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.     

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.     

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)     

Reliability and validity of depressive personality disorder

OBJECTIVE: Depressive personality disorder was introduced into DSM-IV's appendix amid controversy. While that disorder appears to be a reliable and valid one, the authors offer new data about its relationship to major depression, dysthymic disorder, and other personality disorders. METHOD: The authors assessed 54 subjects with early-onset, long-standing mild depressive features for depressive personality disorder, axis I and axis II disorders, family history, and treatment history; they conducted follow-up interviews 1 year after the baseline assessment. Subjects with (N=30) and without (N=24) depressive personality disorder were characterized and compared in terms of those variables. RESULTS: Although depressive personality disorder and dysthymia co-occurred in some subjects, 63% of subjects with depressive personality disorder did not have dysthymia, and 60% did not have current major depression. Although subjects with depressive personality disorder were more likely than the mood disorder comparison group to have another personality disorder, 40% had no such disorder. Contrary to study hypotheses, mood disorder was not more common in first-degree relatives of subjects with depressive personality disorder than in relatives of the comparison group. Subjects with and without depressive personality disorder had similar rates of past treatment with medication and psychotherapy; however, the duration of psychotherapy was significantly longer for subjects with than for those without depressive personality. The depressive personality diagnosis was relatively stable over the 1-year follow-up period. CONCLUSIONS: Depressive personality disorder appears to be a relatively stable condition with incomplete overlap with axis I mood disorders and personality disorders. Further studies are needed to better characterize its treatment response and relationship to axis I mood disorders.     

Suicide mortality in patients on lithium maintenance therapy

Mood disorders are frequently recurrent and it has been shown that maintenance treatment can reduce long-term morbidity in this condition. It has also been shown that mood disorders carry an increased risk of suicide and that a significant proportion of individuals who commit suicide suffer from a mood disorder. This paper reports the results of a long term follow-up of a cohort of patients attending a specialist mood disorder clinic over a period of 18 years. Sixty-seven suffered from unipolar depression and 36 had bipolar or schizo-affective disorders In order to qualify for entry to the cohort the unipolar patients had to have had at least three episodes of depression and those with bipolar disorders had to have had at least three episodes - with at least one manic episode and one depressive episode. All patients were treated with lithium. The initial treatment refusal rate and drop our rates were low. The mortality from suicide in this group was compared with that reported in five recent studies - all of which involved patients who had not been given maintenance therapy. The standardised mortality ratio (SMR) for all causes for the whole group was 0.93. There were two suicides. In one case the patient had continued treatment with lithium until death and in the other the patient had discontinued treatment 12 months before death. The overall suicide rate was 1.3 per 1000 patient years. Amongst similar groups of patients who had not been given maintenance therapy suicide rates of about 5.5 per 1000 patient years have been reported. It is concluded that maintenance treatment of mood disorders reduces the suicide rate in this vulnerable group of patients.     

Enhancement of morphine antinociception by ibogaine and noribogaine in morphine-tolerant mice

BACKGROUND: The authors evaluated and compared the efficacy of 20 mg versus 40 mg of paroxetine in a randomized, double-blind, parallel-group study during a maintenance period of 28 months. METHOD: Ninety-nine inpatients with recurrent, unipolar depression (DSM-IV criteria) who had at least 1 depressive episode during the 18 months preceding the index episode were openly treated with paroxetine 40 mg/day. Seventy-two subjects had a stable response (Hamilton Rating Scale for Depression score < 8) to paroxetine treatment and remained in the continuation treatment as outpatients for 4 months. At the time of recovery, 68 patients were randomly assigned to 1 of the 2 maintenance treatment groups: paroxetine 20 mg or paroxetine 40 mg daily. RESULTS: Sixty-seven patients completed the 28-month follow-up period. Seventeen (51.5%) of 33 patients in the 20-mg paroxetine regimen had a single recurrence compared with 8 (23.5%) of 34 subjects in the 40-mg dose regimen (chi2 = 5.56, p = .018). CONCLUSION: These data suggest that a full dose of paroxetine is recommended in unipolar patients who are at high risk for recurrent depressive episodes.     

Effect of acute exposure of the organophosphate insecticide Rogor on some biochemical aspects of Clarias batrachus (Linnaeus)

The prevalence of DSM-IV atypical depression and comparisons between atypical and typical depression were studied in 203 consecutive unipolar and bipolar depressed outpatients presenting for treatment of depression in private practice. The prevalence of atypical depression was 31%. Of the variables investigated (unipolar/bipolar diagnosis, age at baseline/onset of first major depressive episode, gender, psychosis, comorbidity, chronicity, duration of illness, recurrence, and severity), a bipolar II diagnosis was significantly more common, the age at baseline and duration of illness were significantly lower, and the proportion of females and psychiatric comorbidity were significantly higher in atypical versus typical depression. Secondary analysis showed that bipolar II atypical depression had a significantly earlier age at baseline/onset and affected more females, but there were no other significant differences versus typical depression. The findings suggest important clinical differences between atypical and typical depression, and a bipolar II subtype may be separated from the broad category of atypical depression.     

