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DEPRESSION

AND

ANXIETY 23:312–324 (2006)

Theoretical Review A BIOPSYCHOSOCIAL MODEL AS A GUIDE FOR PSYCHOEDUCATION AND TREATMENT OF DEPRESSION Chris K.W. Schotte, Ph.D.,1,2 Bart Van Den Bossche, M.D.,3 Dirk De Doncker, M.A.,1 Stephan Claes, M.D.,4 and Paul Cosyns, M.D.1

Effective treatment of severe or chronic unipolar depression requires the combination of pharmacological and psychotherapeutic interventions, and demands a theoretical paradigm integrating biological and psychosocial aspects of depression. Supported by recent research, we propose in our article a biopsychosocial diathesis–stress model of depression. Its basic aim is psychoeducational: to provide therapists, patients, and their environment a constructive conceptual framework to understand depressive complaints, vulnerability, and stress. The core of the model consists of the concept of psychobiological vulnerability, which is determined by risk factors—of a biogenetic, psychological, somatic, and societal nature—and by protective factors. Life events with an idiosyncratic, stress-inducing value interact with this vulnerability, triggering severe or chronic distress that affects the individual’s resilience and leads to symptoms of depression. The pathogenesis of depression is symbolized by a negative downward loop, in which interactions among symptoms, vulnerability, and stressors drive the patient toward a depressive condition. Moreover, experiencing recurrent depression influences psychobiological vulnerability, the occurrence of stressors, and tremendously increases the risk of further relapse. The model stresses the self-evident integration of biological and psychological therapeutic interventions that need to focus on symptom reduction and on relapse prevention. Moreover, it offers the patient and therapist a psychoeducational context in which the individual’s vulnerability and depressive symptoms can be treated. Finally, applications of the depression model as a therapeutic approach to severe depression in the phases of remoralization, symptom reduction, and relapse prevention are presented. Depression and Anxiety 23:312–324, 2006. & 2006 Wiley-Liss, Inc. Key words: major depression; cognitive-behavioral therapy; biopsychosocial approach; stress; treatment; psychoeducation

1 UZA, University Hospital Antwerp, Department of Psychiatry, Edegem, Belgium, and CAPRI, Collaborative Antwerp Psychiatric Research Institute, Faculty of Medicine, University of Antwerp, Campus Drie Eiken, Wilrijk, Belgium 2 VUB, Free University Brussels, Faculty of Psychology, Brussels, Belgium 3 GGZ WNB, Mental Health Care West North Brabant, Halsteren, The Netherlands 4 University Hospital Leuven, Department of Psychiatry, Leuven, Belgium

Correspondence to: C. Schotte, Department of Psychiatry, University Hospital Antwerp (UZA), Wilrijkstraat 10, B-2650 Edegem, Belgium. E-mail: [email protected]

r 2006 Wiley-Liss, Inc.

INTRODUCTION

Numerous epidemiological findings suggest that the era we live in can be described as the ‘‘age of melancholy.’’ Indeed, roughly 1 in 5 women and 1 in 10 men will experience a clinically significant depressive episode during their lifetime. The large-scale

Received for publication 24 June 2005; Revised 5 October 2005; Accepted 9 December 2005 DOI 10.1002/da.20177 Published online 10 May 2006 in Wiley InterScience (www. interscience.wiley.com).

Theoretical Review: Depression Model

epidemiological Depression Research in European Society (DEPRES) study [Tylee, 2000] in which over 78,000 adults from six different European countries were interviewed, revealed a 17% 6-month prevalence of depression. Moreover, the incidence of depression is steadily increasing, and episodes start at an ever-earlier age [Fombonne, 1994]. Depressive disorders have a severe social and economic impact [Sartorius, 2001; ¨ stu¨n et al. [2004] found depression Simon, 2003]. U to be the fourth leading cause of disease burden: It provokes the largest amount of nonfatal burden, accounting for almost 12% of all total years living with disability worldwide. The tendency toward underdiagnosis and undertreatment, the strong association with somatic problems, the high rate of relapse [e.g., Duggan, 1997], and the high prevalence of suicide, which is estimated at 15% [American Psychiatric Association, 1994; Lo¨nnqvist, 2000], further stress the fact that the depressive disorders are some of the most severe mental health problems. With respect to the treatment of depression, the options are multiplying, increasing not only in quantity but also in sophistication. Generally speaking, and most certainly with respect to the severe and chronic forms of depression, increasing numbers of psychiatrists and psychologists are in favor of combined treatments, in which concurrent, sequential, or crossover combinations of pharmacological and psychotherapeutic approaches are used [e.g., Arean and Cook, 2002; Kornbluh et al., 2001; Lenze et al., 2002; Nierenberg, 2001; Segal et al., 2002; Thase et al., 1997]. However, combined treatments demand a biopsychosocial [Engel, 1977, 1980] depression model that integrates biological and psychosocial aspects. The integration of theories of depression, such as the cognitive and biological, is an important direction for theory and research [Abramson et al., 2002]. Moreover, treatments are most effective when therapists, patients, and families have a shared, constructive view of the pathology and a rationale for the treatment [Margison et al., 2000]. Starting from this psychoeducational viewpoint, we propose in this article an integrative model of unipolar depression.

THEORETICAL MODELS OF UNIPOLAR DEPRESSION To avoid misunderstanding, it is useful to define the term ‘‘depression.’’ As a normal expression of mood, depression refers to a combination of ‘‘misery and lethargy’’ [Wilner, 1985]: It is an emotion with functional and adaptive aspects [Nesse, 2000]. Depression can also be considered as a syndrome, referring to a constellation of depressive symptoms, and as a nosological category, such as that described in DSMIV classification of the affective disorders [American Psychiatric Association, 1994]. In this article, the term ‘‘depression’’ refers to the severe, often chronic, and

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highly dysfunctional unipolar major depressive disorders: Because we concentrate on these severe forms of depression, the ‘‘sickness’’ aspect is emphasized in our model. First, we briefly review the various theoretical schools that influenced our view on depression. Descriptive diagnostic models concern themselves with recording, describing, measuring, and classifying depressive phenomena. In the Department of Psychiatry of the University of Antwerp, dimensional depression assessment tools such as the Beck Depression Inventory and Hamilton Depression Rating Scale [Schotte et al., 1997b] and the Zung Self-Rating Depression Scale [Schotte et al., 1996] were examined for their psychometric qualities. Research on the categorical DSM-IV classification of affective disorders supported the validity of the melancholic/vital depression and proposed the ‘‘integrated threshold model,’’ which integrates the quantitative and qualitative views of the taxonomy of depressive disorders (Schotte et al., 1997b; Schotte and Maes, 2001). An adequate description and classification of depression is a necessary precondition for diagnosis, treatment, and research: It is crucial to determine the form and the severity of the depressive disorder and to assess suicidal behavior. However, this is only a point of departure: A second, essential step involves the consideration of theoretical models that take etiological and pathogenic mechanisms into account and that are therapy-oriented. Modern models are based on the biological, cognitive, interpersonal, and life-events research [e.g., Gotlib and Hammen, 2002]. All these models belong to the class of diathesis–stress models [Akiskal, 1995], which are based on the hypothesis that certain genetic dispositions or other characteristics, such as a particular cognitive style, a biological dysfunction, or a social skills problem, make people vulnerable to depression when they are confronted with specific life events or forms of stress. Biological models view depression as a consequence of genetic vulnerability or of biological disturbances of the biochemical, neuroendocrine, immune, or chronobiological systems. One of the most influential models starts from the phenomenological similarities between depressive symptomatology and a hyperarousal of the stress response, and assumes that depressive disorders imply dysregulations of the stress system such as hypothalamic–pituitary–adrenal (HPA) axis hyperactivity and alterations in the autonomous nervous system [for reviews, see Gold and Chrousos, 2002; Holsboer, 2000]. In melancholic depression, for example, one observes a hyperactive stress response, anxiety, fear of the future, reduction in responsiveness to the environment, insomnia, loss of appetite, and diurnal mood variation. These symptoms are associated with an activated corticotropin-releasing hormone (CRH) system and a reduced level of activity of the growth hormone and reproductive systems [Gold and Chrousos, 2002]. Another burgeoning line of research, the affective neurosciences, try to gain Depression and Anxiety DOI 10.1002/da

