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Biomedical subjects

C F Reynolds

Publications and source records attributed to C F Reynolds.

At least 91 records · Page 5Linked to original sources
PubMed1999

Age at onset in geriatric bipolar disorder. Effects on clinical presentation and treatment outcomes in an inpatient sample.

The authors report on 62 inpatients over age 60 who met DSM-III-R criteria for bipolar disorder, divided into early- and late-onset groups by their median age at lifetime onset, 49 years, in order to examine differences in demographic and clinical characteristics, treatment parameters, and outcome in the two groups during a short-term hospitalization. The late-onset group was more likely to have psychotic features and to demonstrate cerebrovascular risk/burden. However, both groups had similar and highly significant improvements in the Brief Psychiatric Rating Scale, Global Assessment Scale, and the Mini-Mental State Exam, and 87% were able to be discharged to settings no more restrictive than those at admission.

Age of Onset↗
PubMed1998

Reduced binding of [18F]altanserin to serotonin type 2A receptors in aging: persistence of effect after partial volume correction.

The serotonin (5-HT) neurotransmitter system, which has a widespread distribution in the central nervous system, has been implicated in regulating mood and many human behaviors. There is evidence from postmortem human studies and limited information from prior in vivo studies to support a decline in 5-HT2A receptor density with aging. We examined nine elderly (ages 61-76) and nine young (ages 18-29) healthy individuals with positron emission tomography (PET) and [18F]altanserin, a ligand with high affinity for the 5-HT2A binding site. The PET data were corrected for differences in brain tissue volume between the young and elderly subjects using a magnetic resonance (MR) imaging-based partial volume correction method. Highly significant and widespread cortical reductions in 5-HT2A specific binding were demonstrated in the elderly group relative to young controls. Regional losses averaged 61% before and 57% following correction for effects of cerebral atrophy. This finding, which is consistent with prior postmortem and in vivo studies, has both etiological and potential therapeutic implications for behavioral changes commonly observed in the elderly, including geriatric depression.

Adolescent↗
PubMed1998

Electroencephalographic sleep profiles before and after cognitive behavior therapy of depression.

BACKGROUND: Previous studies have not fully resolved the state-dependent vs traitlike behavior of the electroencephalographic sleep abnormalities associated with depression. We therefore examined the sleep profiles of depressed patients before and after 16 weeks of treatment with cognitive behavior therapy to determine the stability or reversibility of selected abnormalities. METHODS: Seventy-eight unmedicated patients with major depressive disorder were stratified into abnormal and normal subgroups on the basis of pretreatment sleep study results. Two prospectively defined types of sleep variables were studied: those expected to be traitlike or state independent (type 1) and those predicted to be reversible or state dependent (type 2). RESULTS: The type 1 sleep disturbances (reduced rapid eye movement latency, decreased delta sleep ratio, and decreased slow wave sleep [in percentage]) were stable, as predicted, across time. A composite measure of type 2 disturbances (based on rapid eye movement latency, sleep efficiency, and rapid eye movement density) improved significantly, although a minority of patients in remission had persistent abnormalities. CONCLUSIONS: The electroencephalographic sleep correlates of depression can be disaggregated into state-independent and partially reversible subgroups. Persistent sleep disturbances in remitted patients may have ominous prognostic implications.

Adult↗
PubMed1998

Delta sleep deficits in schizophrenia: evidence from automated analyses of sleep data.

BACKGROUND: Several, though not all, polysomnographic studies that use conventional visual scoring techniques show delta sleep deficits in schizophrenia. Delta sleep (in particular, > or = 1- to 2-Hz frequency range), mediated by thalamocortical circuits, is postulated to be abnormal in schizophrenia. We investigated whether deficits in delta sleep occur in schizophrenia and whether these are primarily related to the illness or are epiphenomena of previous medication use or illness chronicity. METHODS: We compared 30 unmedicated schizophrenic patients and 30 age- and sex-matched controls for sleep data evaluated by visual scoring as well as automated period amplitude analyses and power spectral analyses. RESULTS: Schizophrenic patients had reduced visually scored delta sleep. Period amplitude analyses showed significant reductions in delta wave counts but not rapid eye movement counts; power spectral analyses showed reductions in delta as well as theta power. Delta spectral power was also reduced in the subset of 19 neuroleptic-naive, first-episode schizophrenic patients compared with matched controls. Delta deficits were more pronounced in the greater than 1- to 2-Hz frequency range. CONCLUSIONS: Delta sleep deficits that occur in schizophrenia may be related to the primary pathophysiological characteristics of the illness and may not be secondary to previous neuroleptic use. Automated sleep quantification by means of period amplitude and power spectral analyses can complement the use of conventional visual scoring for understanding electrophysiological abnormalities in psychiatric disorders.

