Social Disability and Symptomatic Outcome in Schizophrenia

-Where are the Unmet Needs of Schizophrenia Patients?


Rebecca Schennach-Wolff 1

Markus Jäger 1

Florian Seemüller 1

Michael Obermeier 1

Hans-Jürgen Möller 1

Max Schmauss 2

Gerd Laux 3

Herbert Pfeiffer 4

Dieter Naber 5

Lutz G. Schmidt 6

Wolfgang Gaebel 7

Joachim Klosterkötter 8

Isabella Heuser 9

Wolfgang Maier 10

Matthias R. Lemke 11

Eckart Rüther 12

Stefan Klingberg 13

Markus Gastpar 14

Michael Riedel 15


Affiliations:
1Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany;
2Psychiatric Clinic, District Hospital Augsburg, Germany;
3Psychiatric Clinic, Inn-Salzach Hospital Wasserburg/Inn, Germany;
4Psychiatric Clinic, Isar-Amper Hospital, Munich-Haar,, Germany;
5Department of Psychiatry and Psychotherapy, University of Hamburg, Germany;
6Department of Psychiatry and Psychotherapy, University of Mainz, Germany;
7Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany;
8Department of Psychiatry and Psychotherapy and Psychotherapy, University of Cologne, Germany;
9Department of Psychiatry and Psychotherapy, Charite Berlin, Campus Benjamin Franklin, Germany;
10Department of Psychiatry and Psychotherapy, University of Bonn, Germany;
11Department of Psychiatry, Alsterdorf Hospital, Hamburg, Germany
12Department of Psychiatry and Psychotherapy, University of Göttingen, Germany;
13Department of Psychiatry and Psychotherapy, University of Tübingen, Germany and
14Department of Psychiatry and Psychotherapy, University of Essen, Germany.
15 Psychiatric Clinic, Vinzenz-Von-Paul-Hospital, Rottweil, Germany

 

Abstract
Purpose
Aim of the study was to assess social disability and its influencing factors in acutely ill schizophrenia inpatients and to evaluate its predictive validity of subsequent symptomatic outcome in order to evaluate the unmet needs of schizophrenia patients.
Methods
107 inpatients suffering from schizophrenia spectrum disorders were examined within a multicenter trial by the German Research Network on Schizophrenia with biweekly PANSS ratings. Social disability was assessed using the WHO's Disability Assessment Schedule (DAS) at baseline. Early response was defined as a 20% PANSS total score reduction within the first two treatment weeks, response as a 50% PANSS total score reduction from baseline to discharge and remission according to the Andreasen consensus criteria. Regression analyses and CART-analyses were performed to evaluate the predictive validity of social disability regarding symptomatic outcome at discharge.
Results
The global evaluation of the DAS in 107 patients with schizophrenia at admission revealed 21 patients (20%) to have no social disability, 50 patients (47%) to have some disability and 36 patients (33%) to suffer from severe social disability. Patients without social disability achieved early response significantly more often (p=0.0292) and scored significantly lower on the PANSS general psychopathology subscore (p=0.0102) at admission. The DAS item "interests and information" was found to be a significant predictor of symptomatic outcome by both statistical methods.
Conclusions
The prevalence of social disability in acutely ill patients with schizophrenia is emphasized concurrently identifying targets for improving psychosocial rehabilitation.

Key words: Schizophrenia, social functioning and adjustment, symptomatic remission, predictive validity
 

Introduction:
Remarkable attempts have been made to identify predictors of treatment outcome in schizophrenia in the past decades. For reliable predictors would bear considerable benefits in the treatment of schizophrenic patients by avoiding unnecessary continuation with ineffective treatment before attempting alternative strategies [1]. Additionally, poor treatment responders could be identified timely resulting in early treatment adjustments in turn reducing the risk of accruing morbidity, the level of care required and the overall costs incurred. Amongst others, the duration of untreated psychosis [2], negative symptoms [3] as well as the development of parkinsonism during antipsychotic treatment [4] have been identified to predict poorer treatment outcome. 

Other researchers have focused on the assessment of social functioning as an influencing factor of treatment outcome especially after its importance was recognized with the introduction of social functioning into the Diagnostic and Statistical Manual of Mental Health, 3rd edition in 1980 [5]. Consistently, social dysfunction was found to predict an unfavorable course and impaired outcome in patients with schizophrenia [6] underlining primarily the prognostic importance of this dimension in addition to psychopathological or anamnestic variables. Secondly, the importance of adequately treating and supporting the patient's handicaps in this field was emphasized [7].

Different rating scales to assess this dimension have been developed since then. For example, in 1988 the World Health Organization (WHO) proposed a semi-structured interview, the Disability Assessment Schedule (DAS), designed for the comprehensive evaluation of social functioning of patients with mental and, in particular, psychiatric disorders [8]. The DAS was tested and used in the WHO Collaborative Study on the Assessment and Reduction of Psychiatric Disability and found to be a reliable and valid tool for the assessment and cross-cultural comparison of psychiatric disability [9]. The DAS examines several areas of functioning such as self-care, social activities, partnership as well as work and general interests [10]. Also, as a semi-structured interview the DAS provides advantages of both an observer- as well as a self-rating instrument. The patient himself can describe his behavior and experiences on the one hand, on the other hand the professionally trained observer decides how much weight is put on the information the patient gives during the interview [11]. This reduces the scope for inaccurate assessment resulting from difficulties in the patients' perception of themselves.

