Quality of Life and Major Depression

CHAPTER 12 QUALITY OF LIFE AND MAJOR DEPRESSION Current findings and future perspectives

MARCELO T. BERLIM1 AND MARCELO P.A. FLECK2 1 Depressive Disorders Program, Douglas Hospital Research Centre, FBC Pavilion, Rm. F-3116-B, 6875 LaSalle Blvd., Montréal, Québec, H4H 1R3, Canada 2 Department of Psychiatry and Forensic Medicine; Head, Mood Disorders Program Hospital de Clínicas de Porto Alegre, Brazil

Abstract:

Major depression (MD) is a public health problem that is associated with grave consequences in terms of excessive mortality, disability, and secondary morbidity. Indeed, it ranked fourth in 1990 and could rise to second by 2020 in terms of the overall burden of all diseases worldwide. Therefore, it is now clear that current research on the health impact of depression should go beyond estimating its prevalence, symptoms severity, and complications to include studies that seek to establish how it influences the quality of life (QOL) of the affected individuals. In the present chapter we will outline how measures of QOL may reveal differences between patients with depression and control groups, be sensitive to change in status during treatment, have predictive value for outcome measures and provide additional information about timelines for improvement in psychosocial functioning, which may occur at a different rate than changes in other depressive symptoms. More specifically, we will summarize recent investigations that have generally shown that: (1) depressed patients have QOL deficits that are directly attributable to the mood disturbance, (2) the degree of the decrement in QOL is proportional to the severity of depressive symptoms, (3) the negative relation between depression and QOL is as great as (or worse than) that observed in chronic medical disorders such as rheumatoid arthritis and diabetes, and (4) the adequate treatment of depression is usually associated with a significant improvement in the QOL of patients. Finally, we will discuss future perspectives involved in the evaluation of QOL in populations of depressed subjects

DEPRESSIVE DISORDERS: EPIDEMIOLOGY, SYMPTOMATOLOGY AND PSYCHOSOCIAL IMPACT Unipolar major depression has a lifetime prevalence of around 21-24% in women and 12-15% in men 1 . It is characterized by the presence of depressed mood and/or lack of interest in activities that would usually be pleasurable, and generally associated with appetite and sleep disorders, with feelings of guilt and/or depreciation, among others, all present for at least two weeks 2,3 . 241 M.S. Ritsner and A.G. Awad (eds.), Quality of Life Impairment in Schizophrenia, Mood and Anxiety Disorders, 241–252. © 2007 Springer.

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Depressive disorder represents, worldwide, a significant public health problem not only due to its high prevalence 4 , but also to its high annual direct and indirect costs which, in the United States alone, reached around 43 billion dollars in 1990 5,6 . In fact, projections for the year 2020 indicate that major depression will occupy the second place in terms of impact on human health, being second only to ischemic heart disease. If incapacity alone is taken into consideration, major depression occupied the first position in 1990 7 . Depressive disorders are also associated with serious consequences in terms of mortality and secondary morbidity leading, for example, to a lack of work productivity and interpersonal problems 8 . Furthermore, they can adversely influence longevity and well being during the episode and, potentially, for the rest of the afflicted person’s life and its functional effects in the long term are as devastating as those found in chronic medical diseases, such as diabetes mellitus and cardiovascular disease 6,9 . High mortality rates are also a major problem, since almost 15% of depressed patients commit suicide during their lives 10 . For these reasons, current research on the impact of depressive disorders should go beyond estimating its prevalence, the seriousness of its symptoms and complications, and begin to include studies that attempt to establish how they affect the quality of life (QOL) of the affected individuals 11−13 . DEPRESSIVE DISORDERS AND QUALITY OF LIFE In the specialized literature, there is strong evidence that depressed patients present a significant reduction in their QOL 11,13,14 . This is especially due to the fact that depressive disorders affect various domains that are part of the global assessment of the QOL 15 . Below, we summarize the main conceptual aspects – methodological and empirical, involved in the assessment of the QOL in depression. How to Assess the QOL in Depressed Patients Present controversies Present controversies regarding the measurement of QOL in depression include the following dilemmas 11,13,15 : • Subjective scales (i.e., self-rated) versus objective scales (i.e., applied by the clinician). Many studies have demonstrated that there are disagreements between physicians and patients over the severity of the symptoms and the success of medical treatments. Clinicians generally base their assessment of treatment results on the improvement of the symptoms or, preferably on the “non-progression” of the disease process. This reveals that the focus of the clinician is, in general, on the status of the patient’s health. On the contrary, patients most commonly evaluate the results of the treatment in relation to feeling more comfortable or being able to do daily activities satisfactorily again. In any event, the sensation of the patient’s well-being is the main point of reference here. Since the psychosocial elements

