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In this chapter the author describes the conceptual basis of the health related quality of life (HRQL) impairment syndrome in severe mental disorders (SMD) such as schizophrenia, schizoaffective, mood and anxiety disorders. He presents the evidence for its validity, and identifies some likely directions for future research and development. Based on the author’s and his team research contributions and complementary theoretical considerations, the author explores four issues in this chapter: the quality of life concept, interpreting HRQL findings, conceptualizing HRQL impairment in the framework of the Distress/Protection Vulnerability Model (DPV), and implications for future research. Evidence for the concept’s validity is assessed, followed by a discussion of the possible evolvement of the concept, to encompass biologic domains. Finally, there is a review of the research implications of the HRQL impairment concept and the DPV model followed by a discussion of some major areas of unresolved questions for future research

This chapter will attempt to accomplish a seemingly impossible task of characterizing the concept of quality of life in terms of pleasure centres, neuronal circuits and chemical mechanisms in the brain. The supporting explanations will be presented in three parts: first, identifying three key characteristics of quality of life – first, the central doctrine of subjectivity, the time frame of appraisal, and the relevance of immediate affective tone in determining quality of life ratings; second, a review of the cumulative knowledge on the neuroanatomical and neurochemical mechanisms underlying subjective responses to pleasurable stimuli such as food and drugs. Thirdly, evidence is presented to support that interference with these brain reward mechanisms leads to feelings of lack of pleasure and poor quality of life, citing antipsychotic drug therapy in schizophrenia as an example. Laboratory experiments in animals and neurochemical imaging studies in humans suggest that dopaminergic mechanisms in nucleus accumbens, amygdala, hippocampus and prefrontal cortex are key players in determining the qualitative and quantitative aspects of subjective responses to pleasurable stimuli. Antipsychotic drug induced dopaminergic blockade in these neuronal circuits leads to persistent feelings of dysphoria and pervasive lack of pleasure, leading to subjective distress and compromised quality of life. The nuances of subjective responses to antipsychotic drugs thus have enormous implications for long term care of the mentally ill people

The neuroendocrine system and the distribution of hormones through the brain and their modulatory role and influence in behaviour and mood have been studied for a long time. The most evident changes associated with mood disorders are in the hypothalamic-pituitary-adrenal (HPA), the hypothalamic-pituitary-thyroid (HPT), the hypothalamic-pituitary-GH (HPGH) and the hypothalamic-pituitary-gonadal (HPGn) axes. Hypotheses referring to the psychophysiological meaning and the development of these alterations are discussed. In order to improve the quality of life for patients suffering from mood disorders, it would be important to define which specific hormonal axes contribute to mood symptoms and which medications that normalize neuroendocrine function are conditioning the impact of mood symptoms. The identification and detailed characterization of these pathways will ultimately lead to the development of novel neuropharmacological intervention strategies. Future directions for research are described. All data derived from studies focusing on central neuropeptidergic circuits and peripheral hormone systems add to the understanding of the pathophysiology of mood disorders and indicate the importance of investigating neuroendocrine dysfunctions in psychiatric patients both to ensure proper diagnosis and adequate pharmacotherapies

It has been suggested that Quality Of Life (QOL) is greatly affected by the individual way in which one emotionally experience the world. The nature of the emotional experience, however, is particularly divergent among people. It seems that this individual uniqueness depends more on mental representations than physical attributes of a~stimulus . In line with this idea, it was suggested that subjective emotional experiences are determined by the individual tendency to either focus attention on internal self-oriented or external world-grounded signals . This personal characteristic depends by and large on the unique operating system of attention and awareness, as driven mainly by vigilance or cognition. Accordingly, an individual bias for enhanced focus on negative signals can be attributed to modified attention operations through fast engagement, slow disengagement, or poor signal differentiation. In other words, a resilient affective style may be associated with weak reaction and fast recovery from negative stressful events, while affective vulnerability may result in excessive response to and long standing distress from the same stressful event. Thus, the ability to assign appropriate emotional significance to incoming information and to form suitable associations between stimuli and emotional state are probably essential for QOL. The present chapter aims to present possible brain mechanisms that subserve the individual emotional experience, and through that mediate QOL

Health-related quality of life is concerned with the relationship between the effect of treatment on the patient’s life with society’s value for this effect. It is only through balancing these two concerns that transparent decisions concerning the best choice of treatment at the intervention level and, at the policy level, the allocation of scarce health resources can incorporate both the patient’s and society’s views. Where these decisions are important, the appropriate form of evaluation is cost-utility analysis (CUA). With rising health care costs, the ageing of populations and the determination of governments to cap health care expenditure, the mental health field will increasingly be asked for evidence of its cost-effectiveness. In the absence of such evidence, patients access to mental health services in the future may be hindered and the choice of treatment restricted as decision-makers may be disinclined to increase or even maintain funding. This paper reviews the axioms of cost-utility analysis and the role of multi-attribute (MAU) utility instruments. Seven leading instruments are reviewed, and examples of their use in cost-utility analysis in the mental health field are presented. It is concluded that none of the existing instruments fully meet the axioms of either utility or measurement theory, and that the instruments provide HRQoL estimates that are so different that study outcomes are likely to be as much a function of the instrument chosen for a particular study as the effectiveness of the intervention itself. It is recommended that mental health professionals undertaking CUAs review available instruments carefully, use two MAU-instruments in any particular study, and report both sets of results. The shortcomings of existing MAU-instruments should not be taken as a reason to avoid economic evaluation; at the moment they are the only practical way of capturing the balance described above. Few CUA studies have been carried out in the mental health field, there is thus an opportunity to undertake studies providing the evidence needed by clinicians and decision-makers for transparent decisions regarding treatment options and the future funding of mental health care

