Stressful life events severity in patients with first and recurrent depressive episodes

Background

Stressful life events are associated with depression and their role in first onset and recurrences is a promising but controversial perspective of research. The objective is to analyze the role of number of previous episodes and life events exposure in a large sample of primary care depressive patients taking into account life events severity.

Method

10,257 patients with DSM-IV criteria for a current single or recurrent major depressive episode were recruited by 2,056 general practitioners in a cross-sectional epidemiological study. Patients answered the Montgomery-Asberg Depression Rating Scale, the Patient Health Questionnaire and the Social Readjustment Rating Scale (SRRS). Stressful life events were categorized into three levels of severity (severe, moderate and mild). All relevant confounding variables were analyzed: age, gender, depression severity, somatic symptoms severity and length of episode.

Results

We found a significant positive correlation with number of episodes and depression severity. There was no significant correlation of SRRS scores with age, gender and length of episode. ANOVA exploring life events severity with regard to number of episodes showed statistically differences in SRRS total score, moderate life events and mild life events (F = 15.14, p < 0.001) but not for severe life events.

Conclusions

Prevention and treatment strategies for recurrent depression need to manage life stressful events during mild and long-term periods and not just in the initial recurrences of the disease.     

Emotional information processing in first and recurrent major depressive episodes

Depressive states are classically associated to increased sensitivity to negative events. However this hypersensitivity may not be stable in time, being absent in remission periods or further reinforced with recurrent depressive episodes, or may concern positive stimuli instead, e.g. in young depressive patients. To study the evolution of the processing of emotional information in depression we recorded late components of evoked potentials in first-episode and recurrent depressed patients before and after recovery. We used a visual attentional paradigm manipulating the processing of emotional information. Subjects first counted words with positive valence, and then words with negative valence from lists of usual words. The results showed that recurrent patients had increased P300 amplitudes for negative words selection only in negative words counting situation, while first-episode patients had decreased P300 amplitudes for positive words selection. After clinical improvement, the negative biases in recurrent patients group disappeared but P300 amplitudes of first-episode patients remained significantly low for positive words. First-episode depressed patients show a selective impairment for positive stimuli, with decreased response to pleasant stimuli, while recurrent depressive subjects show signs of hyperesthesia for negative stimuli. These results suggest that responses to emotional stimuli in word processing are related to the duration of the mood disorders.     

The interrelationship of neuroticism, sex, and stressful life events in the prediction of episodes of major depression

OBJECTIVE: Three potent risk factors for major depression are female sex, the personality trait of neuroticism, and adversity resulting from exposure to stressful life events. Little is known about how they interrelate in the etiology of depressive illness. METHOD: In over 7,500 individual twins from a population-based sample, the authors used a Cox proportional hazard model to predict onsets of episodes of DSM-III-R major depression in the year before the latest interviews on the basis of previously assessed neuroticism, sex, and adversity during the past year; adversity was operationalized as the long-term contextual threat scored from 15 life event categories. RESULTS: In the best-fit Cox model for prediction of depressive onsets, neuroticism, female sex, and greater adversity all strongly increased risk for major depression. An interaction was seen between neuroticism and adversity such that individuals with high neuroticism were at greater overall risk for major depression and were more sensitive to the depressogenic effects of adversity. An interaction was also seen between adversity and sex, as the excess risk for major depression in women was confined to individuals with low stress exposure. CONCLUSIONS: Psychosocial adversity interacts both with neuroticism and with sex in the etiology of major depression. The impact of neuroticism on illness risk is greater at high than at low levels of adversity, while the effect of sex on probability of onset is the opposite--greater at low than at high levels of stress. Complete etiologic models for major depression should incorporate interactions between risk factor classes.     

Clinical differences between first and recurrent episodes in depressive patients

Background

Depressive disorder is one of the most common mental disorders in primary care. Depression is often a chronic disorder with recurrent episodes. Little is known about the differences in clinical profile between first and recurrent episodes. The aim of the study is to analyze the differences between clinical presentation of first and subsequent episodes of depressive disorders in primary care patients.

Method

A cross-sectional epidemiologic study in primary care centers in Spain was designed. A total of 10?257 primary care patients having a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition major depressive episode were analyzed. Clinical symptoms were measured using the Montgomery Asberg Depression Scale. Patient Health Questionnaire was used to assess somatic symptoms.

Results

There were 40.6% of patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for recurrent depression. Compared with those diagnosed of their first major depressive disorder, recurrent patients had greater rates and severity of depressive (t = −7.85, P < .001) and somatic symptoms (t = 5.64, P < .001). The severity of symptoms also increases with number of episodes (F = 40.2, P < .001, for depressive symptoms; F = 27.8, P < .001, for somatic symptoms). First-episode patients were more likely to experience reduced appetite (adjusted odds ratio, 1.2) and suicidal thoughts (adjusted odds ratio, 1.2).

