Biomedical subjects
C F Reynolds
Publications and source records attributed to C F Reynolds.
Life events and the research diagnostic criteria endogenous subtype. A confirmation of the distinction using the Bedford College methods.
BACKGROUND: Despite the advances in biological and psychosocial assessment methods, reliable distinction between depressed patients with endogenous presentations or melancholic symptom features and those with nonendogenous presentations has remained elusive. METHODS: Ninety patients with histories of frequent unipolar episodes classified as endogenous or nonendogenous by the Research Diagnostic Criteria were interviewed with the Bedford College Life Events and Difficulties Schedule regarding the 6 months before onset of their most recent episode of depression. RESULTS: Patients meeting the Research Diagnostic Criteria for definite endogenous subtype differed significantly from patients with nonendogenous features in terms of the proportion experiencing severe life stress in the 6 months before onset of their depressive episode (P < = .04). Furthermore, survival analysis revealed a closer temporal association between severe event and depression onset among patients with nonendogenous features (P < .02). CONCLUSION: Even among patients with a history of multiple recurrences of depression, psychological stress plays an important role in the timing of onset of episodes characterized by nonendogenous features.
Stressful life events, social rhythms, and depressive symptoms among the elderly: an examination of hypothesized causal linkages.
This study sought to determine possible causal linkages among stressful life events, social rhythms, and levels of depressive symptomatology for 81 elderly subjects (51 recently widowed, 30 healthy controls). We examined the associations among stressful life events (i.e., bereavement status at baseline or a severely threatening event occurring between baseline and followup), social rhythm stability, and the level of depressive symptoms. Results indicated that while stressful life events were not associated with significant changes in social rhythm stability, social rhythm stability was a significant negative correlate of both baseline and followup levels of depressive symptomatology; that is, lower levels of social rhythm stability at baseline were associated with high levels of depressive symptoms at baseline (rho = -0.33, n = 81, p < 0.001) and at followup (rho = -0.23, n = 81, p < 0.05). Bereavement was also a significant positive correlate of depressive symptomatology both at baseline (rho = 0.79, n = 81), p < 0.0001) and at followup (rho = 0.55, n = 81, p < 0.0001). It is likely that future research will benefit from social rhythm assessment obtained temporally closer to major life events and from the use of structured interviews to ascertain the presence of syndromal major depression at followup as well as the inclusion of subjects with a wider range of functional impairments. Nevertheless, these results represent a first step in disentangling possible causal connections among stressful life events, social rhythms, and depressive symptomatology.
Affect intensity and phasic REM sleep in depressed men before and after treatment with cognitive-behavioral therapy.
This article explored the relationship between daytime affect and REM sleep in 45 depressed men before and after treatment with cognitive-behavioral therapy and in a control group of 43 healthy subjects. The intensity of daytime affect (as measured by the sum of positive and negative affects) in depressed men correlated significantly and positively with phasic REM sleep measures at both pre- and posttreatment. This relationship was not found in healthy control subjects. In depressed men, both affect intensity and phasic REM sleep measures decreased over the course of treatment. The results suggest a relationship between phasic REM sleep and intensity of affect reported by depressed men. On the basis of this preliminary observation, it was hypothesized that abnormalities in phasic REM sleep in depressed patients are related, in part, to fundamental alterations in the intensity of their affective experience.
Psychosocial correlates and sequelae of electroencephalographic sleep in healthy elders.
This research examines longitudinal data on psychosocial status and polysomnographic sleep collected annually from 57 healthy, community-residing elders aged 61-89. Cluster analysis of variables reflecting sleep continuity and architecture at the baseline assessment was used to identify three groups of elders: those whose sleep was either (a) superior to all remaining respondents across a variety of measures, (b) marred only by significantly reduced sleep efficiency relative to other respondents, or (c) poorer than all other respondents in multiple areas. Cross-validation procedures suggested that the three-group cluster solution was stable and replicable over persons and over time. Subsequent multivariate analyses indicated that recent life events, as well as psychosocial stability and support variables at baseline, distinguished between the sleep pattern groups. Moreover, sleep pattern group membership itself predicted subjects' subsequent sleep characteristics and psychosocial status at follow-up. Implications of these results for conceptualizing psychosocial factors that affect, and are ultimately affected by, sleep disturbances in late life are discussed.
