Lewis L. Judd

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 role and clinical significance of subsyndromal depressive symptoms (SSD) in unipolar major depressive disorder

Analyses conducted in 10,526 community respondents investigated by the NIMH Epidemiological Catchment Area (ECA) Program, revealed the 1-month point prevalence of depressive symptoms and disorders in the general population, at the first ECA interview (Wave 1) to be 10%, as follows: 2.3% major depressive disorder (MDD); 2.3% dysthmic disorder (DD); 1.5% minor depressive disorder (MinD); and 3.9% subsyndromal depressive symptoms (SSD, defined as two or more depressive symptoms beneath the diagnostic threshold of MinD, DD or MDD). There appears to be two classes of SSD in this community sample: first, SSD, which occurred as an integral component of the course of unipolar major depressive disorder (MDD); and, second, SSD occurring spontaneously in non-unipolar depressed community subjects. In the first instance, SSD was frequently prodromal to episodes of MinD or MDD or residual to resolving episodes. Analyses also support the conclusion that SSD is a clinically significant, interepisode, depressive subtype of unipolar MDD, since SDD is associated with harmful dysfunction in five of six measures of adverse outcome, has a significantly increased prevalence of past histories of major depressive episodes, and an elevated lifetime prevalence of suicide attempts. Comparison of subsyndromal depressive symptomatology or depressive disorder diagnoses at Wave 1 with diagnoses obtained, 1 year later, at the Wave 2 interview, confirm the persistent and chronic nature of depression in this large representative sample of community respondents, in which 71% of subjects with depressive symptoms or disorders at Wave 1 continued to be symptomatic at Wave 2. In addition, subjects experienced a surprising degree of change in depressive symptom and disorder diagnoses during the 1-year observational window between Wave 1 and Wave 2, in which a remarkable percentage of individuals, who began the year in a depressive symptom or disorder diagnostic category, ended the year in another. This has led us to hypothesize that the typical clinical picture of unipolar MDD is dynamic and pleomorphic in nature, characterized by substantial symptomatic fluidity, in which patients frequently change diagnoses from one depressive subtype to another during their courses of illness.

The comparative clinical phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders?

BACKGROUND The present analyses were designed to compare the clinical characteristics and long-term episode course of Bipolar-I and Bipolar-II patients in order to help clarify the relationship between these disorders and to test the bipolar spectrum hypothesis. METHODS The patient sample consisted of 135 definite RDC Bipolar-I (BP-I) and 71 definite RDC Bipolar-II patients who entered the NIMH Collaborative Depression Study (CDS) between 1978 and 1981; and were followed systematically for up to 20 years. Groups were compared on demographic and clinical characteristics at intake, and lifetime comorbidity of anxiety and substance use disorders. Subsets of patients were compared on the number and type of affective episodes and the duration of inter-episode well intervals observed during a 10-year period following their resolution of the intake affective episode. RESULTS BP-I and BP-II had similar demographic characteristics and ages of onset of their first affective episode. Both disorders had more lifetime comorbid substance abuse disorders than the general population. BP-II had a significantly higher lifetime prevalence of anxiety disorders in general, and social and simple phobias in particular, compared to BP-I. Intake episodes of BP-I were significantly more acutely severe. BP-II patietns had a substantially more chronic course, with significantly more major and minor depressive episodes and shorter inter-episode well intervals. BP-II patients were prescribed somatic treatment a substantially lower percentage of time during and between affective episodes. LIMITATIONS BP-I patients with severe manic course are less likely to be retained in long-term follow-up, whereas the reverse might be true for BP-II patients who are significantly more prone to depression (i.e., patients with less inclination to depression and with good prognosis may have dropped out in greater proportions); this could increase the gap in long term course characteristics between the two samples. The greater chronicity of BP-II may be due, in part, to the fact that the patients were prescribed somatic treatments substantially less often both during and between affective episodes. CONCLUSIONS The variety in severity of the affective episodes shows that bipolar disorders, similar to unipolar disorders, are expressed longitudinally during their course as a dimensional illness. The similarities of the clinical phenotypes of BP-I and BP-II, suggest that BP-I and BP-II are likely to exist in a disease spectrum. They are, however, sufficiently distinct in terms of long-term course (i.e., BP-I with more severe episodes, and BP-II more chronic with a predominantly depressive course), that they are best classified as two separate subtypes in the official classification systems.

