Major Depression and Its Recurrences: Life Course Matters.

Major depression is one of the most prevalent and debilitating personal and public health conditions worldwide. Less appreciated is that depression's tremendous burdens are not shared equally among all who become depressed. Some will suffer recurrences over the rest of their lives, whereas half or more will never have a recurrence. Based on these two distinctive life course prototypes, we propose a subtype distinction for research on the origins and lifetime course of major depression. A pressing goal is to determine at the time of depression's first onset who will follow which clinical trajectory. The lack of recognition of this distinction has resulted in many obstacles, including conceptual biases, methodological oversights, and definitional dead ends. Current theories are reviewed and compared. The implications for contemporary diagnostic controversies, reevaluating research on treatment and prevention, and enhancing the predictive strength of traditionally weak indicators of recurrences and recurrent depression are discussed.

More treatment but no less depression: The treatment-prevalence paradox.

Treatments for depression have improved, and their availability has markedly increased since the 1980s. Mysteriously the general population prevalence of depression has not decreased. This "treatment-prevalence paradox" (TPP) raises fundamental questions about the diagnosis and treatment of depression. We propose and evaluate seven explanations for the TPP. First, two explanations assume that improved and more widely available treatments have reduced prevalence, but that the reduction has been offset by an increase in: 1) misdiagnosing distress as depression, yielding more "false positive" diagnoses; or 2) an actual increase in depression incidence. Second, the remaining five explanations assume prevalence has not decreased, but suggest that: 3) treatments are less efficacious and 4) less enduring than the literature suggests; 5) trial efficacy doesn't generalize to real-world settings; 6) population-level treatment impact differs for chronic-recurrent versus non-recurrent cases; and 7) treatments have some iatrogenic consequences. Any of these seven explanations could undermine treatment impact on prevalence, thereby helping to explain the TPP. Our analysis reveals that there is little evidence that incidence or prevalence have increased as a result of error or fact (Explanations 1 and 2), and strong evidence that (a) the published literature overestimates short- and long-term treatment efficacy, (b) treatments are considerably less effective as deployed in "real world" settings, and (c) treatment impact differs substantially for chronic-recurrent cases relative to non-recurrent cases. Collectively, these a-c explanations likely account for most of the TPP. Lastly, little research exists on iatrogenic effects of current treatments (Explanation 7), but further exploration is critical.

Life stress and major depression: The mysteries of recurrences.

Approximately half of the people who suffer a major depressive episode for the first time experience recurrences, while the other half do not. Among the initially depressed, however, who will have recurrences remains a mystery, and cannot be forecasted with any statistical or clinical confidence. It is well documented, though, that highly stressful life events commonly precede first episodes of major depression, and that these experiences become progressively less common prior to recurrences. Determining the basis for this consistent empirical observation holds promise for discovering among the initially depressed who will become recurrent, helping to solve the current-day conundrum of recurrences. The present article has 2 overarching objectives. First, we evaluate stress sensitization, the prevailing theory for explaining the decreasing association of major life events with successive recurrences. Conceptual gaps, discrepancies, and misunderstandings are found for understanding the decreasing association, as well as for understanding recurrences. Research practices and logical errors also are exposed that compromise the integrity of the existing empirical record. Second, alternative theoretical accounts are proposed to explain the decreasing association of major life stress with recurrences. Two "dual pathway models" provide viable alternative explanations, fill in existing theoretical gaps, and supply additional advantages for understanding life stress, depression, and recurrences. Recommendations are made for evaluating the 3 respective models. In closing, limitations and remaining questions are discussed for discovering who, early in the lifetime course of major depression, is likely to have a lifetime of repeated recurrences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The assessment and measurement of adult life stress: Basic premises, operational principles, and design requirements.