A longitudinal study of laboratory- and diary-based sleep measures in healthy "old old" and "young old" volunteers.
The major aim of this study was to examine laboratory- and diary-based measures of sleep in a group of healthy ("successfully aging") "old old" subjects (> or = 75 years of age), as contrasted with a group of "young old" subjects (60-74 years of age), who were followed longitudinally for 2 years. We hypothesized that sleep would deteriorate to a greater extent over time among the old old subjects than among the young old. The study group consisted of 50 elders (21 male, 29 female; 23 old old, 27 young old), each studied at baseline and then again at 1- and 2-year follow-up. Analysis of variance was used to determine main effects of age group, gender and time on key sleep measures. Most measures were found to be remarkably stable over time. However, some decay was detected in sleep efficiency among the old old, but not among the young old. In a multiple regression model for the cohort as a whole, age, cognitive status and medical burden at baseline predicted subsequent declines in sleep efficiency over the 2-year period. To our knowledge, this is the first longitudinal data set on sleep in the healthy old old.
Clinical diagnoses in 216 insomnia patients using the International Classification of Sleep Disorders (ICSD), DSM-IV and ICD-10 categories: a report from the APA/NIMH DSM-IV Field Trial.
Three diagnostic classifications for sleep disorders have been developed recently: the International Classification of Sleep Disorders (ICSD), the Diagnostic and Statistical Manual, 4th edition (DSM-IV), and the International Classification of Diseases, 10th edition (ICD-10). No data have yet been published regarding the frequency of specific diagnoses within these systems or how the diagnostic systems relate to each other. To address these issues, we examined clinical sleep disorder diagnoses (without polysomnography) in 257 patients (216 insomnia patients and 41 medical/psychiatric patients) evaluated at five sleep centers. A sleep specialist interviewed each patient and assigned clinical diagnoses using ICSD, DSM-IV and ICD-10 classifications. "Sleep disorder associated with mood disorder" was the most frequent ICSD primary diagnosis (32.3% of cases), followed by "Psychophysiological insomnia" (12.5% of cases). The most frequent DSM-IV primary diagnoses were "Insomnia related to another mental disorder" (44% of cases) and "Primary insomnia" (20.2% of cases), and the most frequent ICD-10 diagnoses were "Insomnia due to emotional causes" (61.9% of cases) and "Insomnia of organic origin" (8.9% of cases). When primary and secondary diagnoses were considered, insomnia related to psychiatric disorders was diagnosed in over 75% of patients. The more narrowly defined ICSD diagnoses nested logically within the broader DSM-IV and ICD-10 categories. We found substantial site-related differences in diagnostic patterns. These results confirm the importance of psychiatric and behavioral factors in clinicians' assessments of insomnia patients across all three diagnostic systems. ICSD and DSM-IV sleep disorder diagnoses have similar patterns of use by experienced clinicians.
Sleep and suicidality in psychotic patients.
The purpose of the study was to determine whether polysomnographic rapid eye movement (REM) sleep parameters distinguish between psychotic patients with and without a history of suicidal behavior. We examined both hand-scored and automated measures of rapid eye movement (REM) sleep in psychotic patients with and without a history of suicidal ideation or attempts. Patients with suicidal behavior had significantly increased REM activity and time both in the whole night data and in the first REM period. These findings suggest an association between REM sleep abnormalities and suicidal behavior, perhaps related to alteration in serotonergic function.
Polysomnographic studies of unmedicated depressed men before and after cognitive behavioral therapy.
