid functioning was associated with worse outcomes in all three diagnostic groups. Specifically, it was associated with more negative symptoms early in the course of illness, less improvement in negative symptoms, poorer overall clinical functioning, and poorer social functioning. Consistent with new epidemiological research, early assessment of premorbid functioning could provide an avenue for targeted interventions that might improve outcomes.     

Patterns of premorbid functioning in first episode psychosis: relationship to 2-year outcome

OBJECTIVE: To determine how different patterns of premorbid functioning relate to outcome longitudinally. METHOD: Premorbid adjustment was assessed in 194 first-episode of psychosis subjects. Positive and negative symptoms, depression, substance misuse and social and cognitive functioning were assessed over 2 years. RESULTS: Four patterns of premorbid adjustment: stable-good, stable-intermediate, poor-deteriorating and deteriorating were identified. Relative to the stable-good group, the deteriorating and poor-deteriorating groups had significantly more positive symptoms at 1-year follow-up but not at 2-year follow-up and significantly more negative symptoms and significantly poorer social functioning at both 1 and 2-years. Only verbal fluency and memory differentiated between the groups with the stable-good group having a superior performance. CONCLUSION: Those who demonstrated poor or deteriorating functioning prior to the onset of acute psychosis have a poorer outcome up to at least 2 years in terms of negative symptoms and social functioning.     

Premorbid sociosexual functioning and long-term outcome in schizophrenia

Chronic schizophrenic patients with the most severe social deterioration have been shown to differ from other chronic schizophrenic patients with respect to measures of left-to-right ventricular asymmetry, negative symptoms, and response to haloperidol treatment. In the current study, the authors investigated the social antecedents of these characteristics of very poor outcome schizophrenia in 69 chronic schizophrenic patients. Poor premorbid sociosexual functioning was associated with more severe left-to-right ventricular asymmetry, greater severity of negative symptoms, fewer positive symptoms, and worse current social functioning. These data suggest that factors associated with severe social deterioration in the end stage of schizophrenia are also associated with premorbid sociosexual impairment.     

Association between duration of untreated psychosis, premorbid functioning, and cognitive performance and the outcome of first-episode schizophrenia in Japanese patients: prospective study

OBJECTIVE: The aim of the present study was to identify the relationship between duration of untreated psychosis (DUP), premorbid functioning, and cognitive dysfunction and the outcome of first-episode schizophrenia. METHOD: Thirty-four neuroleptic-na?ve patients who consulted hospitals in Tokyo and who were treated by psychiatrists for the first time were evaluated with regard to DUP, premorbid functioning, psychiatric symptoms, and global functioning. The neuropsychological test battery consisted of the Letter Cancellation Test, Trail-Making Test, Digit Span and Verbal Fluency Test. One year later, 24 of the subjects were reassessed for psychiatric symptoms, global functioning, and social functioning, and the relationships between DUP, premorbid functioning, and cognitive performance and the outcome was investigated. RESULTS: Short DUP, good premorbid functioning, and good Letter Cancellation Test, Digit Span and Verbal Fluency Test scores were significantly associated with good outcome. CONCLUSIONS: The present results in a Japanese sample are consistent with previous international evidence that delay of initial treatment, premorbid functioning, and cognitive deficits are associated with outcome. A major limitation of the present study was the small size of the subject group. But because the subjects were relatively homogeneous and not influenced by psychoactive substances, the results reflect the essence of the disorder.     

The role of cognition in vocational functioning in schizophrenia

Schizophrenia is associated with long-term unemployment. Cognitive dysfunction, rather than clinical symptoms, may be the most important factor in the ability to work for patients with this disorder. To evaluate the relationship of clinical symptoms and cognitive functioning to work status, thirty patients with schizophrenia, who were participants in a vocational rehabilitation program, were evaluated with a comprehensive neuropsychological battery and assessment of psychopathology. Subjects were classified as being in stable full-time, part-time or unemployed work status for at least a year. Univariate analysis indicated that patients who were working full-time were significantly better educated, more likely to be treatment-resistant, more likely to be treated with an atypical antipsychotic medication, had more positive symptoms, and were engaged in work tasks which were more cognitively complex than the part-time employed and unemployed work groups. An ANCOVA controlling for education demonstrated that the full-time employed group performed significantly better than the unemployed group on measures of executive functioning, working memory and vigilance; and significantly better than the part-time group on measures of vigilance and executive functioning. Although negative symptoms did not significantly relate to work status in the univariate analysis, a multiple regression indicated that negative symptoms, level of education, and executive functioning differentiated the work groups. These results suggest that poor premorbid function, negative symptoms and cognitive dysfunction are significantly associated with unemployment in schizophrenia.     