Life stress is a central factor in the onset and course of a wide range of medical and psychiatric conditions. Determining the precise etiological and pathological consequences of stress, though, has been hindered by weaknesses in prevailing definitional and measurement practices. The purpose of the current paper is to evaluate the primary strategies for defining and measuring major and minor acute life events, chronic stressors, and daily hassles as informed by 3 basic scientific premises. The first premise concerns the manner in which stress is conceptualized and operationally defined, and specifically we assert that stress measures must not conflate the stress exposure with the stress response. The second premise concerns how stress exposures are measured, and we provide guidelines for optimizing standardized and sensitive indicators of life stress. The third premise addresses the consequences of variations in the procedures for life event measurement with regard to the validity of the research designs employed. We show that life stress measures are susceptible to several sources of bias, and if these potential sources of bias are not controlled in the design of the research, spurious findings may result. Our goal is to provide a useful guide for researchers who consider life stress to be an important factor in their theoretical models of disease, wish to incorporate measures of life stress in their research, and seek to avoid the common pitfalls of past measurement practices. (PsycINFO Database Record

Questioning kindling: An analysis of cycle acceleration in unipolar depression.

The kindling hypothesis for depression predicts that with more recurrences, the interval between successive recurrences decreases. Studies with unipolar and bipolar samples generally have been consistent with this premise. However, previous research is subject to a statistical artifact. Slater's fallacy maintains that these intermorbid intervals appear to decrease because highly recurrent individuals with consistently shorter intervals become a larger proportion of the remaining sample with each recurrence. Correcting for this bias, research on bipolar disorder no longer evidences such an effect. We predicted similar results for unipolar depression when correcting for this bias, and proposed an alternative model: individuals who are highly recurrent have consistently shorter intermorbid periods, even following the very first lifetime episode. As predicted, correcting for Slater's fallacy removed the appearance of decreasing intermorbid intervals. Further, highly recurrent individuals exhibited shorter intermorbid intervals in general, and for the very first interval, supporting the alternative model.

Life stress and family history for depression: the moderating role of past depressive episodes.

Three of the most consistently reported and powerful predictors of depression are a recent major life event, a positive family history for depression, and a personal history of past depressive episodes. Little research, however, has evaluated the inter-relations among these predictors in depressed samples. Such information is descriptively valuable and potentially etiologically informative. In the present article we summarize the existing literature and test four predictions in a sample of 62 clinically depressed individuals: (1) participants who experienced a major life event prior to onset would be less likely than participants who did not experience a major life event to have a positive family history for depression; (2) participants with a recent major life event would have fewer lifetime episodes of depression than would participants without; (3) participants with a positive family history for depression would have more lifetime episodes of depression than would participants with a negative family history for depression; and (4) we would obtain a 3-way interaction in which participants with a positive family history and without a major life event would have the most lifetime episodes, whereas participants with a negative family history and a major life event would have the fewest lifetime episodes. The first three predictions were confirmed, and the fourth prediction partially confirmed. These novel findings begin to elucidate the complex relations among these three prominent risk factors for depression, and point to avenues of research that may help illuminate the origins of depressive episodes.

Recurrence in major depression: a conceptual analysis.

Theory and research on major depression have increasingly assumed a recurrent and chronic disease model. Yet not all people who become depressed suffer recurrences, suggesting that depression is also an acute, time-limited condition. However, few if any risk indicators are available to forecast which of the initially depressed will or will not recur. This prognostic impasse may be a result of problems in conceptualizing the nature of recurrence in depression. In the current paper we first provide a conceptual analysis of the assumptions and theoretical systems that presently structure thinking on recurrence. This analysis reveals key concerns that have distorted views about the long-term course of depression. Second, as a consequence of these theoretical problems we suggest that investigative attention has been biased toward recurrent forms of depression and away from acute, time-limited conditions. Third, an analysis of how these theoretical problems have influenced research practices reveals that an essential comparison group has been omitted from research on recurrence: people with a single lifetime episode of depression. We suggest that this startling omission may explain why so few predictors of recurrence have as yet been found. Finally, we examine the reasons for this oversight, document the validity of depression as an acute, time-limited disorder, and provide suggestions for future research with the goal of discovering early risk indicators for recurrent depression.