Interestingly, despite the proven importance of social functioning for treatment outcome its influence and predictive validity have not been evaluated yet applying the recently proposed remission criteria [12]. 

Therefore, we evaluated social functioning at baseline in acutely ill inpatients with schizophrenia applying the DAS and analyzed the predictive validity in respect of symptomatic treatment outcome.
Aims of the study were to:
1) assess social functioning at baseline in acutely ill patients suffering from schizophrenia and to
2) identify influencing variables of social disability and to
3) evaluate the predictive validity of social functioning for early response, response and remission.

Methods
Subjects
Data were collected in a multicenter follow-up programme (German Research Network on Schizophrenia) [13] at eleven psychiatric university hospitals and three psychiatric district hospitals in the region surrounding Munich. From all patients who were admitted between January 2001 and December 2004 to one of the above mentioned hospitals patients with the diagnosis of schizophrenia (paranoid, disorganized, catatonic or undifferentiated subtype), schizophreniform disorder, delusional disorder and schizoaffective disorder according to DSM-IV criteria were randomly selected to be eligible for inclusion. The patient selection resulted from a randomisation software. Subjects were aged between 18 and 65 years. Exclusion criteria  were a head injury, a history of major medical illness and alcohol or drug dependency. An informed written consent had to be provided to participate in the study. The study protocol was approved by the local ethics committees [14].

Assessments
DSM-IV diagnoses were established by clinical researchers on the basis of the German version of the Structured Clinical Interview for DSM-IV [15]. Using a standardized documentation system [16] during interviews with patients, relatives and care providers sociodemographic variables (partnership, employment status) and course-related variables such as age at onset, age at first hospitalization or episodes of illness were collected. 

Symptom severity was assessed using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) [17]. Depressive symptoms were evaluated via the Hamilton Depression Rating Scale [18]. The Subjective Well-being Under Neuroleptic Treatment Scale, short version (SWN-K) was used to assess subjective well-being. [19].

Social disability was assessed using the Disability Assessment Schedule (DAS) [20]. The WHO-DAS is a semi-structured interview with an informant and with the patient to elicit responses to a number of questions on several areas of functioning: self-care, social withdrawal, participation in the household, relationship with spouse or partner, occupational role and general interests [20]. Guiding questions and descriptions of anchor points for the assessment lead to the rating of a dysfunction on a six points scale : 0, no dysfunction; 1, minimum dysfunction; 2, obvious dysfunction; 3±5, serious to maximum dysfunction. At the end of the interview an overall judgement of total functioning is required for a Global Evaluation on a six-point scale (0, excellent adjustment to 5, severe maladjustment). The global evaluation can also be categorized according to the following classification: no disability (0) ; some disability (1±2); and, severe disability (3±5) [21].
PANSS ratings were performed within the first three days after admission, biweekly as well as at discharge. The DAS was rated within the first three days after admission. All raters had been trained using the applied observer scales. A high inter-rater reliability was achieved (ANOVA-ICC > 0.8).

Statistical analysis
Outcome definitions:
1) Early response: Early response was defined as a 20% PANSS total score improvement within the first two treatment weeks [22].

2) Response: Response was defined as a 50% PANSS total score reduction from baseline to discharge [23].

3) Remission: Symptomatic remission was defined using the symptom-severity component of the standardized remission criteria [24] as a PANSS score of three or less of the following items: delusions (P1), unusual thought contents (G9), hallucinatory behavior (P3), conceptual disorganization (P2), mannerism/posturing (G5), blunted affect (N1), social withdrawal (N4) and lack of spontaneity (N6). Discharge was chosen as the final endpoint because we implied that clinicians would judge the mental state at the time point as stable. Due to the study design the time component of the remission criteria could not be considered.

For descriptive analysis of singular variables mean scores and standard deviation were used as well as the median and interquartils range. Furthermore, the non-parametric Wilcoxon test or, in case of assumed normality, the t-test was used. A forward-backward selection based on the Akaike Information Criterion (AIC) was used to identify the relevant predictors of early response, response and remission in a linear logistic model. All single DAS items and the categorized DAS total were regarded as possible predictors. To adjust for the influence of the patients' baseline psychopathology the PANSS total score was considered in the prediction models. Predictive value, sensitivity and specificity levels depend on the cut-off point of the model. The discriminative ability of the regression model was also evaluated using a receiver-operating characteristic (ROC) curve. The area under the curve (AUC) is a measure of the overall discriminative power. A value of 0.5 for the AUC does not represent discriminative ability, whereas a value of 1.0 indicates a perfect power. A value of 0.7-0.8 is considered as a reasonable value and a value greater than 0.8 as a good discriminative capacity. Additionally, Classification and Regression Trees (CART) were used to confirm the results of the regression model.
All statistical analyses were performed using the statistical software environment R (25).

Results
Patients
The entire multicenter study comprised 474 patients. Forty-six patients dropped out for different reasons (e.g. retrospective violation of inclusion criteria, withdrawal of informed consent, incomplete information). 28 patients were furthermore excluded because they were discharged from the hospital within 7 days after admission. 293 patients did not complete the semi-structured DAS-interview. 

Therefore, the sample available for analyses enrolled 107 patients (60 male/47 female) with a mean age of 27.47 years (±9.76). The mean age at first treatment was 27.75 years (±9.41). The mean duration of illness was 5.14 years (±9.15) and the mean number of clinical treatments 3.62 (±5.50). The duration of current episode was ≤12 months for 61 patients (57%) and >12 months for 46 patients (43%). The mean duration of current hospital stay was 64.19 days (±46.44). 23 patients (21%) lived within a partnership, 84 patients (79%) did not. 59 patients (55%) had a job, 28 patients (26%) were jobless and 20 patients (19%) were retired.