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understanding of the structures in the brain, the mechanisms and cognitive functions involved in the regulation and dysregulation of mood and emotion, by using functional brain imaging techniques and experimental psychological procedures. Recent findings indicate that depression is associated with abnormalities in the structure and functions of the prefrontal cortex, the hippocampus, the anterior cingulate, and the amygdala [e.g., Davidson et al., 2002; Pine, 2002; Pizzagalli et al., 2002]. Cognitive-behavioral models [Beck et al., 1979] emphasize the relationship between depression and automatic, negative thinking processes and dysfunctional patterns of information processing, and state that dysfunctional schemas, which are memory representations regarding the self and its relationships with others, increase one’s vulnerability to depression. Interpersonal models [Coyne, 1976; Joiner, 2002; Klerman et al., 1984; Markowitz, 1999] relate several levels of social functioning to depression: (1) vulnerability as a result of interpersonal factors, (2) social skills and behavior of patients with depression, and (3) the effect of depression on social interactions and relations. Research into the association between depression and stressful or adverse life events corroborates the idea that serious losses, threatening occurrences, or difficulties in life play a major etiological role, particularly in initial depressive episodes [e.g., Brown, 1993; Brown and Harris, 1978; Brown et al., 1994; Jenaway and Paykel, 1997]. The individual, idiosyncratic attribution of meaning regarding the degree of stress or emotional disturbance elicited by an event does matter greatly: The perceived effect on self-esteem and self-effectiveness is an important intermediary factor for determining the stressfulness of the event. Apart from the influence of acute life events, other research reveals relations between chronic stress and depression [e.g., Ingram et al., 1998; Turner and Lloyd, 1995]. Another particularly relevant line of life events research looks at the effect of trauma early in life on biological [e.g., Ladd et al., 2000; Van Voorhees and Scarpa, 2004] and psychological [e.g., Young et al., 2003] vulnerability. Finally, epidemiological studies of depression indicate the rising incidence of depression in everyounger cohorts: This finding may be indicative of the importance of stress factors, situated in a societal context. Despite their essential contributions, each of these depression theories as such is too fragmentary and reductionistic. Seen in etiological terms, depressive disorders are an extremely heterogeneous group and form the final stage of a wide variety of causal pathways. The models sketched here often give too simple explanations for the complex pathogenetic processes in the heterogeneous diagnostic depression groups and take too little account of developmental aspects and the reciprocal effects of biological processes and interactions between persons, environments, and symptoms. Clinicians, who combine biological and psychological therapeutic interventions, need a more eclectic vision that integrates biological and individual Depression and Anxiety DOI 10.1002/da

psychological factors, as well as social, environmental, and stress factors into a biopsychosocial [Engel, 1977, 1980] depression paradigm.

VULNERABILITY THE PSYCHOBIOLOGICAL SUBSTRATE The notion of vulnerability is considered from the psychological (mind) and the biological (brain and body) view: Both systems are essentially and irreversibly linked. The psychological aspect is the substrate of the biological aspect and vice versa. Just a few of the numerous research findings that support this view are mentioned below [for a review, see Gabbard, 2000]. The research group headed by Kendler in Virginia has provided striking examples of how genes, biology, psychology, and stressors need to work in ‘‘harmony’’ to provoke a depressive episode. This research group monitored a sample of more than 2,000 female twins for a period of 17 months on average [Kendler et al., 1995]. Recent severely stressful life events appeared to be the most powerful risk factor for an episode of major depression; genetic factors played a substantial, albeit not dominant, role. The twins with the lowest genetic risk factors had 0.5% probability of depression onset if they were not exposed to a serious life event. If a severe stressor occurred, this probability rose to 6.2%. The group of twins with the highest genetic risk had a 1.1% chance of developing a depressive episode in the absence of a stressor, but this risk soared to 14.6% with the occurrence of a serious life event. Thus, genetic factors affect the sensitivity or vulnerability of persons to the depression-inducing effects of stressful life events. In a further study of this survey of twins [Kendler et al., 2002] 18 risk factors associated with five phases in life—childhood, early and late adolescence, adulthood, and the previous year—were used to develop a model for predicting depressive episodes. For example, risk factors associated with childhood include genetic risks, a disturbed family environment, sexual abuse, and loss of a parent. The Kendler model states that the risk for a depressive disorder in women is the result of three broad, interacting pathways that reflect internalizing symptoms (neuroticism and earlyonset anxiety disorders), externalizing systems (conduct disorders and substance misuse), and psychosocial misfortune in the various phases of life. Genetic risk factors for major depression appear to contribute to the three paths. These findings illustrate the complex interweaving and interactions of psychosocial and genetic vulnerability factors. Psychotherapists have for a long time been aware that severe traumatic experiences (e.g., abuse, neglect, and maltreatment) in (early) childhood can have disastrous effects on most aspects of adult functioning and increase vulnerability to depression [e.g., Browne and Finkelhor, 1986; Toth et al., 1992]. An important recent line of research shows that such psychologically


traumatic experiences also lead to significant and often permanent dysregulations of many aspects of biological functioning: HPA axis, stress parameters, heart rate, neurotransmitters, and hormonal and immunological parameters [e.g., Heim et al., 2001; Ladd et al., 2000; Van Voorhees and Scarpa, 2004]. Severe early traumas are likewise associated with neurotoxicity and may, for example, lead to atrophy in the hippocampus [Andersen and Teicher, 2004; Teicher et al., 2002; Vythilingam et al., 2002]. Moreover, brain imaging studies have consistently described hippocampal atrophy in mood disorders [e.g., Sheline et al., 1999]. The discovery of neurogenesis—the adult mammalian brain creating new neurons from pools of stemlike cells—meant a breakthrough in neuroscience. Although a role for neurogenesis in mood disorders is speculative, it has been suggested that a fall in neurogenesis in the dentate gyrus of the hippocampal formation contributes, together with atrophy and death of hippocampal neurons, to hippocampal attrition. This neurotoxicity can be the target of novel ‘‘plasticity enhancing’’ strategies [Abrous et al., 2005; Glitz et al., 2002; Gold and Chrousos, 2002; Manji et al., 2003]. In severe, treatment-resistant depression, the application of chronic deep brain stimulation might reverse symptoms in otherwise untreatable conditions [Mayberg et al., 2005]. Antidepressants and mood stabilizers such as lithium and valproate [Gray et al., 2003], and electroconvulsive therapy (ECT) may exert some of their therapeutic effects on mood disorders by stimulating neurogenesis [Abrous et al., 2005]. Finally, a further striking illustration of how closely psychology and biology are linked is the finding that effective cognitive-behavioral, interpersonal, and psychodynamic psychotherapeutic interventions influence various aspects and parameters of biological functioning [e.g., Brody et al., 2001; Gabbard, 2000; Thase, 2001]. In summary, it may therefore be said that numerous research paradigms emphasize the interrelatedness of the psychological and the biological: These aspects are like the two sides of a coin. The psychological is the substrate of the biological and vice versa: One’s emotional life, one’s self-image, and one’s being are all governed by biological processes, but biological functioning is equally influenced by what one experiences or has experienced, by how one feels, and by what one believes he or she is. Consequently, we consider the concept of vulnerability as a psychobiological substrate that determines the vulnerability to depression.

RISK FACTORS AND PROTECTIVE FACTORS Figure 1 gives an overview of the risk factors of a biogenetic, psychological, somatic, and social/societal nature, and of the protective factors that influence the vulnerability for depression.

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Figure 1. The psychobiological vulnerability for depression: risk and protective factors.