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.     

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)     

Manic-depressive disease

Manic-depressive illness (MDI) is a periodic major affective disorder defined by successive depressive and manic episodes, separated by free intercritic periods. Unipolar manic-depressive illness is defined by successive depressive episodes, whereas bipolar manic-depressive illness is defined by successive depressive and manic episodes. Clinical, familial and biological studies have demonstrated the heterogeneity of unipolar depression and its relationship with bipolar depression leading to questions about common etiopathogeny of those two disorders. Manic-depressive heterogeneity led to the identification of several subgroups defining "manic-depressive spectrum". The reunion of these different clinical entities is based on phenomenological, clinical and familial arguments. MDI is an endogenous pathology, as vulnerability to this disorder is mostly determined by genetic and/or biological factors. Treatment consist first on treatment of major episodes, based on curative and consolidation treatment and secondly on prophylactic treatment.     

Social adjustment and the course of affective illness: a one-year controlled longitudinal study involving bipolar and unipolar outpatients

The association between social adjustment and recurrent affective episodes was examined in 27 recovered bipolar patients and 24 recovered unipolar patients who had been receiving maintenance treatment for at least 1 year. Social adjustment variables and psychiatric status were assessed by bimonthly interviews over the 1-year period using the Social Adjustment Scale (SAS) and the Research Diagnostic Criteria (RDC). Variations in the social adjustment scores were analyzed in the 2 months preceding the onset of a recurrent affective episode. Furthermore, social adjustment variables at entry into the study were assessed to investigate whether there was any association between these and the potential timing of a recurrent episode. Results revealed no significant deterioration in social adjustment during the 2 months preceding a recurrent affective episode. However, it was demonstrated that there was a relationship between a patient's overall social adjustment score at entry into the study and the onset of recurrent affective episodes, independent of any residual depressive symptomatology. Specifically, impaired work adjustment in bipolar and unipolar patients was associated with recurrent episodes. Impaired social and leisure activities adjustment in bipolar patients was also associated with recurrent episodes, and impaired marital adjustment in unipolar patients was associated with recurrent episodes. These results suggest that social maladjustment could be a risk factor for both unipolar and bipolar recurrent affective episodes and that impairment in specific areas of social functioning could be used to predict outcome.     

The prevalence of verbal communication disability in patients with Parkinson''s disease

BACKGROUND: We evaluated and compared the efficacy and safety of sertraline and fluvoxamine in a randomized, double-blind, parallel-group study during a follow-up of 24 months. METHOD: Sixty-four patients with recurrent, unipolar depression (DSM-IV criteria) who had at least one depressive episode during the 18 months preceding the index episode were accepted into the trial. Patients were randomly assigned to one of the two long-term treatment groups and evaluated monthly by trained psychiatrists, blinded to treatment option, on the basis of the Hamilton Rating Scale for Depression. RESULTS: All patients completed the 24-month follow-up period. Sertraline and fluvoxamine showed an equal efficacy in preventing new recurrences. In fact, there was no significant difference in survival rates between the two medication groups: 7 sertraline-treated patients (21.9%) and 6 fluvoxamine-treated patients (18.7%) had a single new recurrence (z = 0.14; p = .88). Moreover, recurrence observed during maintenance therapies was less severe and/or of shorter duration than index episodes. CONCLUSION: Long-term treatment with sertraline or fluvoxamine has been shown to be effective for prevention of highly recurrent unipolar depression. The high tolerability of these compounds, together with their prophylactic effectiveness, has an important role in improving the quality of life of these patients.     

Demographics, family history, premorbid functioning, developmental characteristics, and course of patients with deteriorated affective disorder

OBJECTIVE: This exploratory study examined the characteristics of a group of unusual and previously undescribed patients with major affective disorder who not only had been continuously symptomatic for prolonged periods of time but were also so functionally impaired that they required years of continuous care in psychiatric facilities or by family members. METHOD: Twenty-seven inpatients with major mood disorders and 29 inpatients with schizophrenia were recruited from a large state hospital; 27 outpatients with major mood disorders were recruited from an affiliated outpatient facility. The research battery included the Structured Clinical Interview for DSM-III-R--Patient Version, the Premorbid Adjustment Scale, and a semistructured interview designed to assess demographic, family history, developmental, and course information. RESULTS: Inpatients with deteriorated affective disorder differed from outpatients with nondeteriorated affective disorder along several important dimensions, including family history of mental illness, birth-related problems, physical disorders in infancy, premorbid functioning, presence of mixed episodes and rapid cycling, and medication non-compliance between hospitalizations. Inpatients with deteriorated affective disorder differed from inpatients with schizophrenia on the Premorbid Adjustment Scale. Patients with bipolar affective disorder differed from those with unipolar disorder on many of the variables associated with deterioration of functioning. CONCLUSIONS: Birth-related problems, physical disorders in infancy, and poor premorbid adjustment in childhood and adolescence appear to play an important role in deterioration of functioning among patients with unipolar depression. Disruption in treatment because of medication noncompliance and the appearance of mixed episodes and rapid cycling are associated with functional decline in bipolar affective disorder. Several characteristics previously considered specific to deterioration of functioning in schizophrenia, such as a high rate of birth complications and poor premorbid adjustment, appear to be associated with functional deterioration among patients with major depression as well.     

