Stability Limits and Defect Dynamics in Ag Nanoparticles Probed by Bragg Coherent Diffractive Imaging.

Dissolution is critical to nanomaterial stability, especially for partially dealloyed nanoparticle catalysts. Unfortunately, highly active catalysts are often not stable in their reactive environments, preventing widespread application. Thus, focusing on the structure-stability relationship at the nanoscale is crucial and will likely play an important role in meeting grand challenges. Recent advances in imaging capability have come from electron, X-ray, and other techniques but tend to be limited to specific sample environments and/or two-dimensional images. Here, we report investigations into the defect-stability relationship of silver nanoparticles to voltage-induced electrochemical dissolution imaged in situ in three-dimensional detail by Bragg coherent diffractive imaging. We first determine the average dissolution kinetics by stationary probe rotating disk electrode in combination with inductively coupled plasma mass spectrometry, which allows in situ measurement of Ag+ ion formation. We then observe the dissolution and redeposition processes in single nanocrystals, providing unique insight about the role of surface strain, defects, and their coupling to the dissolution chemistry. The methods developed and the knowledge gained go well beyond a "simple" silver electrochemistry and are applicable to all electrocatalytic reactions where functional links between activity and stability are controlled by structure and defect dynamics.

Three Dimensional Variable-Wavelength X-Ray Bragg Coherent Diffraction Imaging.

We present and demonstrate a formalism by which three-dimensional (3D) Bragg x-ray coherent diffraction imaging (BCDI) can be implemented without moving the sample by scanning the energy of the incident x-ray beam. This capability is made possible by introducing a 3D Fourier transform that accounts for x-ray wavelength variability. We demonstrate the approach by inverting coherent Bragg diffraction patterns from a gold nanocrystal measured with an x-ray energy scan. Variable-wavelength BCDI will expand the breadth of feasible in situ 3D strain imaging experiments towards more diverse materials environments, especially where sample manipulation is difficult.

The Bionanoprobe: hard X-ray fluorescence nanoprobe with cryogenic capabilities.

Hard X-ray fluorescence microscopy is one of the most sensitive techniques for performing trace elemental analysis of biological samples such as whole cells and tissues. Conventional sample preparation methods usually involve dehydration, which removes cellular water and may consequently cause structural collapse, or invasive processes such as embedding. Radiation-induced artifacts may also become an issue, particularly as the spatial resolution increases beyond the sub-micrometer scale. To allow imaging under hydrated conditions, close to the `natural state', as well as to reduce structural radiation damage, the Bionanoprobe (BNP) has been developed, a hard X-ray fluorescence nanoprobe with cryogenic sample environment and cryo transfer capabilities, dedicated to studying trace elements in frozen-hydrated biological systems. The BNP is installed at an undulator beamline at sector 21 of the Advanced Photon Source. It provides a spatial resolution of 30 nm for two-dimensional fluorescence imaging. In this first demonstration the instrument design and motion control principles are described, the instrument performance is quantified, and the first results obtained with the BNP on frozen-hydrated whole cells are reported.

The association between course of illness and subsequent morbidity in bipolar I disorder.

OBJECTIVE: We examined the relationship between certain bipolar I disorder clinical course variables over 5 years with outcome over the subsequent 5-year period. METHODS: Prospective observational follow-up data of 123 bipolar I subjects were analyzed. Predictive clinical variables included the frequency and direction of switches, and the quantity, polarity and length of affective periods. Outcome variables were an affective burden index (ABI) accounting for week-by-week severity and weeks hospitalized. Bivariate analyses guided the selection of predictors for multivariable analyses against the outcome variables. RESULTS: Affective burden index: while the number and direction of switches, the number of polyphasic episodes, weeks in hypomania/mania/mixed state, weeks in minor/major depression, weeks in at least marked affective syndrome, and weeks in any affective syndrome all had bivariate correlation (p<0.01) with the ABI, only weeks in hypomania/mania/mixed state and weeks in minor/major depression made significant contributions in the multivariable analysis (p<0.01) with the ABI. Weeks hospitalized: weeks in at least marked affective syndrome were significantly correlated with weeks hospitalized in bivariate analysis (p<0.01), and maintained a contribution to weeks hospitalized in the multivariable analysis (p<0.01). CONCLUSIONS: The quantity and severity of weeks in symptomatic affective states are possibly greater predictors of affective burden in bipolar I patients than the quantity and direction of affective switches.