Conclusion

There are differences in the clinical profile of initial and recurrent episodes in primary care depressive patients. Each recurrent depressive episode seems to have a greater impact on symptoms and well-being. The identification of a specific depression symptom profile in first or recurrent episodes is needed to improve the long-term management of major depressive episode patients in primary care settings.     

Genetic risk, number of previous depressive episodes, and stressful life events in predicting onset of major depression

OBJECTIVE: The association between stressful life events and the onset of major depression decreases as the number of previous depressive episodes increases. How do genetic risk factors for major depression impact on this "kindling" phenomenon? In particular, do those at high genetic risk exhibit an increase in the speed of kindling, or are they "prekindled"? METHOD: Using discrete-time survival analysis, the authors examined the interaction between genetic risk, number of previous depressive episodes, and life event exposure in the prediction of episodes of major depression in female-female twin pairs from a population-based registry. The twins were interviewed four times over a 9-year period, producing 92,521 person-months of exposure. RESULTS: The decline in the association between stressful life events and risk for major depression as the number of previous depressive episodes increased was strongest in those at low genetic risk and was weak to absent in those at high genetic risk. In the absence of previous depressive episodes, those at high genetic risk frequently experienced depressive episodes without major environmental stressors. CONCLUSIONS: Genetic risk factors for depression produce a "prekindling" effect rather than increase the speed of kindling. The "kindled" state, wherein depressive episodes occur with little provocation, may be reached by two pathways: many previous depressive episodes, perhaps driven by multiple adversities, and high genetic risk.     

The role of life events in onset and recurrent episodes of schizophrenia and schizoaffective disorder

The experience of both positive and negative recent life events has long been recognized as a possible precipitant of episodes of psychiatric illness. Among individuals with recurrent mood disorders, investigators have found that recent life events are more likely to be associated with initial and early episodes of illness, with later episodes less likely to be temporally associated with life events. This study investigated the relationship between recent life events and episodes of illness in schizophrenia (defined as the number of acute episodes of schizophrenia requiring hospitalization). Among 32 male U.S. Military veteran inpatients, those with three or fewer episodes of illness reported significantly more recent life events than those patients with more than three episodes of illness (P = 0.01). Overall, recent life events were negatively correlated with number of episodes (P < 0.05). These data suggest that initial or early episodes of schizophrenic illness are more likely to be associated with recent life events than are later episodes.     

Stressful life events and previous episodes in the etiology of major depression in women: an evaluation of the "kindling" hypothesis

OBJECTIVE: Although previous evidence has suggested that the etiologic role of stressful life events in major depression is reduced in recurrent versus first-onset cases, this question deserves reexamination because of potential methodological limitations of the previous studies. METHOD: Members of female-female twin pairs from a population-based registry (N=2,395), who were interviewed four times over a period of 9 years, formed a study group that contained 97,515 person-months and 1,380 onsets of major depression. Discrete-time survival, proportional hazards model, and piece-wise regression analyses were used to examine the interaction between life event exposure and number of previous depressive episodes in the prediction of episodes of major depression. RESULTS: For those with zero to nine previous depressive episodes, the depressogenic effect of stressful life events declined substantially with increasing episode number. However, the association between stressful life events and major depression was not substantially influenced by additional episodes. This pattern of results was robust to the addition of indices of event severity, measures of genetic risk, and restriction to independent stressful life events. The same pattern was also seen upon examining within-person changes in number of episodes. CONCLUSIONS: The association between previous number of depressive episodes and the pathogenic impact of stressful life events on major depression is likely causal and biphasic. Through approximately nine episodes, the association between stressful life event exposure and risk of major depression progressively declines but is largely unchanged with further episodes. These results are consistent with the kindling hypothesis but suggest a threshold at which the mind/brain is no longer additionally sensitized to the depressive state.     

The persistent risk of chronicity in recurrent episodes of nonbipolar major depressive disorder: a prospective follow-up

The authors report on the course of illness in 101 patients who were in an episode (the "index episode") of major depressive disorder when they entered a clinical research study, recovered from that episode, and then relapsed into a new episode (the "first prospective episode") of the disorder. They found a 22% probability that these patients' first prospective episode would last at least 1 year, similar to the 21% rate of chronicity previously reported for the index episode. A long prior episode, older age, and low family income were found to predict chronicity in the first prospective episode.     

Mastery and neuroticism predict recovery of depression in later life.

