Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse

BACKGROUND: The study tested whether level of recovery from major depressive episodes (MDEs) predicts duration of recovery in unipolar major depressive disorder (MDD) patients. METHODS: MDD patients seeking treatment at five academic centers were followed naturalistically for 10 years or longer. Patients were divided on the basis of intake MDE recovery into residual depressive symptoms (SSD; N=82) and asymptomatic (N=155) recovery groups. They were compared on time to first episode relapse/recurrence, antidepressant medication, and comorbid mental disorders. Recovery level was also compared to prior history of recurrent MDEs ( > 4 lifetime episodes) as a predictor of relapse/recurrence. RESULTS: Residual SSD compared to asymptomatic recovery patients relapsed to their next MDE > 3 times faster (median=68 vs. 23 weeks) and to any depressive episode > 5 times faster (median=33 vs. 184 weeks). Residual SSD recovery status was significantly associated with early episode relapse (OR=3.65) and was stronger than history of recurrent MDEs (OR=1.64). Rapid relapse in the SSD group could not be attributed to higher comorbidity or lower antidepressant treatment. LIMITATIONS: Although inter-rater agreement on weekly depressive symptom ratings was very high (ICC > 0.88), some error may exist in assigning recovery levels. Antidepressant treatments were recorded, but were not controlled. CONCLUSIONS: MDE recovery is a powerful predictor of time to episode relapse/recurrence. Residual SSD recovery is associated with very rapid episode relapse which supports the idea that SSD is an active state of illness. Asymptomatic recovery is associated with prolonged delay in episode recurrence. These findings of this present study have important implications for the goals of treatment of MDD and for defining true MDE recovery.     

Complex patterns of immediate early gene induction in rat brain following brightness discrimination training and pseudotraining

Data presented during the 1996 CINP President's Workshop supported the conclusion that unipolar major depressive disorder (MDD) is a pleomorphic mood disorder consisting of a cluster of depressive subtypes existing in a relatively homogeneous symptomatic clinical continuum, extending from subsyndromal depressive symptomatology (SSD) through minor depressive episode, dysthymic disorder, major depressive episode and double depression. This indicates that common unipolar depressive subtypes can be conceptualized as alternate forms or different symptomatic phases of the same parent illness. Although there appears to be great overlap across time in the symptomatological expressions of these clinical depressive subtypes, they may be derived from different etiological and genetic factors. The one exception may be major depressive episode with psychotic features, which exists on a severity continuum with other subtypes of unipolar MDD, but does not appear to be on a symptomatic continuum with dysthymic, subsyndromal or minor depressions. By contrast, SSD and minor depressive disorder represent clinically significant depressive subtypes, which are commonly observed during the course of illness of patients with unipolar major depressive illness. Compared to no depressive symptoms, SSD is associated with harmful dysfunction, as evidenced by significant increases in psychosocial impairment, signifying that SSD is an active, inter-episode disease state of unipolar major depressive disorder. Finally, SSD, possibly jointly with subthreshold anxiety symptoms, may also represent potent risk factors for rapid depressive episode relapse. In the aggregate, these findings and conclusions have broad and important implications for diagnostic and treatment strategies of unipolar MDD.     

Minor depressive disorder and subsyndromal depressive symptoms: functional impairment and response to treatment

BACKGROUND: This study quantifies functional impairment and depressive symptomatology in patients with minor depressive disorder (MinD) and subsyndromal depressive symptomatology (SSD) before and after 8 weeks of treatment with fluvoxamine. Study patients were compared and contrasted with archival data from a sample of the general population measured by the Medical Outcome Survey Short Form 36. METHOD: Fifteen patients with MinD and 15 patients with SSD were identified from primary care clinics, referrals and newspaper advertisements. Patients signed informed consent and were offered open label treatment with fluvoxamine 25-100 mg/day. Patients were seen biweekly and measures of functional impairment and depressive symptomatology were gathered systematically. RESULTS: MinD and SSD were associated with dysfunction and disability when compared to archival normative data from the general population. Eight week treatment with fluvoxamine was associated with a substantial decrease in depressive symptomatology and a normalization of psychosocial functioning. CONCLUSION: This is the first study to quantify functional impairment and the severity of depressive symptomatology in a clinical sample of patients with MinD and SSD, and to demonstrate that treatment with a selective serotonin reuptake inhibitor decreases depressive symptomatology and improves psychosocial functioning. Placebo-controlled double-blind confirmation of these preliminary observations seems warranted.     

