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Biomedical subjects

M B Keller

Publications and source records attributed to M B Keller.

At least 37 records · Page 2Linked to original sources

Gender differences in chronic major and double depression.

BACKGROUND: While the sex difference in prevalence rates of unipolar depression is well established, few studies have examined gender differences in clinical features of depression. Even less is known about gender differences in chronic forms of depression. METHODS: 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were administered an extensive battery of clinician-rated and self-report measures. RESULTS: Women were less likely to be married and had a younger age at onset and greater family history of affective disorder compared to men. Symptom profile was similar in men and women, with the exception of more sleep changes, psychomotor retardation and anxiety/somatization in women. Women reported greater severity of illness and were more likely to have received previous treatment for depression with medications and/or psychotherapy. Greater functional impairment was noted by women in the area of marital adjustment, while men showed more work impairment. LIMITATIONS: Since our population consisted of patients enrolling in a clinical trial, study exclusion criteria may have affected gender-related differences found. CONCLUSIONS: Chronicity of depression appears to affect women more seriously than men, as manifested by an earlier age of onset, greater family history of affective disorders, greater symptom reporting, poorer social adjustment and poorer quality of life. These findings represent the largest study to date of gender differences in a population with chronic depressive conditions.

Adult↗

A brief assessment of psychosocial functioning of subjects with bipolar I disorder: the LIFE-RIFT. Longitudinal Interval Follow-up Evaluation-Range Impaired Functioning Tool.

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.

Adaptation, Psychological↗

Suicidal behavior in patients with current or past panic disorder: five years of prospective data from the Harvard/Brown Anxiety Research Program.

OBJECTIVE: The authors' goals were to examine predictors of suicidal behavior and provide guidelines for assessing suicide risk in patients with panic disorder. METHOD: Four hundred ninety-eight patients with panic disorder were followed for 5 years. Survival analysis was used to examine variables correlated with prospectively observed suicidal behavior. RESULTS: Subjects had a 0.06 probability of suicidal behavior during follow-up. Affective disorders, substance abuse, eating disorders, personality disorders, and being female were risk factors. Two subjects were suicidal in the absence of risk factors; both developed depression during follow-up. CONCLUSIONS: Panic disorder is not associated with suicidal behavior in the absence of other risk factors.

Adolescent↗

Multiple recurrences of major depressive disorder.

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.

Adolescent↗

Lost human capital from early-onset chronic depression.

OBJECTIVE: Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. METHOD: The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. RESULTS: Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. CONCLUSIONS: Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

Adult↗

Gender differences in treatment response to sertraline versus imipramine in chronic depression.

OBJECTIVE: The authors examined gender differences in treatment response to sertraline, a selective serotonin reuptake inhibitor (SSRI), and to imipramine, a tricyclic antidepressant, in chronic depression. METHOD: A total of 235 male and 400 female outpatients with DSM-III-R chronic major depression or double depression (i.e., major depression superimposed on dysthymia) were randomly assigned to 12 weeks of double-blind treatment with sertraline or with imipramine after placebo washout. RESULTS: Women were significantly more likely to show a favorable response to sertraline than to imipramine, and men were significantly more likely to show a favorable response to imipramine than to sertraline. Gender and type of medication were also significantly related to dropout rates; women who were taking imipramine and men who were taking sertraline were more likely to withdraw from the study. Gender differences in time to response were seen with imipramine, with women responding significantly more slowly than men. Comparison of treatment response rates by menopausal status showed that premenopausal women responded significantly better to sertraline than to imipramine and that postmenopausal women had similar rates of response to the two medications. CONCLUSIONS: Men and women with chronic depression show differential responsivity to and tolerability of SSRIs and tricyclic antidepressants. The differing response rates between the drug classes in women was observed primarily in premenopausal women. Thus, female sex hormones may enhance response to SSRIs or inhibit response to tricyclics. Both gender and menopausal status should be considered when choosing an appropriate antidepressant for a depressed patient.

Adult↗

Does incomplete recovery from first lifetime major depressive episode herald a chronic course of illness?

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.