Adult↗
PubMed1998

Serotonin in aging, late-life depression, and Alzheimer's disease: the emerging role of functional imaging.

Serotonin (5-HT) neuron and neurotransmitter loss in normal aging and neuropsychiatric diseases of late life may contribute to behavioral changes commonly observed in the elderly population. Extensive evidence implicates a deficit in serotonergic neurotransmission in the development of major depression. It has been further suggested that the age-related changes in 5-HT neurons may predispose the elderly to develop depression. There is also increasing evidence that a combination of disturbances in cholinergic and serotonergic function may play a role in cognitive impairment in Alzheimer's disease (AD), with serotonergic dysfunction potentially responsible for a significant portion of the behavioral aspects of the disease. This implication of the 5-HT system in aging and age-related cognitive and mood disorders rests in large part on post mortem studies and animal models, which are limited in their capacity to predict dynamic human biochemical-behavior relationships or to accurately model the living human brain. Initial applications of functional brain imaging with positron emission tomography (PET) in the in vivo study of the brain in aging depression, and dementia focused on characterizing alterations in physiological measurements of cerebral metabolism and perfusion. However, recent advances in PET radiochemistry, instrumentation, and image processing have paved the way for noninvasive means to test specific hypotheses regarding the direct involvement of 5-HT neurons in the behavioral features of aging and to define and monitor therapeutic regimens for neuropsychiatric conditions of late life. Coupling of clinical trials in well-characterized subject populations with PET imaging using ligands specific for 5-HT receptor subtypes and transporter proteins promises to increase our understanding of the role of the 5-HT system in affective and cognitive aspects of treatment response. Longitudinal studies in aging, late-life depression, and AD are also needed to evaluate the complex interplay between neurodegenerative processes and serotonergic neurotransmission.

Aged↗
PubMed1998

A method for the assessment of the functional neuroanatomy of human sleep using FDG PET.

Although sleep is characterized by relative behavioral inactivity, cortical activity is known to cycle in well-defined periods across this state. Cognitive function during sleep has been difficult to define, although disturbances in sleep are known to result from, and to cause, various human pathologies, including neuropsychiatric disorders. Assessment of brain function in humans (related to cognitive operations) during sleep has been limited, until recently, to surface electrophysiologic recordings that limit analysis of regional function, particularly in deep structures. The current report describes one method of assessing human forebrain activation during sleep using the [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) method and positron emission tomography (PET) measures of regional cerebral glucose utilization. In comparison with other functional brain imaging techniques (e.g., assessment of blood flow or functional magnetic resonance imaging), this method offers the advantage of a more naturalistic study of sleep since subjects do not have to sleep in a scanning device. This leads to a higher rate of successful completion of studies. The primary disadvantage of this method is the decreased temporal resolution necessitating assessments of global sleep states (e.g., REM or NREM) as opposed to assessing events within a sleep state (e.g., sleep spindles or rapid eye movements).

Electroencephalography↗
PubMed1998

Morbidity of homebound versus inpatient elderly psychiatric patients.

This study compares the demographic and clinical characteristics of homebound (HB) elders referred for psychiatric services (N = 251) with those of inpatients (IP) admitted to a geriatric psychiatry unit (N = 594). Demographically, HB patients were older (78.8 vs 74.7 years), were more likely to be women (83% vs 68%), were widowed (54% vs. 44%), and had fewer years of education (10.3 vs. 11.1), but were similar in race, income, and proportion living alone. Clinically, HB patients had less functional disability, less severe depression, less cognitive impairment, and fewer medical problems. However, they were similar in the distribution of most psychiatric diagnoses except dementia (higher in the IP group) and dementia with depression (higher in the HB group). Outcome data for the HB group over 15 (range, 1 to 38) months revealed medical hospitalization in 20.7%, psychiatric hospitalization in 16.3%, nursing home placement in 9.2% and mortality in 8.4%. These preliminary data show that the HB group had psychiatric problems that were comparable to those of the IP group but were not as severely impaired.