Early parental loss and depression history: associations with recent life stress in major depressive disorder.

Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss.

Gender differences in life events prior to onset of major depressive disorder: the moderating effect of age.

Theoretical models attempting to explain why approximately twice as many women as men suffer from depression often involve the role of stressful life events. However, detailed empirical evidence regarding gender differences in rates of life events that precede onset of depression is lacking, due in part to the common use of checklist assessments of stress that have been shown to possess poor validity. The present study reports on a combined sample of 375 individuals drawn from 4 studies in which all participants were diagnosed with major depressive disorder and assessed with the Life Events and Difficulties Schedule (Bifulco et al., 1989), a state-of-the-art contextual interview and life stress rating system. Women reported significantly more severe and nonsevere, independent and dependent, and other-focused and subject-focused life events prior to onset of depression than did men. Further, these relations were significantly moderated by age, such that gender differences in rates of most types of events were found primarily in young adulthood. These results are discussed in term of their implications for understanding the etiological role of stressful life events in depression.

Stressful life events, chronic difficulties, and the symptoms of clinical depression.

Major life events and chronic difficulties have been found to be associated with the onset of depression. Little is known, however, about how exposure to such stressors is related to the clinical presentation of this disorder. We addressed this issue by administering an interview-based measure of life stress, the Beck Depression Inventory, and the Global Assessment of Functioning scale to 100 adults diagnosed with major depressive disorder. Participants who experienced a preonset severe life event exhibited greater overall levels of depression severity, endorsed more cognitive and somatic symptoms of depression, and functioned at lower levels than did their counterparts without preonset severe life events. In contrast, exposure to a preonset severe difficulty was unrelated to participants' severity of depression, cognitive and somatic symptoms, or level of global functioning. These findings highlight the potentially greater importance of acute stress compared with chronic stress for influencing these key clinical features of depression.

TARGETED REJECTION PREDICTS HASTENED ONSET OF MAJOR DEPRESSION.

Although severe life stress frequently precipitates the onset of major depression, little is known about the basic nature of stressors in this general category of adversity and how exposure to different life events might be related to clinical aspects of the disorder. We addressed this issue by introducing, and examining the effects of, targeted rejection (TR), which involves the exclusive, active, and intentional social rejection of an individual by others. Twenty-seven adults with major depressive disorder were administered an interview-based measure of life stress. Severe life events that occurred prior to the onset of depression were subsequently coded as TR or as non-TR. Participants who experienced a pre-onset severe TR event became depressed approximately three times faster than did their non-TR counterparts. These findings highlight the potential importance of TR as a marker of hastened depression onset and demonstrate how refining characterizations of stress may advance our understanding of depression.

Gene-environment interactions in depression research: genetic polymorphisms and life-stress polyprocedures.

Recent studies on life stress, depression, and polymorphisms in the promoter region of the serotonin transporter gene (5-HTTLPR) are characterized by powerful genetic techniques, but are also characterized by unconventional and inconsistent approaches to assessing life stress. The present review addresses this problem by critically evaluating this rapidly growing literature with regard to the concepts and procedures employed to assess life stress and the research designs used to test causal associations. The existing body of evidence is seriously compromised by the predominance of ad hoc approaches for measuring life stress and by a lack of attention to key issues concerning research design. Principles and procedures for more refined and rigorous stress measurement are outlined. Improved guidelines are needed to direct future research on interactive effects of life stress and genes in psychopathology, pathophysiological processes, and disease.

Placing the mnemonic model in context: diagnostic, theoretical, and clinical considerations.