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of the patient’s experience cannot be easily assessed by the physician, one can argue that the patient is the best judge of his/her health status. As well, numerous studies indicate that the search for medical attention is much more related to the subjective impact of the disease on patient’s life than with the presence, by itself, of symptoms. Additionally, the effectiveness of any kind of treatment depends mainly on whether the patient considers or not that his/her health status showed improvement after beginning a therapeutic approach. Finally, it is a current consensus that, to the extent that interventions in the health area have as an objective making life more comfortable (instead of “curing” diseases), the most valid source of information is the patient him/herself. In short, it is inappropriate to value only the clinician’s evaluation, particularly when the degree of disagreement between the physician and the patient is taken into consideration, and the point of view of the latter should be emphasized whenever possible. However, “objective” assessments can be useful and should be complementary to subjective ones. • Generic scales (i.e., those developed to be used with varying diseases and virtually applicable to all people) versus disease-specific scales (i.e., those developed for people with specific diseases). Amongst the arguments that defend the disseminated use of disease-specific scales, the most important one is that probably special aspects of each disease uniquely contribute to the perception of the QOL in the affected individuals and cannot be captured by generic instruments. As well, some authors believe that a more specific measurement would be more sensitive to symptomatic changes in a certain disease. However, if the objective is to assess the influence of a disease (or of their symptoms) on the QOL understood in a broader way (i.e., involving a series of domains not specifically linked only to health problems) there are strong arguments for the use of generic scales (even if disease-specific measurements can be used as complementary strategies). Additionally, another limitation of specific instruments is that they are not effective in comparing the QOL of different clinical conditions. • Medical versus mediational models. At present, there is still a belief that the QOL is primarily a product of the symptoms of a disease and of the side effects of medications (medical model). However, there is increasing evidence that two patients can have different levels of QOL even if they present the same seriousness of the disease and/or the same degree of treatment side effects. In this way, individual characteristics of each patient can, in fact, mediate the relation between QOL and symptoms/para-effects (mediational model). • Scales that reflect a functionalistic model (i.e., assessing the individual’s capacity of fulfilling certain functions that are considered “normal” for the average person in western society [e.g. physical mobility, conducting a job, socialization], with a divergence from the norm indicating a reduced QOL) versus scales that reflect a model based on basic needs (i.e., assessing if the individual is capable of accomplishing his/her basic needs, such as shelter, feeding and safety and his/her psychological needs, such as autonomy, friendship and pleasure). In short, the proponents of the functionalistic model believe that the disease only becomes a

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problem when it affects the fulfillment of the individual’s functions, while the proponents of the basic needs model suggest that life gains quality through the ability and the capacity of the individual in satisfying his/her own needs. Theoretical implications of the relationship between quality of life and depression Even though there is no definitive consensus on the concept of QOL, emphasis on the subjective dimension (i.e., the perception of the individual regarding the different domains of his/her life) is undoubtedly a central element 16 . To the extent that in mental disorders the sick “organ” is the mind, it is expected that perception and/or the processing of such perception (cognition) will be altered 11 . Because of its prevalence and nature, depression presents an extra challenge 17 . In depression the possibility of superposition of the measurements of depression and QOL can occur in at least three levels: (a) conceptual (i.e., depression and QOL could be representations of the same phenomenon); (b) mediational (the affective state could lead to a distorted perception of reality), and (c) metric (even though they are supposedly different,constructs, there are some items that are common) 17 . From the conceptual point of view, “well being” and “degree of satisfaction” can be understood as antagonistic constructs and considered as “antonyms” of depression. When someone says he/she is “depressed,” he/she is implicitly communicating that they “do not feel well” and that they are “not satisfied.” From the mediational point of view, the cognitive model illustrates this possible relationship. Beck 18 proposed that depression could be defined through a cognitive triad according to which the individual (1) sees him/herself in a negative way, (2) interprets the majority of the events in his/her life in an unfavorable way, and (3) believes that his/her future has no hope. Thus, it is expected that a depressed person will assess the different domains of his/her life, based on the evaluation of the quality of life, negatively and that once his/her state has improved, that same objective reality will be assessed differently (i.e., more positively). From the metric point of view, many items present in the assessment of QOL are also present in the scales of depression. For example, in the case of the World Health Organization’s Quality of Life Instrument - Brief Version (WHOQOL BREF) 19 , using item response theory, 11 of the 26 items present DIF for depression and 11 of the 26 items are also conceptually assessed with the Hamilton Rating Scale for Depression (HAM-D) 20 (positive feelings, spirituality, thoughts, energy, leisure, sleep, daily life activities, work, self-esteem, sexual life and negative feelings) 21 . Various studies have shown high correlation coefficients, especially in the psychological and physical domains, with the Beck Depression Inventory (BDI) 22 , and lower ones for the other domains 23−25 . Even though the concepts of depression and QOL are closely related and some authors consider them as “tautologic” measurements 26 , there is empirical evidence that those two concepts do not measure the same phenomenon: (1) QOL and depression are synchronic measurements, but correlation coefficients are only moderate in some domains 24,27,28 ; (2) there seems to be a gap between