Assessment of AIDS-related cognitive changes: recommendations of the NIMH Workshop on Neuropsychological Assessment Approaches.

This article presents an extended (7-9 hours) and a brief (1-2 hours) battery designed to evaluate early cognitive changes associated with seropositive, asymptomatic persons. The battery was recommended by an NIMH Workgroup which was guided by 10 principles in its development. The domains assessed by the battery are: (1) Indicators of Premorbid Intelligence; (2) Attention; (3) Speed of Processing; (4) Memory; (5) Abstraction; (6) Language; (7) Visuoperception; (8) Constructional Abilities; (9) Motor Abilities; and (10) Psychiatric Assessment. Although the battery assesses a wide range of psychological functioning, specific emphasis has been placed on divided and sustained attention as well as speed of processing and retrieval from working and long-term memory. Descriptions of both the traditional clinical tests and tasks used in cognitive psychology are provided. Although the Workgroup strongly recommends the use of the extended battery in order to ensure the most sensitivity, it recognizes that there may be situations in which this is not possible. In order to increase the likelihood that neuropsychological tests will identify neurologically affected CDC Stage II and III seropositive individuals, the Workshop recommends that each patients protocol be rated by two trained neuropsychologists using the same clinical criteria. The Workgroup also recommends that a concerted effort be made to incorporate data from the extended and the brief batteries in some central data bank.

Residual Symptom Recovery From Major Affective Episodes in Bipolar Disorders and Rapid Episode Relapse/Recurrence

CONTEXT Both bipolar disorder type I and type II are characterized by frequent affective episode relapse and/or recurrence. An increasingly important goal of therapy is reducing chronicity by preventing or delaying additional episodes. OBJECTIVES To determine whether the continued presence of subsyndromal residual symptoms during recovery from major affective episodes in bipolar disorder is associated with significantly faster episode recurrence than asymptomatic recovery and whether this is the strongest correlate of early episode recurrence among 13 variables examined. DESIGN An ongoing prospective, naturalistic, and systematic 20-year follow-up investigation of mood disorders: the National Institute of Mental Health Collaborative Depression Study. SETTING Five academic tertiary care centers. PARTICIPANTS Two hundred twenty-three participants with bipolar disorder (type I or II) were followed up prospectively for a median of 17 years (mean, 14.1 [SD, 6.2] years). MAIN OUTCOME MEASURE Participants defined as recovered by Research Diagnostic Criteria from their index major depressive episode and/or mania were divided into residual vs asymptomatic recovery groups and were compared according to the time to their next major affective episodes. RESULTS Participants recovering with residual affective symptoms experienced subsequent major affective episodes more than 3 times faster than asymptomatic recoverers (hazard ratio, 3.36; 95% confidence interval, 2.25-4.98; P < .001). Recovery status was the strongest correlate of time to episode recurrence (P < .001), followed by a history of 3 or more affective episodes before intake (P = .007). No other variable examined was significantly associated with time to recurrence. CONCLUSIONS In bipolar disorder, residual symptoms after resolution of a major affective episode indicate that the individual is at significant risk for a rapid relapse and/or recurrence, suggesting that the illness is still active. Stable recovery in bipolar disorder is achieved only when asymptomatic status is achieved.

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 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.

Subthreshold Depression and Successful Aging in Older Women

OBJECTIVES Subthreshold depression (StD) is common in older adults and is associated with poor self-rated health. However, the impact of StD on broader indicators of successful aging, such as positive psychological constructs, cognitive functioning, or quality of well-being, has not been assessed. The authors compared persons with scores above and below a predetermined threshold on the Center for Epidemiological Studies Scale for Depression (CES-D) with nondepressed (ND) persons on measures of multiple domains associated with successful aging. DESIGN Cross-sectional survey-based psychological assessments. PARTICIPANTS A total of 1,979 community-dwelling older women participating in the Womens Health Initiative study. MEASUREMENTS ND was defined as a CES-D score below 8, StD as a score between 8 and 15, and CES-D Depression (CD) as a score of 16 or above. The study questionnaire consisted of multiple self-reported measures of positive psychological functioning (e.g., optimism and resilience), cognitive functioning and complaints, and quality of well-being. The authors also obtained a history of diagnosis, treatment, and hospitalization related to mental health problems. RESULTS Overall 20.2% of women met CES-D criteria for StD and 7% for CD. Women with StD had worse self-rated successful aging, worse physical and emotional functioning, lower optimism, more negative attitudes toward aging, lower personal mastery and self-efficacy, and greater anxiety and hostility than ND women but scored better on all these measures than women with CD. Subjects with StD also had higher self-reported rates of previous diagnosis, treatment, and hospitalization for mental health problems than the ND group. Subjects with StD with depressed mood and/or anhedonia were largely similar to those without these symptoms. CONCLUSIONS Mild-moderate levels of depressive symptoms that likely fall under a general category of StD were common and were associated with worse functioning on virtually every component of successful aging that the authors examined. StD represents a clinical entity that may affect the longitudinal course of successful aging for large numbers of persons and is a potential target for clinical intervention.