The mnemonic model of posttraumatic stress disorder (PTSD) proposed by D. C. Rubin, D. Berntsen, and M. K. Bohni presents some provocative and potentially insightful ideas about this mental disorder. D. C. Rubin et al. suggested that PTSD is caused and maintained through a "pathogenic memory" (D. C. Rubin et al., 2008, p. 985) of a negative event rather than by exposure to a traumatic event per se. The present authors examine the mnemonic model in the context of relevant diagnostic, theoretical, and clinical considerations. Specifically, to evaluate the arguments and evidence provided in support of the mnemonic model of PTSD, the present authors focus on 4 issues: (a) problems inherent with comparing a theoretical model (i.e., the mnemonic model) with a diagnostic model (i.e., the DSM-IV-TR model), (b) problems with not comparing the mnemonic model with relevant cognitive and memory models of PTSD, (c) problems with the degree to which the research reviewed provides support for the mnemonic model, and (d) concerns that memory in PTSD is confounded with the basic disorder, rather than causing PTSD. The present authors conclude with suggestions for future theory and research to help differentiate between memory's role in the origins of PTSD and memory's role in the clinical course of the disorder.

Modern approaches to conceptualizing and measuring human life stress.

The idea that adverse life circumstances and negative life events contribute to disorder and disease has long been held. Advances in conceptualizing and defining these conditions under the common label of life stress have led to progress in measuring both the environmental and individual response characteristics that may promote disorder and disease. In general, a substantial and growing research literature supports the basic premise that life stress plays an important role in the development of many psychological and physical problems. Recent research, too, strongly suggests that interest in life stress in relation to health and disease will accelerate over the coming years. Yet debates and controversies remain concerning how to best conceptualize and measure life stress, which presents distinctive challenges for advancing the field. The present review examines the major issues pertaining to these debates, controversies, and challenges, for they will be crucial to resolve if progress is to be made in understanding ways in which life stress may or may not contribute to psychological and physical disorders.

Severe life events predict specific patterns of change in cognitive biases in major depression.

BACKGROUND: A long-standing debate concerns whether dysfunctional cognitive processes and content play a causal role in the etiology of depression or more simply represent correlates of the disorder. There has been insufficient appreciation in this debate of specific predictions afforded by cognitive theory in relation to major life stress and changes in cognition over time. In this paper we present a novel perspective for investigating the etiological relevance of cognitive factors in depression. We hypothesize that individuals who experienced a severe life event prior to the onset of major depression will exhibit greater changes in dysfunctional attitudes over the course of the episode than will individuals without a severe life event. METHOD: Fifty-three participants diagnosed with major depression were assessed longitudinally, approximately 1 year apart, with state-of-the-art measures of life stress and dysfunctional attitudes. RESULTS: Depressed individuals with a severe life event prior to episode onset exhibited greater changes in cognitive biases over time than did depressed individuals without a prior severe event. These results were especially pronounced for individuals who no longer met diagnostic criteria for major depression at the second assessment. CONCLUSIONS: Specific patterns of change in cognitive biases over the course of depression as a function of major life stress support the etiological relevance of cognition in major depression.

Major life events and major chronic difficulties are differentially associated with history of major depressive episodes.

Major life events have been found to precede onsets of a 1st lifetime episode of depression more commonly than subsequent recurrences. Despite general empirical support for this finding, few data directly address how the role of major life events may change over successive recurrences. Further, little research has examined major chronic difficulties in relation to a 1st lifetime episode versus a recurrence of depression. The present study tested the associations between major life events and major difficulties in relation to lifetime history of depressive episodes in a sample of 96 individuals diagnosed with major depression. Using investigator-based measures of life stress, the authors found that, whereas major life events were associated with fewer lifetime episodes, major chronic difficulties were related to more prior episodes. These findings are discussed in terms of underlying mechanisms that may account for the changing role of major life stress over successive recurrences of depression.

Major depressive disorder in adolescence: the role of subthreshold symptoms.