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the improvement of depression and the improvement in some domains of the QOL, especially in relation to antidepressant use, which shows a more precocious improvement of the symptoms of depression followed by an improvement in the QOL 29 ; (3) the quality of life measured by the Quality of Life in Depression Scale (QLDS) 30 and not intensity of depression was found as a predictive factor for complete remission within 9 month follow-up 31 ; (4) for the same intensity of depression it is possible to have different QOL scores and this finding can have important clinical implications 32,33 . Assessment instruments Traditional scales used to assess depressive symptoms, such as the HAM-D 20 , the BDI 22 , do not encompass important aspects of the QOL in that they are restricted to descriptive investigations of symptomatology and not necessarily to its repercussions in the psychosocial life of the depressed patient 15 . Thus, should the clinician or researcher use them exclusively to assess the results of the treatment, they will not capture important aspects of the QOL perception of the patient (e.g., the presence or quality of interpersonal relations are not verified) 11,14 . Because of that, many authors have argued for the use of additional scales that aim at investigating the QOL in a broader way, i.e., not limited only to secondary aspects of the depressive symptomatology 13 . Below are examples of psychometric instruments that have been largely used in the assessment of QOL in patients presenting with depressive disorders. WHOQOL BREF 19,27,28 According to what has been seen before, the QOL assessment can be based both on the generic and the specific models. As an example of the generic model we can cite the WHOQOL-BREF, a shorter version of the WHOQOL-100, which is composed of 26 items that encompass four domains of QOL (i.e., physical, psychological, social and environmental). The WHOQOL BREF also contains two items that are examined separately: question 1 asks about an individual’s “overall perception of QOL,” and question 2 asks about an individual’s “overall perception of their general health.” Items are rated on a 5-point Likert scale where 1 indicates low and negative perceptions, and 5 indicates high and positive perceptions. Respondents judge their QOL over the previous 2 weeks, and high scores demonstrate good QOL. The mean score of items within each domain is used to calculate the domain score. Quality of Life in Depression Scale (QLDS) 30,34 The QLDS is a disease-specific instrument used to assess QOL in depressed patients. It is based on the model that measures the QOL as arising from the ability and capacity of the patients to meet their basic needs. This model arose from qualitative non-structured interviews that the authors of the QLDS applied with individuals exhibiting depressive disorders. In those interviews, a consistent finding was that the depressive subjects described the impact of the disease in their lives in terms of their