Gender,premorbid characteristics and negative symptoms in schizophrenia

The interrelationships among gender, premorbid functioning, and negative symptoms were examined in a first-admission inpatient sample with DSM-III-R schizophrenia. Fifty-two subjects were assessed with the Schedule for the Assessment of Negative Symptoms (SANS) at baseline and 6-month follow-up. Three indicators of premorbid functioning were examined: the Premorbid Adjustment Scale, the Quick Test, and the GAF for the best month in the year prior to the baseline interview. Men and women had relatively similar ratings on each of the 5 SANS global subscales at both times; they were also relatively similar on most of the indicators of premorbid functioning. The men and women were categorized into low vs moderate-high negative symptom groups at baseline, and no differences in premorbid functioning were detected. When the sample was classified into those with and without consistent negative symptoms at baseline and 6-month follow-up, the enduring negative men and women had significantly poorer premorbid functioning in several areas than the consistently non-negative patients. Our findings support the importance of assessing negative symptoms longitudinally and suggest that gender is not strongly associated with negative symptoms and premorbid functioning in patients ascertained at early stages of schizophrenia.     

Gender differences in poor outcome patients with lifelong schizophrenia

Gender effects have been reported quite consistently in schizophrenia, with male patients having an earlier age of onset, poorer functional outcome, greater negative symptoms and cognitive impairment, and less severe positive symptoms. Because age of onset, cognitive impairments, and negative symptoms are all correlated with poorer functional status, it is not clear if previously reported gender differences in symptoms are just recapturing gender differences in functional outcome. In this study, 205 geriatric patients with lifelong poor-outcome schizophrenia (43% male) were examined for the severity of schizophrenic symptoms, cognitive impairments, and specific deficits in adaptive skills, as well as for demographic differences such as age at first psychiatric admission, premorbid education, and current treatment status. Previously reported gender differences were replicated in these patients with a uniformly poor functional outcome, with male patients having more severe negative symptoms and an earlier age of first psychiatric admission. No differences in cognitive functioning or specific functional deficits were found, however. These findings suggest that negative symptom severity is greater in male patients regardless of functional outcome and that the association of cognitive deficits with gender may be found only in patients with better functional outcome. The study of gender-related differences in brain structure or function and their interaction with overall course of illness might help understand these differences in symptom presentation.     

Gender, premorbid social functioning, and long-term outcome in DSM-III schizophrenia

The present study examined the relationships among premorbid social functioning, gender, and long-term outcome in a group of 82 subjects (41 men and 41 women) who were retrospectively rediagnosed to meet the criteria for DSM-III schizophrenia. The Premorbid Adjustment Scale was used to assess premorbid social functioning along a developmental continuum. The Community Adjustment Scale provided outcome data related to the subjects' degree of productivity, ability to maintain close relationships, and presence/absence of symptomatology an average of 32 years after initial admission. The results indicated that females tended to exhibit better premorbid functioning than males. Although the outcome data did not reveal a statistically significant relationship between gender and long-term functioning, the results were in the predicted direction, with females again demonstrating more favorable outcome than males. Despite the absence of a statistically significant gender effect, a relationship did appear to exist between premorbid functioning and very long-term outcome, with premorbid asocial functioning predicting poor outcome.     

Patterns of premorbid functioning in first-episode psychosis: initial presentation

Premorbid functioning in first-episode psychosis has been reported to be associated with poorer outcome. We assessed premorbid functioning in a sample of 306 subjects newly admitted to an early-psychosis program. Using cluster analyses, we identified four patterns: stable-good, stable-moderate, deteriorating and poor-deteriorating. Results were that relative to the stable-good group, the deteriorating and the poor-deteriorating groups had more negative symptoms, poorer social functioning and some evidence of poorer cognitive functioning. The deteriorating group had increased positive symptoms compared to the stable-good group. These results suggest that prior to the onset of the acute psychosis those who have poor social and interpersonal functioning premorbidly present initially with increased social impairment and negative symptoms compared to those who have better premorbid functioning.     

Phenomenology and functioning in first-episode schizophrenia.

