Prognostic factors in major depression: a long-term follow-up study of 323 patients

BACKGROUND: Optimal long-term treatment of major depression should assess the background factors affecting remission and recurrent episodes. The duration and number of previous depressive episodes has been shown to be important for recurrence. This long-term prospective study of patients with major depression assessed the prognostic effect of variables related to childhood, social life and occupation. METHODS: The study examined 323 patients in two follow-up examinations 12-25 years from the initial examination to the second follow-up. Stepwise logistic regression was used to evaluate the prognostic effect for depression at the second follow-up. RESULTS: The risk of depression at the second follow-up was associated with several psychosocial factors in childhood, female gender, social isolation and a negative attitude towards one's own occupation. LIMITATIONS: The patient group was selected from the practice of only one psychiatrist. CONCLUSIONS: Several psychosocial factors in childhood, female gender, social isolation and a negative attitude towards one's own occupation have previously been shown to be associated with the risk of depression. The results in this study suggest that these factors are also important in predicting the outcome of a major depressive episode and the risk of recurrent episodes.     

Childhood adversity,gender and depression over the life-course

BACKGROUND: Full investigation of hypotheses concerning early risk factors and episodes of depression in adult life requires consideration of the separate risks of first onset and of recurrent episodes. This paper is based upon such an investigation. METHODS: A sample of participants in a large-scale population study (n=3491) provided information through retrospective assessment of lifetime history of (putative) major depressive disorder and of their adverse experiences in childhood. A statistical model based on Poisson regression, that combined both the (survival) distribution of first onset times with the subsequent rate of episode recurrence was specified to permit investigation of the gender difference in lifetime depression and the influence of childhood adversities on adult depression. RESULTS: A gender difference (with women at increased risk) was revealed for first onsets of depression only and was found to decrease with increasing age, being no longer apparent in those aged over 50. Experience either of a frightening event or of physical abuse in childhood was associated with an increased risk of first onset in younger adults (those aged < or =30). LIMITATIONS: The method of data collection used in this study warrants some caution in the interpretation of substantive findings. CONCLUSIONS: The relationships revealed concerning the risk for early and for late first onset and the risk of recurrence suggest different causal pathways underlying the associations between risk factors experienced early in life and depression in adulthood. Analyses that take full account of episode history can aid understanding of the origins of depression in adulthood.     

Predicting time to recovery among depressed adolescents treated in two psychosocial group interventions

Aims were to identify the demographic, psychopathology, and psychosocial factors predicting time to major depressive disorder (MDD) recovery and moderators of treatment among 114 depressed adolescents recruited from a juvenile justice center and randomized to a cognitive behavioral treatment (CBT) condition or a life skills-tutoring control condition. Nine variables predicted time to recovery over 1-year follow-up (e.g., earlier MDD onset, attention-deficit/hyperactivity disorder, functional impairment, hopelessness, negative thoughts, low family cohesion, coping skills); suicidal ideation and parental report of problem behaviors were the best predictors. CBT resulted in faster recovery time relative to control treatment, specifically among adolescents of White ethnicity, with recurrent MDD, and with good coping skills. Results suggest that psychopathology plays a more prominent role in maintaining adolescent depression than demographic or psychosocial factors.     

A 3.5-year naturalistic follow-up study of depressed out-patients

Outcome studies of patients suffering from depression indicate high relapse rates and a tendency towards chronicity. The present study describes the long-term outcome of 95 depressed outpatients in a third-level referral centre. and examines the relationship between baseline-variables (age, sex, level of psychopathology, age at onset of first psychiatric disorder, duration of illness at baseline, diagnosis) and outcome variables. After 3.5 years, 34 patients (36%) had a chronic course, 24 patients (25%) had at least one recurrence and 37 patients (39%) had a non-recurrent course. Chronicity was significantly correlated with an early age of onset of the first psychiatric disorder, a high level of psychopathology and a high level of depressive symptoms at baseline. The duration of depression at index did not differentiate chronic course from recurrent or non-recurrent course. After 1 year of follow-up, patients with recurrence were significantly more likely to stop antidepressant treatment. The results confirm the great chance for chronicity and recurrence in depression and the need to develop long-term treatment programs to prevent relapse.     