Biogenetic risk factors. When researchers consider biological vulnerability, they often refer to genetic factors. Traditional methods for the assessment of genetic factors, such as twin, adoption, and family studies, have demonstrated the influence of genetic vulnerability factors in the etiology of depressive disorders [Hamet and Tremblay, 2005; Souery et al., 1997; Tsuang and Faraone, 1990]. Although, as of this date, molecular biological research has not turned up any genetic factor that can be linked with certainty to a predisposition to mood disorders, it may nonetheless be assumed that biological dysregulations associated with depression are influenced by genetic variations. Researchers who consider dysfunctions in neurohormonal stress regulation have observed that first-degree family members—even though they have never been depressed—of persons with depression display a defect in this regulation that is stable in time [Modell et al., 1998]. Caspi et al. [2003] found that a functional polymorphism in the promoter region of the serotonin transporter gene moderates the influence of stressful life events on depression. In the same vein, it is supposed that temperament characteristics such as ‘‘harm avoidance’’ and ‘‘reward dependence’’ are associated with specific biological functions and increase vulnerability to depression [Cloninger et al., 1993]: There is evidence that these temperamental dispositions are influenced by genetic factors [Heath et al., 1994]. Psychological risk factors. Psychological risk factors for depression are considered in the cognitivebehavioral approach to therapy [Beck et al., 1979; Gloaguen et al., 1998; Young et al., 2003], which postulates that cognitive phenomena such as schemas and automatic thoughts mediate depressive emotions and behaviors. Schemas reflect the individual’s fundamental views and are organized representations of earlier experiences in life that govern information Depression and Anxiety DOI 10.1002/da

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processing at the present time. Dysfunctional schemas are immature, absolutistic, and display major themes such as helplessness and being unloved [Beck, 1995]. Stressful life events can activate these dysfunctional schemas, facilitate cognitive distortions, and result in automatic thoughts (i.e., the virtually reflexive patterns of thought and internal discourse that mediate between situation and emotions, behavior, and physiological reactions). The content of depressive automatic thoughts reflects the negative cognitive triad about the self, the world, and the future [Beck et al., 1979]. Basic elements of the therapy are the identification and modification of the automatic thoughts and schemas. This Beckian cognitive-behavioral therapy is especially effective in mild and moderately severe forms of depression [Gloaguen et al., 1998]. In the case of comorbidity with personality disorders, one can consider schema therapy as an entry [Young et al., 2003]. Young’s model particularly emphasizes psychological vulnerability; in the current integrative model, chronic or severely stressful experiences in early life are just as likely to cause hypersensitivity or damage to numerous biological systems, thus increasing overall psychobiological vulnerability to psychopathology [e.g., Ladd et al., 2000; Van Voorhees and Scarpa, 2004]. Moreover, it should be emphasized that dysfunctional schemas and coping styles are self-perpetuating and elaborated throughout one’s lifetime, and consequently generate chronic stress and problems that are a constant burden on the psychobiological substrate. It is a well-known fact that the occurrence of depression in the family likewise increases psychobiological vulnerability to depression. Apart from the genetic aspects, there are risk factors that can be described as ‘‘intergenerational.’’ For example, a number of authors [e.g., Newport et al., 2002] found that depression in pregnant women has a biochemical effect on the developing fetus. Moreover, witnessing the depression of one of the parents can constitute a learning experience or life example that increases one’s psychobiological vulnerability to depression in later life [e.g., Essex et al., 2002]. Research on the psychological risk factors for depression from an interpersonal context distinguishes three nonexclusive domains of vulnerability. Impaired social skills, excessive interpersonal dependency, and excessive interpersonal inhibition may render people vulnerable to future onset of depression [Joiner, 2002]. Somatic risk factors. Depression is especially common in the medically ill: Research reveals comorbidity with numerous somatic disorders, such as— among many others—pain, thyroid disease, immunity problems, cancer, viral infections, cardiovascular disorders, and skin diseases [for a review, see Robertson and Katona, 1997]. These physical illnesses give rise to a heightened psychobiological vulnerability to depression; particularly in elderly people, the likelihood of depression increases in persons who have physical disease. The reverse phenomenon is also true: RegardDepression and Anxiety DOI 10.1002/da

less of age, and when suicide is discounted, depression leads to greater morbidity and mortality in a number of somatic clinical disorders. For example, the presence of depressive characteristics promotes susceptibility to heart disease [Gold and Chrousos, 2002], heightens mortality in cardiovascular diseases [Denollet et al., 2000], and increases the risk of breast cancer in women [Gallo et al., 2000]. Vulnerability to depression is also associated with the abuse of, intoxication with, or withdrawal from substances such as alcohol, amphetamines, and sedatives [e.g., American Psychiatric Association, 1994]. Sociocultural risk factors. The last group of risk factors lies in the realm of the societal and the sociocultural. Our basic proposition is that the changes and instability of many societal aspects of economically advanced countries have an impact on the vulnerability of the individual [e.g., Fullilove, 2002; Millon and Davis, 2000; Paris, 1996]. Some relevant observations include the following: Myers [2000] describes the ‘‘American paradox,’’ which can be extended to all economically advanced countries: On the one hand, one observes an ‘‘economic expansion,’’ a prodigious increase in the wealth produced; on the other hand, there is an increase in numerous indicators of ‘‘social recession,’’ such as a strong erosion of the social link and increasing divorce, suicide, violence, and depression rates. Americans are less happy today than they were 40 years ago, despite the fact that they make 2.5 times as much money. Millon and Davis [2000] describe how traditional social structures, the nuclear familial and extrafamilial structures are being broken down, and how there is less intergenerational continuity, with less importance attached to family values. In fact, these observations recapture the ideas of E´mile Durkheim on the growing social disintegration and anomie in modern society at the beginning of the previous century. Social networks are important and protect the individual: Social disintegration and weak social networks result in all kinds of problems, such as substance abuse, violence, neglect, suicide, and psychopathology. For many people in Western societies, global social structures are becoming uncertain and unclear, even though it is important for people to be aware of their roots, to have a place in social networks. A good example of this longing is the immense success of new social networks, such as the mobile phone, short message service (SMS), Internet chatting, and similar information technology novelties. By participating in an electronic network, one has a feeling of belonging to and being part of a larger but in many aspects artificial social network. More generally, there seems to be a significant ideological vacuum in the Western World now that communism has collapsed and society is becoming increasingly secular. Since the victory of the free market economy and ‘‘globalization,’’ ethical and social values are subordinate to profit and profit taking. Considering this, Hunout et al. [2003] argue that the mainstream individualistic, hedonistic, and consumer-


ist system of values erodes contemporary society in economically advanced countries. In short, our social and ideological world is changing immensely and quickly. People experience their living environment as unstable, unpredictable, unclear, and unsafe. The (post)modern man or woman has trouble finding his or her own place, identity, and role: This uncertainty is stressful and undermines the quality of life. Also worth mentioning is the link between poverty and a heightened vulnerability to depression [e.g., Brown, 1997; Yen and Kaplan, 1999]. Finally, we may wonder whether the high prevalence of depressive complaints and fatigue should be linked to environmental factors such as exposure to contamination or harmful agents in water, air, soil, crops or foods, or changes in our daily diet [e.g., Sparks et al., 1991; Vozoris and Tarasuk, 2003]. Gender as a risk factor for psychobiological vulnerability. It is a fairly consistent epidemiological finding that the prevalence of depressive disorders in women is roughly twice as high as that in men [Kessler, 2000; Piccinelli and Wilkinson, 2000; Smith and Weissman, 1991]. This observation can be explained in terms of greater psychobiological vulnerability, with female gender as a factor in all four risk groups (see Fig. 1) and in terms of women’s higher frequency and severity of stressful life events. Sociocultural ideas about female and male identity have such an impact on the development of self-image that women display more internalizing disorders, such as depression and anxiety, and men display more externalizing problems, such as antisocial behavior and substance abuse [e.g., Rosenfield, 2000]. Women identify more closely with the feelings of others, are more interpersonally dependent, and have a greater need for emotional support. Compared to men, women experience the well-being of their family members as a major source of concern; stressful life events experienced by significant others are associated with more distress in women than in men [Rosenfield, 2000]. The latter observations may explain to a certain extent the interesting finding [Thase et al., 2000] that women with severe depression respond better to interpersonal therapy than to cognitive-behavioral therapy. At any rate, one assumes that women in general do have a role that entails more stress, with more limited personal autonomy and access to resources, and greater uncertainty [e.g., Cotton, 1990; Fullilove, 2002]. For example, working mothers are exposed to overload and often conflicting demands between work and family roles. Thus, the idea here is that the responsibilities and obligations associated with the female role make women more vulnerable and at higher risk for depression when confronted with events that foil the fulfillment of their duties. In more somatic terms, there are numerous psychological and somatic problems related to the female reproductive cycle [e.g., Parry, 2000], and sex hormones most certainly play a role in creating vulnerability for depression [Kessler, 2000].