The symptomatic expression of major depressive disorder in adolescents and young adults.

Data from the Oregon Adolescent Depression Project were used to examine the symptomatic expression of major depressive disorder (MDD) as a function of age and gender. The objective was to investigate the phenomenological nature of MDD among a cohort of adolescents as they progressed into early adulthood. The analyses were based on 564 participants who had experienced MDD in their lifetime. No systematic differences in the relative rate of occurrence of specific symptoms across episodes and only minor symptom differences between male and female participants were found. Age did not significantly influence the symptom picture. Stability of specific symptoms and episode severity across episodes was low. The results are discussed within the context of a stressor-symptom matching model. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prevalence of depressive symptoms early in the course of schizophrenia

OBJECTIVE: The rate of depressive symptoms early in the course of schizophrenia was determined. METHOD: Seventy subjects with recent-onset schizophrenia were followed for 5 years by using semistructured interview instruments. The initial assessment included ratings of each criterion A symptom of a DSM-III-R major depressive episode. The rates of symptoms experienced with at least moderate severity were calculated, and an algorithm based on DSM identified subjects meeting the criteria for a major depressive episode. RESULTS: Four symptoms were present to at least a moderate degree in a majority of subjects, while no symptom was present in fewer than 12% of subjects. More than one-third of the subjects met the algorithmic criteria for a major depressive episode at the time of intake. CONCLUSIONS: Depressive symptoms are common early in the course of schizophrenia. This finding is consistent with other recent data and has potential implications for current diagnostic and treatment practices.     

Effect of arginine vasopressin (AVP) inhibitor in the inhibition of the peritumoral edema

BACKGROUND: Major depressive disorder is often marked by repeated episodes of depression. We describe recovery from major depression across multiple mood episodes in patients with unipolar major depression at intake and examine the association of sociodemographic and clinical variables with duration of illness. METHODS: A cohort of 258 subjects treated for unipolar major depressive disorder was followed up prospectively for 10 years as part of the Collaborative Depression Study, a multicenter naturalistic study of the mood disorders. Diagnoses were made according to the Research Diagnostic Criteria, and the course of illness was assessed with the Longitudinal Interval Follow-up Evaluation. Survival analyses were used to calculate the duration of illness for the first 5 recurrent mood episodes after recovery from the index episode. RESULTS: Diagnosis remained unipolar major depressive disorder for 235 subjects (91%). The median duration of illness was 22 weeks for the first recurrent mood episode, 20 weeks for the second, 21 weeks for the third, and 19 weeks for the fourth and fifth recurrent mood episodes; the 95% confidence intervals were highly consistent. From one episode to the next, the proportion of subjects who recovered by any one time point was similar. For subjects with 2 or more recoveries, the consistency of duration of illness from one recovery to the next was low to moderate. None of the sociodemographic or clinical variables consistently predicted duration of illness. CONCLUSION: In this sample of patients treated at tertiary care centers for major depressive disorder, the duration of recurrent mood episodes was relatively uniform and averaged approximately 20 weeks.     

Family functioning and mood disorders: A comparison between patients with major depressive disorder and bipolar I disorder.

Within a sample of patients with major depressive disorder (MDD; n = 121) and bipolar affective disorder (BPAD; n = 69), the authors examined (a) diagnostic differences in family functioning at acute episode, (b) diagnostic differences in family functioning at episode recovery, (c) within-group changes in family functioning from acute episode to recovery, and (d) whether within-group changes from acute episode to recovery varied by diagnosis. Using a multidimensional model, the authors evaluated interviewer, patient, and family ratings. Overall, patients with MDD and BPAD evidenced similar levels of family impairment at acute episode and recovery. Generally, patients in both groups experienced improvement in family functioning over time, yet mean scores at recovery continued to range from fair to poor. Although certain specific differences emerged, diagnostic groups appeared to be more similar than different in level and pattern of family functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive patterns and major depressive disorder: A longitudinal study in a hospital setting.

