A prospective 12-year study of subsyndromal and syndromal depressive symptoms in unipolar major depressive disorders

BACKGROUND: Investigations of unipolar major depressive disorder (MDD) have focused primarily on major depressive episode remission/recovery and relapse/recurrence. This is the first prospective, naturalistic, long-term study of the weekly symptomatic course of MDD. METHODS: The weekly depressive symptoms of 431 patients with MDD seeking treatment at 5 academic centers were divided into 4 levels of severity: (1) depressive symptoms at the threshold for MDD; (2) depressive symptoms at the threshold for minor depressive or dysthymic disorder (MinD); (3) subsyndromal or subthreshold depressive symptoms (SSDs), below the thresholds for MinD and MDD; and (4) no depressive symptoms. The percentage of weeks at each level, number of changes in symptom level, and medication status were analyzed overall and for 3 subgroups defined by mood disorder history. RESULTS: Patients were symptomatically ill in 59% of weeks. Symptom levels changed frequently (1.8/y), and 9 of 10 patients spent weeks at 3 or 4 different levels during follow-up. The MinD (27%) and SSD (17%) symptom levels were more common than the MDD (15%) symptom level. Patients with double depression and recurrent depression had more chronic symptoms than patients with their first lifetime major depressive episode (72% and 65%, respectively, vs 46% of follow-up weeks). CONCLUSION: The long-term weekly course of unipolar MDD is dominated by prolonged symptomatic chronicity. Combined MinD and SSD level symptoms were about 3 times more common (43%) than MDD level symptoms (15%). The symptomatic course is dynamic and changeable, and MDD, MinD, and SSD symptom levels commonly alternate over time in the same patients as a symptomatic continuum of illness activity of a single clinical disease.     

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.     

The many faces of depression following spousal bereavement

While it is becoming increasingly clear that mood disorders tend to be chronic, intermittent and/or recurrent conditions with different manifestations over time, little is known of the variability or course of mood disorders that are associated with severe psychosocial stress. This paper reports on the prevalence and course of major, minor, and subsyndromal depressions in 328 widows and widowers followed prospectively from 2 to 25 months following one of the most disruptive of all naturally occurring stressors, spousal bereavement. The results are consistent with the following conclusions: (1) past major depression (prior to the death) predicts an increased risk for major depression following bereavement; (2) membership in any of the unipolar subgroups, in turn, predicts future depression throughout the unipolar depressive spectrum; (3) subsyndromal and minor depression stand between major depression, on the one hand, and no depression, on the other, in terms of their effects on overall adjustment to widowhood. Thus, the results support the validity of subsyndromal depression, and that the three subgroups (major, minor and subsyndromal depression) are pleiomorphic manifestations of the same unipolar depression disorder.     

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)     

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.     

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)     

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.     

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.     

Psychosocial characteristics of adolescents with a past history of dysthymic disorder: comparison with adolescents with past histories of major depressive and non-affective disorders, and never mentally ill controls

Little is known about the psychosocial functioning of persons who have recovered from dysthymic disorder. Such information might be useful in identifying trait markers for dysthymia, and for guiding continuation and maintenance treatment. We explored this issue using data from the Oregon Adolescent Depression Project, a large community-based study of the epidemiology of psychiatric disorders in a high school population. Four groups of adolescents were identified: 38 with a past history of dysthymic disorder; 217 with a past history of major depressive disorder; 142 with a past history of non-affective disorders; and 1079 with no lifetime history of psychopathology. The groups were compared on an extensive battery of psychosocial variables. The most consistent and diagnostically specific finding was that adolescents with a past history of dysthymic disorder reported having a significantly lower level of social support from friends than each of the other three groups of adolescents. Adolescents with a past history of dysthymic disorder also reported significantly higher levels of depressive, internalizing and externalizing symptoms and daily hassles than adolescents with no lifetime history of psychopathology. In addition, they reported higher levels of depressive symptoms and self-consciousness, but fewer externalizing symptoms than adolescents with a past history of non-affective disorders. These data suggest that adolescents with dysthymic disorder continue to experience significant difficulties in psychosocial functioning even after recovery.     

Teaching students to diagnose depression: A pilot study of Research Diagnostic Criteria.

Describes a training program for psychology graduate students that was designed to help them distinguish major depressive disorders from other unipolar depressions and to differentiate subtypes of major depressive disorders, using the Research Diagnostic Criteria. Evaluative data support the growing belief that individuals can be trained to differentiate subtypes of depressive illness. (8 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Emotional reactivity to daily events in major and minor depression.

Although emotional dysfunction is an important aspect of major depressive disorder (MDD), it has rarely been studied in daily life. Peeters, Nicolson, Berkhof, Delespaul, and deVries (2003) observed a surprising mood-brightening effect when individuals with MDD reported greater reactivity to positive events. To better understand this phenomenon, we conducted a multimethod assessment of emotional reactivity to daily life events, obtaining detailed reports of appraisals and event characteristics using the experience-sampling method and the Day Reconstruction Method (Kahneman, Krueger, Schkade, Schwarz, & Stone, 2004) in 35 individuals currently experiencing a major depressive episode, 26 in a minor depressive (mD) episode, and 38 never-depressed healthy controls. Relative to healthy controls, both mood-disordered groups reported greater daily negative affect and lower positive affect and reported events as less pleasant, more unpleasant, and more stressful. Importantly, MDD and mD individuals reported greater reductions in negative affect following positive events, an effect that converged across assessment methods and was not explained by differences in prevailing affect, event appraisals, or medications. Implications of this curious mood-brightening effect are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychiatric diagnoses as contemporaneous risk factors for suicide attempts among adolescents and young adults: Developmental changes.

