Health-Related Quality of Life Impairment in

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American Journal of Neuroprotection and Neuroregeneration Vol. 2, 1–9, 2010

Health-Related Quality of Life Impairment in Schizophrenia and Related Disorders as a Target for Neuroprotective Therapy Michael S. Ritsner Department of Psychiatry, The Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa and Sha’ar Menashe Mental Health Center, Mobile Post Hefer 38814, Hadera, Israel

Keywords: Health Related Quality of Life, Schizophrenia, Schizoaffective Disorders, Distress/ Protection Vulnerability Model, Neuroprotection.

1. SCHIZOPHRENIA Schizophrenia is characterized by psychopathological symptoms, elevated emotional distress and disturbed coping abilities, a significant decline in cognition, psychosocial functioning and quality of life. In particular, the clinical picture includes a range of positive, and negative symptoms such as delusions, hallucinations, agitation, hostility, emotional and social withdrawal, lack of spontaneity, poverty of speech and a wide range of mood symptoms, and neurocognitive deficits (Fig. 1). Positive symptoms usually first begin in adolescence or early adulthood, but are often preceded by varying degrees of negative symptoms, cognitive and quality of life impairments. Schizophrenia’s course over time varies considerably from person to person with variable degrees of functional and quality of life impairments and social disability, frequent comorbid substance abuse, and decreased longevity. However, overall, schizophrenia tends to be a chronic and relapsing disorder with generally incomplete remissions (Fig. 2). Am. J. Neuroprotec. Neuroregen. 2010, Vol. 2, No. 1

A few disorders have some of the same symptoms as schizophrenia including schizoaffective disorders, schizophreniform disorder, schizotypal and schizoid personality disorders, delusional disorder, and autism (schizophrenia spectrum disorders). Since the 2000 there has been significant progress in our understanding of the early presentations, assessment, suspected neuropathology, and treatment of these disorders.

2. TARGETS FOR NEUROPROTECTIVE AGENTS The main targets for neuroprotective therapy may be divided on: (1) neurodegenerative processes in schizophrenia (e.g., apoptosis, excitotoxicity, oxidative stress, stress sensitization, neurotrophic factor expression, and alteration of neurosteroids); and (2) psychopathological symptoms, and behavioral characteristics of schizophrenia patients, which used as ‘outcome measures’ in order to test efficacy and safety of a new candidate for treatment agent (Fig. 3).

1947-2951/2010/2/001/009

doi:10.1166/ajnn.2010.1012

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Schizophrenia is a chronic, severe, and disabling brain disease. Today the neuroscience and clinical researches have advanced sufficiently to develop neuroprotective approach for discovery a novel generation of compounds with neuroprotective properties. However, the use of neuroprotective agents in schizophrenia is not yet well established. There are two main targets for neuroprotective therapy: (1) neurodegenerative processes in schizophrenia (e.g., apoptosis, excitotoxicity, oxidative stress, stress sensitization, neurotrophic factor expression, and alteration of neurosteroids); and (2) clinical, and behavioral presentations of illness including psychopathological symptoms, a significant decline in cognition, psychosocial functioning and in health related quality of life (HRQL) of patients. The HRQL deficit or impairment is a core feature of schizophrenia spectrum disorders. Based on the author’s and his team research contributions for last ten years, and complementary theoretical considerations, this paper presents the Distress/Protection Vulnerability Model of HRQL impairment in schizophrenia and related disorders. This model has reshaped our understanding of schizophrenia phenotype and will be essential useful for designing more effective clinical and neuroprotective trials.

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Health-Related Quality of Life Impairment in Schizophrenia and Related Disorders as a Target for Neuroprotective Therapy Ritsner

Fig. 1. Phenotypic domains in schizophrenia and related disorders. The term positive symptoms refers to symptoms that most individuals do not normally experience. They include delusions, auditory hallucinations, and thought disorder, and are typically regarded as manifestations of psychosis. Negative symptoms are so-named because they are considered to be the loss or absence of normal traits or abilities, and include features such as flat or blunted affect and emotion, poverty of speech (alogia), inability to experience pleasure (anhedonia), lack of desire to form relationships (asociality), and lack of motivation (avolition). For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care, are markedly below the level achieved prior to the onset. A third symptom grouping, the disorganization syndrome, is commonly described, and includes chaotic speech, thought, and behavior. Reprinted with permission from [7], American Psychiatric Association, Diagnostic and statistical manual of mental disorders, Washington, DC (1994). © 1994.