Standardized assessment for panic disorder research. A conference report.

Lively controversies related to panic disorder are under active investigation by research groups around the world. However, publications from different laboratories are difficult to compare since there has been little consistency in measures or even in types of assessment used to characterize and follow up patients. Participants in the recently convened National Institutes of Health Consensus Development Conference on the Treatment of Panic Disorder noted this problem and recommended establishment of procedures to ensure comparability of studies. We organized a conference of clinical investigators whose objective was to develop a standard assessment package. Participants represented biological and psychosocial panic disorder treatment research sites in the United States and Canada. The 2-day conference resulted in agreement on a battery of assessments considered essential for panic disorder studies. The purposes of our report are to disseminate the conference conclusions and to encourage adoption of the proposed standards by clinical researchers, journal editors, Public Health Service peer review committees, and the Food and Drug Administration. We also identify some problematic issues that require further work.

The time course of nonchronic major depressive disorder. Uniformity across episodes and samples. National Institute of Mental Health Collaborative Program on the Psychobiology of Depression--Clinical Studies.

BACKGROUND: Most natural history studies of affective disorders have emphasized the prediction of eventual recovery. Little is known of changes over time in the immediate probability of recovery. METHODS: To identify regularities in the timing of recovery from nonbipolar major depressive disorders, we considered only episodes that began during follow-up to increase the accuracy with which onsets were timed and to limit the study sample to individuals who had a demonstrably episodic course. Five participating centers conducted baseline assessments and followed probands (N = 605) and nonclinical subjects (relatives, controls, and spouses, N = 826) up for 6 years. During that time, 359 probands had at least one prospectively observed episode, and 181 had two episodes; corresponding numbers for the nonclinical subjects were 216 and 78, respectively. Our analyses considered the distribution of episode lengths across ascertainment source (probands vs nonclinical subjects), center, and episode number (first vs second prospectively observed episode). RESULTS: Distribution was remarkably uniform. Regardless of ascertainment source, center, or episode number, recovery occurred within 3 months in 40% of episodes, within 6 months in 60%, and within 1 year in 80%; 20% had more protracted courses. CONCLUSIONS: Once triggered, the immediate likelihood of recovery changes over time in a predictable fashion. This has practical implications for the study of antidepressant efficacy and theoretical implications for factors involved in affective dysregulation.

Switching from 'unipolar' to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients.