OBJECTIVE: The authors examined whether personality characteristics such as mastery, self-efficacy, and neuroticism predict the likelihood of recovery of depression among elderly in the community. It was hypothesized that these personality characteristics do predict recovery but that their effect is overwhelmed by the effect of deteriorations in physical health, cognitive decline, and loss of social resources. The second research question investigated whether these personality characteristics moderate the negative impact of the other prognostic factors on the chance of recovery. METHODS: A prospective (nine-year) follow-up study of 206 depressed elderly (55-85 years at baseline) participants of the Longitudinal Aging Study Amsterdam. Data on chance of recovery were analyzed using Cox proportional regression analyses. RESULTS: Both in the univariate and in the multivariate model, the personality characteristics, especially neuroticism, predicted recovery of depression. The effect of neuroticism was similar to that of physical health and stronger than the impact of cognitive decline or social resources. No support was found for personality as a moderator of the negative impact of age-related stressors. CONCLUSIONS: Personality characteristics, i.e., neuroticism and physical health-related variables are separate but equally important domains for the chance of recovery of depression in later life.     

The dexamethasone suppression test in panic disorder and major depressive episodes

Dexamethasone Suppression Tests (DST) were performed on 30 patients with panic disorder and on 30 patients treated for major depressive episodes in order to seek an answer to the question of whether or not the two disorders have a common biological background. The hypothesis was based on the results of family studies known from the literature and on the favorable therapeutic response obtained with tricyclic antidepressants. Normal suppressive (i.e., negative in our terminology) DSTs were found in 16.7% of the patients with panic disorder and in 56.7% of patients suffering from major depressive episodes. The anxiety indices of the two groups differed significantly from each other. The results do not suggest the possibility of a close genetic relationship between the two conditions.     

Increased prevalence of negative life events in subtypes of major depressive disorder

The prevalence of negative life events is known to be increased among patients with depression. Little data exist on the specific subtypes of depression that are related to negative life events. Our study aimed to address this issue. We compare 115 patients with major depressive disorder (MDD) to 60 normal controls. MDD patients reported experiencing one (P = .0001) or two (P = .01) negative life events more frequently than controls. Patients reported marital, other personal problems, and medical events significantly more often than controls (P < .01). Patients did not report more positive life events, and did not attribute greater severity to their adversities than controls. Younger MDD patients experienced four (P = .01) negative life events significantly more often than older patients. Similarly, patients with mild-moderate depression, nonmelancholic depression, or first episode of depression (FDE), respectively, experienced three or four life events significantly more often than patients with severe, melancholic, or recurrent depression (RDE). Other patient and illness characteristics such as gender, early parental loss, family history of depression or other mental disorders, psychotic features, suicide attempts, and chronicity were not related to increased prevalence of negative life events. Our results support the hypothesis that a subset of patients with MDD is especially prone to suffer from a cluster of negative life events. This subgroup is at increased risk for relapse and poor prognosis. The implications of these results for further research and for treatment are discussed.     

应激性生活事件及相关因素对重性抑郁障碍的影响

重性抑郁障碍（Major Depression Disorder,MDD）是常见的精神疾病,其发病机制尚未完全阐明。近年来,随着社会经济的高速发展,人们面临更多的竞争和压力,应激性生活事件作为可能的危险因素,与MDD的关系受到了学者们的关注,并逐步得到证实,越来越多的研究显示应激性生活事件与MDD有着密切的关系,并在一定程度上增加了MDD的发病风险。现从应激性生活事件诱导MDD的机制、相关调节因素方面就应激性生活事件与MDD的关系进行阐述。     

Preferences for treatment in primary care: a comparison of nondepressive, subsyndromal and major depressive patients

OBJECTIVE: In recent years, patients' preferences concerning treatment of emotional distress in general and of depression in particular have received more emphasis in the clinical setting as well as in research. METHODS: The treatment preferences of 607 primary care patients were assessed in a cross-sectional study using a questionnaire. Besides having the opportunity to choose between psychotherapy and pharmacological treatment, the patients could also decline or choose both treatment options at one time. Moreover, the preferences of subsyndromal, major depression and nondepressive patients were compared. RESULTS: A total of 305 (51%) patients exclusively preferred psychotherapy and 110 (18%) exclusively preferred pharmacological treatment. Although 70 (12%) patients declined both forms of treatment, 113 (19%) could imagine using both treatment options. Patients with subsyndromal depression did not differ from patients with major depression in their preferences. Both groups, however, less frequently declined pharmacological treatment compared to nondepressive patients. CONCLUSIONS: Patients with subsyndromal and major depression are similar in the primary care setting with regard to their treatment preferences. The preference for combination treatment is rather low, which should be considered in routine clinical care [corrected]     

Life events exposure before a treated major depressive episode depends on the number of past episodes.

A cross-sectional survey investigated the relationship between the number of previous depressive episodes and life events, testing the kindling hypothesis, in a sample of 13,377 treated patients with unipolar depression. A linear decline of average life events exposure is observed for more frequent past episodes, even when age, gender and severity are taken into account.     