Antidepressive Agents↗

Factors predicting the clinical course of generalised anxiety disorder.

BACKGROUND: Cross-sectional data show that generalised anxiety disorder (GAD) is a chronic condition with episodes lasting much longer than the six-month minimum required by DSM-III-R and DSM-IV. Although GAD is chronic, little is known about factors influencing illness duration. AIMS: To investigate variables that influence the clinical course of GAD. METHOD: A total of 167 patients with GAD participated in the Harvard-Brown Anxiety Research Program. Patients were assessed at intake and re-examined at six- to twelve-month intervals for five years. Kaplan-Meier curves were constructed to assess the likelihood of remission. Regression analysis was used to investigate factors predicting full or partial remission. RESULTS: The rate of remission was 0.38 after five years. Diminished likelihood of remission was associated with low overall life satisfaction, poor spousal or family relationships, a concurrent cluster B or C personality disorder and a low global assessment score. CONCLUSIONS: Full or partial remissions were less likely to occur in patients with poor relationships and personality disorders. These patients should be given more intensive and possibly multi-modal therapy.

Adolescent↗

The Collaborative Longitudinal Personality Disorders Study: development, aims, design, and sample characteristics.

This paper describes the aims, background, design, and methods used in a collaborative longitudinal study of Axis II personality disorders (PDs). This study examines the putative stability of selected PD diagnoses and criteria, what factors affect their course, and whether their stability and course distinguishes them from a representative Axis I disorder. This article also describes the acquisition and demographics of the sample on whom the study is being done. A prospective, repeated measures investigation of the stability of PDs is now underway at multiple clinical settings in four collaborating urban sites in Boston. New Haven, New York, and Providence. Diagnostic assignments are based on semistructured interview assessments (by clinically trained raters) and confirmed by at least one additional contrasting diagnostic method. The sample consists of 668 treatment seeking and reliably diagnosed adults recruited from a broad range of clinical sites. By design, patients in the sample met standards for one of five diagnostic subgroups: (a) schizotypal (N = 86); (b) borderline (N = 175); (c) avoidant (N = 157); (d) obsessive-compulsive (N = 153) personality disorders or a control group having (e) major depressive disorder without personality disorder (N = 97).

Adolescent↗

Social functioning in depression: a review.

OBJECTIVE: This article reviews the available data on social functioning in depression and provides clinical guidelines and opinion on this important and expanding field. DATA SOURCES: A MEDLINE search was conducted to identify all English-language articles (1988-1999) using the search terms depression and social functioning, depression and social adjustment, depression and psychosocial functioning, and social functioning and antidepressant. Further articles were obtained from the bibliographies of relevant articles. DATA SYNTHESIS: Depressive disorders are frequently associated with significant and pervasive impairments in social functioning, often substantially worse than those experienced by patients with other chronic medical conditions. The enormous personal, social, and economic impact of depression, due in no small part to the associated impairments in social functioning, is often underappreciated. Both pharmacologic and psychotherapeutic approaches can improve social impairments, although there is a lack of extended, randomized controlled trials in this area using consistent assessment criteria. CONCLUSION: Despite this lack, it is becoming clear that not all treatments are equally effective in relieving the impaired social functioning associated with depressive disorders. Furthermore, efficacy in relieving the core symptoms of depression does not necessarily guarantee efficacy in relieving impaired social functioning.

Adaptation, Psychological↗

Comparison of DSM-III-R chronic major depression and major depression superimposed on dysthymia (double depression): validity of the distinction.

The nosology of chronic depression has become increasingly complex since the publication of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), but there are few data available to evaluate the validity of the distinctions between the subtypes of chronic depression. The validity of the distinction between DSM-III-R chronic major depression (CMD) and major depression superimposed on dysthymia (double depression, DD) was examined. Participants were 635 patients with chronic depression in a 12-week trial of antidepressant medications. Patients with CMD, DD, and a 3rd group with a chronic major depressive episode superimposed on dysthymia (DD/CMD) were compared on demographic and clinical characteristics, family history, and response to treatment. Few differences were evident, although the depression of patients with DD/CMD tended to be more severe.