OBJECTIVE: Differentiation of stable, trait-like characteristics from more episodic or state-dependent disturbances will be helpful in gaining a better understanding of the pathophysiology of depression. However, research in this area has been complicated by artifactual and clinical problems associated with pharmacologic treatment. In this investigation the authors used EEG sleep studies to assess medication-free depressed male patients before and after cognitive behavioral therapy. METHOD: Forty-five male patients with the diagnosis of major depression according to the DSM-III-R criteria and the Research Diagnostic Criteria underwent EEG sleep studies before and after 16 weeks of cognitive behavioral therapy, during which they were free of medication. In addition to the documentation of changes within these patients, the findings were compared with those for 47 healthy subjects, including 15 who were restudied 12-24 months after their baseline assessments. RESULTS: The EEG sleep profiles of the depressed patients showed a significant reduction in REM sleep density after treatment, suggesting "normalization" of an abnormal state-dependent process. By contrast, slow wave sleep and tonic REM measures, including reduced REM latency, were unchanged after treatment. CONCLUSIONS: These findings suggest that early in remission there is disaggregation of irreversible, trait-like correlates of depression (e.g., diminished slow wave sleep and reduced REM latency) from more reversible disturbances (e.g., increased REM density).
Hopelessness in suicide attempters after acute treatment of major depression in late life.
The relation between hopelessness and suicide attempts in the elderly was examined by studying the course of hopelessness in depressed patients. Sixty-three elderly patients with recurrent major depression were treated with nortriptyline and interpersonal psychotherapy and underwent serial ratings of hopelessness and depression during the acute and continuation phases of treatment. Patients who had made a suicide attempt in the past had significantly higher hopelessness scores than nonattempters during both phases of treatment. They were also more likely to drop out of treatment. A high degree of hopelessness persisting after remission of depression in elderly patients appears to be associated with a history of suicidal behavior. It may also increase the likelihood of premature discontinuation of treatment and lead to future suicide attempts or suicide.
Treatment of consecutive episodes of major depression in the elderly.
OBJECTIVE: The purpose of this study was to determine treatment outcome in elderly patients with consecutively treated episodes of recurrent unipolar major depression. METHOD: Subjects were 32 "young" elderly patients with recurrent unipolar depression (mean age = 66.8 years, SD = 5.1) and with two consecutively treated episodes of major depression. Both index and subsequent episodes of major depression were treated in open trial with combined nortriptyline and interpersonal psychotherapy. Rates of remission in index and subsequent episodes were compared by using nonparametric statistics and survival analysis with proportional hazards modeling. RESULTS: Of 30 patients who completed treatment of the subsequent episode, 27 (90%) achieved stable remission of symptoms in both consecutively treated episodes, whereas three patients (10%) did not. Twenty-two (81%) of 27 patients who responded to treatment had a shorter time to remission in treatment of the subsequent episode than in the index episode. Survival analysis with proportional hazards modeling detected a significant difference in time to remission of the index and subsequent episodes (32 paired observations). CONCLUSIONS: In this research study group, recurrent episodes of unipolar major depression in the young elderly were successfully treated to remission in over 80% of patients by using combined pharmacotherapy and psychotherapy similar to that employed in treatment of the index episode. Remission rate and time to remission in consecutively treated episodes were comparable to those in a group of midlife patients with recurrent depression reported by Kupfer et al. in 1989. Thus, recurrent depressive disorder appears to be as treatable in the young elderly as it is in midlife patients.
Do depressed men and women respond similarly to cognitive behavior therapy?
OBJECTIVE: A great majority of the evidence pertaining to the effectiveness of the time-limited psychotherapies as treatments of major depression are derived from studies of either predominantly or entirely female subject groups. Depressed men and women differ in a number of important respects that may alter the course of affective disorder, and as a result, they may also differ in their responses to psychotherapy. In this study the outcomes of 40 men and 44 women treated with cognitive behavior therapy were compared. METHOD: The patients were interviewed with the Schedule for Affective Disorders and Schizophrenia and diagnosed according to the Research Diagnostic Criteria and DSM-III-R criteria. Subsequently, they were assessed every other week (with the Hamilton Depression Rating Scale, Beck Depression Inventory, and Global Assessment Scale) during a standardized, time-limited cognitive behavior therapy protocol. The outcomes of the men and women were compared by means of a series of analyses of variance and covariance and survival analyses. RESULTS: There were several significant pretreatment differences, and the men attended significantly fewer therapy sessions than the women. Although the men and women generally had comparable responses, patients with higher pretreatment levels of depressive symptoms, particularly women, had poorer outcomes. CONCLUSIONS: This study provides further evidence of gender-specific differences in depressed patients' symptoms and treatment utilization. Cognitive behavior therapy appears to be a comparably useful outpatient treatment for men and women. However, either more intensive cognitive behavior therapy or alternative methods of treatment may be warranted for patients with more severe syndromes.