The effects of neuroticism, extraversion, and positive and negative life events on a one-year course of depressive symptoms in euthymic previously depressed patients versus healthy controls

We investigated a) the concurrent impact of positive and negative life events on the course of depressive symptoms in persons remitted from depression and healthy controls, b) whether the impact of life events on symptom course is moderated by the history of depression and the personality traits of neuroticism and extraversion, and c) whether life events mediate possible relationships of history of depression and personality traits with symptom course. Using data from the Netherlands Study of Depression and Anxiety, we examined 239 euthymic participants with a previous depressive disorder based on DSM-IV and 450 healthy controls who completed a) baseline assessments of personality dimensions (NEO Five-Factor Inventory) and depression severity (Inventory of Depressive Symptoms [IDS]) and b) 1-year follow-up assessments of depression severity and the occurrence of positive and negative life events during the follow-up period (List of Threatening Events Questionnaire). Remitted persons reported higher IDS scores at 1-year follow-up than did the controls. Extraversion and positive and negative life events independently predicted the course of depressive symptoms. The impact of life events on symptom course was not moderated by history of depression or personality traits. The effect of extraversion on symptom course was partly caused by differential engagement in positive life events.     

Duloxetine treatment of major depressive episodes in the course of psychotic disorders

During the course of psychotic disorders, patients often suffer from intercurrent major depressive episodes (MDEs), and suicides frequently occur. This constellation challenges further improvements in psychopharmacological therapy. The antidepressant duloxetine was recently introduced as a novel reuptake inhibitor of serotonin and noradrenaline. We provide the first reports on duloxetine treatment of MDEs in the course of psychotic disorders. In two cases this substance was successfully involved as an add-on to antipsychotic treatment consisting of clozapine or amisulpride. We achieved a response of the MDEs, as reflected by psychopathological rating scales. A significant rise in the clozapine serum level was detected, most likely because of pharmacokinetic interactions. Overall, the application of duloxetine was well tolerated; therefore, further investigations in prospective studies seem to be recommendable.     

The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication

CONTEXT: Prior evidence from twin studies suggested genetic moderation of the depressogenic effects of stressful life events (SLEs). Can the specific genes involved in this effect be identified? OBJECTIVE: To replicate and extend a recent study that a functional variant in the serotonin transporter (5-HTT) might in part explain these findings. DESIGN: Characterizing risk for major depression and generalized anxiety syndrome in the last year as a function of 5-HTT genotype, sex, and the occurrence of SLEs and ratings of the SLE-associated level of threat. SETTING: A population-based sample of adult twins. PARTICIPANTS: Five hundred forty-nine male and female twins with a mean age at participation of 34.9 years (SD 9.1). MAIN OUTCOME MEASURE: Episodes of major depression and generalized anxiety syndrome in the last year with onset measured to the nearest month. RESULTS: Individuals with 2 short (S) alleles at the 5-HTT locus were more sensitive to the depressogenic effects of all SLEs than were those with 1 or 2 long (L) alleles. When level of SLE-associated threat was examined, the interaction between genotype and SLE resulted from an increased sensitivity of SS individuals to the depressogenic effects of common low-threat events. These events had little impact on risk for those possessing the SL and LL genotypes. The 5-HTT genotype did not modify the effects of SLEs on risk for generalized anxiety syndrome. CONCLUSION: Variation at the 5-HTT moderates the sensitivity of individuals to the depressogenic effects of SLEs largely by producing, in SS individuals, an increased sensitivity to the impact of mild stressors. Replication of these intriguing results is needed.     

Social integration,perceived discrimination,and self-esteem in mid- and later life: intersections with age and neuroticism

Objectives: Social relations can influence well-being throughout the life course. Integration in one's community may serve as a source of social support whereas negative interactions such as day-to-day discrimination can be psychosocial stressors, particularly for neurotic persons. Yet social connectedness may vary in importance across the age range. Individuals trim their social networks in later life to optimize emotional well-being, but older adults may also be at heightened risk of social isolation. This study examines the impacts of social integration and perceived discrimination on self-esteem, and whether such impacts differ according to individuals’ age and/or neuroticism.

Method: Random effects models analyzed 2,982 observations from 1,882 individuals who participated in at least one of the two most recent waves of the National Survey of Midlife Development in the United States (2004–2014).

Results: Self-esteem displayed a minor cubic trajectory across the age range, including declines after age 70. Social integration, perceived discrimination, and neuroticism were all significantly associated with self-esteem, in the expected directions. Self-esteem trajectories varied according to the level of social integration, such that low social integration exacerbated later life declines in self-esteem. The influence of social integration on self-esteem was also stronger at higher levels of neuroticism. Perceived discrimination's influence on self-esteem did not vary by participants’ age or neuroticism.

Discussion: Social ties are influential for well-being across the life course, but may take on added importance in later life. Oldest-old and neurotic adults are at particular risk of experiencing low self-esteem if they lack integration with their community.