Adult↗

Citalopram therapy for depression: a review of 10 years of European experience and data from U.S. clinical trials.

BACKGROUND: This review summarizes and evaluates clinical experience with citalopram, the latest selective serotonin reuptake inhibitor (SSRI) to be approved for the treatment of depression in the United States. DATA SOURCES: Published reports of randomized, double-blind, controlled clinical studies of citalopram were retrieved using a MEDLINE literature search. Search terms included citalopram, SSRI, TCA (tricylic antidepressant), depression, and clinical. For each study, data on antidepressant efficacy and adverse events were evaluated. Pharmacokinetic studies and case reports were reviewed to supplement the evaluation of citalopram's safety and tolerability. Data presented at major medical conferences and published in abstract form also were reviewed. STUDY FINDINGS: Thirty randomized, double-blind, controlled studies of the antidepressant efficacy of citalopram were located and reviewed. In 11 studies, citalopram was compared with placebo (1 of these studies also included comparison with another SSRI). In 4 additional studies, the efficacy of citalopram in preventing depression relapse or recurrence was investigated. In another 11 studies (including 1 meta-analysis of published and unpublished trials), citalopram was compared with tricyclic and tetracyclic antidepressants. Finally, results are available from 4 studies in which citalopram was compared with other SSRIs. A placebo-controlled study of citalopram for the treatment of panic disorder was reviewed for data on long-term adverse events. CONCLUSION: Data published over the last decade suggest that citalopram is (1) superior to placebo in the treatment of depression, (2) has efficacy similar to that of the tricyclic and tetracyclic antidepressants and to other SSRIs, and (3) is safe and well tolerated in the therapeutic dose range of 20 to 60 mg/day. Distinct from some other agents in its class, citalopram exhibits linear pharmacokinetics and minimal drug interaction potential. These features make citalopram an attractive agent for the treatment of depression, especially among the elderly and patients with comorbid illness.

Adolescent↗

Age of onset in chronic major depression: relation to demographic and clinical variables, family history, and treatment response.

BACKGROUND: The clinical and etiological significance of the early-late onset distinction in chronic major depressive disorder was explored. METHOD: Subjects were 289 outpatients with DSM-III-R chronic major depression drawn from a multi-site study comparing the efficacy of sertraline and imipramine in the acute and long-term treatment of chronic depression. Patients received comprehensive evaluations using semi-structured interviews and rating scales. RESULTS: Early-onset chronic major depression was associated with a longer index major depressive episode and higher rates of recurrent major depressive episodes, comorbid personality disorders, lifetime substance use disorders, depressive personality traits, and a history of psychiatric hospitalization. In addition, more early-onset patients tended to have a family history of mood disorders. The early-late onset distinction was not associated with differences in symptom severity, functional impairment, or treatment response. LIMITATIONS: Family members were not interviewed directly; there were a large number of statistical comparisons; and interrater reliability of the assessments was not evaluated. CONCLUSIONS: Early-onset chronic major depression has a more malignant course and is associated with greater comorbidity than late-onset chronic major depression.

Adult↗

The Range of Impaired Functioning Tool (LIFE-RIFT): a brief measure of functional impairment.

BACKGROUND: The literature documents that functional impairment is associated with affective disorders. Nevertheless, the choice among thorough, yet brief, well-validated assessments of functional impairment is limited. The objective of this study was to evaluate the psychometric properties of a brief scale of functional impairment, the Range of Impaired Functioning Tool (LIFE-RIFT). METHOD: The study sample included subjects who presented with major depressive disorder at intake into the NIMH Collaborative Depression Study (CDS). The LIFE-RIFT is composed of items that are included in the Longitudinal Interval Follow-up Evaluation (LIFE). The reliability and validity were examined using data from LIFE-RIFT assessments conducted at four points in time: 6, 12, 18 and 24 months after intake into the CDS. RESULTS: Cross-sectional one factor models accounted for the covariance structure among the four scale items. A longitudinal factor model, with an invariant factor structure over time, also fitted the data well and indicated that the scale items are measures of one construct, namely functional impairment. The internal consistency reliability of the scale was supported with alpha coefficients ranging from 0.81 to 0.83. The inter-rater reliability intraclass correlation coefficient (ICC) was 0.94. Mixed-effect linear regression models showed that those in episode were significantly more impaired than those in recovery. Furthermore, in analyses of predictive validity, impairment was positively associated with subsequent recurrence and negatively associated with subsequent recovery. CONCLUSIONS: This psychometric evaluation provides empirical support for the reliability and validity of the LIFE-RIFT, a brief measure of functional impairment.