Assessed the cognitive patterns of individuals suffering from unipolar major depressive disorder, episodic and nonpsychotic type, shortly after admittance to an inpatient psychiatric facility and again shortly before discharge. In addition to the depressive group, a nondepressed psychiatric and a nondepressed normal group were administered the same measures (Hopelessness Scale, the Dysfunctional Attitude Scale, and the Attributional Style Questionnaire) at comparable points in time. In contrast to the concept of a traitlike depressive cognitive style that persists beyond remission of the current depressive episode, the depressives showed dramatic changes on all of the cognitive measures as their symptoms abated. Results suggest that unipolar major depressive disorder, episodic and nonpsychotic type, may be heterogeneous with respect to cognitive patterns. Whereas a sizeable group of Ss suffering from this disorder exhibited the hypothesized depressive cognitive profile during the depressive episode, others did not. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Predicting response to depression treatment: The role of negative cognition.

Repeated experiences with major depressive disorder (MDD) may strengthen associations between negative thinking and dysphoria, rendering negative cognition more accessible and pronounced with each episode. According to cognitive theory, greater negative cognition should lead to a more protracted episode of depression. In this study of 121 adults with MDD, number of previous episodes was associated with slower change in depression across inpatient and outpatient treatment. Further, although pretreatment negative cognition and pretreatment family impairment both uniquely predicted slower change in depressive symptoms, only negative cognition mediated the association between depression history and depression change. Findings suggest that repeated MDD episodes are specifically associated with increased negative cognition, which in turn contributes to a more pernicious course of symptom change during treatment for depression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The early course of depression: A longitudinal investigation of prodromal symptoms and their relation to the symptomatic course of depressive episodes.

The present study explored longitudinal evidence for prodromal symptoms of depression episodes. A model based on previous findings of the relations between prodromal and residual symptoms was described and used to generate hypotheses tested in this study. Data were analyzed from 160 participants from the Cognitive Vulnerability to Depression (CVD) project (L. Alloy & L. Abramson, 1999) who experienced an episode of depression during the prospective follow-up period and 60 CVD participants who did not. Congruent with the hypothesis, individuals who subsequently developed an episode of depression experienced significantly greater numbers of depression symptoms in the period of time leading up to the acute episode compared with those who did not develop a depressive episode. Seven depression symptoms were particularly likely to appear before the onset of an acute episode. Furthermore, all 3 predictions from the model were supported: the durations of prodromal and residual phases were correlated, the prodromal and residual symptom profiles were quite similar, and the order of symptom onset was significantly and highly negatively correlated with the order of symptom remission. Additionally, residual symptom profiles were similar to subsequent prodromal symptom profiles in individuals who experienced more than 1 depressive episode. These findings are discussed in terms of the importance of understanding the earliest prodromal symptoms to appear and their relation to the symptomatic course of depression episodes. Implications for early intervention are also discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinical characteristics of patients with concurrent major depressive disorder and panic disorder

OBJECTIVE: This study was designed to test the hypothesis that patients with both major depressive disorder and panic disorder exhibit more clinical symptoms and have a more protracted course of illness than patients with major depressive disorder only. METHOD: The authors compared standardized clinical evaluations (from Schedule for Affective Disorders and Schizophrenia interviews) of 119 patients with major depressive disorder only and 57 patients with major depressive disorder and concurrent panic disorder. Clinical and demographic variables were included. RESULTS: The patients with both disorders reported symptoms of major depressive disorder earlier in life and also required treatment and hospital admission earlier in life. Many clinical features during the index episode were significantly more severe in the patients with both disorders. A logistic regression identified a "panic index" consisting of the symptoms of somatic anxiety, phobia, indecisiveness, and feelings of inadequacy. Scores on this index allowed proper classification of patients to either of the two diagnostic groups with high reliability. CONCLUSIONS: In major depressive disorder, the presence of panic disorder is suggestive of a more severe and precocious form of illness.     

Toward a generalizable model of symptoms in major depressive disorder

BACKGROUND: This study has two goals: 1) to establish a generalizable model of the symptoms observed in outpatients with major depressive disorder (MDD); and 2) to compare symptom coverage of the Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) to that of the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). METHODS: A factor analysis of IDS-C, IDS-SR, HDRS, and BDI items was carried out on 324 adult outpatients with MDD. Patients with coexisting Axis I or III illness or those taking psychotropic medication were excluded. RESULTS: Ten primary factors were identified, six of which were substantially intercorrelated, defining a second-order factor of general depression severity. Schmid-Leiman orthogonalization identified the symptoms most associated with general severity. CONCLUSIONS: The IDS provided more complete factors coverage than did the HDRS or BDI and thus may be more useful in research on symptom profiles.     