OBJECTIVE: To examine the longitudinal association between individual subthreshold symptoms and onset of major depressive disorder (MDD) in adolescence. METHOD: Data for analysis come from the Oregon Adolescent Depression Project, a prospective epidemiological study of psychological disorders among adolescents, ages 14 to 18 years, from the general community. A total of 1,709 adolescents completed the initial diagnostic assessments between 1987 and 1989 (T1) and approximately 1 year later (T2), 1,507 adolescents returned for readministration of assessments (88% response). RESULTS: After controlling for history of depression and gender, seven of the nine DSM-III-R symptoms of depression predicted MDD incidence when tested in separate models. Endorsement of each symptom at T1 increased the likelihood of MDD incidence between T1 and T2. A summary model that included the seven DSM-III-R symptoms as predictors was significant, with sad mood contributing unique variance to the prediction of MDD onset (odds ratio = 2.01). CONCLUSIONS: These findings suggest that much of the variance is shared among symptom predictors and the co-occurrence of symptoms is what constitutes the greatest risk. Moreover, the presence of sad mood contributes additional unique variance to prediction and supports the centrality of depressed mood to MDD.

Life stress and the long-term treatment course of recurrent depression: III. Nonsevere life events predict recurrence for medicated patients over 3 years.

Research has consistently documented the significance of severe life events for onset of major depression. Theory, however, suggests other forms of stress are relevant for depression's recurrence. Nonsevere life events were tested in relation to depression for 126 patients with recurrent depression in a 3-year randomized maintenance protocol. Life stress was assessed every 12 weeks and rated along dimensions of severity, focus, and independence. A significant interaction between specific types of nonsevere life events and medication was found. For medicated patients, subject-focused independent nonsevere life events predicted recurrence; for unmedicated patients, these events predicted fewer recurrences. Other nonsevere life events did not predict recurrence. The findings underscore the potential importance of specific stressors for triggering recurrences of depression.

Severe melancholic depression is more vulnerable than non-melancholic depression to minor precipitating life events.

BACKGROUND: The present study examines the moderating role of global depression severity on the relation of melancholic versus non-melancholic depression to severe and non-severe levels of stress. METHOD: A community sample of 50 women with unipolar major depressive disorder, of which 54% met Research Diagnostic Criteria for melancholic depression, were interviewed regarding stressful life events experienced prior to onset. Events were coded as severe or non-severe based on the rigorous Bedford College contextual rating system. RESULTS: Greater severity of depression was related to a higher likelihood of a severely stressful event prior to onset only for women with non-melancholic major depression. By contrast, greater severity of depression was related to a higher likelihood of a non-severe, more minor, stressful event prior to onset only for women with melancholic major depression. LIMITATIONS: The present study was limited by its use of a female volunteer sample, which might not be entirely representative of the population of individuals with major depression. In addition, the study employed a cross-sectional design, which limits conclusions relating to the causal relation of stress to melancholic versus non-melancholic depression. CONCLUSIONS: Far from being autonomous of stress, individuals with severe melancholic depression may be especially sensitive to stress, such that their episodes are influenced by more minor stressors than those of individuals with non-melancholic depression.

Life stress, the "kindling" hypothesis, and the recurrence of depression: considerations from a life stress perspective.

Major depression is frequently characterized by recurrent episodes over the life course. First lifetime episodes of depression, however, are typically more strongly associated with major life stress than are successive recurrences. A key theoretical issue involves how the role of major life stress changes from an initial episode over subsequent recurrences. The primary conceptual framework for research on life stress and recurrence of depression is the "kindling" hypothesis (R. M. Post, 1992). Despite the strengths of the kindling hypothesis, a review of the research literature reveals inconsistencies and confusion about life stress and its implications for the recurrence of depression. Adopting a life stress perspective, the authors introduce 3 major themes that resolve the inconsistencies in the current literature. They integrate these themes and extrapolate the ideas with available data to develop a preliminary framework for evaluating competing explanatory models and to guide research on life stress and the recurrence of depression.