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In short, not only do women have a greater psychobiological vulnerability to depression but they are also exposed to more stressful, traumatizing life events and circumstances that heightens the risk of depressive disorders. Protective factors. Protective qualities, such as material prosperity, adopting a less hectic or stressful life, being in good health, being raised in a warm and loving home, and having loved ones, a functioning and supportive social network, social solidarity, well-developed social skills, and meaningful activities, can buffer or diminish the vulnerability to depression. A short list of the relatively sparse research findings about potential protective factors includes physical activity and sports [Fox, 1999; Gore et al., 2001]; a long-term intimate or marriage-like relationship [Heath et al., 1998]; religiosity [Miller et al., 1999]; well-developed problemsolving skills for adolescents and young adults, and social connectedness among young men [Donald and Dower, 2002]; being married [for men; Kessler, 2000]; a healthy and regular diet, with regular breakfasts and slow weight reduction [for overweight women; Lombard, 2000] or dietary supplements when being treated for depression [Peet and Horrobin, 2002]. Worth mentioning here is the research conducted by the group associated with Brown [Harris et al., 1999] on factors that promote recovery from chronic depression. Befriending a female volunteer and ‘‘fresh start’’ experiences—occurrences that bring hope and change to a situation of deprivation—combined with the absence of new, severe stressors and markedly poor coping strategies appear to have a positive effect on chronic depression in women with a standard attachment style. In particular, the ‘‘fresh start’’ experience appears to be a basic predictor for recovery from depression.

DISTRESS AS A CONSEQUENCE OF INTERACTIONS BETWEEN STRESSORS AND VULNERABILITY The pathogenesis of depression stems from dynamic interactions between psychobiological vulnerability and stressors or life events. Between 66% and 90% of depressive episodes in adults are preceded by one or more life events that have a long-term, threatening impact, if they are to provoke a depression [Brown and Harris, 1978]. As already mentioned, the depressogenic quality of the life events is highly dependent on the individual’s idiosyncratic interpretation of the events [Brown, 1997]. The distress caused by a life event is largely determined by personal and contextual factors; the degree of intrinsic stressfulness is perhaps less important. It is therefore an oversimplification to speak of positive and negative life events: The clinician needs to assess the life events within the heuristic framework Depression and Anxiety DOI 10.1002/da

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of the patient’s individual context and cognitive schemas [Young et al., 2003], and to interpret them in terms of congruence with psychobiological vulnerability [or verstehen; Brown, 1997]. A life event such as a divorce, a loss, or a promotion may affect one person very deeply, causing serious distress or even a breakdown, whereas another person may be hardly affected at all and may be even buoyed up by the event. Attribution models [e.g., Abramson et al., 2002] have shown that the likelihood of a depressive reaction increases when the individual feels unable to control the situation or when his or her objectives and goals seem unattainable [Nesse, 2000]. Characteristic is a developing sense of hopelessness, of being trapped in a desperate situation that the individual nonetheless continues to resist and refuses to accept, resulting in a subversion of the individual’s strength, causing a low mood state. This state of being imprisoned, this ‘‘entrapment’’ [Brown et al., 1995; Gilbert and Allan, 1998] and hopeless struggle are essential to the pathogenesis of many depressive episodes and states of exhaustion: Entrapment and humiliation appear to be crucial elements for determining to what extent a life event will have a depressive impact [Brown, 1998; Brown et al., 1995]. Apart from acute life events, persons suffering from depression are often found to be exposed to chronic stress factors [Ingram et al., 1998; Turner and Lloyd, 1995], in which the pressure of the stressors slowly undermines the subject’s psychobiological resistance and abilities to recover.

DEPRESSION: DEVELOPMENT OF A NEGATIVE SPIRAL Severe, threatening life events initiate a stress reaction or a low-mood emotional state. This can be regarded as an adaptive process [e.g., Nesse, 2000]: In much the same way that the sensation of pain is unpleasant and makes clear that action is needed to stop it, the depressive mood is a signal that action is necessary. However, if the state of distress persists too long, it leads to a dysregulation of the stress feedback system, which results in the individual getting psychobiologically ‘‘stuck’’ in a permanent condition of hyperarousal. This hyperarousal entails major changes to the functioning of the central nervous system and the remainder of the body as well [e.g., Holsboer, 2000]. Neuroimaging studies reveal that prolonged or chronic conditions of stress and hyperarousal can result in neurotoxicity: Changes in the central nervous system, for example, entail the suppression of the flexible cognitive reaction patterns of the prefrontal cortex by the fixed reaction patterns of the amygdala governing behavior [Gold and Chrousos, 2002]. It is characteristic of this maladaptive condition that the ‘‘normal,’’ flexible coping mechanisms for reducing stress are no longer effective. Depression and Anxiety DOI 10.1002/da

In clinical practice, reconstructions of the depressogenic process reveal that the emotional distress sets off a ‘‘negative spiral,’’ a process in which interactions among cognitive factors, biological processes, depressive symptoms, and interpersonal factors reinforce one another and push the individual further into depression. At the behavioral level, one observes highly inadequate stress management: Even though the patient feels bad, severely stressed, and exhausted, he or she will persist in trying to fight the depression and keep control over the situation. Patients often neglect themselves, deny themselves the rest and relaxation they absolutely need, and get stuck in a depressive state characterized by the peculiar combination of cognitive hyperactivity—endless, anxious ruminations—and physical exhaustion. Several factors influence the derailment of distress or low mood into depression: the degree of psychobiological vulnerability, the severity of the life events, the coping skills of the individual, the number of previous depressive episodes [Duggan, 1997], the extent to which the subject feels that he or she is entrapped in a hopeless situation [Brown et al., 1995], and the degree of potential support from the social network. From a life-span viewpoint, one can identify moments of difficult transition between phases in life, such as adolescence and young, midlife, and late-life adulthood. Each of these life stages has its specific developmental tasks and social, psychological, and biological issues. For instance, by midlife, individuals are expected to have established a family, to have found a clear career direction in which they will peak, and to have have taken on responsibility with respect to their children, their own aging parents, and sometimes their community. Researchers have explored issues such as ‘‘midlife crisis,’’ menopause, ‘‘empty nest,’’ caring for both parents and children, and the transition to retirement and leisure [e.g., Staudinger and Bluck, 2001]. Quite often there is an unfortunate convergence of circumstances: too much stress in several areas of life at the wrong moment. Personality factors such as dependency, perfectionism, and the flexibility to adjust aims and values also constitute well-known key mediating factors [e.g., Enns et al., 2002]. Finally, the duration of the depression episode is quite important [e.g., Keller et al., 1992]: The longer a person is afflicted with severe distress, the greater will be the burden on the psychobiological substrate and the greater the likelihood of a psychological and physical attrition resulting in a depressive picture that will be more difficult to treat. Figure 2 summarizes the broad lines of the depression model.

RECURRENT DEPRESSION The diathesis–stress model works satisfactorily and stands up well as a frame of reference for patients with first episodes of depression. Indeed, etiologically


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fact, one can assume a relationship between the number of depressive episodes, an increased vulnerability and a rise in chronic, disease-related psychosocial stressors, causing episodes to arise quickly and apparently independently of life events.

SOME PRACTICAL IMPLICATIONS OF THE DEPRESSION MODEL

Figure 2. The diathesis–stress model for depression. The dotted line highlights feedback effects in recurrent depression.

relevant, stressful life events are almost always observed when first episodes of severe depression arise [Brown, 1993; Brown et al., 1994; Jenaway and Paykel, 1997]. However, in chronic and recurring depression, episodes often seem to arise even though no significant life events are manifest. The explanation for this ‘‘endogenous’’ quality lies in the fact that the greater the number of depressive episodes already experienced, the likelier it is that new episodes will arise independently of external stress factors [e.g., Kendler et al., 2000] and the higher the risk for new depressive episodes [e.g., Rakel, 1999; Solomon et al., 2000]. Additionally, partial remission and residual symptoms after a depressive episode seem to be strongly associated with relapses [e.g., Pintor et al., 2003]. Using the model, we propose various complementary etiological mechanisms, indicated by the feedback effects (dotted lines) in Figure 2. Repeated depressive episodes are a burden for the psychobiological substrate and increase the vulnerability to depression. It might be that the substrate becomes so excessively sensitive or vulnerable [e.g., Post, 1992] that stressors that originally would have had a rather low depression-inducing power can generate a depressive episode. Supporting this assumption is the previously mentioned evidence from neuroimaging and postmortem studies that severe mood disorders are associated with neuronal atrophy and with impairments of structural plasticity and cellular resilience that enhance biological vulnerability [e.g., Shelines et al., 1999]. The experience of repeated depressive episodes is itself a very significant psychosocial stress factor: It goes without saying that chronic psychiatric problems are intrinsically severely stressful in individual, relational, social, professional, and financial terms. In