BACKGROUND: Given the therapeutic and prognostic importance of the unipolar-bipolar dichotomy, predicting which patients will become bipolar subsequent to index diagnosis of major depressive disorder (MDD) is of paramount clinical significance. We sought to characterize the profile of patients with MDD who would convert to the more subtle bipolar subtype (known as BPII) on the basis of clinical and personality variables obtained during MDD episodes. METHODS: A total of 559 patients, comprehensively evaluated with the Schedule of Affective Disorders and Schizophrenia and "unipolar" MDD at entry, were administered 17 self-report personality measures. Hypomanic and manic episodes were systematically recorded over a prospective observation period of up to 11 years. We compared 48 converters to BPII (8.6%) with 22 converters to bipolar I (BPI) (3.9%) and the remaining larger group of unipolar patients. RESULTS: Except for greater acuteness, severity, and psychotic symptomatology, BPI converters were essentially similar to MDD nonconverters. By contrast, BPII converters were robustly distinguished from those with MDD who remained unipolar on the basis of self-report measures along the newly derived factors of Mood Lability, Energy-Activity, and Daydreaming. This profile was associated with early age at onset of MDD and pleomorphic psychopathology beyond the usual affective realm, high rates of substance abuse, as well as educational, marital, and occupational disruption and minor antisocial acts prior to discrete hypomanic episodes. Overall, BPII switchers had a more protracted and tempestuous course with shorter well intervals. "Habitual self" descriptions of temperamental instability during MDD episodes provided useful clinical information for predicting which depressed patients will switch to BPII, attaining a sensitivity of 91% for all three factors combined (23 items); Mood Lability alone (nine items) was the most specific predictor (86%), though of lower sensitivity (42%). CONCLUSIONS: The BPII subtype is best understood by such lability intruding into, and possibly its accentuation during, depressive episodes, thereby creating an intimate interweaving of trait and state. Clinicians must note that the foregoing temperamental profile appears more fundamental in defining the affective dysregulation of the BPII subtype than hypomanic episodes emphasized in DSM-IV.

Recovery from major depression. A 10-year prospective follow-up across multiple episodes.

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.

Psychosocial disability during the long-term course of unipolar major depressive disorder.

BACKGROUND: The goal of this study was to investigate psychosocial disability in relation to depressive symptom severity during the long-term course of unipolar major depressive disorder (MDD). METHODS: Monthly ratings of impairment in major life functions and social relationships were obtained during an average of 10 years' systematic follow-up of 371 patients with unipolar MDD in the National Institute of Mental Health Collaborative Depression Study. Random regression models were used to examine variations in psychosocial functioning associated with 3 levels of depressive symptom severity and the asymptomatic status. RESULTS: A progressive gradient of psychosocial impairment was associated with a parallel gradient in the level of depressive symptom severity, which ranges from asymptomatic to subthreshold depressive symptoms to symptoms at the minor depression/dysthymia level to symptoms at the MDD level. Significant increases in disability occurred with each stepwise increment in depressive symptom severity. CONCLUSIONS: During the long-term course, disability is pervasive and chronic but disappears when patients become asymptomatic. Depressive symptoms at levels of subthreshold depressive symptoms, minor depression/ dysthymia, and MDD represent a continuum of depressive symptom severity in unipolar MDD, each level of which is associated with a significant stepwise increment in psychosocial disability.

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.

Quality of life in rheumatoid arthritis: impact of disability and lifetime depressive spectrum symptomatology.

OBJECTIVE: The aim of this study was to investigate the impact of disability and lifetime subthreshold depressive symptoms on Health-Related Quality of Life (HRQoL) among patients with rheumatoid arthritis (RA). METHODS: Ninety-two subjects with a diagnosis of RA according to the American College of Rheumatology (ACR) criteria were recruited at the Department of Rheumatology of the University Hospital, Pisa, Italy. Participants who met DSM-IV-TR diagnostic criteria for current or previous Axis I disorders were excluded. Assessments of functional status and disability was conducted using both the ACR classification and the Stanford Health Assessment Questionnaire (HAQ). Health-related Quality of Life was assessed using the Medical Outcomes Study Short Form 36 health survey questionnaire (MOS-SF36) and lifetime depressive spectrum symptomatology using the Mood Spectrum Questionnaire, Self-Report version (MOODS-SR). RESULTS: Comparison with MOS-SF36 Italian normative values indicated that RA patients were significantly impaired on mental and physical HRQoL areas. Correlations between MOODS-SR depressive scores and ACR severity (Spearman rho = 0.15, p = 0.07) and HAQ score (Spearman rho = 0.20, p = 0.05) were modest in absolute value and borderline significant. Lifetime mood depressive spectrum was related with impaired HRQoL levels, both in physical (except for bodily pain) and mental (except for social functioning) domains. Associations of mood depressive spectrum and general health, vitality, role emotional and mental health continued to be significant after controlling for functional status, duration of illness, age and gender. CONCLUSIONS: Because lifetime mood depressive symptoms significantly contribute to impairment in HRQoL in RA patients without a past psychiatric history, even after controlling for functional status, duration of illness and demographic characteristics, these symptoms should be assessed for an accurate clinical evaluation and appropriate clinical management of RA patients.