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personal needs (for example work, love, conversation, pleasure, self-care and nutrition) being frustrated by depression. In its final format, the QLDS is a self-applicable questionnaire comprised of 34 items (with dichotomous answers, i.e., yes/no or true/false) that describe each one of the basic physical and psychological needs of the depressed patients. They, in turn, answer the questions of the QLDS based on a defined period of time (i.e., the previous week), with the result that the higher the scores on the QLDS, the worst is the QOL. The QLDS is very responsive to changes in the QOL. In its original version it was found to be very trustworthy, consistent internally and valuable. Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) 35 The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) is a selfadministered questionnaire developed to measure the degree of contentment and satisfaction in relation to various aspects of daily life. Even though the Q-LES-Q has not been developed specifically for depressed patients, it was originally tested in a sample for depressed patients and has been used with this aim. It is comprised of 93 items, 91 of them grouped into 8 sub-scales. Five of those scales are to be filled out by all individuals: physical health (13 items), subjective feelings (14 items), time of leisure activities (6 items), social relations (11 items) and general activities (14 items). The other three sub-scales are to be filled out by the individuals depending on their particular activities: work (13 items), domestic services (10 items), and activities in school/courses (10 items). The Q-LES-Q was developed for use not only in depression, but also in other psychiatric conditions or even in other medical areas. The items are proposed as questions and the respondent assesses the degree of satisfaction on Likert-type scale of 5 options. The original version of the instrument presents good internal consistency with all coefficients of Cronbach above 0.90. The test-retest trustworthiness, however, obtained low values (between 0.63 and 0.89). The different sub-scales of the Q-LES-Q presented correlation coefficients that vary between −034 to −068 with Clinical Global Impression (CGI) 36 , and correlations in the same order with two scales of depression, namely the HAM-D 20 and the BDI 22 . SmithKline Beecham Quality of Life Scale (SBQOL) 37 Even though the SmithKline Beecham Quality of Life Scale (SBQOL) has not been developed as a specific measure for depression, its validation study was based on patients presenting with major depression and general anxiety. It is a self-report questionnaire composed of 28 items. The items are scored on a decimal scale with an extreme positive anchor point on one side and a negative anchor point on the opposite side. The questionnaire includes psychological and physical well-being, social relations, activities/interests/hobbies, humor, control, sexual function, work/job, religion and finances. The answers are given from three perspectives: “me now”, “the ideal me”, and “the sick me”, and the instrument generates three total scores (“me now,” “the ideal me,” “the sick me”) and two comparisons (“me now” vs. “the sick me” and


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“me now” vs. “the ideal me”). The SBQOL demonstrated adequate internal consistency. Additionally, it was shown that its total scores had good correlations with clinical improvement (as measured by the HAM-D 20 ), and with comparison scores of generic QOL instruments (i.e., the Sickness Impact Profile 38 , and the General Health Questionnaire 39 ). Depression and QOL: Summary of Current Evidence QOL measurement in depression Recent studies on the QOL in depression have demonstrated that depressed patients present with deficits in interpersonal, psychological and even physical functioning that is only partially explained by the variation in the intensity of the depressive symptoms 11,13−15 . Recent evidence indicates that mood disorders are associated with important deficits in the QOL and the global functioning of their bearers. In fact, patients with major depression presented QOL scores inferior not only to that of individuals with subsyndromal depressive disorders, but also to that of non-depressive subjects in the general population 40 . Moreover, studies have consistently shown that depressed patients present with significant deficits in many areas of social functioning (e.g., leisure, work, interpersonal relations, health status and academic performance) when compared with healthy controls 13 . A recent study 41 evaluated the impact of major depression, double depression and dysthymia (and other anxiety disorders) on the QOL of the affected subjects (as assessed by the Q-LES-Q) and compared them to a control group. Demographic variables (e.g., age, sex), co-morbidities, duration and seriousness of the specific symptoms of each disease were assessed as predictive QOL factors. The authors demonstrated that all groups with psychiatric disorders presented reduced scores on the Q-LES-Q when compared to control individuals, but that patients with major depression and double depression (as well as posttraumatic stress disorder) were the ones with the lower QOL scores. In addition, they observed that the depression scores were responsible for less than 10% of the variance on the Q-LES-Q 41 . In sum, current findings reinforce the impression that QOL is a measurement that is semi-independent from the perception of the patient regarding his/her disease, and that it is important for researchers and clinicians to use not only scales that take into account the severity of the depressive symptoms, but also non-medical aspects of the patient’s life (e.g., his/her subjective QOL). 13,15 QOL deficits in depressed patients versus patients with general medical conditions The long term effects of depressive disorders are as serious as those observed in many general medical conditions 13 . However, when one refers to the immediate impact, those effects are even more noteworthy. This was highlighted in the important Medical Outcomes Study (MOS) 42 , which caught the attention of researchers and clinicians at the end of the 1980s and led the way for many