The model is a biopsychosocial–theoretical frame of reference offering an explanatory rationale for depression acquisition and maintenance, and providing a theory-driven basis for diagnostic assessment and treatment planning. Concerning psychodiagnostic assessment, we advocate a two-tier strategy [e.g., Van Praag, 1990; Schotte, 2002]: The first tier comprises a dimensional or categorical descriptive diagnosis of the depressive phenomena, whereas the second tier is linked to a biopsychosocial theory and is therapyoriented. The model can be used as a guide, as a blueprint for the second-tier diagnostic assessment, in which the vulnerability, risk, and protective factors and interactions with life events are the elements of an individual case formulation. To conclude we mention some of our reflections on the impact of the model on the therapeutic approach to severe depressive disorders. The implementation of the model has an impact on how we shaped the inpatient treatment context at the University Hospital Antwerp for patients with severe depression [Schacht, 2004; Schotte et al., 2003]. An individually oriented approach with combined biological and psychological interventions is sought. Essentially, the treatment process is organized in three consecutive phases: remoralization, remediation or symptom reduction, and rehabiliation and relapse prevention [Howard and Marinovitch, 1996]. Special attention is given to the consideration of suicidal ideation in all phases of treatment: Suicidal tendencies are assessed regularly, need to be discussable, and for each patient, specific agreements and actions are negotiated in the event of the patient being overwhelmed by the suicidal thoughts. In the remoralization phase the aims are to generate hope and to educate the patient and his or her family using the reference frame of the model. Specific therapeutic communication techniques have been developed to break through the demoralization of depression [Schacht, 2004]: Therapists emphasize the possibilities for remission and recognize that depression is a severe but curable disease with very high levels of suffering and burden caused by the psychobiological consequences of stress and hyperarousal. The essence of the model is nondiscriminatory and constructive toward patients: One of the central assumptions is well reflected by the adage ‘‘all men (women) are equal.’’ Every human being is vulnerable to depression because of the interplay between psychological and biological Depression and Anxiety DOI 10.1002/da

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characteristics, genes, and life experiences. Psychoeducation, using an explanatory rationale and having a formulation is about the core beliefs with regard to etiology and treatment helps to maintain the therapeutic alliance and consolidates adherence of compliance [Jorm, 2000; Pampallona et al., 2002]. Feedback according to the model suggests a treatability, a malleability of psychological and biological factors that can lead to an improved resistance, coping, and stress management, and to the modification of life objectives and values. The model gives information on depression and its symptoms and helps to formulate hypotheses on the ‘‘negative spiral’’: the etiological factors and pathogenesis of the patient’s depression. In this idiosyncratic model, this case formulation is generally more constructive, beneficial, and hopeful compared to the fatalistic and self-denigrating illness and treatment models of the depressed patients and their family. Furthermore, several aids are used for the psychoeducation on depression and its treatment: Worth mentioning is the video program Depressionythe Answers [Schotte et al., 1993]. The tape consists of three parts: In the first part, ‘‘The Psychiatric Ward’’ (6 min), patients are welcomed and sympathy is expressed for the painful experience of being admitted to the ward. However, the hospitalization can help to alleviate the symptoms of depression. The second part, ‘‘Symptoms, Causes, and Therapy’’ (11 min) provides information from a medical, psychiatric/biological viewpoint on symptomatology, etiology, and antidepressive medication and its possible side effects. The third part, ‘‘Thinking, Acting, and Feeling’’ (18 min), provides concrete, role-played, and lifelike examples of the cognitive, behavioral, and affective characteristics of depression. The tape is shown to each inpatient by a trained nurse, and if they so desire, to the family members. Research [Schotte et al., 1993] and experience with the video program indicate that patients and their families respond well to the videotape and believe in its utility as an introduction to the psychotherapeutic and medical treatments. In the remediation or symptom reduction phase, it is stressed that initially recovery is possible without the patient explicitly being responsible for it: The idea behind this ‘‘deresponsibilization’’ strategy is to bring an end to the ‘‘entrapment’’ situation. The patient and persons in his or her environment learn how to stop the senseless and exhausting ‘‘battle against depression’’ and come to realize that—apart from compliance with the medication schedules and the endeavor to strive for tranquillity, recuperation, and rest—no direct active effort is expected of him or her at the beginning of the treatment. The core characteristics of the treatment approach harmonize well with the assumptions and principles from new developments in behavioral therapy such as the mindfulness-based stress reduction program and the acceptance and commitment therapy approach [ACT; Hayes et al., 1999]. In the first days after admission, the importance of medication and Depression and Anxiety DOI 10.1002/da

rest is therefore stressed. Simply stated, the message here is: ‘‘As a person with depression, a severe but treatable illness, take good care of yourself.’’ Rumination, agitation or retardation, and disability are regarded as depressive symptoms, and are ‘‘normalized’’ and treated in the context of severe depression. Gaining peace of mind, rest, and medication play the most important role in the initial objective of reducing symptoms. In fact, the ward creates an initial treatment context in which patients learn to develop an attitude of ‘‘mindfulness’’ with respect to their severe depressive symptomatology, rather than working directly to change dysfunctional cognitions or decrease levels of negative emotions. This mindfulness attitude does not imply a passive coping style: On the contrary, all ‘‘pleasant’’ activities that enhance physical recuperation, that distract the patient from depressive ruminations, are encouraged and proposed by therapists and by the nursing staff. Patient-mindedness and patient/family–friendliness are of primary importance in this phase. Therapists and nursing staff present themselves as competent experts in their knowledge of depression and its treatment, but patients and staff stand on an equal footing. The ward is open and applies its rules flexibly; therapeutic activities are offered, and participation is reinforced but is not obligatory. On the other hand, when the acute symptomatology is diminished, the responsibility of and the possibilities for patients are gradually emphasized. During the phases of rehabilitation and relapse prevention, patients are stimulated and encouraged to participate in activities within and outside the ward; weekends can be used to try out leisure and task activities at home. The improvements during treatment are considered a symbol of the first steps of the ‘‘fresh start.’’ This element is further enhanced by a reconsideration of the idiosyncratic model at the end of the admission. Patients, their families, and therapists discuss realistic expectations for further recovery and formulate shortand long-term strategies to cope with remaining depression symptoms to decrease patients’ psychobiological vulnerability—increase protective factors and diminish risk factors—and to reduce (the harm of) stressful life events. The likelihood of relapse can be drastically limited by improving loyalty to outpatient antidepressant psychiatric treatment and, with the eventual aid of outpatient psychotherapeutic followup, working toward improved stress resistance and optimizing the quality of life. Ultimately, the aim of a treatment strategy for severe depression, rooted in the present biopsychosocial model, is not only the reduction of symptoms and the prevention of subsequent episodes but also the optimization of the quality of life, social (re)integration, and engagement in the community. The deduction that effective treatment of depression should be more than a mere alleviation of the symptoms and equally should bring about a