Age Distribution↗
PubMed1998

Cognitive and motor slowing in Alzheimer's disease and geriatric depression.

While response slowing on psychological tasks is a symptom of both depression and Alzheimer's disease (AD), the underlying mechanisms may be quite different: a slowing of cognitive processing in AD and a motor retardation in depression. This hypothesis was tested by examining the rate at which participants performed a simple cognitive operation: subvocal pronunciation. Participants were shown words of between one and three syllables and were asked to decide whether each word ended in a particular sound. This task required participants to transform the written word into its phonological representation, an operation thought to involve subvocal pronunciation. Decision time rose linearly with the number of syllables in all three subject groups. The linear function of the AD patients had a significantly greater slope, indicating a slower rate of subvocal pronunciation, whereas the slope was the same for the normal old and depressed. Both the depressed and AD patients had a higher intercept than the normal old, suggesting a sensorimotor slowing. After treatment, the intercept of the linear function for depressed patients fell, but there was no change in the slope. Thus, this study suggests that AD produces a slowing in both cognitive and motor processes, whereas depression results solely in a motor retardation.

Aged↗
PubMed1998

High levels of hopelessness persist in geriatric patients with remitted depression and a history of attempted suicide.

OBJECTIVE: To determine whether a high level of hopelessness after treatment of a depressive episode is an indicator of a history of lifetime suicide attempts in older people. DESIGN: Groups of suicide attempters, suicidal ideators, and nonsuicidal patients were compared via analysis of variance with respect to levels of hopelessness, depression, anxiety, and global functioning before and after treatment of depression. SETTING: An outpatient research clinic providing two treatment protocols of late-life mood disorders. PARTICIPANTS: A total of 107 consecutive outpatients (mean age 67) with major depression who responded to treatment. MEASUREMENTS: Levels of hopelessness, severity of depression, anxiety, and global functioning were compared across the three groups at the beginning of treatment and at remission. RESULTS: After remission there were no differences between the three groups in depression severity, anxiety, and global functioning. Hopelessness remained significantly higher in the attempter group than among ideators or nonsuicidal patients. CONCLUSIONS: Suicide attempts, the most important risk factor for subsequent suicide, are associated with persistent, high levels of hopelessness following remission of depression in late-life patients. These findings suggest that treatments designed specifically to lower hopelessness (such as cognitive, behavioral or interpersonal therapy) may be effective in reducing suicide risk.

Aged↗
PubMed1998

Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients.

OBJECTIVE: The goal of this study was to examine treatment outcome differences in relation to age at onset of first lifetime episode of recurrent major depression in elderly patients. METHOD: Patients were grouped as having early-onset (N = 129) or late-onset (N = 58) depression. Early onset was defined as having a first lifetime episode of major depression at age 59 or earlier; late onset was defined as age 60 or later. The two groups of patients were compared with respect to demographic and clinical characteristics, types of treatment given (nortriptyline and interpersonal psychotherapy), and treatment outcomes. RESULTS: The groups did not differ in the percentage of patients who remitted, recovered, or relapsed during continuation treatment or in the percentage who experienced a recurrence of major depression during the first year of maintenance treatment. However, early-onset patients took 5-6 weeks longer to achieve remission than did late-onset patients, and a higher proportion had a history of suicide attempts. CONCLUSIONS: These data suggest that age at lifetime onset of recurrent major depression does not influence short- or long-term treatment response in elderly patients treated with combined interpersonal psychotherapy and nortriptyline, with the exception of slowing the speed of remission in early-onset cases. Difference in remission speed may reflect the greater number of previous episodes in the early-onset patients. Nevertheless, the likelihood of a longer time to remission, together with a higher rate of past suicide attempts, suggests that elderly depressed patients with a history of early-onset illness need particularly careful management.