Perinatal risk factors for schizophrenia: diagnostic specificity and relationships with maternal psychopathology

Although a growing body of evidence supports the hypothesis that exposure to obstetric complications (OCs) increases the vulnerability for schizophrenia, some questions remain unanswered regarding the diagnostic specificity and the etiological significance of this association. Associations with a history of OCs have been reported for other severe psychiatric disorders, such as autism, anorexia nervosa, or psychotic affective disorder. Thus, OCs may increase in a relatively non-specific way the vulnerability for a range of severe mental disorders, the expression of this vulnerability depending on the interaction between OCs and other risk factors, such as the genetic liability for specific psychiatric disorder, or exposure to later environmental risk factors. The causal pathway between OCs, maternal psychopathology, and psychotic outcome in the offspring is not fully elucidated. The directions of the associations are often bi-directional, and the mediating variables, if any, are not clearly identified. OCs may have a direct negative impact on fetal brain development, may be on the causal pathway between prepartum maternal depression/exposure to stress and increased risk of schizophrenia, or may indirectly increase the risk of child's later psychiatric disorder by acting as risk factors for maternal postpartum depression. The links and possible interactions between somatic perinatal risk factors and maternal psychopathology in the association with offspring's increased vulnerability for psychosis have to be further explored.     

Aging and depression: Vulnerability and stress across adulthood

This paper reviews research on the relationship between age and depression in adulthood, with a focus on depression in late life. Age differences in prevalence rates of major depression and depressive symptomatology raise questions about presentation and measurement of depression across adulthood, and suggest a changing salience of risk factors for depression from young adulthood through old age as well as to cohort differences in risk for depression. Applying a developmental perspective on biological change, psychological adaptation, and stress processes throughout adulthood shows that risk for depression onset in young adults is typified more through psychological vulnerability and stress, as well as genetic factors, while risk for depression in older adults typified more through comorbid medical and neurological disorder. Implications for research and clinical practice are discussed. This review of the relationship of age to depression shows that the study of psychopathology and adult development can inform each other.     

Socio-economic status, family disruption and residential stability in childhood: relation to onset, recurrence and remission of major depression

BACKGROUND: Childhood adversity significantly increases the risk of depression, but it is unclear whether this risk is most pronounced for depression occurring early in life. In the present study, we examine whether three aspects of childhood adversity--low socio-economic status (SES), family disruption, and residential instability--are related to increased risk of depression during specific stages of the life course. We also examine whether these aspects of childhood adversity are related to the severity of depression. METHOD: A sample of 1089 of the 4140 births enrolled in the Providence, Rhode Island cohort of the National Collaborative Perinatal Project was interviewed between the ages of 18 and 39. Measures of parental SES, childhood family disruption and residential instability were obtained upon mother's enrolment and at age 7. Age at onset of major depressive episode, lifetime number of depressive episodes, and age at last episode were ascertained via structured diagnostic interviews. Survival analysis was used to identify risk factors for depression onset and remission and Poisson regression was used to model the recurrence rate of depressive episodes. RESULTS: Low parental SES, family disruption and a high level of residential instability, defined as three or more family moves, were related to elevated lifetime risks of depression; the effects of family disruption and residential instability were most pronounced on depression onset by age 14. Childhood adversity was also related to increased risk of recurrence and reduced likelihood of remission. CONCLUSIONS: Childhood social disadvantage significantly influences risk of depression onset both in childhood and in adulthood. Early childhood adversity is also related to poor prognosis.     