Overall, changes in six clinical and behavioral areas may be evaluated during a clinical trial. (1) Severity of psychopathology usually assessed using the Clinical Global Impression Scale,1 the Positive and Negative Syndromes Scale (PANSS;2 ), the Scale for the Assessment of Negative Symptoms,3 and the Calgary Depression Scale for Schizophrenia.4 For instance, PANSS is a 30-item rating instrument evaluating the presence/absence and severity of positive, negative and general psychopathology of schizophrenia. Changes in the PANSS factors (or clusters) are evaluated according to several models (Table I). (2) The presence and severity of adverse effects of medication as well as psychological responses to them are measured with the Extrapyramidal Symptom Rating Scale,5 Barnes Akathisia Scale,6 and others scales. (3) Neurocognitive functions may be assessed using tests from the computerized Wisconsin Card Sorting Test (http://www3.parinc.com/products/product.aspx?Productid =WCST), and the computerized Cambridge Automated Neuropsychological Test Battery (CANTAB), and other test batteries. The CANTAB battery consists of a series 2

of interrelated computerized tests of visual and movement skills, attention and memory, and executive function, administered via a touch sensitive screen. The nonverbal nature of the CANTAB tests makes them largely language independent and culture free. These tests are run on an IBM-compatible personal computer with a touch-sensitive screen. For a description of the nature of these tests, the performance measures used and how the test scores are derived, see (http://www.cantab.com/camcog/default.asp). (4) The level of general functioning is assessed with the Global Assessment of Functioning Scale.7 (5) Some personality traits and psychosocial factors may be evaluated with the Insight and Treatment Attitudes Questionnaire,8 the Talbieh Brief Distress Inventory,9 Brief Symptom Inventory-Somatization Scale,10 General SelfEfficacy Scale,11 12 the Coping Inventory for Stressful Situations,13 Self-Esteem Scale,14 and Multidimensional Scale of Perceived Social Support.15 (6) In addition, health related quality of life measures should be essential tools for designing neuroprotective interventions. Am. J. Neuroprotec. Neuroregen. 2, 1–9, 2010

Ritsner Health-Related Quality of Life Impairment in Schizophrenia and Related Disorders as a Target for Neuroprotective Therapy

The three-hit vulnerability model I. Genetic vulnerability

Mechanisms of Neurodegeneration

III. Life stress vulnerability

Apoptosis

II. Neuronal vulnerability

Good

Glutamate excitotoxicity

Oxidative stress

Brain dysfunctions Structural brain abnormalities Neurodegeneration

I

Symptom cognition functioning

Premorbid

II

Schizotaxia

Prodromal period

III IV

Poor

Birth

10

V

First episode, active progression

20

Chronic stage with stable relapsing

30

40

60 Age (yr.)

Subclinical states

Unaffected

Residual stage

Neurodegeneration mechanisms

Clinical and behavioral characteristics

Apoptosis

Stress sensitization

Psychopathological symptoms

Side effects

Oxidative stress

Neurotrophic factor expression

Cognitive deficit

General functioning

Excitotoxicity

Alteration of neurosteroids

Personality features

Health-related quality of life

Fig. 3. Neurodegenerative, clinical and behavioral targets for neuroprotective therapy in schizophrenia and related disorders. HRQL—health-related quality of life.