Serotonergic function and negative and depressive symptomatology in schizophrenia and major depression

BACKGROUND: Serotonergic abnormalities are found in both major depressive disorder (MDD) and schizophrenia. Depressive symptoms commonly occur alongside the negative or defect symptoms in schizophrenia and antiserotonergic drugs may be particularly effective in their treatment. We wished to explore whether these symptoms could be distinguished biologically by directly comparing serotonergic function in these two illnesses. METHOD: Fifteen patients with MDD and 13 patients with schizophrenia underwent testing with the specific serotonin releasing agent D-fenfluramine (D-FEN). Prolactin and cortisol responses were measured to ascertain central serotonergic function. Individual patient results were compared with their own carefully matched control to correct for the effect of age, sex, weight and menstrual cycle, before the two patient groups were then compared. RESULTS: Prolactin responses differed significantly between the two patient groups, being lower in MDD patients and higher in schizophrenia patients than their individually matched controls. Cortisol responses did not differ. Within the schizophrenia group, increased serotonergic function correlated positively with depressive symptoms, but there was no such correlation with defect symptoms. Depressive scores were negatively correlated with the presence of negative symptoms in the schizophrenic group. CONCLUSIONS: Schizophrenia and MDD have distinct and opposite neuroendocrine responses to D-FEN. There is no evidence that depressive symptoms in these two conditions have a common serotonergic basis. Moreover, these responses distinguished between negative and depressive symptoms in our schizophrenic group.     

Psychosocial predictors of the short-term course and outcome of major depression: A longitudinal study of a nonclinical sample with recent-onset episodes.

Three variables have been hypothesized to play important roles in prolonging the course of depressive episodes: a ruminative response style, significant interpersonal relationships, and childhood adversity. The authors examined whether these variables predicted the short-term course of major depressive disorder (MDD). Participants (n/&=/&84) were college students with a recent-onset major depressive episode. Assessments included several interview and self-report measures, and data on interpersonal relationships were obtained from close confidants. Follow-up interviews were conducted 6 mo later. After controlling for baseline severity, harsh discipline in childhood significantly predicted mean level of depression across the follow-up and level of depression at follow-up. Harsh discipline was also significantly associated with relapse but not with recovery. After controlling for baseline severity, rumination and the interpersonal variables did not predict the outcome of MDD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spectral properties of human cognition and skill

PURPOSE: To identify the predictors of depressive and anxiety disorders in general medical patients presenting with physical complaints and to determine the effect of these mental disorders on patient outcome. PATIENTS AND METHODS: In this cohort study, 500 adults presenting to a general medicine clinic with a chief complaint of a physical symptom were interviewed with PRIME-MD to diagnose DSM-IV depressive and anxiety disorders. Clinical predictors were identified by logistic regression analysis. Outcomes were assessed immediately postvisit and at 2 weeks and 3 months. These included symptomatic improvement, functional status, unmet expectations, satisfaction with care, clinician-perceived patient difficulty, and health care utilization and costs. RESULTS: A depressive or anxiety disorder was present in 146 (29%) of the patients. Independent predictors of a mental disorder included recent stress, multiple physical symptoms (ie, 6 or more), higher patient ratings of symptom severity, lower patient ratings of their overall health, physician perception of the encounter as difficult, and patient age less than 50. Patients with depressive or anxiety disorders were more likely to have unmet expectations postvisit (20% versus 8%, P < 0.001), be considered difficult (26% versus 11%, P < 0.0001), and report persistent psychiatric symptoms and ongoing stress even 3 months following the initial visit. Psychiatric status was not associated with symptomatic improvement, health care utilization, or costs. CONCLUSION: Simple clinical clues in patients with physical complaints identify a subgroup who may warrant further evaluation for a depressive or anxiety disorder. Such disorders are associated with unmet patient expectations and increased provider frustration.     

Thirty-month naturalistic follow-up study of early-onset dysthymic disorder: Course, diagnostic stability, and prediction of outcome.

