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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.

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This paper reports on the acceptability, reliability and validity of the Structured Clinical Interview for the Spectrum of Substance Use (SCI-SUBS), a new instrument exploring the interactive pathway between substance abuse and psychiatric disorders. Psychiatric outpatients with (n = 21) and without (n = 32) substance abuse comorbidity according to the DSM-IV, non-psychiatric subjects with opioid dependence (OD, n = 14) and normal controls (n = 33) were assessed with the SCI-SUBS. The presence or absence of psychiatric disorders was determined with the Structured Clinical Interview for DSM IV (SCID). The SCI-SUBS was well accepted by participants. The internal consistency of the domains was satisfactory (between 0.64 and 0.93). Domain scores of OD subjects were significantly higher than those of controls and of psychiatric patients without substance abuse. The cut-off point on the SCI-SUBS total score at which there was optimal discrimination between the presence and the absence of a DSM-IV diagnosis of substance abuse was 45. The pilot version of the SCI-SUBS has satisfactory internal consistency and construct validity.

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DSM IV is a simple, reliable diagnostic system with many advantages. However, DSM diagnostic criteria may not provide sufficient characterization of clinically significant symptoms. We have undertaken a project to assess an array (spectrum) of clinical features associated with different DSM Disorders. The purpose of this paper is to report on reliability of assessment instruments for Panic-Agoraphobic Spectrum (PAS), to document convergent validity of PAS symptom groupings, and to confirm the relationship between PAS and DSM IV Panic Disorder (PD). We studied 22 normal controls and 95 outpatients who met criteria for Panic Disorder with and without lifetime Major Depression, and Major Depression or Obsessive Compulsive Disorder without lifetime Panic Disorder. Assessment instruments had excellent reliability and there was good concordance between interview and self-report formats. PAS scores were highest in subjects with PD, followed by outpatients without PD, and were lowest in normal controls. PAS scores varied among PD patients, and a subgroup of patients without PD scored high on PAS. We conclude that PAS can be reliably assessed, and that it describes a valid, coherent constellation of features associated with DSM IV Panic Disorder, but providing additional important clinical information.

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OBJECTIVE: This study investigated the influence of incomplete recovery from first lifetime major depressive episodes on long-term outcome. METHOD: After their first lifetime major depressive episode, patients were divided into asymptomatic (N=70) and residual subthreshold depressive symptom (N=26) recovery groups and compared on longitudinal course during up to 12 years of prospective naturalistic follow-up. RESULTS: Patients with residual subthreshold depressive symptoms during recovery had significantly more severe and chronic future courses. Those with residual symptoms relapsed to major and minor depressive episodes faster and had more recurrences, shorter well intervals, and fewer symptom-free weeks during follow-up than asymptomatic patients. CONCLUSIONS: Resolution of major depressive episodes with residual subthreshold depressive symptoms, even the first lifetime episode, appears to be the first step of a more severe, relapsing, and chronic future course. When ongoing subthreshold symptoms continue after major depressive episodes, the illness is still active, and continued treatment is strongly recommended.

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OBJECTIVE: The authors tested the hypothesis that a lifetime history of panic-agoraphobic spectrum symptoms predicts a poorer response to depression treatment. METHOD: A threshold for clinically meaningful panic-agoraphobic spectrum symptoms was defined by means of receiver operating characteristic curve analysis of total scores on the Structured Clinical Interview for Panic-Agoraphobic Spectrum in a group of 88 outpatients with and without panic disorder. This threshold was then applied to a group of 61 women with recurrent major depression, who completed a self-report version of the same instrument, in order to compare treatment outcomes for patients above and below this clinical threshold. RESULTS: Women with high scores (> or =35) on the Panic-Agoraphobic Spectrum Self-Report were less likely than women with low scores (<35) to respond to interpersonal psychotherapy alone (43.5% versus 68.4%, respectively). Women with high scores also took longer (18.1 versus 10.3 weeks) to respond to a sequential treatment paradigm (adding a selective serotonin reuptake inhibitor when depression did not remit with interpersonal psychotherapy alone). This effect was only partially accounted for by the higher likelihood that patients with high scores required the addition of antidepressants. Although four domains from the Panic-Agoraphobic Spectrum Self-Report were individually associated with a longer time to remission, only stress sensitivity emerged as significant in multivariate regression analyses. CONCLUSIONS: A lifetime burden of panic-agoraphobic spectrum symptoms predicted a poorer response to interpersonal psychotherapy and an 8-week delay in sequential treatment response among women with recurrent depression. These results lend clinical validity to the spectrum construct and highlight the need for alternate psychotherapeutic and pharmacologic strategies to treat depressed patients with panic spectrum features.