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Fig. 2. The three-hit vulnerability model and course of schizophrenia and related disorders. Schizotaxia—term for the predisposition to schizophrenia.61 62 86 Figure presents the three-hit model, which postulates that schizophrenia is a spectrum disorders included several syndromes have caused by interaction between: (1) genes with major and minor effects with the possibility of disorder specific and nonspecific effects, respectively, gene–gene interactions and a diversity of genetic causes in different families or populations (a genetic load first hit); (2) a neuronal vulnerability77–79 to triggers during early neurodevelopment is a second hit (its underlying causes both genes with major effects and environmental stress); and (3) a stress sensitization that could act as a third hit, facilitating mechanisms of neurodegeneration such as apoptosis, excitotoxicity or oxygen radical formation due to environmental factors.

Health-Related Quality of Life Impairment in Schizophrenia and Related Disorders as a Target for Neuroprotective Therapy Ritsner Table I. Structure of the PANSS factors. Factors

Items

Reference

N1–N7 P1–P7 G1–G16

[2]

N1–N4, N6, G5, G7, G8, G13, G14 P1, P3, P5, G1, G9 P4, P7, N3, G4, G8, G14 G1–G4, G8 P3, N5, N7, G11, G13, G15

[83]

Negative factor Positive factor Cognitive factor Hostility factor Mood factor

N1–N4, N6, G7, G16 P1, P3, P5, P6, G9 P2, N5, N7, G5, G10–G13, G15 P4, P7, G8, G14 G1–G4, G6

[84]

Negative factor Positive factor Cognitive factor Excited factor Depressive factor

N1–N4, N6, G7, G16 P1, P3, P5, P6, G9 P2, N5, G10 P4, P7, G4, G8, G14 G1–G3, G6

[85]

Negative subscale Positive subscale General psychopathology Negative factor

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Positive factor Activation Dysphoric mood Autistic preoccupations

PANSS-the Positive and Negative Syndromes Scale. P1-Delusions; P2-Conceptual disorganization, P3-Hallucinatory behavior, P4-Excitement, P5-Grandiosity, P6-Suspiciousness, persecution, P7-Hostility; N1-Blunted affect, N2-Emotional withdrawal, N3-Poor rapport, N4-Passive/apathetic social withdrawal, N5-Difficulty in abstract thinking, N6-Lack of spontaneity, N7-Stereotyped thinking; G1-Somatic concern, G2-Anxiety, G3-Guilt feelings, G4-Tension, G5-Mannerisms and posturing, G6-Depression, G7-Motor retardation, G8-Uncooperativeness, G9-Unusual thought content, G10-Disorientation, G11-Poor attention, G12-Lack of judgment and insight, G13-Disturbance of volition, G14-Poor impulse control, G15-Preoccupation, G16-Active social avoidance. Source: Reprinted with permission from [2], S. R. Kay et al., The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261 (1987). © 1987.

3. HEALTH RELATED QUALITY OF LIFE The concept of quality of life (QOL) has both an objective (social functioning and environment) and a subjective (well being, life satisfaction or happiness) component. Broadly speaking, the subjective approach centers on issues such as life satisfaction, satisfaction with defined needs, happiness, self-realization and growth.16 Maslow’s theory uses the concept of human needs (physiological, safety, belonging, love, self-esteem and the need for selfactualization) as a basis for development of happiness and true being.17 Conceptualization, operationalization and measurement of quality of life have been the subject of many publications (reviewed in Refs. [18–20]). The term health-related quality of life (HRQL) refers the physical, psychological, and social domains of health. In other words, HRQL includes dimensions of physical and social functioning: mental health and general health perceptions including such important concepts as energy, fatigue, pain, and cognitive functioning.21 HRQL is multidimensional in the sense that the subjects may simultaneously evaluate several dimensions to arrive at an overall judgment. Two persons with the same mental health status may have different HRQL levels since elements such as differences in personality and illness related 4