Patients were treated under naturalistic conditions as follows: 39% of the patients received first-generation antipsychotics, 75% second-generation antipsychotics and 30% first- as well as second-generation antipsychotics. 62% of the patients were treated with tranquilizers and 11% with mood stabilizers. 25% of the patients also received antidepressants. DSM-IV diagnosis are listed in Table 1.

Table 1: DSM-IV diagnoses

 

Patients' diagnoses

schizophrenia: §          disorganized type      (295.1): 5 §          paranoid type             (295.3): 48 §          catatonic type            (295.2): 1 §          residual type              (295.6): 2 §          undifferentiated type (295.9): 6

schizophreniform disorder     (295.4): 20

schizoaffective disorder         (295.7): 17

delusional disorder                 (297.1): 1

brief psychotic disorder         (298.8): 7

 

Assessments
Patients with and without DAS ratings
Complete data were available from 107 patients, 293 patients did not complete the semi-structured interview of the DAS. Comparing patients with/without a completed DAS rating we found patients with a DAS rating to have significantly more insight into their illness (p=0.0015), to be significantly more depressed (0.0239), to have significantly worse subjective well-being (p=0.0401) and to have significantly more often a duration of current episode of < 12 months (p<0.01) (Table 2).

Table 2: Comparing patients with/without DAS scale

 

	Patients with DAS scale (27% of the patients)	Patients without DAS scale (73% of the patients)	p-value
	Mean (SD)	Mean (SD)
Age	27.47 (±9.76)	27.85 (±9.3)	0.7305
PANSS total score	70.98 (±17.6)	71.24 (±19.7)	0.899
PANSS positive subscore	18.36 (±5.75)	19.3 (±6.56)	0.1631
PANSS negative subscore	17.42 (±7.52)	17.58 (±7.3)	0.85
PANSS general psychopathology subscore	35.21 (±9.81)	34.36 (±10.21)	0.4522
HAMD 21 total score	16.77 (±7.96)	14.64 (±8.2)	0.0239
SWN total score	77.3 (±18.52)	82.32 (±18.15)	0.0401
	N	N
Male Female	60 47	166 127	1
Duration of current episode < 12 months Duration of current episode ≥ 12 months	65 42	248 45	<0.001
Suicidal Non suicidal	89 18	230 63	0.3974
	Median (IQR)	Median (IQR)
PANSS insight item G 12	3 (3)	3 (4)	0.0015
Duration of illness	2 (7)	4 (13)	0.1093

Social disability at admission
The global evaluation of the DAS in 107 patients with schizophrenia at admission revealed 21 patients (20%) to have no social disability, 50 patients (47%) to have some disability and 36 patients (33%) to suffer from severe social disability. Figure 1 shows the 15 single items of the DAS scale at admission. Patients with severe disability performed very poorly in the item "underactivity" examining the time during the day spent in what the society considers to be doing nothing, the item "slowness" evaluating the overall speed of movement and agility in carrying daily activities, and the item "work performance" examining whether the patient goes to work regularly and also the quality of performance as well as output. 

Comparing patients with/without social disability
To identify influencing variables of social disability patients were grouped according to their global evaluation of the DAS: patients with some and severe disability were grouped into the subgroup "patients with disability" and compared to patients without social disability, the subgroup "patients without disability". Table 3 shows the results of univariate tests between these two patient subgroups. Patients without social disability achieved early response significantly more often (p=0.0292) and scored significantly lower on the PANSS general psychopathology subscore at admission (p=0.0102).

Table 3: Comparing patients with/without social disability

 

	Patients without social disability (20%)	Patients with some and severe social disability (80%)	p-value
	Mean (SD)	Mean (SD)
Age	36.62 (±12.25)	32.52 (±10.89)	0.1714
PANSS total score at admission	65.76 (±15.59)	72.26 (±17.91)	0.1061
PANSS positive subscore at admission	17.95 (±4.99)	18.45 (±5.95)	0.6943
PANSS negative subscore at admission	16.9 (±8.09)	17.55 (±7.42)	0.7429
PANSS general psychopathology subscore at admission	30.9 (±7.6)	36.26 (±10.04)	0.0102
HAMD 21 total score at admission	14.06 (±6.35)	17.36 (±8.18)	0.0676
	N	N
Male Female	10 11	37 49	0.8076
Current episode < 1 year Current episode > 1 year	18 6	47 36	0.2016
First episode of illness Multiple illness episode	12 9	55 31	0.619
Suicidal at admission Non suicidal at admission	1 21	17 68	0.1887
With partner at admission Without partner at admission	5 12	22 68	0.5541
In job at admission Jobless at admission Retired at admission	16 10 2	44 19 16	0.2552
Early response at week 2 No early response at week 2	15 6	43 43	0.0292
Response at discharge Non response at discharge	15 6	46 40	0.7669
Remission at discharge Non remission at discharge	11 7	53 24	0.6541
	Median (IQR)	Median (IQR)
PANSS insight item (G12) at admission	2 (3)	3 (3)	0.7299
Duration of illness	1 (6.25)	2 (8)	0.1136
Number of previous hospitalizations	0 (1)	0 (1)	0.4103

 

Social disability and symptomatic outcome
Social disability and its predictive validity for early response
54% of the patients achieved early response with 26% of them not suffering from social disability, 48% featuring some disability and 26% featuring severe disability. In comparison, 46% of the assessed patients did not achieve early response at week 2 with 12% of them not suffering from social disability, 45% featuring some disability and 43% featuring severe disability.
Comparing patients with/without early response regarding the DAS single items we found patients with early response to perform significantly better in terms of interest and care of child, relationships with persons other than marital partner, interests and information and the global evaluation of social disability (Table 4). 