A prospective study of risk factors for unipolar depression.

The purpose of this study was to identify variables that are antecedents for unipolar depression. Information regarding a number of sociodemographic and psychosocial variables was collected on a community sample of adults (N?=?998), 562 of whom were interviewed and diagnosed according to Schedule for Affective Disorders and Schizophrenia-Research Diagnostic Criteria procedures and received a second assessment on most of the variables. The average time elapsed between Time 1 and Time 2 was 8.3 months. Depressive symptomatology was also assessed with the Center for Epidemiologic Studies Depression Scale CES-D. A number of variables emerged, which predicted both the development of an episode of depression and elevated CES-D scores. These include reporting an elevated level of depressive and other symptoms and having experienced an elevated level of stress. Variables that are predictive of developing an episode of depression include young age, being female, and having had a previous episode of depression. The presence of depressogenic cognitions was uniquely predictive of an elevation of depression symptoms as measured by the CES-D. Virtually no variables demonstrated a significant moderating effect on the stress–depression relation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ligation of internal iliac arteries in pelvic haemorrhage

Considerable evidence implicates the neurotransmitter gamma-aminobutyric acid (GABA) in the biochemical pathophysiology of mood disorders. In this study, we investigated the possibility that the gene for the gamma-aminobutyric acid type A (GABAA) receptor alpha-1 subunit (GABRA1) might be associated with depressive symptomatology in a sample of mood disorder subjects. Sixty-seven inpatients affected by unipolar (n = 37) and bipolar (n = 30) disorder (DSMIV) were assessed at admission by the Hamilton depression rating scale (HAMD) and were typed using polymerase chain reaction (PCR) techniques. GABRA1 variants were not associated with depressive symptomatology, and consideration of possible stratification effects such as sex, psychiatric diagnosis and illness severity did not reveal any association either. GABAA alpha-1 subunit gene is not, therefore, associated with depressive symptomatology in mood disorder subjects.     

First onset versus recurrence of depression: Differential processes of psychosocial risk.

Differential risk factors for the onset of depression were prospectively examined in a community-based sample of adolescents (N?=?1,709), some of whom had a history of major depressive disorder (MDD; n?=?286) and some of whom did not (n?=?1,423). From the theories of J. Teasdale (1983, 1988) and R. Post (1992) concerning the etiology of initial versus recurrent episodes of depression, the authors hypothesized that (a) dysphoric mood and dysfunctional thinking styles would be correlated more highly among those with a previous history of MDD than among those without a history of MDD; (b) dysphoric mood or symptoms and dysfunctional thinking would be a stronger predictor of onset of recurrent episodes (n?=?43) than of first onsets (n?=?70); and (c) major life stress would be a stronger predictor of first onsets of MDD than of recurrent episodes. The results provide support for the 3 hypotheses and suggest that distinct processes are involved in the onset of first and recurrent episodes of MDD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Headache as a manifestation of myocardial infarction

A 33-year-old pregnant woman at 26 weeks gestation, who had a history of bipolar mood disorder, type I, was admitted to the hospital for hypomania and poorly controlled diabetes mellitus. The patient had had her first episode of affective illness at age 28, after the birth of her second child. After an initial postpartum depression, she had cycled into a manic state. She had subsequently been hospitalized seven times for acute mania. A combination of valproate and chlorpromazine had proven effective in managing most of her manic episodes, while her two most severe episodes had been successfully managed with bilateral ECT.     

Adolescent depressive symptoms as predictors of adult depression: moodiness or mood disorder?

OBJECTIVE: The authors' goal was to examine the relationship between subclinical depressive symptoms in adolescence and major depressive episodes in adulthood. METHOD: An epidemiologic sample of 776 young people received psychiatric assessments in 1983, 1985, and 1992. Among adolescents not meeting criteria for major depression, the authors estimated the magnitude of the association between subclinical adolescent depressive symptoms and adult major depression. RESULTS: Symptoms of major depression in adolescence strongly predicted an adult episode of major depression: having depressive symptoms more than two-standard-deviations above the mean in number predicted a two-fold to three-fold greater risk for an adult major depressive episode. CONCLUSIONS: Symptoms of depression in adolescence strongly predict an episode of major depression in adulthood, even among adolescents without major depression.