The purpose of this prospective, naturalistic study was to examine the relationships between suicide attempts and contemporaneous psychiatric disorders, and developmental changes in these relationships from adolescence to young adulthood. The sample consisted of 180 adolescents, 12–19 years of age at hospitalization, repeatedly assessed for up to 13 years (n = 1,825 assessments). Semistructured psychiatric diagnostic instruments were administered at repeated assessments to assess psychiatric disorders and suicide attempts. After controlling for demographic variables and prehospitalization suicide attempts, most contemporaneous psychiatric disorders (major depressive disorder [MDD], dysthymic disorder, generalized anxiety disorder [GAD], panic disorder, attention-deficit/hyperactivity disorder [AD/HD], conduct disorder, and substance use disorder [SUD]) were related to increased risk of attempts. The relationship between suicide attempts and MDD, GAD, AD/HD, and SUD strengthened as participants got older. MDD, dysthymic disorder, GAD, and panic disorder were more commonly associated with repeat than 1st-time suicide attempts. In sum, most major psychiatric disorders are associated with increased risk for suicide attempts, but the strength of the relationships between these disorders and attempts changes over the course of development. (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)     

Maintenance of gains versus relapse following brief psychotherapy for depression.

Cross-sectional and longitudinal data are presented from a 2-year follow-up study of 91 older adults, initially diagnosed as in an episode of major depressive disorder (MDD), who were treated with brief cognitive, behavioral, or psychodynamic psychotherapy. Using research diagnostic criteria (RDC), 52%, 58%, and 70% of the sample did not meet criteria for any RDC depressive disorder at posttherapy, and 12- and 24-month follow-ups, respectively. There were no significant differences in response rate by therapy modality. Using Longitudinal Interval Follow-Up Evaluation (LIFE) by R. Shapiro and M. Keller (1979) and M. B. Keller et al (see record 1988-01549-001) methodology, we noted that patients not depressed at posttreatment remained depression-free for longer time periods than those who were minor or MDD. These rates compare favorably with published reports on younger depressed patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

New minimal substrate structural requirements in the enzymatic peroxidation of alkenes with soybean lipoxygenase

A longitudinal study was conducted to investigate the association between human immunodeficiency virus (HIV) infection, history of major depressive disorder (MDD), and persistent or recurrent MDD among intravenous drug users. Psychiatric disorders were assessed in a sample of HIV-positive (HIV+) and HIV-negative (HIV-) intravenous drug users every 6 months for 3 years. Results indicated that HIV status and baseline MDD independently predicted persistent or recurrent episodes of MDD after gender, drug use, ethnicity, income, and the presence other psychiatric disorders were controlled statistically. Among HIV+ intravenous drug users with baseline MDD, 90% experienced at least one subsequent episode of MDD and 47% experienced at least three subsequent episodes of MDD. However, less than 40% of intravenous drug users with current MDD received treatment for emotional problems. These findings indicate that intravenous drug users with HIV infection and a history of MDD are at considerable risk for future episodes of MDD or recurrent MDD, and that increased provision of treatment for intravenous drug users with MDD may be necessary.     

Affect and alcohol use: An ecological momentary assessment study of outpatients with borderline personality disorder.

Alcohol use may be viewed as an attempt (albeit maladaptive) to regulate negative emotional states. We examined associations between both negative and positive affects and alcohol use in outpatient women diagnosed with borderline personality disorder (BPD; n = 74), a prototype of emotional dysregulation, as well as a psychiatric control group of women with current depressive disorder (major depressive disorder/dysthymic disorder [MDD\DYS]; n = 50). Participants completed randomly prompted reports of mood and alcohol use up to six times a day over a 28-day period using electronic diaries. Mean levels of either positive or negative affects did not distinguish between drinkers and nondrinkers in either diagnostic group. However, levels of both negative and positive affects were positively associated with alcohol use at the momentary level in BPD drinkers. More robust findings were obtained with respect to within-person affective variability, which was related to alcohol use in multiple ways. BPD drinkers showed higher within-person variability for most negative affects than BPD nondrinkers; MDD\DYS drinkers in general showed less within-person variability than MDD\DYS nondrinkers for negative affects. Multilevel lagged analyses for BPD drinkers indicated that alcohol use was positively related to variability in all affects, concurrently, but fewer significant effects of affect variability on the next day's drinking or significant effects of alcohol use on the next day's affect variability were observed. Among MDD\DYS drinkers, we observed more significant associations between affect variability on next day's alcohol use and of alcohol use on next day's affect variability. We discuss theoretical and methodological issues relevant to these findings as well as implications for future research. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Relation of age at onset to duration of episode in unipolar depression.

On the basis of elevated scores on the Center for Epidemiologic Studies Depression Scale, 2,020 persons were selected from a larger community sample to be interviewed and diagnosed using the Schedule for Affective Disorders and Schizophrenia and the Research Diagnostic Criteria procedures. 865 Ss (aged 18–88 yrs) had a history of one or more episodes of unipolar depression. The potential effects of the following variables (singly and in interaction) on duration of episode were assessed by means of multiway frequency table analysis and chi-square: age at onset, sex of S, interval since occurrence of the episode, and type of disorder (major vs minor depressive disorder). The hypothesis that duration of episodes of depression increases with age at onset was not supported. Women, who formed 73.5% of the sample, were more likely to have multiple episodes but did not have longer-lasting episodes. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)