Table 4: Comparing patients with/without early response regarding social disability at admission, higher scores indicating higher impairment
 

	Early responder (54%)	Non early responder (46%)	p-value
	Median (IQR)	Median (IQR)
Patient's self-care	0 (1)	1 (2)	0.01
Underactivity	2 (1)	2 (2)	0.05
Slowness	2 (2)	2 (2)	0.55
Social withdrawal	2 (1)	2 (2)	0.19
Social contacts	1 (2)	1 (2)	0.52
Patient's behavior in emergencies	1 (2)	2 (2)	0.05
Participation in household activities	1 (2)	2 (3)	0.04
Affective relationship to spouse	1 (2)	1.5 (2)	0.30
Sexual relations with spouse	0 (1.25)	0.5 (2)	0.52
Interest and care of child	0 (0)	0 (2)	0.01
Relationships with persons other than marital partner	1 (2)	2 (2.75)	0.01
Work performance	2 (2)	2 (1)	0.11
Interest in getting a job	1 (2)	2 (3)	0.06
Interests and information	1 (2)	2 (1)	<0.001
Global evaluation	2 (1)	2 (2.5)	0.01

 

Logistic regression analysis revealed the DAS item "interests and information" to be significantly predictive of early response with moderate predictive power (AUC=0.686), see Table 7. The regression model reached statistical significance (p=0.005). The additionally performed CART-analysis also revealed the item "interests and information" to be significantly predictive for early response as well as the items "interest and care of child", "relationships with persons other than the marital partner", "work performance", "patient's behavior in emergencies" and the PANSS total score. 

Social disability and its predictive validity for response
57% of the patients were treatment responder at discharge with 25% of them having no social disability, 39% with moderate disability and 36% with severe disability. In comparison, 43% did not achieve the response criterion. Of these, 13% were rated to have no social disability, 57% to have moderate disability and 30% to have severe disability.
Comparing patients with/without response no significant differences in ratings of the DAS single items could be observed (Table 5). Performing logistic regression analysis the DAS items "slowness" and "interests and information" were found to be significantly predictive for response with the statistical model reaching significance (p=0.015) (Table 7). The logistic regression model showed moderate predictive capacity (AUC=0.662). CART-analysis however did not reveal any significant social disability predictor in terms of response.

Table 5: Comparing patients with/without response regarding social disability at admission, higher scores indicating higher impairment
 

	Responder (57%)	Non responder (43%)	p-value
	Median (IQR)	Median (IQR)
Patient's self-care	0 (2)	0 (2)	0.92
Underactivity	2 (2)	2 (2)	0.68
Slowness	2 (2)	2 (2)	0.20
Social withdrawal	2 (2)	2 (1)	0.51
Social contacts	1 (2)	1 (2)	0.34
Patient's behavior in emergencies	2 (2)	1 (2)	0.76
Participation in household activities	1 (2)	2 (1)	0.13
Affective relationship to spouse	1 (2)	1 (2)	0.63
Sexual relations with spouse	0 (1)	1 (2)	0.22
Interest and care of child	0 (0)	0 (1.5)	0.18
Relationships with persons other than marital partner	1 (2.25)	1 (2)	0.64
Work performance	2 (2)	2 (1)	0.17
Interest in getting a job	1 (2)	2 (3)	0.21
Interests and information	1 (2)	2 (1)	0.17
Global evaluation	2 (2)	2 (1)	0.59

 

Table 7: Logistic regression model on the predictive validity of social disability of outcome
 

	Estimate	Std. Estimate	z-value	p-value
Early response Interests and information	-1.4402	0.5551	-2.59	0.0095
Response Slowness Interests and information	0.9045 -1.2097	0.3835 0.4787	2.36 -2.53	0.0184 0.0115
Remission Interests and information Global evaluation	-1.58 1.13	0.58 0.47	-2.74 2.40	0.0061 0.0162

  

Social disability and its predictive validity for remission
60% of the patients achieved the symptom severity component of the remission criteria with 17% of them suffering from no social disability, 49% featuring some disability and 34% severe disability. In comparison, 40% of the examined patients were not treatment remitter at discharge, with 23% of them having no social disability, 45% having some disability and 32% having severe disability.

Comparing patients with/without remission the patients achieving remission at discharge performed significantly better in terms of the patients' behavior in emergencies and well as the patients' interests and information (Table 6). The item "interests and information" and the DAS global evaluation were identified to be significantly predictive for remission by the logistic regression model with satisfying discriminative capacity (AUC=0.722) reaching statistical significance (p=0.007) (Table 7). The CART-analysis confirmed the predictive validity of the item "interests and information" and further identified the items "interest and care of child" and "sexual relations with spouse" to be significantly predictive of remission.