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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.

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OBJECTIVE: The authors of this study examined multiple recurrences of unipolar major depressive disorder. METHOD: A total of 318 subjects with unipolar major depressive disorder were prospectively followed for 10 years within a multicenter naturalistic study. Survival analytic techniques were used to examine the probability of recurrence after recovery from the index episode. RESULTS: The mean number of episodes of major depression per year of follow-up was 0. 21, and nearly two-thirds of the subjects suffered at least one recurrence. The number of lifetime episodes of major depression was significantly associated with the probability of recurrence, such that the risk of recurrence increased by 16% with each successive recurrence. The risk of recurrence progressively decreased as the duration of recovery increased. Within subjects, there was very little consistency in the time to recurrence. CONCLUSIONS: Major depressive disorder is a highly recurrent illness. The risk of the recurrence of major depressive disorder progressively increases with each successive episode and decreases as the duration of recovery increases.

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SCOPE: The Collaborative Spectrum Project aims to define subthreshold and atyical conditions not sufficiently characterized in the current diagnostic nomenclature and for which adequate assessment instruments are not available. This paper reports on the development and validation of new instruments to assess the spectrum of five psychiatric disorders. DESIGN: Three multicenter studies and one single-site study were conducted in Italy to assess the validity and reliability of the five spectrum interviews. Another cross-sectional study to validate the panic-agoraphobia spectrum has been conducted in Pittsburgh. SETTING: Outpatients attending various university clinics, university students and, in one Italian study, gym attenders were recruited for the studies. MAIN OUTCOME MEASURES: Five structured clinical interview to assess the spectrum of panic-agoraphobia (SCI-PAS), mood (SCI-MOODS), social phobia (SCI-SHY), and the obsessive-compulsive (SCI-OBS) and eating disorder spectra (SCI-ABS) were administered along with a diagnostic interview and a number of self-report and interviewer-rated instruments. RESULTS: All the domains of the interview showed high test-retest reliability (intraclass correlation coefficient > 0.61) and satisfactory internal consistency. Mean domain scores were significantly higher in cases than in controls and in patients with the disorder of interest than in patients with other disorders. Convergent validity was satisfactory for panic-agoraphobia, social phobia and obsessive-compulsive spectrum domains. Differences emerged between SCI-ABS and self-report instruments assessing eating disorders. A cut-off score for the panic-agoraphobia spectrum was defined and its clinical validity was tested. CONCLUSIONS: The psychometric properties of the five spectrum interviews are very satisfactory, and studies are currently ongoing to test the clinical validity of all the spectra. Subthreshold and atypical symptoms deserve attention in epidemiological investigation.