reduction in psychological vulnerability and improved resistance to depression is fairly self-evident: The therapeutic plan should stress both symptom reduction and prophylactic measures. Prophylaxis implies influencing patients’ psychobiological vulnerability; moreover, one should aim at preventing or minimizing the effects of stressful, traumatic life circumstances [Lam et al., 1996]. Psychotherapeutic interventions that appear to be most effective in the treatment of depression are cognitive-behavioral and interpersonal therapy [e.g., Arean and Cook, 2002; Jarrett et al., 2001; Kornbluh et al., 2001; Lenze et al., 2002; Michalak and Lam, 2002; Nierenberg, 2001; Segal et al., 2002; Thase et al., 1997]. In view of the high risk of relapse [Duggan, 1997], the importance of a long-term treatment of depressive disorders is being increasingly stressed [e.g., Geddes et al., 2003]. There are indications that combinations of psychotherapeutic and pharmacological interventions offer better outcomes in severe depression over extended periods of time than do monotherapies; this applies to improved recovery and to the reduction of the risk of relapse [e.g., Arean and Cook, 2002; Arnow and Constantino, 2003; Lenze et al., 2002; Michalak and Lam, 2002; Segal et al., 2002; Thase et al., 1997]. This superior effect can be achieved, for example, by cognitive-behavioral techniques that concentrate specifically on the residual symptomatology following a response or partial remission resulting from pharmacotherapy [Segal et al., 2002]. Such sequential combination therapies highlight the possibilities of integrated cooperation between the psychiatric and psychological disciplines. Combined therapies reduce the likelihood of dropout or therapy disloyalty, and patients experience them as being more ‘‘customerfriendly’’ [e.g., De Jonghe et al., 2001]. ECT is a significant option for treating severe forms of depression [UK ECT Review Group, 2003]; however, there has been little or no work investigating the sequential, combined integration of ECT and psychotherapeutic interventions. The application of meditation techniques to the treatment of chronic depression and particularly the mindfulness-based stress reduction program appears to be a promising development in treating chronic depression [Bishop, 2002; Kabat-Zinn, 1990; KabatZinn et al., 1992]. ‘‘Awareness’’ or ‘‘mindfulness’’ meditation techniques are used to teach people how to distance themselves from their feelings and thoughts by regarding them as events rather than as products of the self. Unlike the conventional cognitive therapeutic interventions in the tradition of Beck, it is not the content of the thoughts that comes under scrutiny; rather, the therapy tries to influence the attitude of the patient toward the depressive thoughts and feelings. Applications of these techniques in a cognitivebehavioral program appear to be effective in preventing relapse into depression [Teasdale et al., 2000, 2002; Mason and Hargreaves, 2001].

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CONCLUSION Because of the high burden of depression worldwide, there is a need for effective strategies to shorten episode duration and to prevent recurrence. For severe forms of depression, treatments combining pharmacological and psychotherapeutic approaches are preferred. This requires interdisciplinary teamwork and an integration of biological and psychological theories of depression. Unfortunately, these two lines of research and theory proceed in relative isolation from each other. In this article, we have proposed an integrative biopsychosocial model, describing onset and treatment of depression, and introducing the concept of psychobiological vulnerability. Our intention is that the framework inform clinical practice by providing a context for psychoeducation and dialogue between clinician and patient that aims to enhance treatment compliance and improve outcome. Despite the fact that contemporary research lines are accumulating important knowledge that contributes to the understanding of depression, future research needs to emphasize the development of integrative theories of depression.

REFERENCES Abramson LY, Alloy LB, Hankin BL, Haeffel GJ, MacCoon DG, Gibb, BE. 2002. Cognitive vulnerability–stress models of depression in a self-regulatory and psychobiological context: The evaluation of the theories validities. In: Gotlib IH, Hammen C, editors. Handbook of depression. New York: Guilford Press. p 268–294. Abrous DN, Koehl M, Le Moal M. 2005. Adult neurogenesis: From precursors to network and physiology. Physiol Rev 85:523–569. Akiskal HS. 1995. Mood disorders: Introduction and overview. In: Kaplan HI, Sadock BJ, editors. Comprehensive textbook of psychiatry. 6th ed. Baltimore, MD: Lippincott, Williams and Wilkins. p 1067–1079. American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: Author. 886p. Andersen SL, Teicher MH. 2004. Delayed effects of early stress on hippocampal development. Neuropsychopharmacology 29: 1988–1993. Arean PA, Cook BL. 2002. Psychotherapy and combined psychotherapy/ pharmacotherapy for late life depression. Biol Psychiatry 52: 293–303. Arnow BA, Constantino MJ. 2003. Effectiveness of psychotherapy and combination treatment for chronic depression. J Clin Psychol 59:893–905. Beck AT, Rush A, Shaw BF, Emery G. 1979. Cognitive therapy of depression. New York: Guilford Press. 425p. Beck J. 1995. Cognitive therapy: Basics and beyond. New York: Guilford Press. 338p. Bishop SR. 2002. What do we really know about mindfulness-based stress reduction? Psychosom Med 64:71–83. Brody AL, Saxena S, Stoessel P, Gillies LA, Fairbanks LA, Alborizan S, Phelps ME, Huang SC, Wu HM, Ho ML, Ho MK, Au SC, Maidment K, Baxter LR Jr. 2001. Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: Preliminary findings. Arch Gen Psychiatry 58:631–640. Depression and Anxiety DOI 10.1002/da

322

Schotte et al.

Brown GW. 1993. Life-events and affective disorder: Replications and limitations. Psychosom Med 55:248–259. Brown GW. 1997. A psychosocial perspective and the aetiology of depression. In: Honig A, Van Praag HM, editors. Depression: neurobiological, psychopathological, and therapeutic advances. Chichester, UK: Wiley. p 343–362. Brown GW. 1998. Genetic and population perspectives on life events and depression. Soc Psychiatry Psychiatr Epidemiol 33:363–372. Brown GW, Harris TO. 1978. Social origins of depression: A study of psychiatric disorder in women. London: Tavistock. 399p. Brown GW, Harris TO, Hepworth C. 1994. Life events and endogenous depression: A puzzle re-examined. Arch Gen Psychiatry 51:525–534. Brown GW, Harris TO, Hepworth C. 1995. Loss, humiliation and entrapment among women developing depression: A patient and non-patient comparison. Psychol Med 25:7–21. Browne A, Finkelhor D. 1986. Impact of child sexual abuse: A review of the research. Psychol Bull 99:66–77. Caspi A, Sugden K, Moffit T, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R. 2003. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science 301:386–389. Cloninger CR, Svrakic DM, Pryzbeck TR. 1993. A psychobiological model of temperament and character. Arch Gen Psychiatry 50: 975–990. Cotton D. 1990. Stress management: An integrated approach to therapy. New York: Brunner/Mazel. 288p. Coyne JC. 1976. Toward an interactional description of depression. Psychiatry 39:28–40. Davidson RJ, Pizzagalli D, Nitschke JB, Putnam K. 2002. Depression: Perspectives from affective neuroscience. Ann Rev Psychol 53:545–574. De Jonghe F, Kool S, Van Aalst G, Dekker J, Peen J. 2001. Combining psychotherapy and antidepressants in the treatment of depression. J Affect Disord 64:217–229. Denollet J, Vaes J, Brutsaert DL. 2000. Inadequate response to treatment in coronary heart disease: Adverse effects of type D personality and younger age on 5-year prognosis and quality of life. Circulation 102:630–635. Donald M, Dower J. 2002. Risk and protective factors for depressive symptomatology among a community sample of adolescents and young adults. Aust NZ J Public Health 26:555–562. Duggan CF. 1997. Course and outcome of depression. In: Honig A, Van Praag HM, editors. Depression: Neurobiological, psychopathological, and therapeutic advances. Chichester, UK: Wiley. p 31–40. Engel GL. 1977. The need for a new medical model: A challenge for biomedicine. Science 196:129–136. Engel GL. 1980. The clinical application of the biopsychosocial model. Am J Psychiatry 137:535–544. Enns MW, Cox BJ, Clara I. 2002. Adaptive and maladaptive perfectionism: Developmental origins and association with depression proneness. Pers Indiv Diff 33:921–935. Essex MJ, Klein MH, Cho E, Kalin NH. 2002. Maternal stress beginning in infancy may sensitize children to later stress exposure: Effects on cortisol and behavior. Biol Psychiatry 52:776–784. Fombonne E. 1994. Increased rates of depression: Update of epidemiological findings and analytical problems. Acta Psychiatr Scand 90:145–146. Fox K. 1999. The influence of physical activity on mental well-being. Public Health Nutr 2:411–418. Fullilove MT. 2002. Social and economic causes of depression. J Gend Specif Med 5:38–41. Depression and Anxiety DOI 10.1002/da