Table 6: Comparing patients with/without remission regarding social disability at admission, higher scores indicating higher impairment
 

	Remitter (60%)	Non remitter (40%)	p-value
	Median (IQR)	Median (IQR)
Patient's self-care	0 (2)	1 (2)	0.58
Underactivity	2 (2)	2 (1.75)	0.10
Slowness	2 (2)	2 (2)	0.32
Social withdrawal	1.5 (1.25)	2 (1)	0.16
Social contacts	1 (2)	1 (1.5)	0.27
Patient's behavior in emergencies	1 (2)	2 (2)	0.04
Participation in household activities	1 (2)	2 (0.75)	0.07
Affective relationship to spouse	1 (2)	1.5 (2)	0.77
Sexual relations with spouse	0 (1)	1 (2.75)	0.15
Interest and care of child	0 (0)	0 (2)	0.08
Relationships with persons other than marital partner	1 (2)	1 (2.5)	0.24
Work performance	2 (2)	2 (1)	0.23
Interest in getting a job	1 (2)	1 (2)	0.66
Interests and information	1 (2)	2 (1)	0.03
Global evaluation	2 (2)	2 (2)	0.88

 

Discussion
Social disability in acutely ill patients with schizophrenia
General aspects
In the present study 80% of acutely ill and admitted patients with schizophrenia suffered from social disability. Despite the fact that it is well known that social impairment is a core feature of schizophrenia affecting the patient's social interaction, vocational and instrumental functioning skills, self-care and recreation [25] there are only few studies explicitly examining the prevalence and course of this domain in schizophrenia patients. Wiersma et al. evaluated 349 patients with schizophrenia regarding their social disability over 15 years in six European countries also applying the DAS and found 13% of the patients to have no social disability whereas 69% of the patients were identified to have moderate to severe social disability at study entry [21]. After 15 years only 14% of the examined patients suffered from no social disability and still 59% of the patients from moderate to severe disability [21]. In a similar study with a 15 year follow-up period comparing social disability between patients suffering from schizophrenia, schizoaffective disorder and depression Bottlender et al. [10] reported that 64% of the patients with schizophrenia suffered from at least moderate social disability compared to schizoaffective patients (19%) and patients with depression (5%). These results underline the high prevalence of deficits in social functioning in acutely ill schizophrenia patients, but most important also during the course of the illness. One of the latest biological models proposed to explain social deficits in schizophrenia is the dysregulation of the peptide hormone oxytocin, which was found to be important in regulating affiliative behavior such as social recognition, separation distress or pair-bond information [26].

Influencing variables
Comparing patients with/without social disability we found patients not suffering from social disability to score significantly lower on the PANSS general psychopathology subscore and to achieve early response significantly more often. It might be surprising on the first glance that symptoms not specific for schizophrenia illness were found to be important for social functioning. However, it has been reported before that especially depressive symptoms are significantly associated with social functioning in patients with schizophrenia [27, 28]. Jin et al. examined 202 middle-aged or elderly outpatients with schizophrenia and  reported that even after adjusting for severity of other psychopathology, patients with more severe depressive symptoms had significantly worse everyday functioning [29]. Furthermore, depression was found to predict interpersonal and work skills in schizophrenia patients [30]. This is in line with our results of the univariate tests (Table 3) finding patients without social disability to score lower on the HAMD total score by more than 2 points in the mean. 

Also, in the present study patients without social disability suffered from less negative symptoms than patients suffering from social disability which has been consistently reported [31, 32]. In contrast to several other studies reporting a significant association between the degree of social disability and work, partnership or family [33] we were not able to find a significant difference between patients with or without social disability in terms of working of family status. One possible explanation for this discrepancy might be that the patients in the present study had a rather low mean duration of illness with more than 60% of the patients suffering from their first illness episode. This patient population might not yet suffer from so much social and vocational consequences of the illness as it might be the case in patients suffering from schizophrenia for a longer time. Interestingly, comparing 969 patients from the F2, F3, F4, F5 and F6 diagnostic groups (according to ICD-10) Rymaszewska did also not find an association between social disability and education, the number of episodes, psychiatric hospitalisation or duration of the disorder [34].
Regarding social functioning and its association with early treatment response our result is less surprising. Early antipsychotic response was found to closely parallel and predict later overall outcome and to be significantly associated with achieving functional remission also for the long-term course of the illness [1, 35].

Social disability and its predictive validity of symptomatic outcome
General aspects
In the present study we found social disability at baseline to be predictive of symptomatic outcome and patients without social disability achieved early response significantly more often. Already in the 1980s the influence of social functioning on the course and outcome of schizophrenia has been stated [36]. Since then, several authors found the patient's functional status to be an important predictor of symptomatic outcome and of response to pharmacologic treatment [37-39]. There is a general consensus that supportive relationships both diminish the effects of stressful events and serve to prevent their occurrence [40] resulting in a favorable treatment outcome. The significance of social functioning deficits is furthermore emphasized by results finding impairments in social functioning and adjustment to be a marker of risk for schizophrenia [41]. Deficiencies in several areas of functioning including behavioral and social domains have also consistently been observed in studies of high-risk individuals supporting the hypothesis that alterations in social development might be a marker for a genetic liability toward the illness [42].

Interestingly, impairments in social functioning have also been found to significantly influence symptomatic outcome beyond the diagnostic boarder of schizophrenia for there are several reports that functioning and remission status are highly associated in patients suffering from depression [43]. The influence of social satisfaction, functioning and deprivation has even been analyzed and reported in patients with somatic illness, such as rheumatoid arthritis [44].