One current view of schizophrenia is that its clinical and functional features show a deteriorating course, particularly for negative symptoms. However, this is difficult to study in chronic patients who have been exposed to pharmacologic treatment and institutionalization. Examining first-episode (FE) patients can help clarify which symptoms are present initially and how the symptom pattern is linked to functioning. We evaluated a sample of 37 FE patients with schizophrenia and compared them to 70 other schizophrenia (OS) patients on standard clinical scales, measures of premorbid functioning, and quality of life. FE patients showed a symptom profile similar to OS patients; in particular, there was no evidence that negative symptoms are less severe in the FE group. Analysis of the clinical data led us to the conclusion that the symptom profile of schizophrenia exists at the outset, that negative symptoms are associated with poor premorbid and current functioning, but that the role of positive symptoms is more complex and may vary in subtypes.     

The longitudinal relationship of clinical symptoms, cognitive functioning, and adaptive life in geriatric schizophrenia

Cognitive dysfunction is increasingly being recognized as a major contributor to the adaptive impairment seen in most patients with schizophrenia. Reported here is a prospective longitudinal evaluation of the relationship between cognitive and adaptive functioning in elderly patients with schizophrenia. It was hypothesized that baseline cognitive and negative, but not positive symptoms, would be predictive of cross-sectional impairment and longitudinal outcome. Subjects were 168 elderly patients with schizophrenia, free of major neurological disorders, who were residents of a long-term psychiatric facility. Subjects were assessed at baseline and again an average of 15months later. The PANSS was used to assess the severity of symptoms of schizophrenia. Cognitive symptoms were assessed using the components of the CERAD cognitive battery. Social and adaptive functioning was assessed using the SAFE scale. Spearman correlations were determined among clinical variables, and the rank ordering of prediction of SAFE scale scores at follow-up was determined using a stepwise regression procedure. At follow-up, adaptive life skills correlated with cognitive performance and negative symptoms (Spearman rho values 0. 41-0.57, all p values <0.0001), but not positive symptoms (r=0.09, n. s.). Among cognitive tasks, verbal learning and memory were most highly correlated with adaptive skills at follow-up. These results confirm and extend previous studies that indicate that cognitive impairments are predictive, both cross-sectionally and longitudinally, of adaptive life skills in persons with schizophrenia. Negative symptoms, but not positive symptoms, were correlated with impaired adaptive skills. Taken together, these results underscore the need to develop more effective treatments for cognitive and negative symptoms in schizophrenia.     

Premorbid functioning of patients with first-episode nonaffective psychosis: a comparison of deterioration in academic and social performance, and clinical correlates of Premorbid Adjustment Scale scores

BACKGROUND: Motivated by a previous study among male veterans [Allen, D.N., Frantom, L.V., Strauss, G.P., van Kammen, D.P., 2005. Differential patterns of premorbid academic and social deterioration in patients with schizophrenia. Schizophr. Res. 75, 389-397], the present analysis examined: (1) patterns of premorbid academic and social functioning during childhood, early adolescence, and late adolescence, and (2) associations between these premorbid functioning dimensions and a number of clinical variables. METHODS: Data on premorbid functioning were collected using the Premorbid Adjustment Scale (PAS) in 95 hospitalized first-episode patients. Analyses were similar to those conducted by Allen and colleagues (2005). RESULTS: Deterioration was evident in both academic and social functioning from childhood to early adolescence, along with a pronounced/accelerated deterioration in academic functioning from early adolescence to late adolescence, occurring in both male and female patients. Age at onset of prodromal symptoms was predicted by childhood/early adolescent/late adolescent academic functioning scores, and age at onset of psychotic symptoms was significantly associated only with childhood academic functioning. Severity of negative symptoms was predicted by childhood and late adolescent social functioning scores, and severity of general psychopathology symptoms was predicted by late adolescent academic functioning, as well as childhood and late adolescent social functioning scores. CONCLUSIONS: Consistent with prior findings, deterioration in premorbid functioning appears to be more pronounced in the academic than social dimension of the PAS. Some PAS scores are predictive of ages at onset of prodrome/psychosis and severity of psychotic symptoms. Ongoing research on premorbid adjustment in schizophrenia may have implications for future prevention goals.     