Diagnostic concordance for DSM-IV sleep disorders: a report from the APA/NIMH DSM-IV field trial.
OBJECTIVE: The frequency and ranking of DSM-IV sleep disorder diagnoses of clinical patients with complaints of insomnia, as well as rates of diagnostic agreement and disagreement between two types of interviewers, were investigated. METHOD: Interviewers at five clinical sites assessed 216 patients referred for insomnia complaints. One sleep specialist and one general clinician interviewed each patient in an unstructured clinical interview, assigned DSM-IV diagnoses, and indicated their reactions to the diagnostic system. RESULTS: Insomnia due to another mental disorder was the most frequent DSM-IV diagnosis across sites, followed by primary insomnia. Interviewers at the five sites differed significantly in the rankings they assigned to different diagnoses. In addition, sleep specialists at most sites diagnosed psychiatric forms of insomnia more frequently than nonspecialists. Kappa values for agreement between the two types of clinicians on multiple DSM-IV sleep diagnoses ranged from 0.26 to 0.80 across sites, indicating moderate agreement overall. Kappa values for individual diagnoses varied across sites and specific diagnoses and ranged from poor to excellent. Interviewers' ratings of their confidence in diagnoses and the fit and ease of use of the DSM-IV categories also showed significant variability related to site and type of interviewer. CONCLUSIONS: The distribution of diagnoses highlights the importance of psychiatric and behavioral factors in the assessment of insomnia. Site-related variability indicates a need for greater standardization in the application of sleep disorder diagnostic criteria. Diagnostic concordance for these diagnoses, while only moderately good, likely reflects actual clinical practice and would be improved through the use of standardized (or structured) interviews and increased training.
The Pittsburgh Sleep Diary.
Increasingly, there is a need in both research and clinical practice to document and quantify sleep and waking behaviors in a comprehensive manner. The Pittsburgh Sleep Diary (PghSD) is an instrument with separate components to be completed at bedtime and waketime. Bedtime components relate to the events of the day preceding the sleep, waketime components to the sleep period just completed. Two-week PghSD data is presented from 234 different subjects, comprising 96 healthy young middle-aged controls, 37 older men, 44 older women, 29 young adult controls and 28 sleep disorders patients in order to demonstrate the usefulness, validity and reliability of various measures from the instrument. Comparisons are made with polysomnographic and actigraphic sleep measures, as well as personality and circadian type questionnaires. The instrument was shown to have sensitivity in detecting differences due to weekends, age, gender, personality and circadian type, and validity in agreeing with actigraphic estimates of sleep timing and quality. Over a 12-31 month delay, PghSD measures of both sleep timing and sleep quality showed correlations between 0.56 and 0.81 (n = 39, P < 0.001).
Metabolic and physiologic consequences of nortriptyline treatment in the elderly.
The challenge in the pharmacotherapy of affective disorders is shifting to maintenance treatment. Hence, there is a need for systematic data on the somatic effects of long-term medication use. Twenty-six depressed patients (age > 60 yr) treated with therapeutic concentrations of nortriptyline were evaluated after an average of 7 months for changes in lipoproteins and cardiovascular parameters. Twelve patients were tested for debrisoquine (P450 2D6) metabolic status and creatinine clearance at these same intervals. There was no significant change in cholesterol levels, but triglycerides and very-low-density lipoproteins (VLDL) were significantly increased. Heart rate was also elevated by a mean of 15 beats per minute, and there were modest but significant increases in cardiac conduction parameters. Creatinine clearance declined significantly (by 34%), and blood pressure was unchanged. Small decrements in P450 2D6 could be quantitated. Older patients treated with maintenance psychotropic medications should be evaluated at the regular intervals, particularly with regard to the age-related complications of multiple illness and medications.