Life stress, chronic subclinical symptoms and vulnerability to clinical depression

Prospective enquiries of the role of social factors in the aetiology of depression are faced with the problem of who to exclude from the enquiry in terms of psychiatric symptomatology present at first contact. With this problem in mind the role of subclinical symptoms among women not cases of depression has been examined in terms of their relation with a subsequent onset of caseness depression. Psychosocial factors of particular importance in the development of such depression were low self-esteem, marked long-term difficulties and severe life events arising out of (or 'matching') these difficulties. These psychosocial factors were also correlated with the presence of subclinical symptoms. It is concluded that although subclinical symptoms relate to a raised risk of subsequent depression at a caseness level there is no evidence that there is inherent vulnerability stemming from such subclinical symptoms over and above that explained by the psychosocial correlates.     

Life Stress as a Risk Factor for Postpartum Depression: Current Research and Methodological Issues

There is compelling evidence to suggest that acute adverse life events and certain stressors specific to motherhood increase the risk of maternity blues and diagnoses of postpartum depression. Other psychosocial factors that are likely to explain vulnerability to postpartum depression include previous history of depression and the stress-moderating effects of social support and coping responses. This article reviews the emerging empirical literature on stress and postpartum depression and presents a discussion of methodological issues relevant to advancing this area of research. Multivariate models that examine the interplay of these variables are now required to further our understanding of these syndromes.     

Lack of coordination of nonverbal behaviour between patients and interviewers as a potential risk factor to depression recurrence: vulnerability accumulation in depression

BACKGROUND: Coordination of nonverbal behaviour during interactions is a prerequisite for satisfactory relationships. Lack of coordination may form a risk factor for depression. The 'vulnerability-accumulation hypothesis' assumes that vulnerability to recurrence of depression will increase with increasing experience of depressive episodes. Therefore it is expected that interviewers and patients remitted from a recurrent episode of depression would reach less coordination during a clinical interview compared to interviewers and patients remitted from a first lifetime episode. Moreover, we assumed that prior severity of depression modifies this reciprocal coordination process. METHODS: During discharge interviews, interviewers were videotaped in interaction with remitted patients with unipolar major depression recurrent depression (REC); n=28; first episode (SEP); n=22. Durations and frequencies of nonverbal involvement behaviour was registered during the first 15 min. Involvement of the patients consisted of gesticulating, looking at the interviewer, and general head movements; yes--nodding and hm, hm, yes, yes reflected involvement of the interviewer. Coordination between patients and interviewers was analyzed per 3-min epochs and defined as 'attunement': the absolute difference between patients' and interviewers' involvement. Averaged attunement, its time course and variability (presumably reflecting control of the attunement process) were assessed. RESULTS: The time course of nonverbal attunement differed between the REC and SEP condition. A larger variability of attunement was found in patients remitted from a relatively severely depressed episode, compared to patients remitted from a severe first life time episode. No other significant differences were found. CONCLUSIONS: Partial support was found for the notion that nonverbal vulnerability accumulates in depression and that the severity of prior depression modifies this process.     

The course of depression in individuals at high and low cognitive risk for depression: a prospective study

BACKGROUND: Negative cognitive styles have been shown to prospectively predict depression onset and recurrence. Research has also begun to suggest that cognitive styles may be associated with the course of depression as well. This study examined whether cognitive risk for depression onset also predicts the course of depression in a prospective design. METHODS: One hundred fifty-nine initially nondepressed participants from the Temple-Wisconsin Cognitive Vulnerability to Depression Project who experienced a depressive episode while in the study were followed prospectively for 2.5 years. Four indicators of the course of depression were assessed from diagnostic interviews and questionnaires administered every 6 weeks: the number, severity and duration of episodes and the chronicity of the depression experienced. RESULTS: Cognitive high-risk participants experienced more episodes of depression, more severe episodes, and more chronic courses than low-risk participants. There were no risk group differences observed for the duration of episodes. LIMITATIONS: This study's sample was chosen to include individuals with high and low cognitive vulnerability to depression, potentially limiting the generalizability of the findings to other individuals. Also, the study included some participants with a past history of depression. CONCLUSIONS: Negative cognitive styles predict a worse course of depression as well as rendering an individual prone to depression onset. This highlights that the cognitive factors impacting depression's course overlap, at least partly, with those that initiate depression. Thus, knowledge of a depressed individual's cognitive styles could aid in prognosis and treatment planning.     