Age Factors↗
PubMed1998

How common is resistance to treatment in recurrent, nonpsychotic geriatric depression?

OBJECTIVE: Effective treatments are available for major depressive disorder in later life. The purpose of this study was to elucidate the frequency of treatment resistance among the elderly. METHOD: Treatment resistance, defined as lack of recovery despite combined pharmacotherapy and psychotherapy, was prospectively examined in 180 elderly patients in an episode of recurrent, nonpsychotic major depression who were referred to a university medical center for treatment. They received open acute and continuation treatment with nortriptyline and interpersonal psychotherapy. RESULTS: Among the 159 patients who completed acute treatment, 19 (11.9%) did not experience a remission of depression. In addition, nine patients who had achieved remission relapsed during continuation therapy and did not recover despite vigorous treatment. Hence, excluding dropouts, 18.4% of the patients met the criteria for treatment resistance by their lack of response to acute treatment or by relapsing during continuation therapy and not recovering subsequently despite further vigorous treatment. CONCLUSIONS: The study suggests a relatively low rate of resistance to treatment among depressed geriatric patients referred to a university tertiary care setting.

Academic Medical Centers↗
PubMed1998

Serum anticholinergicity in elderly depressed patients treated with paroxetine or nortriptyline.

OBJECTIVE: The authors' goal was to compare serum anticholinergicity of 61 elderly depressed patients randomly assigned to double-blind treatment with paroxetine (N=31) or nortriptyline (N=30). METHOD: Both antidepressants were titrated in a standardized manner, and plasma was sampled weekly for measurement of paroxetine and nortriptyline and its hydroxy metabolite concentrations. Serum anticholinergicity was measured at baseline and after 1, 4, and 6 weeks of treatment. Side effects were assessed by using a validated scale. RESULTS: After correcting for pretreatment anticholinergicity, the authors found that mean serum anticholinergicity for the nortriptyline-treated patients was significantly greater than that for the paroxetine group at all weeks assessed. Serum anticholinergicity was significantly correlated with nortriptyline but not with paroxetine plasma levels. Complaints of dry mouth and tachycardia were significantly more frequent and severe in the nortriptyline group. CONCLUSIONS: These findings suggest that, at therapeutic plasma concentrations, paroxetine has approximately one-fifth the anticholinergic potential of nortriptyline in older patients.

Aged↗
PubMed1998

Characteristics and course of major depression in older primary care patients.

OBJECTIVE: Identify the morbidity patterns displayed by older primary care patients experiencing depressive symptomatology who do and do not meet criteria for a major depression. METHOD: Patients ages sixty and older presenting at two ambulatory internal medicine centers were administered the CES-D. Among those scoring > or = 11, 104 completed a comprehensive assessment of their psychiatric symptomatology, medical illness, and functional abilities. The assessment battery was again administered six months later. RESULTS: The point prevalence of major depression in older primary care patients is estimated at 9 percent based on SCID interviews. Patients meeting criteria for this diagnosis compared to those who are symptomatic but not experiencing a major depression described more extensive psychopathology but also significantly more limitations in performing social and functional roles. At six-month follow-up, only 11.5 percent of those initially diagnosed with a major depression were considered fully recovered. CONCLUSIONS: Major depression is a prevalent disorder in older primary care patients which affects their ability to perform expected social and physical roles. Mechanisms for delivering efficacious treatments in routine medical practice are of a high priority.

Age Factors↗
PubMed1998

A post hoc comparison of paroxetine and nortriptyline for symptoms of traumatic grief.