factors influence a person’s perception of health and satisfaction with life. Perceptions of HRQL are based on a cognitive process, which involves identifying the relevant domains comprising QOL, determining which domains are self relevant to one and integrating separate domain assessments into an overall QOL assessment.22 Each domain of health has many components that need to be measured. HRQL is a heterogeneous concept, as reflected in the different perceptions of this construct by psychiatrists and their patients. Such differences are obviously dependant on whether observer rated or self-reporting instruments are used. Self-reported and observer-rated HRQL data provide distinct types of information, and appear to have different indicators for HRQL.23–30 There are several limitations in the interpretation of self reported measures of HRQL, namely, self-report bias, the lack of universally accepted measures, the lack of reliability and validity data for many of the scales, and difficulty in generalizing findings from the various instruments. Observer-rated instruments include mostly negative and deficit symptom items. There is a general consensus regarding the importance of using both self-reported and observer-rated measures of HRQL. HRQL Measures. Today there is no universal instrument that can be recommended for all studies. Specific features and psychometric properties of self-reported, observerrated, and combined (observer and self-reported) instruments have been reviewed.30 Differences between these instruments in terms of the underlying HRQL concepts and data collection procedures are substantial. The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q31 ), and the Quality of Life Scale for schizophrenia (QLS32 ) present both self-reported and observer-rated scores of the main quality of life domains, respectively. The Q-LES-Q93 is a self-report questionnaire comprised of 93-items grouped into ten summary scales as follows: Physical Health, Subjective Feelings, Leisure Time Activities, Social Relationships, and General Activities, Work, Household Duties, Medication Satisfaction, and School/Course Work, and Life Satisfaction and Enjoyment. Responses are scored on a 1- to 5-point scale, with higher scores indicating better HRQL. Recently a parsimonious subset of items from Q-LES-Q93 was sought and evaluated in 339 inpatients meeting DSM-IV criteria for schizophrenia, schizoaffective, and mood disorders [Q-LES-Q18 33 ). It was found that 18-items predicted basic Q-LES-Q93 domains (physical health, subjective feelings, leisure time activities, social relationships) and general index scores with high accuracy. The Q-LES-Q18 indicated that the testretest ratings had high reliability, validity, and stability. Thus, Q-LES-Q18 , a brief, self-administered questionnaire, may aid in monitoring the quality of life outcomes of schizophrenia, schizoaffective, and mood disorder patients. The QLS21 is a semi-structured, clinician-rated interview that includes 21 items rated by the clinician on Am. J. Neuroprotec. Neuroregen. 2, 1–9, 2010


4. HRQL MODELS Despite the increasing importance of quality of life in the mental health field, the theoretical conceptualization of the construct remains poorly developed. The rationale for a HRQL assessment in psychiatric research should be outlined in an analytic model that tests the relationship between predictors and response variables. A Conceptual Integrative Model. According to that model, HRQL is the outcome of interaction between the three major determinants (symptoms, side effects, and psychosocial performance) and with several modulators such as personality characteristics, premorbid adjustment, values and attitudes toward health and illness, resources and their availability.36 Testing validity of this model indicated Am. J. Neuroprotec. Neuroregen. 2, 1–9, 2010

Healthy controls (n = 175) Schizophrenia (N = 370)

70 60

Mean score

50 40 30 20 10 0 Physical health

Subjective Leisure time Social General Life Q-LES-Q feelings activities relationships activities satisfaction global index (*10) (*10)

Q-LES-Q domains and global index

Fig. 4. Quality of life profile of 370 patients with schizophrenia and 175 healthy subjects. Reprinted with permission from [35], M. S. Ritsner and A. Gibel, Quality of life impairment syndrome in schizophrenia, Quality of Life Impairment in Schizophrenia, Mood and Anxiety Disorders, New Perspectives on Research and Treatment, edited by M. S. Ritsner and A. G. Awad, Springer (2007), pp. 173–226. © 2007, Springer.