Dysthymic disorder (DD) is defined and distinguished from major depressive disorder (MDD) largely on the basis of its course. Surprisingly, however, there have been few prospective, longitudinal studies of the naturalistic course of DD. This article reports the major findings from a prospective, longitudinal 30-month follow-up study of 86 outpatients with early-onset DD (EOD) and 39 outpatients with episodic MDD. Follow-up assessments included the Longitudinal Interval Follow-Up Evaluation and Hamilton Rating Scale for Depression. Compared with patients with episodic MDD, patients with EOD exhibited less improvement from the baseline evaluation and were more symptomatic at follow-up. Only 39% of patients with EOD recovered from DD during the follow-up period. The diagnosis of DD was fairly stable, with 52% of the EOD group meeting full criteria for DD at follow-up. These data provide prospective confirmation of the chronic course of DD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Life events, symptom course, and treatment outcome in unipolar depressed women.

Although a large number of studies have addressed issues of etiology associated with stressful life events and diverse forms of disorder, little attention has been focused on the importance of such psychosocial parameters for the course and remission of symptoms once the disorder has begun. The authors review research on this latter topic, with special reference to the depressive disorders. A longitudinal study of 130 22–60 yr old unipolar depressive females receiving treatment was conducted. Results indicate that life events preceding entry into treatment significantly predicted certain forms of depressive symptomatology and of clinical outcome over a 6-mo follow-up period. In contrast, events occurring during the treatment and/or posttreatment period were not related to any of the depressive symptom outcome measures. Different subclassifications of events particularly may have relevance for the course and remission of symptoms in unipolar depressives under treatment. (51 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recovery from major depressive disorder among female adolescents: A prospective test of the scar hypothesis.

This study examined the psychosocial consequences of experiencing major depressive disorder (MDD). In a 7-year longitudinal study of 496 female adolescents, the authors identified 49 girls who experienced their first episode of MDD and then recovered. They were compared with a randomly selected group of 98 never depressed participants on 13 psychological, social, psychiatric, and life events variables. None of the variables fit the scar pattern (i.e., a group difference that emerges during the first MDD episode and remains elevated post-recovery). All 13 variables were elevated before, during, and after the MDD episode, although some increased during the MDD episode. Results provide little support for the scar hypothesis among adolescent girls but instead suggest that many risk variables are elevated before and after the MDD episode. Interventions that modify these factors may help to reduce depression incidence and recurrence among female adolescents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Patterns of change in depressive symptoms during smoking cessation: Who's at risk for relapse?

The authors examined patterns of change in depressive symptoms during smoking cessation treatment in 163 smokers with past major depressive disorder (MDD). Cluster analysis of Beck Depression Inventory (A. T. Beck, C. H. Ward, M. Mendelson, J. Mock, & J. Erbaugh, 1961) scores identified 5 patterns of change. Although 40% of participants belonged to clusters characterized by increasing depressive symptoms during quitting (rapid increasers, n=31, and delayed increasers, n=35), almost 47% were in clusters characterized by decreasing symptoms (delayed decreasers, n=24, and rapid decreasers, n=52). Both rapid and delayed increasers had especially poor smoking cessation outcomes. Results suggest that among smokers with an MDD history there is substantial heterogeneity in patterns of depressive symptoms during quitting and that patterns involving increased symptoms are associated with low abstinence rates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The structure of distress following trauma: Posttraumatic stress disorder, major depressive disorder, and generalized anxiety disorder.

The current report used confirmatory factor analysis to examine the latent structures of both key features and associated symptoms of three disorders that commonly develop following a traumatic event: posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD). Participants were 228 motor-vehicle accident survivors who sought treatment for emotional difficulties. PTSD, MDD, and GAD were assessed with a combination of self-report and interview-based measures. The results of construct level analyses suggested that PTSD, MDD, and GAD are distinguishable but highly correlated disorders following a traumatic event. Symptom level analyses supported a model where the Reexperiencing, Avoidance, and Hypervigilance factors were subsumed under the PTSD construct. However, in this model the Dysphoria factor was a higher order construct correlated with the PTSD, MDD, and GAD factors, suggesting that the Dysphoria cluster may not be unique to PTSD. Diagnostic and theoretical implications of these results are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)