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of the current studies on the relationship between QOL and depression. In the MOS, patients with depressive disorders were compared to individuals with diabetes mellitus, hypertension, coronary arterial disease, arthritis, lumbar problems, pulmonary and gastrointestinal diseases. The results of this study clearly demonstrated that depression is associated with higher physical and social deficits, a poorer quality of life, more absenteeism, less pain-free days, higher treatment costs and poorer perception of health status when compared to other chronic physical diseases 42,43 . During the last few years, dozens of studies have corroborated the pioneer findings of the MOS. Impact of antidepressants on the QOL of depressed subjects During a depressive episode, patients experience difficulties in accomplishing physical activities and find that their level of energy is reduced. The perception of their health status is also altered, as is their ability to relate socially, work effectively and conduct day-to-day activities adequately. Therefore, to globally assess the impact of any particular antidepressant treatment it is important to estimate the physical, social and psychological status of the patient 14 . Since this status is generally assessed by QOL instruments, we can infer that the impact of antidepressant treatment can be measured in part by the QOL scales – with the exception that the QOL encompasses other areas than only those of health. 13 As well, QOL instruments have been capable of differentiating depressed patients from control groups 44 . Various studies comparing respondent and non-respondent individuals to many antidepressants demonstrated a significant improvement in social functioning of those presenting a clinical response after the acute phase of treatment 13 . This finding confirms the impression that QOL questionnaires can detect the response to the treatment in depressive subjects 14 . Even though it is largely accepted in the literature that the improvement of depressive symptoms during treatment leads to an improvement in the QOL 11 , few clinical studies of antidepressants have specifically assessed the impact of the treatment on the QOL 45 . In fact, knowing the impact of antidepressants on the QOL is as important as knowing if those treatments are effective in the reduction of depressive symptoms. Moreover, the search for treatment is generally motivated by the subjective impact of a disease on the QOL of the patient, and his/her adherence to any type of treatment is strongly influenced by the subjective perception of improvement. Thus, in depression it is important to emphasize the patient’s point of view, and this is better assessed by QOL scales than by any objective assessment of the symptoms 15,16,46 . Even though the majority of studies indicate that an improvement in the depressive symptoms from treatment leads to a significant improvement in the QOL 13,14 , the correlation between the two measurements is only moderate, indicating that there is no total superposition between those two domains 47 . As well, improvement in the QOL can occur even after the recuperation of the depressive symptoms 29 .


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The QOL questionnaires have already shown sensitivity in detecting residual symptoms in patients that have responded partially to the treatment with antidepressants. In a study patients who had recently become depressed, De Lisio and collaborators 48 found important changes in the subjects’ work performance, as well as in the social and leisure activities. An assessment performed one year later demonstrated that deficits in leisure activities remained even in patients that presented remission of the central depression symptoms 48 . Studies like this support the clinical impression that the psychosocial functioning of the patients can take more time to return to normal than other depressive symptoms. Furthermore, a maintenance study of patients treated with sertraline showed that QOL continues to improve after the remission of symptoms, and that this did not occur with the patients that received a placebo after remitting from the acute clinical condition 49 . In another study 50 with depressed patients, it was demonstrated that even though fluoxetine and amitriptyline equally improved the core symptoms of depression, the former was superior in terms of benefits in social functioning and in the general perception of the individual in relation to health itself. Fluoxetine was also superior to clomipramine in those aspects. According to the authors of this study, the superiority of fluoxetine was probably related with the different profiles of drugs’ side effects and the consequent level of patients’ compliance 50 . Generally speaking, the studies that compared tricyclic antidepressants (TCAs) with selective serotonin reuptake inhibitors (SSRsI) tended to show better QOL for the patients treated with SSRIs, even when significant differences were not detected between the groups in relation to the improvement of depressive symptoms 11 . Comparisons among different SSRIs (e.g., sertraline, paroxetine and fluoxetine) did not show significant differences between them in relation to their effects on QOL 13 . Additionally, there is evidence that some instruments for assessing QOL could be capable of predicting response to the antidepressant treatment, at least to a certain extent. For example, Pyne and collaborators 51 showed that patients with more deficits in social activities presented a worse response to treatment, while patients with significant deficits in physical activities presented a better response. Another study has identified that the level of positive thoughts at the beginning of treatment was associated with higher levels of response after 8 weeks 47 . In short, instruments for the assessment of QOL seem to be sensitive to changes in the patient’s health status during treatment, have predictive value, and also offer information on the time for improvement of psychosocial functioning 14 . Thus, they represent an advance in the assessment of the efficacy of antidepressants, as they can lead to more focused interventions and provide more specific and sensitive measurements of the outcome of treatment. CONCLUSION The assessment of QOL in depression is a promising endeavour that will probably lead to a better understanding of depressed patients and to the development of more rational and individualized treatments.