that the severity of symptoms was the main predictor of HRQL, explaining 32% of its variance, while neuroleptic side effects explained 17%. The contribution of psychosocial indicators and modulators, however, was not significant. A mediational model links subjective HRQL with selfrelated constructs. Zissi, Barry, and Cochrane37 tested this model and concluded that the extended mediational model of HRQL for individuals with long-term mental health problems appears to have important implications for the planning and delivery of mental health programmes. However, this model needs further development, testing and validation. A distress/protection vulnerability model postulated that subjective HRQL is an outcome of the interaction of an array of distressed factors, on the one hand, and protective factors, on the other.38 It suggests that satisfaction with HRQL decreases when distress factors outweigh protective factors, and vice versa. The data included measures of satisfaction with general and domain-specific HRQL such as physical health, subjective feelings, leisure activities, social relationships, general activities, medication, as well as severity of psychopathology, adverse events, psychological distress, expressed emotions, personality traits, self-constructs, coping styles, and perceived social support. In order to validate the DPM model, two kinds of multivariate analyses were conducted using cross-sectional and longitudinal data. Since 2000, the Distress/Protection Vulnerability model has been extensively used by our team to compare HRQL impairment among patients with severe mental disorders,35 38 39 to examine the role of side effects,40 to test mediating effects of coping styles,41 to search longitudinal predictors of general and domain-specific quality of life,42–44 to explore association of HRQL impairment with suicide behavior,45 temperament factors,46 47 and sleep 5

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7-point scales in four domains: interpersonal relations and social network (household member, friends, acquaintances, social activity, social network, social initiatives, social withdrawal, sociosexual relations), instrumental role functioning (extent, adequacy, underemployment, satisfaction), intrapsychic foundations (sense of purpose, motivation, curiosity, anhedonia, time utilization, empathy, interaction), and common objects and activities (objects, activities). We tested and validated a condensed QLS5 , based on QLS21 , which is briefer and thus easier to administer than the complete rating scale (QLS534 ). The analyses suggest that QLS5 has been shown to be a valid predictor of the QLS21 total scores. Psychometric properties (inter-rater, the test-retest reliability, and sensitivity to change) for QLS5 were also high and comparable to QLS21 . In addition, QLS5 does not reflect the presence of psychiatric symptoms as do the QLS21 . The most reliable items in QLS5 are social initiatives, adequacy, acquaintances, time utilization, and motivation. Thus, the five-item condensed Quality of Life Scale for schizophrenia maintains the validity of the full QLS, and has the advantage of a shorter administration time. Utilization of the revised QLS5 in routine care and clinical trials may potentially facilitate evaluation of treatment outcomes in schizophrenia. Schizophrenia Compared to Healthy Subjects. Differences in the HRQL levels between schizophrenia patients and healthy subjects have emerged as the most powerful findings regarding schizophrenia patients, according to many studies made in the last two decades (reviewed in Ref. [19]). Moreover, today there is compelling evidence that schizophrenia patients, compared to healthy subjects, demonstrate significant impairment or deficits regarding satisfaction with their quality of life. As depicted in Figure 4, schizophrenia patients from the database of the Shaar Menashe HRQL study are significantly impaired across general and all domain-specific life qualities compared with healthy subjects (MANOVA, F = 17.2, df = 14,1056, p < 0001 35 ).

Health-Related Quality of Life Impairment in Schizophrenia and Related Disorders as a Target for Neuroprotective Therapy Ritsner

quality,48 and to examine the impact of antipsychotic agents.49 In addition, findings of other research groups also highlighted the importance of addressing psychosocial issues and their interrelationships in the structures of HRQL that have supported this model.50–54

5. HRQL IMPAIRMENT SYNDROME

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A number of empirical findings of HRQL impairments in schizophrenia are reviewed.19 20 35 55–60 Obtained findings lead to following suggestions. (1) Subjects who met criteria for vulnerability to schizophrenia (“schizotaxia”) showed lower total ratings on the QLS32 with significantly higher psychological distress scores.61 60 (2) Despite the absence of psychotic symptoms, individuals with prodromal symptoms (ultra-high-risk) for schizophrenia experience significant HRQL impairments in a manner parallel to that observed in patients with established psychotic illness.63 64 (3) There is an association between poor premorbid adjustment and poor HRQL levels in schizophrenia.65–67 (4) Poor HRQL is associated with long duration of untreated first-episode schizophrenia patients.65 68 (5) There are significant differences in HRQL levels between patients with severe mental disorders.35 69