Development of an in situ temperature stage for synchrotron X-ray spectromicroscopy.

In situ characterization of micro- and nanoscale defects in polycrystalline thin-film materials is required to elucidate the physics governing defect formation and evolution during photovoltaic device fabrication and operation. X-ray fluorescence spectromicroscopy is particularly well-suited to study defects in compound semiconductors, as it has a large information depth appropriate to study thick and complex materials, is sensitive to trace amounts of atomic species, and provides quantitative elemental information, non-destructively. Current in situ methods using this technique typically require extensive sample preparation. In this work, we design and build an in situ temperature stage to study defect kinetics in thin-film solar cells under actual processing conditions, requiring minimal sample preparation. Careful selection of construction materials also enables controlled non-oxidizing atmospheres inside the sample chamber such as H2Se and H2S. Temperature ramp rates of up to 300 °C/min are achieved, with a maximum sample temperature of 600 °C. As a case study, we use the stage for synchrotron X-ray fluorescence spectromicroscopy of CuIn(x)Ga(1-x)Se2 (CIGS) thin-films and demonstrate predictable sample thermal drift for temperatures 25-400 °C, allowing features on the order of the resolution of the measurement technique (125 nm) to be tracked while heating. The stage enables previously unattainable in situ studies of nanoscale defect kinetics under industrially relevant processing conditions, allowing a deeper understanding of the relationship between material processing parameters, materials properties, and device performance.

BATTERIES. Topological defect dynamics in operando battery nanoparticles.

Topological defects can markedly alter nanomaterial properties. This presents opportunities for "defect engineering," where desired functionalities are generated through defect manipulation. However, imaging defects in working devices with nanoscale resolution remains elusive. We report three-dimensional imaging of dislocation dynamics in individual battery cathode nanoparticles under operando conditions using Bragg coherent diffractive imaging. Dislocations are static at room temperature and mobile during charge transport. During the structural phase transformation, the lithium-rich phase nucleates near the dislocation and spreads inhomogeneously. The dislocation field is a local probe of elastic properties, and we find that a region of the material exhibits a negative Poisson's ratio at high voltage. Operando dislocation imaging thus opens a powerful avenue for facilitating improvement and rational design of nanostructured materials.

Long-term stability of polarity distinctions in the affective disorders.

OBJECTIVE: This analysis aimed to quantify the long-term stability of distinctions between nonbipolar, bipolar II, and bipolar I affective disorders and to determine the predictors of shifts in patients' diagnoses among these categories. METHOD: Probands entered the study as they sought treatment for manic, major depressive, or schizoaffective disorder diagnosed according to the Research Diagnostic Criteria. After thorough baseline evaluations, 605 patients with nonbipolar major depressive disorder or schizoaffective disorder, depressed type; 96 with bipolar II disorder; and 231 with bipolar I disorder or schizoaffective disorder, manic type, began the follow-up study. Direct interviews took place at 6-month intervals for the first 5 years and annually thereafter. RESULTS: Only 20 (5.2%) of the 381 initially nonbipolar probands who completed 10 years of follow-up developed mania during that time, and only 19 (5.0%) developed hypomania. A slightly higher proportion of the 67 who began with bipolar II disorder developed mania during the 10 years. Although 101 (66.4%) of the 152 bipolar I or schizoaffective manic probands developed subsequent manic episodes, only 11 (7.2%) developed hypomanic episodes and no mania. Young age at intake and at onset and chronicity of the index episode predicted shifts from nonbipolar to bipolar II disorder. Psychosis and a family history of mania predicted shifts from nonbipolar to bipolar I disorder. CONCLUSIONS: The high stability of baseline distinctions between nonbipolar, bipolar II, and bipolar I disorders, in combination with previously described family study data, strongly supports the separation of these disorders for both clinical and research purposes.