The long-term course of depressive disorders in the Lundby Study

BACKGROUND: The Lundby Study is a longitudinal cohort study on a geographically defined population consisting of 3563 subjects. Information about episodes of different disorders was collected during field investigations in 1947, 1957, 1972 and in 1997. Interviews were carried out about current health and past episodes since the last investigation; for all subjects information was also collected from registers, case-notes and key informants. This paper describes the course and outcome of 344 subjects who had their first onset of depression during the follow-up. METHOD: In this study individuals who had experienced their first episode of depression were followed up. Their course was studied with regard to recurrence of depression related to duration of follow-up, transition to other psychiatric disorders including alcohol disorders, as well as incidence and risk factors of suicide. RESULTS: Median age at first onset of depression was around 35 years for individuals followed up for 30-49 years. The recurrence rate was about 40% and varied from 17% to 76% depending on length of follow-up. Transition to diagnoses other than depression was registered in 21% of the total sample, alcohol disorders in 7% and bipolar disorder in 2%. Five per cent committed suicide; male gender and severity of depression were significant risk factors. CONCLUSION: The low rates of recurrence and suicide suggest a better prognosis for community samples than for in- and out-patient samples.     

Cognitive reactivity and vulnerability: empirical evaluation of construct activation and cognitive diatheses in unipolar depression

Cognitive vulnerability is a central concept in cognitive theories of unipolar depression. This idea suggests that negative cognitive factors emerge during stressful situations, and that this cognitive reactivity is critical for the onset, relapse, and recurrence of depression. The number of empirical investigations that model the diathesis-stress nature of cognitive reactivity has substantially increased within the last decade. This review examines this literature, with a focus on priming and longitudinal designs. Extant research supports the concept of cognitive vulnerability to depression among adults, and support is accruing for the validity of this concept among children. Research that examines direct links between cognitive vulnerability and depression onset, relapse, and recurrence and the attachment origins of cognitive vulnerability is also accruing, although at a slower pace.     

The transmission of risk to children from mothers with schizophrenia: a developmental psychopathology model

Research in children of mothers with schizophrenia (HRsz children) has focused on identifying the early antecedents of adult illness to understand its intergenerational (primarily genetic) transmission. From a developmental psychopathology perspective, the vulnerability of HRsz children may result from multiple environmental factors interacting with ongoing developmental processes. The objectives were: (1) to understand the extent to which having a mother with schizophrenia impacts on developmental and clinical trajectories; (2) to review whether research supports a proposed model for the non-genetic transmission of risk in HRsz offspring; (3) to discuss the implications of the model for early intervention. HRsz children show vulnerability in a range of areas throughout childhood, but the findings are not unanimous in any single domain, and poor developmental functioning in any given domain does not necessarily predict morbidity. Broad support for a developmental psychopathology model is provided by studies suggesting a generalised vulnerability and studies on the impact of psychosocial factors. However, little empirical research has elucidated specific proximal social environmental influences through development. Gaps in the literature are identified where studies in depressed mothers and other groups are potentially informative, and which suggest that conventional psychological therapies may not be sufficient to enhance offspring outcomes. Future research could inform our understanding of developmental psychopathology and the development of preventative interventions.     