Social disability as predictor of symptomatic outcome
The single items of the Disability Assessment Schedule that were predictive of early response, response and remission overlap to a certain degree since the item "interests and information" was found to significantly predict all three outcome domains. This item was also confirmed significant predictor by the additionally performed CART-analysis. One explanation for this phenomenon might be that almost 40% of the patients achieved all three outcome domains implying that similar influencing variables are relevant for these patients. The item "interests and information" evaluates the interest shown by a patient in local, world events or in other matters within the patient's background, education, and level of intelligence. The importance of the patient's interest in things going on for the course of the illness is also underlined by other study results. Moller & Husby, for example, defined four core dimensions of prodrome in schizophrenia and listed a marked and lasting observable shift of interests as one of them [45]. Also, Dworkin et al. examined social competence in patients at risk for schizophrenia, affective disorders as well as in normal-comparison subjects and found subjects at risk for schizophrenia to have a poorer overall social competence and specifically a significantly decrease in interests [46]. 

The other DAS items found to significantly predict response and remission by the regression model were "slowness" and the "global evaluation" of social disability. The item "slowness" examines the overall speed of movement and agility in carrying out daily activities and it is not surprising that patients with impairments in this area have difficulties coping with everyday life challenges. This is underlined by several literature reports finding an association between speed and social performance [47]. Bowie et al. reported on processing speed to predict social competence [48]. Also, in high-functioning schizophrenia patients Vaskinn et al. identified that social problem-solving was significantly associated with psychomotor speed [49]. 

CART-analysis identified further DAS items being predictive of outcome namely "interest and care of child", "relationship with other than marital partner", "sexual relations with spouse" as well as "work performance" and "patient's behavior in emergencies". The importance of partnership and family regarding outcome has already been discussed before and is a well known influencing variable [50]. The significance of this domain is also emphasized by different intervention programs explicitly involving the patient's family which was found to lead to a reduction of stress in families preventing relapse and rehospitalization [51]. 

When discussing predictor variables like family or work it should be kept that it is not only the patient's illness bringing about social impairments but that also environmental related factors and stigma play an important role [52]. For individuals with a mental illness do not only have to cope with their symptoms and consequences of their illness but also with negative public attitude and prejudices [53]. This can lead to further impairment of those affected by a mental disorder [54]. Stigma can be a major stressor for patients with schizophrenia and has been associated with poorer social performance depending on the patient's individual coping styles [55]. Also, when performing cluster analysis in 75 patients with schizophrenia Lysaker et al. found the patient's functioning to be affected by the degree to which the patient internalized stigmatizing views [56]. This should be kept in mind discussing the influence of the patient's social disability for symptomatic outcome especially when resulting in specific treatment approaches.


Limitations
This study is not without limitations. The patients were treated under naturalistic conditions and such a design does not allow a sufficient control of study results for the effect of different pharmacological and psychological treatments. Furthermore, the patient sample included both first-episode patients and chronically ill patients. Also, the Remission in Schizophrenia Working Group developed the symptomatic remission criteria solely for schizophrenic patients. In this study the criteria were used in a wider spectrum of schizophrenia related disorders. The time criterion was likewise not considered, for the criteria were proposed to define remission as the absence of relevant symptoms for at least six months. Substance use, which was just recently reported to significantly influence the patient's level of social functioning [57], could not be examined for it was defined as an exclusion criterion. The study's recall bias should also be kept in mind since only 107 patients accomplished the semi-structured interview which might overestimate the patients' social functioning.

Conclusion
Taken together, our results underline the important influence of social disability for symptomatic outcome. Significant predictors of the Disability and Assessment Schedule could be identified underlining the importance of the patient's interest in local or world events for outcome as well as the patient's speed when coping with everyday life. These results emphasize the need to implement the evaluation and measurement of the patient's social disability in clinical routine as well as in research trials. Furthermore, the necessity to also incorporate special treatment regimes and rehabilitative approaches to improve social functioning and adjustment is highlighted.


Acknowledgements
The study was performed within the framework of the German Research Network on Schizophrenia, which is funded by the German Federal Ministry for Education and Research BMBF (grant 01 GI 0233).
 

 

References

 

1.   Emsley, R., Oosthuizen, P. P., Kidd, M., Koen, L., Niehaus, D. J., & Turner, H. J. (2006) Remission in first-episode psychosis: predictor variables and symptom improvement patterns. J. Clin. Psychiatry 67, 1707-1712.

2.   Bottlender, R., Sato, T., Jager, M., Groll, C., Strauss, A., & Moller, H. J. (2002) The impact of duration of untreated psychosis and premorbid functioning on outcome of first inpatient treatment in schizophrenic and schizoaffective patients. Eur. Arch. Psychiatry Clin. Neurosci. 252, 226-231.

3.   Hafner, H., Loffler, W., Maurer, K., Hambrecht, M., & an der, H. W. (1999) Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia. Acta Psychiatr. Scand. 100, 105-118.

4.   Robinson, D. G., Woerner, M. G., Alvir, J. M. et al. (1999) Predictors of treatment response from a first episode of schizophrenia or schizoaffective disorder. Am. J. Psychiatry. 156, 544-549.

5.   American Psychiatric Association (1980) Diagnostic and Statistical Manual of Mental Disorders. Washington D.C..

6.   Lenzenweger, M. F. & Dworkin, R. H. (1996) The dimensions of schizophrenia phenomenology. Not one or two, at least three, perhaps four. Br. J. Psychiatry. 168, 432-440.

7.   Schennach-Wolff, R., Jager, M., Seemuller, F. et al. (2009) Defining and predicting functional outcome in schizophrenia and schizophrenia spectrum disorders. Schizophr. Res.