Gabbard G. 2000. A neurobiologically informed perspective on psychotherapy. Br J Psychiatry 177:117–122. Gallo JJ, Armenian HK, Ford DE, Eaton WW, Khachaturian AS. 2000. Major depression and cancer: The 13-year follow-up of the Baltimore Epidemiologic Catchment Area sample (United States). Cancer Causes Control 11:751–758. Geddes JR, Carney, SM, Davies C, Furukawa TA. 2003. Relapse prevention with antidepressant drug treatment in depressive disorders: A systematic review. Lancet 361:653–661. Gilbert P, Allan S. 1998. The role of defeat and entrapment (arrested flight) in depression: An exploration of an evolutionary view. Psychol Med 28:585–598. Glitz DA, Manji HK, Moore GJ. 2002. Mood disorders: Treatmentinduced changes in brain neurochemistry and structure. Semin Clin Neuropsychiatry 7:269–280. Gloaguen V, Cottraux J, Cucherat M, Blackburn IM. 1998. A metaanalysis of the effects of cognitive therapy in depressed patients. J Affect Disord 49:59–72. Gold PW, Chrousos GP. 2002. Organisation of the stress system and its dysregulation in melancholic and atypical depression: High vs low CRH/NE states. Mol Psychiatry 7:254–272. Gore S, Farrell F, Gordon J. 2001. Sports involvement as protection against depressed mood. J Res Adolesc 11:119–130. Gotlib IH, Hammen C, editors. 2002. Handbook of depression. New York: Guilford Press. 624p. Gray NA, Zhou R, Du J, Moore GJ, Manji HK. 2003. The use of mood stabilizers as plasticity enhancers in the treatment of neuropsychiatric disorders. J Clin Psychiatry 64(Suppl 5):3–17. Hamet P, Tremblay J. 2005. Genetics and genomics of depression. Metabolism 54(Suppl 5):10–15. Harris T, Brown GW, Robinson R. 1999. Befriending as an intervention for chronic depression among women in an inner city: 2. Role of fresh-start experiences and baseline psychosocial factors in remission from depression. Br J Psychiatry 174:225–232. Hayes SC, Strosahl KD, Wilson KG. 1999. Acceptance and commitment therapy: An experiential approach to behavior change. New York: Guilford Press. 304p. Heath AC, Cloninger CR, Martin NG. 1994. Testing a model for the genetic structure of personality: A comparison of the personality systems of Cloninger and Eysenck. J Pers Soc Psychol 66:762–775. Heath AC, Eaves LJ, Martin NG. 1998. Interaction of marital status and genetic risk for symptoms of depression. Twin Res 1:119–122. Heim C, Newport DJ, Bonsall R, Miller AH, Nemeroff CB. 2001. Altered pituitary–adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am J Psychiatry 158:575–581. Holsboer F. 2000. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23:477–501. Howard KI, Marinovitch Z. 1996. Costs and benefits of psychotherapy. Acta Psychiatr Belg 96:154–170. Hunout P, Le Gall D, Shea B. 2003. The destruction of society— challenging the ‘‘modern’’ tryptique: Individualism, hedonism, consumerism. International Scope Review, Vol. 5. Available online at http://www.socialcapital-foundation.org/journal/synopsis.htm Ingram RE, Miranda J, Segal ZV. 1998. Cognitive vulnerability to depression. New York: Guilford Press. 330p. Jarrett RB, Kraft D, Doyle J, Foster BM, Eaves GG, Silver PC. 2001. Preventing recurrent depression using cognitive therapy with and without a continuation phase: A randomised clinical trial. Arch Gen Psychiatry 58:381–388. Jenaway A, Paykel ES. 1997. Life-events and depression. In: Honig A, Van Praag HM, editors. Depression: Neurobiological, psycho-


pathological, and therapeutic advances. Chichester, UK: Wiley. p 279–296. Joiner TE Jr. 2002. Depression in its interpersonal context. In: Gotlib IH, Hammen C, editors. Handbook of depression. New York: Guilford Press. p 295–313. Jorm AF. 2000. Mental health literacy: Public knowledge and beliefs about mental disorders. Br J Psychiatry 177:396–402. Kabat-Zinn J. 1990. Full catastrophe living. New York: Delacorte. 453p. Kabat-Zinn J, Massion AO, Kristeller J, Peterson LG, Fletcher KE, Pbert L, Lenderking WR, Santorelli SF. 1992. Effectiveness of meditation-based stress reduction program in the treatment of anxiety disorders. Am J Psychiatry 149:939–943. Keller MB, Lavori PW, Mueller TI, Endicott J, Coryell W, Hirschfeld RM, Shea T. 1992. Time to recovery, chronicity, and levels of psychopathology in major depression: A 5-year prospective follow-up of 431 subjects. Arch Gen Psychiatry 49:809–816. Kendler KS, Gardner CO, Prescott CA. 2002. Toward a comprehensive developmental model for major depression in women. Am J Psychiatry 159:1133–1145. Kendler KS, Kessler RC, Walters EE, MacLean C, Neale MC, Heath AC, Eaves LJ. 1995. Stressful life-events, genetic liability, and onset of major depression in women. Am J Psychiatry 152: 282–289. Kendler KS, Thornton LM, Gardner CO. 2000. Stressful life events and previous episodes in the aetiology of major depression in women: An evaluation of the ‘‘kindling’’ hypothesis. Am J Psychiatry 157:1243–1251. Kessler RC. 2000. Gender differences in major depression: Epidemiological findings. In: Frank E, editor. Gender and its effects on psychopathology. New York: American Psychiatric Press. p 61–84. Klerman GL, Weissman MM, Rounsaville BJ, Chevron E. 1984. Interpersonal therapy of depression. New York: Basic Books. 272p. Kornbluh R, Papakostas GI, Petersen T, Neault NB, Nierenberg AA, Rosenbaum JF, Fava M. 2001. A survey of prescribing preferences in the treatment of refractory depression: Recent trends. Psychopharmacol Bull 35:150–156. Ladd CO, Huot RL, Thrivikraman KV, Nemeroff CB, Meaney MJ, Plotsky PM. 2000. Long-term behavioral and neuroendocrine adaptations to adverse early experience. Prog Brain Res 122:81–103 Lam DH, Green B, Power MJ, Checkley S. 1996. Dependency, matching adversities, length of survival and relapse in major depression. J Affect Disord 37:81–90. Lenze EJ, Dew MA, Mazumdar S, Begley AE, Cornes C, Miller MD, Imber SD, Frank E, Kupfer DJ, Reynolds CF III. 2002. Combined pharmacotherapy and psychotherapy as maintenance treatment for late-life depression: Effects on social adjustment. Am J Psychiatry 159:466–468. Lombard CB. 2000. What is the role of food in preventing depression and improving mood, performance and cognitive function? Med J Aust 173(Suppl):S104–S105. Lo¨nnqvist JK. 2000. Psychiatric aspects of suicidal behaviour: Depression. In: Hawton K, Van Heeringen K, editors. The international handbook of suicide and attempted suicide. Chichester, UK: Wiley. p 107–120. Manji HK, Quiroz JA, Sporn J, Payne JL, Denicoff K, Gray N, Zarate CA, Charney DS. 2003. Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 53:707–742. Margison FR, Barkham M, Evans C, McGrath G, Clark JM, Audin, K, Connel J. 2000. Measurement and psychotherapy: Evidencebased practice and practice-based evidence. Br J Psychiatry 177: 123–130.

323

Markowitz JC. 1999. Developments in interpersonal psychotherapy. Can J Psychiatry 4:556–561. Mason O, Hargreaves I. 2001. A qualitative study of mindfulnessbased cognitive therapy for depression. Br J Med Psychol 74: 197–212. Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. 2005. Deep brain stimulation for treatment-resistant depression. Neuron 45:651–660. Michalak EE, Lam RW. 2002. Breaking the myths: New treatment approaches for chronic depression. Can J Psychiatry 47: 635–643. Miller L, Warner V, Wickramaratne P, Weissman A. 1999. Religiosity as a protective factor in depressive disorder. Am J Psychiatry 156:808–809. Millon T, Davis R. 2000. Personality disorders in modern life. New York: Wiley. 610p. Modell S, Lauer CJ, Schreiber W, Huber J, Krieg JC, Holsboer F. 1998. Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders. Neuropsychopharmacology 18:253–262. Myers DG. 2000. The American paradox: Spiritual hunger in an age of plenty. London: Yale University Press. 384p. Nesse RM. 2000. Is depression an adaptation? Arch Gen Psychiatry 57:14–20. Newport DJ, Wilcox MM, Stowe ZN. 2002. Maternal depression: A child’s first adverse life event. Semin Clin Neuropsychiatry 7: 113–119. Nierenberg AA. 2001. Long-term management of chronic depression. J Clin Psyhiatry 62(Suppl 6):17–21. Pampallona S, Bollini P, Tibaldi G, Kupelnick B, Munizza C. 2002. Patient adherence in the treatment of depression. Br J Psychiatry 180:104–109. Paris J. 1996. Social factors in the personality disorders: A biopsychosocial approach to aetiology and treatment. New York: Cambridge University Press. 244p. Parry B. 2000. Hormonal basis of mood disorders in women. In: Frank E, editor. Gender and its effects on psychopathology. New York: American Psychiatric Press. p 3–22. Peet M, Horrobin DF. 2002. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs. Arch Gen Psychiatry 59:913–919. Piccinelli M, Wilkinson G. 2000. Gender differences in depression: Critical review. Br J Psychiatry 177:486–492. Pine DS. 2002. Brain development and the onset of mood disorders. Semin Clin Neuropsychiatry 7:223–233. Pintor L, Gasto C, Navarro V, Torres X, Fananas L. 2003. Relapse of major depression after complete and partial remission during a 2-year follow-up. J Affect Disord 73:237–244. Pizzagalli DA, Nitschke JB, Oakes TR, Hnedrick AM, Horras KA, Larson CL, Abercrombie HC, Schaefer SM, Koger JV, Benca RM, Pasual-Marqui RD, Davidson RJ. 2002. Brain electrical tomography in depression: The importance of symptom severity, anxiety, and melancholic features. Biol Psychiatry 52:73–85. Post RM. 1992. Transduction of psychosocial stress into the neurobiology of recurrent affective disorder. Am J Psychiatry 149: 999–1010. Rakel RE. 1999. Depression. Primary Care 26:211–224. Robertson MM, Katona CLE, editors. 1997. Depression and physical illness. Chichester, UK: Wiley. 576p. Rosenfield S. 2000. Gender and dimensions of the self: Implications for internalising and externalising behavior. In: Frank E, editor. Gender and its effects on psychopathology. New York: American Psychiatric Press. p 23–36. Depression and Anxiety DOI 10.1002/da