The enduring psychosocial consequences of mania and depression.

OBJECTIVE: The authors sought to determine the scope, severity, and persistence of psychosocial impairment arising from bipolar and unipolar affective disorder. METHOD: Patients with bipolar (N = 148) or unipolar (N = 240) major affective disorder were assessed as they sought treatment and again after a 5-year follow-up. Concurrently, parents, siblings, and adult children underwent similar assessments and were followed for 6 years. To quantify the impact of affective disorder, probands were individually matched to relatives who had no lifetime history of affective disorder. Sixty-nine relatives who were depressed at intake constituted a separate, nonclinical study group and were also matched to relatives who were well. RESULTS: Both unipolar and bipolar patients began follow-up with deficits in annual income. Relative to comparison subjects, affective disorder groups were significantly more likely to report declines in job status and income at the end of follow-up and significantly less likely to report improvements. Similarly, both bipolar and unipolar patients showed significant deficits in nearly all other areas of psychosocial functioning measured at follow-up. Except for relationships with spouses, deficits did not differ significantly by polarity. Surprisingly, probands with recovery sustained throughout the final 2 years of follow-up also showed severe and widespread impairment. Relatives with major depression exhibited substantial deficits on follow-up, but job status and income were not significantly affected. CONCLUSIONS: The psychosocial impairment associated with mania and major depression extends to essentially all areas of functioning and persists for years, even among individuals who experience sustained resolution of clinical symptoms.

The panic-agoraphobic spectrum: a descriptive approach to the assessment and treatment of subtle symptoms.

OBJECTIVE: Psychiatric classification is still a topic of considerable discussion and debate in spite of major advances in the past two decades. The debate involves categorical versus dimensional approaches, cutoff numbers of symptoms to define a case, degree of impairment, objective diagnostic criteria versus more theoretically based criteria, episodic versus trait-like symptoms, and the role of atypical and subclinical symptoms. All of these issues have been raised for the anxiety disorders and depression. This article presents the conceptualization of a relatively novel and testable approach to the diagnosis and classification of panic and agoraphobia, the panic-agoraphobic spectrum, and pilot data on a new questionnaire to assess it. METHOD: Pilot testing of the Panic-Agoraphobic Spectrum Questionnaire was undertaken with 100 inpatients who had lifetime diagnoses of panic disorder, unipolar depression, comorbid panic and unipolar depressive disorders, or an eating disorder. The instrument emphasizes impairment related to 144 behaviors and experiences in seven panic-agoraphobic symptom domains. RESULTS: Patients with panic disorder scored highest on the questionnaire, and those with comorbid depression showed even greater severity of illness. The scores of the patients with eating disorders and of the depressed patients differed from those of the other groups but also differed from 0. CONCLUSIONS: The spectrum model of panic and agoraphobia is a flexible and comprehensive means of describing this clinical complex. The proposed model, complementary to the categorical approach, presumably expresses a unitary pathophysiology. Its usefulness is discussed in terms of its value for patient-therapist communication, outcome measures, identification of subtle personality traits, and subtyping of patients for research and treatment.

The long-term stability of depressive subtypes.