The natural history of late-life depression: results from the Amsterdam Study of the Elderly (AMSTEL)

BACKGROUND: This study examines whether risk factors related to incidence of depression are also related to prognosis, and whether a vulnerability-stress model can be established for prognosis. METHODS: A prospective model for prognosis of depression (chronic or remitted course) in later life was studied in 236 depressed community-living elderly. Subjects were interviewed at baseline, and at follow-up 3 years later. Bivariate and multivariate relationships between risk factors and chronic depression (GMS-AGECAT) were assessed. Effect modification was studied between stressors and two types of vulnerability: vulnerability through a personal history of depression, and gender. RESULTS: A personal history of depression, baseline functional limitations and incident anxiety syndrome predicted chronic depression, whereas life-events occurring between assessments, and changes in physical, functional or cognitive status did not. In subjects without a previous history, functional disabilities, male gender and receiving instrumental support correlated with a poor prognosis. The prognosis for subjects with a personal history of depression was not affected by other factors. In women, the development of chronicity was more strongly associated with a personal history than in men, whereas in men recent psychosocial and health-related characteristics were more important than in women. LIMITATIONS: Because the study consisted of two measurements with a 3-year interval, depressive episodes with a short duration may be under-represented. CONCLUSIONS: In the elderly, the impact of risk factors on the course of depression is modified by longstanding vulnerability characteristics, such as a personal history of depression and gender. More recent life stresses are related to prognosis in subjects without a personal history, and in men.     

The psychosocial context of bipolar disorder: environmental, cognitive, and developmental risk factors

In this article, we review empirical research on the role of individuals' current environmental contexts, cognitive styles, and developmental histories as risk factors for the onset, course, and expression of bipolar spectrum disorders. Our review is focused on the following over arching question: Do psychosocial factors truly contribute risk to the onset, course, or expression of bipolar disorders? As a secondary issue, we also address whether the psychosocial risks for bipolar disorders are similar to those for unipolar depression. We begin by discussing the methodological requirements for demonstrating a psychosocial risk factor and the challenges posed by bipolar spectrum disorders for psychosocial risk research. Next, we review the extant studies on the role of recent life events and supportive and non-supportive social interactions (current environment) in bipolar disorders, as well as psychosocial treatments designed to remediate these current environmental factors. We then review the role of cognitive styles featured as vulnerabilities in theories of unipolar depression as risk factors for bipolar disorder alone and in combination with life events, including studies of cognitive-behavioral therapies for bipolar disorder. Finally, we review studies of parenting and maltreatment histories in bipolar disorders. We conclude with an assessment of the state of the psychosocial risk factors literature in bipolar disorder with regard to our guiding questions.     

Prediction of the three-year course of recurrent depression in primary care patients: different risk factors for different outcomes

BACKGROUND: The objectives of this study are: (1) identification of predictors for the three-year course of recurrent depression in the rarely studied, but relevant sample of primary care patients, and (2) investigation whether different outcome indicators, time to recurrence, proportion depression-free time and mean severity of depressive symptoms during follow-up, are associated with different risk factors. METHODS: Depression course was established by assessing 110 patients three-monthly with the Composite International Diagnostic Interview and the BDI, during a three-year period. Eight (groups of) predictors, assessed at baseline, were examined: socio-demographics, parental depression, history and severity of depression, anxiety, coping potential, social dysfunctioning and physical functioning. RESULTS: Time to recurrence was predicted by number of previous episodes (OR=1.91). Both proportion depressive disorder-free time and mean depression severity during follow-up were predicted by: severity of depression (B=-.19 and .21 respectively), anxiety (B=-.32 and .33), social dysfunctioning (B=-.21 and .22) and physical functioning (B=.24 and -.39). Mean severity was additionally predicted by: educational level (B=-.21), duration of the longest prior episode (B=.32), and coping potential (B=-.40). Coping potential and number of previous episodes were marginally significant predictors for all three outcomes. LIMITATIONS: Although substantial, sample size was restricted. CONCLUSION: Different outcome variables are predicted by different risk factors. Restriction to one outcome may lead to missing important determinants of the depression course. Number of prior episodes and coping potential seem to warrant special attention from the GP.     

Life events, difficulties and onset of depressive episodes in later life.