Activities of Daily Living↗

Chronicity in posttraumatic stress disorder (PTSD) and predictors of course of comorbid PTSD in patients with anxiety disorders.

The purpose of this study was to examine the course of comorbid posttraumatic stress disorder (PTSD) in 54 patients with another anxiety disorder. Using a prospective longitudinal design, the present study found that during the first 5 years of follow-up the probability of full remission from a chronic episode of PTSD was .18. Findings from this and other research confirm clinical impressions that a substantial number of people never fully remit from their PTSD even after many years. Variables associated with a longer time to remit from an episode of chronic PTSD were a history of alcohol abuse and a history of childhood trauma.

Adult↗

Recovery and relapse in anorexia and bulimia nervosa: a 7.5-year follow-up study.

OBJECTIVE: To assess the course and outcome of anorexia nervosa (AN) and bulimia nervosa (BN) at a median of 90 months of follow-up in a large cohort of women with eating disorders. METHOD: A prospective, naturalistic, longitudinal design was used to map the course of AN and BN in 246 women. Follow-up data are presented in terms of full and partial recovery, predictors of time to recovery, and rates and predictors of relapse. RESULTS: The full recovery rate of women with BN was significantly higher than that of women with AN, with 74% of those with BN and 33% of those with AN achieving full recovery by a median of 90 months of follow-up. Intake diagnosis of AN was the strongest predictor of worse outcome. No predictors of recovery emerged among bulimic subjects. Eighty-three percent of women with AN and 99% of those with BN achieved partial recovery. Approximately one third of both women with AN and women with BN relapsed after full recovery. No predictors of relapse emerged. CONCLUSIONS: The findings suggest that the course of AN is characterized by high rates of partial recovery and low rates of full recovery, while the course of BN is characterized by higher rates of both partial and full recovery.

Adolescent↗

Long-term prognosis of bipolar I disorder.

This study examined the contribution of demographic, syndromal and longitudinal course variables to the long-term prognosis of 165 bipolar patients prospectively observed over 10 years as part of the National Institute of Mental Health Collaborative Study of Depression. Although most baseline clinical and demographic variables were not strong prognostic indicators, switching polarity within episodes was. Most episodes among the poor-prognosis patients were polyphasic, while most episodes among the comparison group with a better prognosis were monophasic. There was no evidence of shortening of cycle lengths over follow-up for either the poor-prognosis group or the entire sample. The relevance of these findings to the 'kindling' model is discussed.

Adult↗

Psychosocial treatment prescriptions for generalized anxiety disorder, panic disorder, and social phobia, 1991-1996.

OBJECTIVE: Pharmacologic prescriptions for anxiety disorders have changed significantly in the last decade. This article investigates whether psychosocial treatments, as reported by 362 subjects in the Harvard/Brown Anxiety Disorders Research Program from 1991 to 1996, changed as well. METHOD: Subjects were interviewed in 1991 and 1995-1996 to determine which psychosocial treatments (behavioral, cognitive, dynamic, or relaxation or meditation) they had received. RESULTS: The percentage of subjects who received each type of psychosocial treatment either declined or remained the same from 1991 to 1995-1996. Dynamic psychotherapy remained the most frequently used method of these four. The percentage of subjects receiving any such method declined. CONCLUSIONS: Behavioral and cognitive treatment, two empirically validated forms of psychotherapy, were less frequently used than dynamic psychotherapy, which lacks such validation. All use of verbal treatment methods declined from 1991 to 1995-1996.

Adolescent↗