OBJECTIVE: This study used the concept of diagnostic stability to examine the validity of three subtypes of major depression. METHOD: Patients with major depressive disorder (N = 424) were assigned baseline diagnoses according to structured interviews and the Research Diagnostic Criteria. Follow-up evaluations took place at 6-month intervals over the next 5 years and annually for an additional 3 years. During this period 424, 246, 163, and 96 of the patients who had recovered from the index episode had one, two, three, and four recurrences, respectively, of major depressive disorder. The kappa statistic was used to quantify the likelihood that patients with the psychotic, agitated/retarded, or endogenous subtype of depression in a given episode would again manifest that subtype in subsequent episodes. RESULTS: The psychotic subtype showed the most enduring diagnostic stability across multiple subsequent episodes. Even after three intervening episodes, patients with baseline psychotic major depression were five times more likely to develop a psychotic depression than were other depressed patients. For all three subtypes, diagnostic stability was greater for contiguous episodes than for noncontiguous episodes. Psychotic, agitated/retarded, and endogenous subtypes showed significant stability after control for the bipolar/unipolar and primary/secondary distinctions. The endogenous subtype was stable among patients with primary depression but not among those with secondary depression. CONCLUSIONS: The psychotic subtype was the most valid of the subtypes tested from the perspective of diagnostic stability. The fact that stability across adjacent episodes exceeded stability across more distantly spaced episodes may reflect state-dependent determinants, and these are likely to vary by subtype.

Alcoholism in manic-depressive (bipolar) illness: familial illness, course of illness, and the primary-secondary distinction.

OBJECTIVE: This 5-year follow-up study was designed to explore the factors that might lead to alcoholism in patients with bipolar disorder. METHOD: The authors studied patients with bipolar illness (70 with alcoholism and 161 without), their relatives, and a comparison group composed of relatives' acquaintances. All were evaluated with versions of the Schedule for Affective Disorders and Schizophrenia, and diagnoses were made according to the Research Diagnostic Criteria. Thirty of the bipolar alcoholic patients whose affective disorder was primary were also compared with 34 whose alcoholism was primary. RESULTS: Alcoholism was more frequent in the bipolar patients than in the comparison subjects. There no significant differences between the alcoholic and nonalcoholic bipolar patients in family history of alcoholism or affective disorders, suggesting that bipolar illness with alcoholism is not explicable by a family history of alcoholism and that the alcoholism seen in bipolar illness is dissimilar to alcoholism as a primary disorder. Alcoholism associated with bipolar illness was more likely to remit than primary alcoholism. There was no significant difference in family history between the patients with primary alcoholism and those with primary bipolar disorder. The patients with primary alcoholism had significantly fewer episodes of affective disorder during followup, suggesting that their type of bipolar illness was less severe and may have needed the added insult of alcoholism to make it manifest. CONCLUSIONS: The study supports the idea that not all alcoholism is primary with a corresponding familial diathesis. Rather, alcoholism associated with bipolar disorder is often a secondary complication.

Recurrence after recovery from major depressive disorder during 15 years of observational follow-up.

OBJECTIVE: The recurrence of an affective disorder in people who initially recover from major depressive disorder was characterized by using the unique longitudinal prospective follow-up data from the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression-Clinical Studies. METHOD: Up to 15 years of prospective follow-up data on the course of major depressive disorder were available for 380 subjects who recovered from an index episode of major depressive disorder and for 105 subjects who subsequently remained well for at least 5 years after recovery. Baseline demographic and clinical characteristics were examined as predictors of recurrence of an affective disorder. The authors also examined naturalistically applied antidepressant therapy. RESULTS: A cumulative proportion of 85% (Kaplan-Meier estimate) of the 380 recovered subjects experienced a recurrence, as did 58% (Kaplan-Meier estimate) of those who remained well for at least 5 years. Female sex, a longer depressive episode before intake, more prior episodes, and never marrying were significant predictors of a recurrence. None of these or any other characteristic persisted as a predictor of recurrence in subjects who recovered and were subsequently well for at least 5 years. Subjects reported receiving low levels of antidepressant treatment during the index episode, which further decreased in amount and extent during the well interval. CONCLUSIONS: Few baseline demographic or clinical characteristics predict who will or will not experience a recurrence of an affective disorder after recovery from an index episode of major depressive disorder, even in persons with lengthy well intervals. Naturalistically applied levels of antidepressant treatment are well below those shown effective in maintenance pharmacotherapy studies.