(6) Taken together, HRQL findings underscore the relatively stable character of HRQL disturbances with mild fluctuations in the general and domain-specific quality of life scores throughout the course of schizophrenia.35 70–74 (7) HRQL of patients with schizophrenia spectrum disorders is associated with ‘stress related factors’ such as some personality traits, low self-esteem, and self-efficacy, emotion-oriented coping style, and emotional or somatic distress38 75 76 rather than with psychopathological symptoms, and side effects.38 40 (8) Psychopathological symptoms explained a relatively small proportion of the variance in HRQL scores among people with depression or anxiety disorders.69 (9) Some temperament traits, which are not necessarily part of the deterioration process of the illness, are significantly associated with the HRQL in schizophrenia.47 According to our hypothesis, the HRQL deficit in schizophrenia and related disorders refers to the vulnerability to illness, and, consequently, should be viewed as a definitive expression or a particular syndrome, like psychopathology or cognitive impairment. The stressvulnerability model postulates the vulnerability to illness as stable, enduring, and largely attributable to genetic and environmental factors.77–79 Greater vulnerability is associated with higher risk for developing schizophrenia, but the actual expression of this predisposition depends on a

The three-hit vulnerability model Mechanisms of neurodegeneration

I. Genetic vulnerability

Apoptosis

Glutamate excitotoxicity

III. Life stress vulnerability

Oxidative stress

II. Neuronal vulnerability

Schizotaxia

Prodromal period

First episode

Chronic stage

Residual stage

Neurobiological factors

Distressing effects

I

Primary factors: Self-esteem self-efficacy coping styles personality traits stress vulnerability emotional distress somatization social support etc.

Quality of life HRQL impairment syndrome

Protective effects

Secondary factors: Poor premorbid psychopathological symptoms neurocognitive deficits side effects emotional distress poor insight poor sleep expressed emotion suicidal attempts unmet needs employment olanzapine antidepressants anxiolytics mental health care

Fig. 5. The Distress/protection vulnerability model of HRQL impairment, and the three-hit vulnerability model of schizophrenia and related disorders. HRQL—health-related quality of life.

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6. CONCLUSIONS Beyond the use of antipsychotic agents, it will be of interest to examine whether agents that demonstrate neuroprotective properties in preclinical studies may prove to have neuroprotective effects in schizophrenia. Neuroprotection would delay decline of symptoms and side effects and preserve quality of life. In recent years several potential neuroprotective compounds for treatment of schizophrenia patients were investigated. In order to generate meaningful results, clinical trials on neuroprotective agents should ideally be designed to minimize the potential for bias and optimize the ability to detect the neuroprotective effect of a therapeutic intervention in as short a time as possible. Key issues for the design of clinical trials of neuroprotective therapies include identifying appropriate endpoints and determining the ideal timing of the intervention. The HRQL impairment syndrome occurs before the first psychotic episode and persists throughout the course of the illness. It involves every aspect of quality of life and has an important impact on long-term social and Am. J. Neuroprotec. Neuroregen. 2, 1–9, 2010

occupational outcomes. Further research is needed regarding the neuroprotective compounds on the HRQL impairment. In summary, this paper discusses the concept of mental health-related quality of life impairment and the Distress/Protection Vulnerability Model. The definition of HRQL is explored and several studies and related models are reviewed.