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OBJECTIVE: Studies of both community and clinical samples have associated depressive symptoms with risks for subsequent cardiovascular morbidity and mortality. Because the physiological mechanisms thought to underlie this link would be cumulative in their effects, the following analyses tested the prediction that risks for cardiovascular death would increase in proportion to the persistence of depressive symptoms in a long-term follow-up. METHODS: Baseline assessment was performed as patients sought treatment for major depressive disorder, mania, or schizo-affective disorder. Follow-up evaluations occurred semiannually for the next 5 years and annually thereafter. The 903 patients described, observed for a mean of 11.0 years (SD = 5.2 years), were divided into thirds according to the proportion of follow-up weeks in episodes of major depressive disorder, schizoaffective disorder, or intermittent depressive disorder. The resulting groups were then compared by cumulative risks of cardiovascular death. RESULTS: Patients whose depressive symptoms were the most persistent were no more likely to die of cardiovascular causes than were those with the fewest weeks ill. A regression analysis showed that older age and the presence of cardiovascular disease at baseline, but not the subsequent chronicity of depressive symptoms, predicted cardiovascular death. CONCLUSIONS: The physiological concomitants of depressive illness apparently do not promote cardiovascular mortality in a cumulative manner. Efforts should be directed toward identification of risk factors common to both lifetime depressive symptoms and cardiovascular morbidity.

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Vivid imagery and hallucinations are occasionally reported by patients on beta-adrenergic blocking agents. The authors document this side effect with drawings by a well-known commercial artist.

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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.

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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.

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This theoretical paper reviews the status of generalized anxiety disorder (GAD) and the Axis I and Axis II disorders with which it is often comorbid. Differences in comorbidity between the epidemiological and clinical literatures are discussed. Special attention is given to panic disorder, the symptoms of which are similar to those of GAD. The boundaries of GAD and its relationship to other Axis I disorders and to Axis II disorders raise important implications for its classification.

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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.

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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.

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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.

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This study compared the personality traits of subjects with bipolar I disorder in remission to the personality traits of subjects with no history of any mental illness. Subjects were assessed as part of a prospective, multicenter, naturalistic study of mood disorders. Diagnoses were rendered according to Research Diagnostic Criteria, through use of the Schedule for Affective Disorders and Schizophrenia - Lifetime Version. A total of 30 euthymic bipolar I subjects were compared to 974 never-ill subjects on 17 personality scales selected for their relevance to mood disorders. The subjects with bipolar I disorder in remission had more aberrant scores on 6 of the 17 personality measures, including Emotional Stability, Objectivity, Neuroticism, Ego Resiliency, Ego Control, and Hysterical Factor. These findings indicate that patients with bipolar I disorder in remission have personality traits that differ from those of normal controls.

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A retrospective literature survey (1980-1992) was conducted to chronicle the development of panic disorder treatment research. Based on a National Institute of Mental Health conference on assessment standardization in this area (Shear and Maser, 1994), the results and implications of the survey are presented in terms of eight domains of measurement recommended as essential for high quality research.

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Subjects who meet the criteria for an affective syndrome possibly are aetiologically heterogeneous. An approach to this possibility involves examining affectively ill subjects obtained by different methods of ascertainment. This study compares depressed and manic subjects who are related to affectively ill probands with affectively ill subjects who were obtained from a study of a control population, and, therefore, were less likely to be familial. The subjects were identified in a large collaborative study of depression where both family members as well as controls were personally interviewed and followed up for 6 years after admission to the study. Data were obtained on subtypes of affective disorder using the Research Diagnostic Criteria and information was gathered about psychiatric hospitalizations, suicide attempts, alcoholism and psychological functioning prior to admission. Similar assessments were made for the comparison groups for the 6 year period between intake and follow-up. Relatives of bipolar I/schizoaffective manic probands were more likely to show mania than affectively ill controls or relatives of unipolar/schizoaffective depressed probands. Affectively ill controls were less likely to be hospitalized and less likely to suffer from an incapacitating depression. They were also likely to have functioned in a more healthy fashion than the affectively ill relatives of the bipolars and unipolars, in the 5 years before admission to the study. In the 6 year follow-up, both the subjects themselves and raters assessed the depressed controls as functioning better than the affectively ill relatives of the probands. Further, assessment of global adjustment during the 6 year period was worse for the relatives of affectively ill probands than for the depressed controls. Length of major depression was longer in relatives of bipolar and unipolar probands than in controls. Though all of the subjects in this study met research criteria for an affective illness, there were marked differences in the qualitative aspects of these illnesses with the relatives of affectively ill probands, who functioned less well and had longer and more severe episodes and more hospitalizations.

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