Overt Irritability/Anger in Unipolar Major Depressive Episodes Past and Current Characteristics and Implications for Long-term Course

IMPORTANCE Although symptoms of irritability or anger are not central to the diagnosis of unipolar major depressive episodes (MDEs), these symptoms have been found, in cross-sectional studies, to be highly prevalent and associated with increased comorbidity and depressive illness burden. OBJECTIVE To determine the prevalence of overtly expressed irritability/anger and its effect on intake presentation and the long-term course of illness. DESIGN A prospective, naturalistic investigation of patients with unipolar MDEs, studied systematically at intake and during up to 31 years of follow-up. SETTING Five US academic medical centers. PARTICIPANTS Patients entered the National Institute of Mental Health Collaborative Depression Study during an MDE in 1978, 1979, 1980, or 1981. Patients with unipolar MDE at intake (n = 536) were divided into those with and those without current comorbid overtly expressed irritability/anger. EXPOSURE In this observational, longitudinal study, patients received treatment that was recorded but not controlled. MAIN OUTCOMES AND MEASURES Groups were compared on illness severity and chronicity, psychosocial impairment, quality of life, suicidal behavior, lifetime comorbid diagnoses, impulse control, and measures associated with bipolarity. RESULTS Overt irritability/anger was present in 292 of 536 participants with a unipolar MDE at study intake (54.5%). It was associated with significantly increased depressive severity, longer duration of the index MDE, poorer impulse control, a more chronic and severe long-term course of illness, higher rates of lifetime comorbid substance abuse and anxiety disorder, more antisocial personality disorders, greater psychosocial impairment before intake and during follow-up, reduced life satisfaction, and a higher rate of bipolar II disorder in relatives. No association was found with increased suicidal ideation or behavior. Results were not explained by comorbidity or other manic spectrum symptoms. CONCLUSIONS AND RELEVANCE This study extends results of cross-sectional investigations and indicates that irritability/anger during MDEs is a highly prevalent clinical marker of a more severe, chronic, and complex depressive illness. Findings have important implications for assessment and treatment.

A Brief Assessment of Psychosocial Functioning of Subjects with Bipolar I Disorder: The LIFE-RIFT

Those afflicted with bipolar disorder often suffer from substantial functional impairment both when in episode and when in remission. This study examined the psychometric properties of a brief assessment of psychosocial functioning, the Range of Impaired Functioning Tool (LIFE-RIFT), among subjects with bipolar I disorder. The study sample consisted of 163 subjects who presented with bipolar I disorder at intake into the NIMH Collaborative Depression Study (CDS). All LIFE-RIFT items come from the Longitudinal Interval Follow-up Evaluation (LIFE). Follow-up data that were used to examine the reliability and validity of the scale come from assessments of psychosocial functioning that were conducted 6, 12, 18, and 24 months after intake into the CDS. The results of factor analyses indicate that the scale items are measures of one construct, psychosocial functioning. The interrater agreement on the scale score was very good with an intraclass correlation coefficient was 0.94. The internal consistency reliability among the scale items was uniformly satisfactory over the four assessment periods, with coefficient alpha ranging from 0.78 to 0.84. Mixed-effect regression analyses showed that during mood episodes subjects were significantly more impaired than those in recovery. In conclusion, the psychometric properties of the LIFE-RIFT were examined in subjects with bipolar I disorder. The analyses from this longitudinal, observational study provide empirical support for the reliability and validity of the scale. The LIFE-RIFT provides a brief, inexpensive alternative to scales currently used to assess psychosocial functioning and can be easily added to semistructured assessments that are used in clinical and treatment outcome studies.