324

Schotte et al.

Sartorius N. 2001. The economic and social burden of depression. J Clin Psychiatry 62(Suppl 15):8–11. Schacht R. 2004. Spreken met ernstig depressieve patie¨nten. [Talking with severely depressed patients] Tijdschr Klin Psychol 34:45–61. Schotte C, Maes M, Beuten T, Vandenbossche B, Cosyns P, Van Coppenolle F. 1993. A videotape as introduction for cognitive behavioral therapy with depressed inpatients. Psychol Rep 72: 440–442. Schotte CKW. 2002. Assessment of borderline personality disorder: Considering a diagnostic strategy. Acta Neuropsychiatry 14:55–59. Schotte CKW, Maes M. 2001. Descriptive diagnostic assessment of depression: Categorical diagnosis, dimensional assessment and instruments. Acta Neuropsychiatry 13:2–15. Schotte CKW, Maes M, Cluydts R, Cosyns P. 1996. Effects of affective–semantic mode of item presentation in balanced selfreport scales: Biased construct validity of the Zung self-rating depression scale. Psychol Med 26:1161–1168. Schotte CKW, Maes M, Cluydts R, Cosyns P. 1997a. Cluster analytic validation of the DSM melancholic depression: The threshold model: Integration of quantitative and qualitative distinctions between unipolar depressive subtypes. Psychiatry Res 71:181–195. Schotte CKW, Maes M, Cluydts R, De Doncker D, Cosyns P. 1997b. Construct validity of the Beck Depression Inventory in a depressive population. J Affect Disord 46:115–125. Schotte CKW, Van den Bossche B, Van den Bergh R, Claes S, Cosyns P. 2003. Denken over depressie: Een biopsychosociaal model. [Thinking about depression: a biopsychosocial model] Tijdschrift Klinische Psychologie 33:98–117. Segal Z, Vincent P, Levitt A. 2002. Efficacy of combined, sequential and crossover psychotherapy and pharmacotherapy in improving outcomes in depression. J Psychiatry Neurosci 27:281–290. Sheline YI, Sanghavi M, Mintun MA, Gado MH. 1999. Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 19:5034–5043. Simon GE. 2003. Social and economic burden of mood disorders. Biol Psychiatry 54:208–215. Smith AL, Weissman MM. 1991. The epidemiology of depressive disorders: National and international perspectives. In: Feighner JP, Boyer WF, editors. Diagnosis of depression. Chichester, UK: Wiley. p 17–30. Solomon DA, Keller MB, Leon AC, Mueller TI, Lavori PW, Shea MT, Coryell W, Warshaw M, Turvey C, Maser JD, Endicott J. 2000. Multiple recurrences of major depressive disorder. Am J Psychiatry 157:229–233. Souery D, Lipp O, Mahieu B, Mendlewicz J. 1997. Advances in the genetics of depression. In: Honig A, Van Praag HM, editors. Depression: Neurobiological, psychopathological, and therapeutic advances. Chichester, UK: Wiley. p 297–310. Sparks PJ, Ayars GH, Simon GE, Katon WJ, Altman L, Johnson RL. 1991. Depression and panic attacks related to phenol-formaldehyde composite material exposure in an aerospace manufacturing plant. Allergy Proc 12:389–393. Staudinger UM, Bluck S. 2001. A view on midlife development from life-span theory. In: Lachman ME, editor. Handbook of midlife development. New York: Wiley. p 3–39. Teasdale JD, Moore RG, Hayhurst H, Pope M, Williams S, Segal ZV. 2002. Metacognitive awareness and prevention of relapse in

Depression and Anxiety DOI 10.1002/da

depression: Empirical evidence. J Consult Clin Psychol 70: 275–287. Teasdale JD, Segal ZV, Williams JM, Ridgeway VA, Soulsby JM, Lau MA. 2000. Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. J Consult Clin Psychol 68:615–623. Teicher MH, Andersen SL, Polcari A, Anderson CM, Navalta CP. 2002. Developmental neurobiology of childhood stress and trauma. Psychiatr Clin N Am 25:397–426. Thase ME. 2001. Neuroimaging profiles and the differential therapies of depression. Arch Gen Psychiatry 58:651–653. Thase ME, Frank E, Kornstein SG, Yonkers KA. 2000. Gender differences in response to treatments of depression. In: Frank E, editor. Gender and its effects on psychopathology. New York: American Psychiatric Press. p 103–130. Thase ME, Greenhouse JB, Frank E, Reynolds CF III, Pilkonios PA, Hurley K, Grochocinski V, Kupfer DJ. 1997. Treatment of major depression with psychotherapy or psychotherapy– pharmacotherapy combinations. Arch Gen Psychiatry 54: 1009–1015. Toth SL, Manly JT, Cichetti D. 1992. Child maltreatment and vulnerability to depression. Dev Psychopathol 4:97–112. Tsuang M, Faraone SV. 1990. The genetics of mood disorders. Baltimore, MD: Johns Hopkins University Press. 236p. Turner RJ, Lloyd DA. 1995. Lifetime trauma and mental health: The significance of cumulative adversity. J Health Soc Behav 36: 360–376. Tylee A. 2000. Depression in Europe: Experience from the DEPRESS II survey. Depression Research in European Society. Eur Neuropsychopharmacology 10(Suppl 4):S445–S448. UK ECT Review Group. 2003. Efficacy and safety of electroconvulsive therapy in depressive disorders: A systematic review and meta-analysis. Lancet 361:799–808. ¨ stu¨n TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJL. U 2004. Global burden of depressive disorders in the year 2000. Br J Psychiatry 184:386–392. Van Praag HM. 1990.Two-tier diagnosing in psychiatry. Psychiatry Res 34:1–11. Van Voorhees E, Scarpa A. 2004. The effects of child maltreatment on the hypothalamic–pituitary–adrenal axis. Trauma Violence Abuse 5:333–352. Vozoris NT, Tarasuk VS. 2003. Household food insufficiency is associated with poorer health. J Nutr 133:120–126. Vythilingam M, Heim C, Newport J, Miller AH, Anderson E, Bronen R, Brummer M, Staib L, Vermetten E, Charney DS, Nemeroff CB, Bremner JD. 2002. Childhood trauma associated with smaller hippocampal volume in women with major depression. Am J Psychiatry 159:2072–2080. Wilner P. 1985. Depression: A psychobiological synthesis. New York: Wiley. 622p. Yen IH, Kaplan GA. 1999. Poverty area residence and changes in depression and perceived health status: Evidence from the Alameda County Study. Int J Epidemiol 28:90–94. Young J, Klosko J. 1994. Reinventing your life: How to break free from negative life pattern. New York: Plume/Penguin. 365p. Young JE, Klosko J, Weishaar ME. 2003. Schema therapy: A practitioner’s guide. New York: Guilford Press. 436p.