8.   Janca, A., Kastrup, M., Katschnig, H., Lopez-Ibor, J. J., Jr., Mezzich, J. E., & Sartorius, N. (1996) The World Health Organization Short Disability Assessment Schedule (WHO DAS-S): a tool for the assessment of difficulties in selected areas of functioning of patients with mental disorders. Soc Psychiatry Psychiatr. Epidemiol. 31, 349-354.

9.   Jablensky A, Schwarz R, & Tomov T (1980) WHO collaborative study on impairments and disabilities associated with schizophrenic disorders. A preliminary communication: objectives and methods. Acta Psychiatr. Scand. 62, 152-159.

10. Bottlender, R., Strauss, A., & Moller, H. J. (2010) Social disability in schizophrenic, schizoaffective and affective disorders 15 years after first admission. Schizophr. Res. 116, 9-15.

11. Moller, H. J. (2009) Standardised rating scales in Psychiatry: Methodological basis, their possibilities and limitations and descriptions of important rating scales. World J. Biol. Psychiatry. 10, 6-26.

12. de, H. L., van, A. T., Dingemans, P., & Linszen, D. (2007) Risk factors for medication non-adherence in patients with first episode schizophrenia and related disorders; a prospective five year follow-up. Pharmacopsychiatry. 40, 264-268.

13. Wolwer, W., Buchkremer, G., Hafner, H. et al. (2003) German research network on schizophrenia-bridging the gap between research and care. Eur. Arch. Psychiatry Clin. Neurosci. 253, 321-329.

14. Jager, M., Riedel, M., Messer, T. et al. (2007) Psychopathological characteristics and treatment response of first episode compared with multiple episode schizophrenic disorders. Eur. Arch. Psychiatry Clin. Neurosci. 257, 47-53.

15. American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders. Washington DC: American Psychiatric Association.

16. Cording, C. (1998) [Conceptual aspects in development and implementation of basic psychiatric documentation]. Psychiatr. Prax. 25, 175-178.

17. Kay, S. R., Opler, L. A., & Lindenmayer, J. P. (1988) Reliability and validity of the positive and negative syndrome scale for schizophrenics. Psychiatry Res. 23, 99-110.

18. Hamilton, M. (1967) Development of a rating scale for primary depressive illness. Br. J Soc. Clin. Psychol. 6, 278-296.

19. Naber, D. (1995) A self-rating to measure subjective effects of neuroleptic drugs, relationships to objective psychopathology, quality of life, compliance and other clinical variables. Int. Clin. Psychopharmacol. 10 Suppl 3, 133-138.

20. World Health Organization. Psychiatric Disability Assessment Schedule (WHO/DAS).  1988.  WHO, Geneva.
Ref Type: Report

21. Wiersma, D., Wanderling, J., Dragomirecka, E. et al. (2000) Social disability in schizophrenia: its development and prediction over 15 years in incidence cohorts in six European centres. Psychol. Med. 30, 1155-1167.

22. Kinon, B. J., Chen, L., Ascher-Svanum, H. et al. (2008) Predicting response to atypical antipsychotics based on early response in the treatment of schizophrenia. Schizophr. Res. 102, 230-240.

23. Leucht, S., Kane, J. M., Kissling, W., Hamann, J., Etschel, E., & Engel, R. R. (2005) What does the PANSS mean? Schizophr. Res. 79, 231-238.

24. Andreasen, N. C., Carpenter, W. T., Jr., Kane, J. M., Lasser, R. A., Marder, S. R., & Weinberger, D. R. (2005) Remission in schizophrenia: proposed criteria and rationale for consensus. Am. J. Psychiatry 162, 441-449.

25. Bellack, A. S., Sayers, M., Mueser, K. T., & Bennett, M. (1994) Evaluation of social problem solving in schizophrenia. J. Abnorm. Psychol. 103, 371-378.

26. Bartz, J. A. & McInnes, L. A. (2007) CD38 regulates oxytocin secretion and complex social behavior. Bioessays. 29, 837-841.

27. Emsley, R. A., Oosthuizen, P. P., Joubert, A. F., Roberts, M. C., & Stein, D. J. (1999) Depressive and anxiety symptoms in patients with schizophrenia and schizophreniform disorder. J. Clin. Psychiatry. 60, 747-751.

28. Oosthuizen, P., Emsley, R. A., Roberts, M. C. et al. (2002) Depressive symptoms at baseline predict fewer negative symptoms at follow-up in patients with first-episode schizophrenia. Schizophr. Res. 58, 247-252.

29. Jin, H., Zisook, S., Palmer, B. W., Patterson, T. L., Heaton, R. K., & Jeste, D. V. (2001) Association of depressive symptoms with worse functioning in schizophrenia: a study in older outpatients. J. Clin. Psychiatry. 62, 797-803.

30. Bowie, C. R., Reichenberg, A., Patterson, T. L., Heaton, R. K., & Harvey, P. D. (2006) Determinants of real-world functional performance in schizophrenia subjects: correlations with cognition, functional capacity, and symptoms. Am. J. Psychiatry. 163, 418-425.

31. Bottlender, R., Sato, T., Groll, C., Jager, M., Kunze, I., & Moller, H. J. (2003) Negative symptoms in depressed and schizophrenic patients: how do they differ? J. Clin. Psychiatry. 64, 954-958.

32. Bobes, J., Arango, C., Garcia-Garcia, M., & Rejas, J. (2009) Prevalence of negative symptoms in outpatients with schizophrenia spectrum disorders treated with antipsychotics in routine clinical practice: findings from the CLAMORS study. J. Clin. Psychiatry.