BACKGROUND: The importance of stressful life events and long-term difficulties in the onset of episodes of unipolar depression is well established for young and middle-aged persons, but less so for older people. METHOD: A prospective case-control study was nested in a large community survey of older people. We recruited 83 onset cases during a 2-year period starting 2 1/2 years after the survey, via screening (N = 59) and GP monitoring (N = 24), and 83 controls, a random sample from the same survey population. We assessed depression with the PSE-10 and life stress exposure with the LEDS. RESULTS: Risk of onset was increased 22-fold by severe events and three-fold by ongoing difficulties of at least moderate severity. Severe events accounted for 21% of all episodes but ongoing difficulties for 45%. The association of onset with life stress, often health-related such as death, major disability and hospitalization of subject or someone close, was most pronounced in the cases identified by screening. While a clear risk threshold for events was found between threat 2 and 3 (on a scale of 1-4), the risk associated with difficulties increased more gradually with severity of difficulty. Compared with controls, severe events involved a larger risk for cases without a prior history of depression (OR = 39.48) than for cases with (OR = 8.86). The opposite was found for mild events (OR = 2.94 in recurrent episodes; OR = 1.09 in first episodes). The impact of ongoing difficulties was independent of severity of episode and history of depression. CONCLUSION: Although the nature of life stress in later life, in particular health-related disability and loss of (close) social contacts, is rather different from that in younger persons, it is a potent risk factor for onset of a depressive episode in old age. Severe events show the largest relative risk, but ongoing difficulties account for most episodes. The association of severe events with onset tends to be stronger in first than in recurrent episodes. Mild events can trigger a recurrent episode but not a first one.     

Antidepressant monotherapy in pre-bipolar depression; predictive value and inherent risk

OBJECTIVE: To identify specific treatment-emergent symptoms in response to antidepressant therapy in depression preceding bipolar disorder. METHODS: Retrospective chart review of response to antidepressants in "pre-bipolar" depression, compared to a matched unipolar sample. RESULTS: Family history of completed suicide (p=0.0003) and bipolar disorder (p=0.004) were more common in the pre-bipolar subgroup. Earlier age of onset of diagnosed depression (p=0.005) as well as even earlier episodes of untreated retrospectively diagnosed major depression (p<0.0001) were associated with a future bipolar course. The pre-bipolar group was less likely to respond to antidepressant treatment (p=0.009). Treatment-emergent "mixed" symptoms (two or more symptoms of DSM IV mania, mood lability, irritability/rage with co-existing depression) and in particular, "serious symptoms" (treatment emergent or increased agitation, rage or suicidality) occurred more commonly in the bipolar group. The two variables that best accounted for the between-group differences in logistic regression, were early age at first symptoms of depression and treatment-emergent agitation. CONCLUSIONS: Family history of completed suicide and/or bipolar disorder, early onset of depressive symptoms as well as treatment-emergent "mixed" symptoms are common in depression preceding the diagnosis of bipolar disorder.     

The effect of the first manic episode in affective disorder: a case register study of hospitalised episodes.

BACKGROUND: It is poorly understood how the course of illness in depressive patients is affected by a manic episode. METHOD: The course of hospitalised episodes was compared for patients with depressive episodes only, patients who presented with a manic or circular first episode and patients who presented with a depressive first episode and later developed mania. The Danish psychiatric central register was used as a study base, including all hospital admissions with primary affective disorder in Denmark during 1971-1993. RESULTS: A total of 17,447 patients presented with a depressive first episode and 2903 patients with a manic or circular first episode. Among the 17,447 depressive patients, 762 patients presented with mania at later episodes (4.4%). Younger age at onset was associated with increased risk of developing mania. Patients who had a late first manic episode had the same rate of subsequent recurrence as patients with mania at first episode and this rate was higher than the rate of recurrence for patients who remained having depressive episodes only. Time since first manic episode was without importance in relation to the risk of subsequent recurrence. CONCLUSION: Patients who present with depression and later develop mania have from onset the same risk of recurrence as initially bipolar patients. LIMITATION: The data relate to admissions rather than episodes. CLINICAL RELEVANCE: Younger patients who present with depression have increased risk of developing bipolar disorder.