In the present chapter, we compared the psychometric properties of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) with the Quality of Life Scale (QLS) and the Lancashire Quality of Life Profile (LQOLP) in the same patients with schizophrenia, schizoaffective, and mood disorders. These instruments were chosen since they are mental illness-related, and Q-LES-Q is a self-report evaluation scale, whereas QLS is observer-rated, and LQOLP has domains similar to Q-LES-Q, which enables a comparison of the instruments. The compared instruments proved to be mental health-related, but none were mental-disorder-specific. Despite the acceptable psychometric properties and the correlation of the general indices, similar domains proved to be instrument-specific and were not sufficiently compatible. These discrepancies should be considered when comparing evaluations from similar domains in these scales

HRQOL is characterized by definitional uncertainty and a vast amount of heterogeneous assessment tools, and there is no really satisfying integrative theoretical model. The present chapter describes two studies using a bottom-up approach to establish an integrative model of HRQOL. The first study compared seven (inter)nationally validated HRQOL questionnaires in mentally healthy subjects (n=479), patients with major depression (n=171), and patients with schizophrenia (n=139) to explore convergent and divergent aspects of 7 instruments, 45 subscales, and a great number of single items. Multivariate analyses have been primarily conducted by a nonparametric multidimensional scaling technique (faceted similarity structure analysis). A set of seven reliable QOL domains could be extracted by simultaneous analysis of all assessment tools. This set consists of one ‘G-factor’ of general well-being vs. depressed mood and six specific QOL dimensions. This basic structure represents a core module which holds for nonclinical and clinical samples, and which can be completed by specific modules for particular subpopulations (e.g. persons with family, partnership, profession). Reliability, validity, and sensitivity to change (from admission to discharge and 4-month-follow-up) of this Modular System for QOL were investigated in a second study in healthy controls (N=346), patients with depression ( N=114), and patients with schizophrenia (N=91) using the SF-36 as a comparison standard. Results and major conclusions will be discussed with an emphasis on the clear impact of depressive symptoms and current mood on HRQOL, and the implications given by this relationship

To date no data on health related quality of life (HRQL) in subjects at risk for a first episode of psychosis compared with first episode schizophrenia patients (FE) or healthy controls (HC) is available, although the concept of HRQL is of growing relevance in schizophrenia research. Therefore 45 subjects in a putatively early initial prodromal state (EIPS), 40 FE and 45 HC were assessed for demographics, psychopathology and HRQL as measured by the self-rating instrument Modular System for Quality of Life. Results indicated that on a descriptive level in most life areas HC experienced the highest HRQL scores followed in hierarchical order by EIPS and FE. EIPS and FE experienced significantly lower HRQL than HC in 5 and 6 of 7 HRQL domains. When comparing EIPS and FE, EIPS experienced a significantly lower HRQL level in affective HRQL. HRQL ratings in EIPS were negatively correlated with joining school or work and higher positive prodromal symptom scores. In FE HRQL scores were negatively correlated with age and depression. The major finding from the study is that HRQL in subjects at risk for a first episode of psychosis is substantially reduced when compared with HC. Thus, HRQL maybe already reduced prior to the onset of first positive schizophrenia symptoms. These data support the notion that subjects at risk for a first episode of psychosis constitute a clinical population in which further service and intervention research is indicated

Patients with schizophrenia exhibit an exceedingly wide range of symptoms, and a broad spectrum of cognitive impairments. In addition, it has become increasingly apparent that the disorder is, to variable degrees, accompanied by quality of life impairments. This chapter addresses the question of whether the health-related quality of life (HRQL) impairment or deficit is a syndrome in schizophrenia. Therefore, first, we discuss what the general and domain-specific HRQL impairments are. Then, we address distressing and protective factors, and a factor structure of HRQL impairment. The literature, as well as new and previously published findings from the Shaar Menashe Longitudinal Study of Quality of Life will be presented in detail. We argue that HRQL deficit is highly prevalent and fairly marked in schizophrenia patients: 49% of the patients are clinically severely impaired regarding general life quality, 42% - in general activities, 39% - in subjective feelings, 30% - in both leisure time activities and social relationships. The HRQL impairment has been observed before individuals exhibit the signs and psychotic symptoms of schizophrenia; it is relatively stable throughout the course of the illness. HRQL impairment syndrome appears to be relatively independent of symptomatology and neurocognitive deficit. Finally, the authors suggest that impairment in general and the domain-specific quality of life in particular is sufficiently reliable, stable, and specific enough syndromes to warrant inclusion in the diagnostic criteria for schizophrenia. Limitations in the current knowledge in this area are identified, and suggestions for future research are provided