33. Rymaszewska, J., Jarosz-Nowak, J., Kiejna, A. et al. (2007) Social disability in different mental disorders. Eur. Psychiatry. 22, 160-166.

34. Rymaszewska, J. (2007) [The social functioning of individuals with various psychiatric disorders]. Psychiatr. Pol. 41, 39-51.

35. Emsley, R., Chiliza, B., & Schoeman, R. (2008) Predictors of long-term outcome in schizophrenia. Curr. Opin. Psychiatry 21, 173-177.

36. Moller, H. J., Scharl, W., & von, Z. D. (1985) [Prediction of therapeutic success in acute neuroleptic treatment: results of an empirical study of 243 inpatient-treated schizophrenic patients]. Fortschr. Neurol. Psychiatr. 53, 370-383.

37. De, H. M., van, W. R., Wampers, M., Kane, J., Van, O. J., & Peuskens, J. (2007) Remission criteria for schizophrenia: evaluation in a large naturalistic cohort. Schizophr. Res 92, 68-73.

38. Gabbard, G. O. (2001) Empirical evidence and psychotherapy: a growing scientific base. Am. J. Psychiatry. 158, 1-3.

39. Haro, J., Ciudad, A., Alonso, J. et al. (2008) Remission and relapse in the outpatient treatment of patients with schizophrenia. Outcomes at 3 years. Actas Esp. Psiquiatr.

40. Vilhjalmsson, R. (1993) Life stress, social support and clinical depression: a reanalysis of the literature. Soc Sci Med. 37, 331-342.

41. Addington, J., Penn, D., Woods, S. W., Addington, D., & Perkins, D. O. (2008) Social functioning in individuals at clinical high risk for psychosis. Schizophr. Res. 99, 119-124.

42. Glatt, S. J., Stone, W. S., Faraone, S. V., Seidman, L. J., & Tsuang, M. T. (2006) Psychopathology, personality traits and social development of young first-degree relatives of patients with schizophrenia. Br. J. Psychiatry. 189:337-45., 337-345.

43. Romera, I., Perez, V., Menchon, J. M., gado-Cohen, H., Polavieja, P., & Gilaberte, I. (2009) Social and occupational functioning impairment in patients in partial versus complete remission of a major depressive disorder episode. A six-month prospective epidemiological study. Eur. Psychiatry.

44. Harrison, M. J., Tricker, K. J., Davies, L. et al. (2005) The relationship between social deprivation, disease outcome measures, and response to treatment in patients with stable, long-standing rheumatoid arthritis. J. Rheumatol. 32, 2330-2336.

45. Moller, P. & Husby, R. (2000) The initial prodrome in schizophrenia: searching for naturalistic core dimensions of experience and behavior. Schizophr. Bull. 26, 217-232.

46. Dworkin, R. H., Lewis, J. A., Cornblatt, B. A., & Erlenmeyer-Kimling, L. (1994) Social competence deficits in adolescents at risk for schizophrenia. J. Nerv. Ment. Dis. 182, 103-108.

47. Sanchez, P., Ojeda, N., Pena, J. et al. (2009) Predictors of longitudinal changes in schizophrenia: the role of processing speed. J. Clin. Psychiatry. 70, 888-896.

48. Bowie, C. R., Leung, W. W., Reichenberg, A. et al. (2008) Predicting schizophrenia patients' real-world behavior with specific neuropsychological and functional capacity measures. Biol. Psychiatry. 63, 505-511.

49. Vaskinn, A., Sundet, K., Hultman, C. M., Friis, S., & Andreassen, O. A. (2009) Social problem-solving in high-functioning schizophrenia: specific deficits in sending skills. Psychiatry Res. 165, 215-223.

50. Giron, M. & Gomez-Beneyto, M. (2004) Relationship between family attitudes and social functioning in schizophrenia: a nine-month follow-up prospective study in Spain. J. Nerv. Ment. Dis. 192, 414-420.

51. Falloon, I. R., Boyd, J. L., McGill, C. W., Razani, J., Moss, H. B., & Gilderman, A. M. (1982) Family management in the prevention of exacerbations of schizophrenia: a controlled study. N. Engl. J. Med. 306, 1437-1440.

52. Gonzalez-Torres, M. A., Oraa, R., Aristegui, M., Fernandez-Rivas, A., & Guimon, J. (2007) Stigma and discrimination towards people with schizophrenia and their family members. A qualitative study with focus groups. Soc Psychiatry Psychiatr. Epidemiol. 42, 14-23.

53. Ritsher, J. B. & Phelan, J. C. (2004) Internalized stigma predicts erosion of morale among psychiatric outpatients. Psychiatry Res. 129, 257-265.

54. Wolkenstein, L. & Meyer, T. D. (2009) What factors influence attitudes towards people with current depression and current mania? Int J. Soc. Psychiatry. 55, 124-140.

55. Rusch, N., Corrigan, P. W., Powell, K. et al. (2009) A stress-coping model of mental illness stigma: II. Emotional stress responses, coping behavior and outcome. Schizophr. Res. 110, 65-71.

56. Lysaker, P. H., Roe, D., & Yanos, P. T. (2007) Toward understanding the insight paradox: internalized stigma moderates the association between insight and social functioning, hope, and self-esteem among people with schizophrenia spectrum disorders. Schizophr. Bull. 33, 192-199.

57. Jaworski, F., Dubertret, C., Ades, J., & Gorwood, P. (2010) Presence of co-morbid substance use disorder in bipolar patients worsens their social functioning to the level observed in patients with schizophrenia. Psychiatry Res.