Sleep after spousal bereavement: a study of recovery from stress.
AIM: In this study, we compared repeated measures of electroencephalographic (EEG) sleep and subjective sleep quality in nondepressed, spousally bereaved elders and a healthy control group, in order to search for possible psychobiological correlates of bereavement not confounded by concurrent major depression. METHOD: Laboratory-based EEG sleep studies and measures of subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were repeated at 3, 6, 11, 18, and 23 months after spousal bereavement in a study group of 27 elderly volunteers. Data were compared with similar measures from a control group of 27 nonbereaved subjects recorded on three occasions 1 year apart. Repeated-measures analysis of variance (ANOVA), using age as a covariate, examined effects due to time on selected variables in the bereaved group, as well as effects due to group, time, and group-by-time interactions in the experimental and control subjects. RESULTS: Bereaved and control groups showed consistent differences over time in the phasic measures of rapid eye movement (REM) sleep (higher in bereaved subjects during the first and third REM sleep periods), but were similar on all other EEG sleep measures over the 2 years of observation. The bereaved showed a small decline in the percentage of slow-wave sleep over 2 years, but measures of sleep efficiency, REM latency, and delta sleep ratio were stable and did not differ from values seen in control subjects. Bereaved and control subjects were also similar on subjective sleep quality. CONCLUSION: During successful adaptation to the loss of a spouse, and in the absence of major depression, spousal bereavement is associated with elevation in the phasic measures of REM sleep but does not appear to be associated with other physiologic sleep changes typical of major depression when studied at 3 to 23 months after the event. Although this observation does not preclude the possibility of significant sleep disturbance nearer the time of the event, it suggests that preservation of normal sleep following a major negative life event may be an important correlate of the resilience seen in successful aging. The elevation in REM density may provide a psychobiological correlate of bereavement not confounded by concurrent major depression.
Sexual function in depressed men. Assessment by self-report, behavioral, and nocturnal penile tumescence measures before and after treatment with cognitive behavior therapy.
Clinicians have long associated depression with alterations in sexual function, predominantly loss of sexual interest. In a longitudinal study measuring self-report, behavioral, and nocturnal penile tumescence variables before and after treatment with cognitive behavior therapy in an unmedicated sample of 40 outpatient depressed men, we found, contrary to expectation, that sexual activity per se was not reduced during the depressed state. Rather, loss of sexual interest appeared to be related to the cognitive set of depression, ie, loss of sexual satisfaction that then improved with remission from depression. Depressed men were heterogeneous, however, with respect to sexual behavior, eg, an anxious and more chronically depressed subgroup of men who did not have remissions with cognitive behavior therapy reported increased sexual interest and sexual activity. Also, contrary to expectation, nocturnal penile tumescence abnormalities in depressed men did not reverse when measured in early remission, nor did nocturnal penile tumescence measures correlate significantly with behavioral measures of sexual function. Nocturnal penile tumescence alterations in depression may thus be similar to other persistent electroencephalographic sleep abnormalities seen in depressed patients in remission, in being more trait-like than statelike.
Correlation of nocturnal penile tumescence and daytime affect intensity in depressed men.
Although depressed patients have been shown to have diminished nocturnal penile tumescence (NPT), there remains considerable variability of NPT in depression. We hypothesized that affective experience during the day accounts for some of this variability. Forty-five depressed men had assessments of affect intensity and affect balance, NPT, and daytime sexual function, both before and after treatment with Beck's cognitive behavior therapy (CBT). Forty-three normal control subjects were studied for comparison. Daytime affect intensity in depressed men, but not in control subjects, correlated significantly and positively with measures of NPT duration and rigidity both before and after treatment, regardless of the adequacy of daytime sexual function. When the effect of daytime affect on REM activity was controlled, the observed correlations became nonsignificant at pretreatment, but remained significant at posttreatment. Neuropharmacologically mediated changes in arousal responsivity associated with depression may underlie the observed relation between daytime affect intensity, rapid eye movement activity, and NPT.