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To the extent that the individual perceives him/herself, his/her environment and his/her future in a negative and distorted way during the depressive episode, it is expected that his/her QOL will be negatively affected. However, there is evidence that depression and QOL are constructs with areas of intersection, but are not necessarily redundant. Unfortunately, there is a lack of definitive theoretical models in the literature satisfactorily establishing the relationship between those two constructs. Thus, the development and validation of current and new models is fundamental for a better understanding of the existing relationship between depression and QOL. REFERENCES 1. Bland, R.C. Epidemiology of affective disorders: a review. Can J Psychiatry 42, 367–77 (1997). 2. Parikh, S.V. & Lam, R.W. Clinical guidelines for the treatment of depressive disorders, I. Definitions, prevalence, and health burden. Can J Psychiatry 46 Suppl 1, 13S–20S (2001). 3. Doris, A., Ebmeier, K. & Shajahan, P. Depressive illness. Lancet 354, 1369–75 (1999). 4. Andrews, G., Sanderson, K., Slade, T. & Issakidis, C. Why does the burden of disease persist? Relating the burden of anxiety and depression to effectiveness of treatment. Bull World Health Organ 78, 446–54 (2000). 5. Hall, R.C. & Wise, M.G. The clinical and financial burden of mood disorders. Cost and outcome. Psychosomatics 36, S11–8 (1995). 6. Sartorius, N. The economic and social burden of depression. J Clin Psychiatry 62 Suppl 15, 8–11 (2001). 7. Murray, C.J. & Lopez, A.D. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 349, 1436–42 (1997). 8. Ballenger, J.C. et al. Consensus statement on the primary care management of depression from the International Consensus Group on Depression and Anxiety. J Clin Psychiatry 60 Suppl 7, 54–61 (1999). 9. Greden, J.F. The burden of recurrent depression: causes, consequences, and future prospects. J Clin Psychiatry 62 Suppl 22, 5–9 (2001). 10. Angst, J., Angst, F. & Stassen, H.H. Suicide risk in patients with major depressive disorder. J Clin Psychiatry 60 Suppl 2, 57–62; discussion 75–6, 113–6 (1999). 11. Demyttenaere, K., De Fruyt, J. & Huygens, R. Measuring quality of life in depression. Current Opinion in Psychiatry 15, 89–92 (2002). 12. Berlim, M.T., Mattevi, B.S. & Fleck, M.P. Depression and quality of life among depressed Brazilian outpatients. Psychiatr Serv 54, 254 (2003). 13. Papakostas, G.I. et al. Quality of life assessments in major depressive disorder: a review of the literature. Gen Hosp Psychiatry 26, 13–7 (2004). 14. Kennedy, S.H., Eisfeld, B.S. & Cooke, R.G. Quality of life: an important dimension in assessing the treatment of depression? J Psychiatry Neurosci 26 Suppl, S23–8 (2001). 15. Berlim, M.T. & Fleck, M.P. "Quality of life": a brand new concept for research and practice in psychiatry. Rev Bras Psiquiatr 25, 249–52 (2003). 16. Orley, J., Saxena, S. & Herrman, H. Quality of life and mental illness. Reflections from the perspective of the WHOQOL. Br J Psychiatry 172, 291–3 (1998). 17. Fleck, M.P.A. Avaliação de qualidade de vida. in Depressões em Medicina Interna e em Outras Condições Médicas (eds. Fráguas, R. & Figueiró, J.A.B.) 235–257 (Editora Atheneu, São Paulo, 2001). 18. Beck, A.T., Rush, A.J., Shaw, B.F. & Emery, G. Cognitive therapy of depression: A treatment manual, (Guilford Press, New York, 1979). 19. Development of the World Health Organization WHOQOL-BREF quality of life assessment. The WHOQOL Group. Psychol Med 28, 551–8 (1998).


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