Validity and stability of performance-based estimates of premorbid educational functioning in older patients with schizophrenia

This paper presents the results of two studies of the validity of word-recognition reading as an indicator of premorbid functioning in schizophrenia. The first examined the stability over a 6-year follow-up period of word recognition reading compared to other aspects of cognitive functioning, including verbal learning and delayed recall, verbal fluency, constructional skills, and naming ability. The second study examined the relative predictive power of indicators of premorbid functioning as compared to current cognitive functioning for the prediction of current social and self-care skills. In the first study 218 patients with chronic schizophrenia participated. For the second study, 231 male veterans with schizophrenia were assessed for cognitive functioning, indicators of premorbid adjustment, and current functional status. Analyses of the differences between correlations indicated that word recognition reading ability was significantly more stable than other aspects of cognitive functioning over a six-year period during which decline in some other aspects of performance was found. In the second study, premorbid educational and social attainment, word recognition reading skill, and current cognitive functioning were all significantly related to current functional status, defined by correlations with ratings of current functional status. Path analyses indicated, however, that current cognitive functioning was the only significant predictor of current functional status when the intercorrelations of the variables were considered. In sum, Premorbid functioning estimated with word-recognition reading was stable over time (study 1) and correlated with both current cognitive and functional status (study 2). The results of these two studies suggest that word-recognition reading skills are useful screening instruments to estimate premorbid functioning even in deteriorated patients with schizophrenia.     

The level of illicit drug use is related to symptoms and premorbid functioning in severe mental illness

Objective: There is conflicting data on drug abuse and outcome in severe mental illness. This study aims to investigate if the amount of illicit psychoactive drug use is related to symptom load or premorbid functioning across diagnosis in patients with severe mental illness. Method: Symptom load, sociodemographic status, premorbid functioning and the level of use of illicit psychoactive drugs were assessed in 423 subjects with schizophrenia or bipolar disorder in a cross‐sectional study. Results: High amount of illicit drug use was associated with poorer premorbid academic functioning. In schizophrenia, there was a significant positive association between amount of drug use and severity of psychiatric symptoms. The association between symptom load and drug use was significant after controlling for premorbid functioning. Conclusion: The results suggest a direct association between the quantity of current drug use and more severe symptoms in schizophrenia. Poor premorbid functioning was related to high amount of use, but did not explain the difference in symptom load.     

Negative symptoms and specific cognitive impairments as combined targets for improved functional outcome within cognitive remediation therapy

Negative symptoms and poor cognition are both associated with poor functional outcome in schizophrenia. This poor functional outcome has been attributed to poor cognition rather than any independent contribution from symptoms. Identifying target cognitive processes and mechanisms that predict community function, and possible moderator effects of negative symptoms, will allow the development of cognitive remediation programs that are successful in improving functional outcome. A referred sample of 53 in- and outpatients with schizophrenia with general cognitive impairment (including 28 with severe negative symptoms) and 22 healthy controls, balanced for premorbid IQ, were compared cross sectionally on measures of community shopping skills, executive function, and working memory. Across the groups, there were direct relationships between community functioning and specific executive functions, and there were interactions between group membership and the types of associations found. Working memory was independently associated with accurate community functioning only in people with schizophrenia and negative symptoms. This association was not due to the sole presence of working memory impairment or just to negative symptoms. Poor community function is predicted both by specific cognitive impairments that are prominent in people with negative symptoms and through the moderating effect of negative symptoms on the working memory-community function relationship. This may reflect a synergistic association between symptoms and cognition: negative symptoms arise from cognitive impairment but also impact detrimentally on working memory functioning. Both cognitive processes and negative symptoms should be targeted in cognitive remediation to effect the greatest change in community functions.     

Differential patterns of premorbid social and academic deterioration in deficit and nondeficit schizophrenia

Numerous studies indicate that social dysfunction is associated with negative symptoms of schizophrenia during the chronic phase of illness. However, it is unclear whether social abnormalities exist during the premorbid phase in people who later develop schizophrenia with prominent negative symptoms, or whether social functioning becomes progressively worse in these individuals from childhood to late adolescence. The current study examined differences in academic and social premorbid functioning in people with schizophrenia meeting criteria for deficit (i.e., primary and enduring negative symptoms) (DS: n = 74) and non-deficit forms of schizophrenia (ND: n = 271). Premorbid social and academic functioning was assessed for childhood, early adolescence, and late adolescence developmental periods on the Premorbid Adjustment Scale (PAS). Results indicated that both DS and ND participants showed deterioration in social and academic functioning from childhood to late adolescence. However, while ND schizophrenia demonstrated greater deterioration of academic compared to social premorbid functioning from childhood to late adolescence, the DS group exhibited comparable deterioration across both premorbid domains, with more severe social deterioration than the ND group. Findings suggest that people with DS show poorer social premorbid adjustment than those with ND as early as childhood, and are particularly susceptible to accelerated deterioration as the onset of schizophrenia becomes imminent. Thus, poor premorbid social adjustment and significant social deterioration from childhood to adolescence may be a hallmark feature of people who later go on to develop prominent negative symptoms and a unique marker for the DS subtype of schizophrenia.