BACKGROUND: This report presents the results of an open-trial pilot study of paroxetine for symptoms of traumatic grief, compared with the effects of nortriptyline in an archival contrast group. METHOD: Data are presented on 15 subjects (4 men, 11 women), ranging in age from 40 to 79 years (mean age = 57 years), who experienced the loss of a spouse (N = 8), child (N =5), grandchild (N = 1), or parent (N = 1). Subjects were required to have a baseline score on the Inventory of Complicated Grief (ICG) of > or = 20. Treatment with paroxetine began at a median of 17 months (range, 6-139 months) after the loss. Paroxetine-treated subjects received a psychotherapy tailored for traumatic grief. Depressive symptoms were assessed by using the Hamilton Rating Scale for Depression (HAM-D). The ICG and the HAM-D were administered weekly over 4 months of paroxetine treatment (median dose = 30 mg/day). The group receiving paroxetine were then compared with a group (N = 22) participating in a separate trial of nortriptyline (median dose = 77.5 mg/day) for treatment of bereavement-related major depressive episodes. RESULTS: Level of traumatic grief symptoms (ICG) decreased by 53%, and depression ratings (HAM-D) decreased by 54% in paroxetine-treated subjects. Nortriptyline showed clinical effects comparable to those of paroxetine. CONCLUSION: Paroxetine may be an effective agent in the treatment of traumatic grief symptoms. A comparison of the paroxetine-treated group with a nortriptyline-treated group suggests that both agents have comparably beneficial effects on the symptoms of traumatic grief (as well as those of depression). However, the higher rate of diagnostic comorbidity in the paroxetine-treated group, together with the greater chronicity of their symptoms and the greater safety of paroxetine in overdose, leads us to favor paroxetine over nortriptyline for traumatic grief symptoms in general psychiatric practice. Further controlled evaluation of paroxetine for traumatic grief is necessary.

Adjustment Disorders↗
PubMed1998

Long-term ECG changes in depressed elderly patients treated with nortriptyline. A double-blind, randomized, placebo-controlled evaluation.

ECGs of 50 patients who completed a long-term nortriptyline (NT) study are presented at baseline, after 7 weeks on NT, and after 1 year. The ECGs of patients with preexisting cardiac disease were compared with non-cardiac patients. Significant ECG changes and increases in heart rate were observed by Week 7 and persisted at a mean of 55 weeks (range: 24-111) in patients who were continued on NT. No significant difference was found in long-term ECG effects in patients with preexisting cardiac disease; ECG changes reverted to baseline when placebo was substituted. Patients with known cardiac disease did not show significantly worse ECG changes on NT than non-cardiac patients.

Age Factors↗
PubMed1998

Recruitment methods for intervention research in bereavement-related depression. Five years' experience.

The authors compared various strategies for recruiting elderly subjects with bereavement-related depression into a randomized clinical trial. Over 5 years, they empaneled 65 patients from a total of 441 subjects screened (14.7%). Response to media advertisements was the single most effective strategy (54% of subjects). Another effective, but labor-intensive, strategy was using letters to bereaved spouses found through newspaper obituaries (14%); another 14% were referred by friends who had seen study advertisements. Information letters to healthcare providers yielded no study participants. Pathways to study participation did not differ as a function of race or gender and did not influence study retention or remission rates. Our experience suggests that successful intake depends on a personal mode of recruitment.

Advertising↗
PubMed1998

EEG sleep in African-American patients with major depression: a historical case control study.

This study was designed to evaluate the effect of race, specifically African-American, on electroencephalographic (EEG) sleep and clinical symptom profile in unipolar major depression. A clinical research database was used to identify appropriate subjects and a double-matched historical case-control design was implemented. African-American depression patients were double matched within protocol to Euro-American depressed patients. Age, sex, and protocol of origin were matching variables. African-American depressed patients had less total sleep, less slow wave sleep, more stage 2 sleep, longer rapid eye movement (REM) sleep latency, less REM sleep, and lower REM density than Euro-American depressed patients. African-American depressed patients did not differ from Euro-American patients in symptom severity, age of onset, number of episodes, socio-economic status, and, as planned, did not differ in age and sex distribution. Depressive symptom constellation also did not distinguish the two groups. African-American depressed patients demonstrated differences in EEG sleep profile, with less total sleep, overall lighter nonREM sleep, and relatively preserved REM sleep, despite a clinical symptom profile that did not differ from Euro-American depressed patients. The sleep profile appeared to be consonant with the sleep findings in chronic insomnia. The pathological implications of these differences remained to be explored in careful prospective studies of African-American depressed patients and in well-characterized, racially matched normal control comparisons.

Adult↗