References and Notes 1. W. Guy, ECDEU Assessment Manual for Psychopharmacology, Revised, US Department of Health, Education and Welfare, Washington, DC (1976). 2. S. R. Kay, A. Fiszbein, and L. A. Opler, The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261 (1987). 3. N. C. Andreasen, The scale for the assessment of negative symptoms (SANS), conceptual and theoretical foundations. Br. J. Psychiatry Suppl. 7, 49 (1989). 4. D. Addington, J. Addington, E. Maticka-Tyndale, and J. Joyce, Reliability and validity of a depression rating scale for schizophrenics. Schizophr. Res. 6, 201 (1992). 5. G. Chouinard and H. C. Margolese, Manual for the extrapyramidal symptom rating scale (ESRS). Schizophrenia Research 76, 247 (2005). 6. T. R. Barnes, A rating scale for drug-induced akathisia. Br. J. Psychiatry 154, 672 (1989). 7. American Psychiatric Association, Diagnostic and statistical manual of mental disorders, Washington, DC (1994). 8. J. P. McEvoy, S. Freter, G. Everett et al., Insight and the clinical outcome of schizophrenic patients. Journal of Nervous and Mental Disease 177, 48 (1989). 9. M. Ritsner, J. Rabinowitz, and M. Slyuzberg, The talbieh brief distress inventory: A brief instrument to measure psychological distress among immigrants. Comprehensive Psychiatry 36, 448 (1995). 10. L. R. Derogatis and P. M. Spencer, The Brief Symptom Inventory (BSI): Administration, Scoring and Procedures Manual, Johns Hopkins University, School of Medicine (1982). 11. M. Jerusalem and R. Schwarzer, Selbstwirksamkeit [Selfefficacy], Skalen zur Befindlichkeit und Persönlichkeit, edited by R. Schwarzer, Research Report No. 5, Freie Universitut, Institut fur Psychologie, Berlin (1986), pp. 15–28. 12. M. Jerusalem and R. Schwarzer, Self-efficacy as a resource factor in stress appraisal processes, Self-Efficacy: Thought Control of Action, edited by R. Schwarzer, Hemisphere, Washington, DC (1992), pp. 195–213. 13. N. S. Endler and J. D. Parker, Multidimensional assessment of coping: A critical evaluation. J. Pers. Soc. Psychol. 58, 844 (1990). 14. M. Rosenberg, Society and the Adolescent Self-Image, Princeton University Press, Princeton, NJ (1965). 15. G. D. Zimet, N. W. Dahlem, S. G. Zimet, and G. K. Farley, The multidimensional scale of perceived social support. Journal of Personality Assessment 52, 30 (1988). 16. K. C. Calman, Quality of life in cancer patients—An hypothesis. J. Med. Ethics 10, 124 (1984). 17. A. H. Maslow, Toward a Psychology of Being, Van Nostrand, New York (1962). 18. E. Diener and D. R. Rahtz (eds.), Advances in quality of life theory and research, Social Indicators Research Series, Kluwer Academic Publishers, Dordrecht, The Netherlands (2000), p. 266. 19. M. S. Ritsner and A. G. Awad (eds.), Quality of Life Impairment in Schizophrenia, Mood and Anxiety Disorders. New Perspectives on Research and Treatment, Springer (2007), p. 388.

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host of personal and environmental factors, some of which are noxious, while others are protective. It is the interaction of vulnerability, stressors and protective factors that influences both the onset and the course of the disorder. Thus, the Distress/Protection Vulnerability model20 suggested that: (i) HRQL impairment is a particular syndrome observed in the severe mental disorders. This syndrome is an outcome of the interaction of an array of distressing factors, on the one hand, and putative stress process protective factors, on the other hand. HRQL impairment increases if distressing factors overweigh protective factors, and vice versa. (ii) There are primary and secondary factors. Primary or vulnerability related factors are those usually considered inborn or personal characteristics, while secondary factors are related to the illness and the environment.43 Such primary factors as harm avoidance, high levels of neuroticism, poor coping skills, elevated emotional distress, emotion-oriented coping, and weak self-constructs80–82 might lower the vulnerability threshold, and, consequently, result in severe HRQL impairment. Secondary factors influence HRQL impairment via primary factors. Factors influencing HRQL impairment syndrome in schizophrenia according to the Distress/Protection Vulnerability Model are summarized in Figure 5. (iii) HRQL impairment syndrome is characterized on the basis of underlying neurobiology and that may lead to improved understanding of severe mental disorders and to making more effective treatment decisions. Integration of the quality of life and neurobiological investigations may provide new vistas on the HRQL impairment syndrome in mental disorders.

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Received: 12 August 2009. Accepted: 13 February 2010.


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RESEARCH ARTICLE

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