Charles F. Reynolds

Complicated grief and related bereavement issues for DSM‐5

Bereavement is a severe stressor that typically incites painful and debilitating symptoms of acute grief that commonly progresses to restoration of a satisfactory, if changed, life. Normally, grief does not need clinical intervention. However, sometimes acute grief can gain a foothold and become a chronic debilitating condition called complicated grief. Moreover, the stress caused by bereavement, like other stressors, can increase the likelihood of onset or worsening of other physical or mental disorders. Hence, some bereaved people need to be diagnosed and treated. A clinician evaluating a bereaved person is at risk for both over‐and under‐diagnosis, either pathologizing a normal condition or neglecting to treat an impairing disorder. The authors of DSM IV focused primarily on the problem of over‐diagnosis, and omitted complicated grief because of insufficient evidence. We revisit bereavement considerations in light of new research findings. This article focuses primarily on a discussion of possible inclusion of a new diagnosis and dimensional assessment of complicated grief. We also discuss modifications in the bereavement V code and refinement of bereavement exclusions in major depression and other disorders. Depression and Anxiety, 2011.

The Association of Late-Life Depression and Anxiety With Physical Disability: A Review of the Literature and Prospectus for Future Research

Depression and anxiety disorders are associated with excess disability. The authors searched the recent geriatric literature for studies associating late-life depression or anxiety with physical disability. Studies showed depression in old age to be an independent risk factor for disability; similarly, disability was found to be a risk factor for depression. Anxiety in late life was also found to be a risk factor for disability, although not necessarily independently of depression. Increased disability due to depression is only partly explained by differences in socioeconomic measures, medical conditions, and cognition. Physical disability improves with treatment for depression; comparable studies have not been done for anxiety. The authors discuss how these findings inform current concepts of physical disability and discuss the implications for future intervention studies of late-life depression and anxiety disorders.

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 Alzheimers 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 brian 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.

Allelic Variation in the Serotonin Transporter Promoter Affects Onset of Paroxetine Treatment Response in Late-Life Depression

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.

Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies

BACKGROUND Late-life depression may increase the risk of incident dementia, in particular of Alzheimers disease and vascular dementia. AIMS To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimers disease and vascular dementia in individuals with late-life depression in population-based prospective studies. METHOD A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimers disease and vascular dementia in older adults with late-life depression. RESULTS Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimers disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimers disease (P = 0.03). CONCLUSIONS Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimers disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimers disease.

Healthy older adults' sleep predicts all-cause mortality at 4 to 19 years of follow-up.

Objective Evidence concerning whether sleep disturbances in older adults predict mortality is mixed. However, data are limited to self-reported sleep problems and may be confounded with other comorbidities. We examined whether electroencephalographic (EEG) sleep parameters predicted survival time independently of known predictors of all-cause mortality. Methods A total of 185 healthy older adults, primarily in their 60s through 80s, with no history of mental illness, sleep complaints, or current cognitive impairment, were enrolled in one of eight research protocols between October 1981 and February 1997 that included EEG sleep assessments. At follow-up (mean [SD] = 12.8 [3.7] years after baseline, range = 4.1–19.5), 66 individuals were positively ascertained as deceased and 118 remained alive (total N = 184). Results Controlling for age, gender, and baseline medical burden, individuals with baseline sleep latencies greater than 30 minutes were at 2.14 times greater risk of death (p = .005, 95% CI = 1.25–3.66). Those with sleep efficiency less than 80% were at 1.93 times greater risk (p = .014, CI = 1.14–3.25). Individuals with rapid eye movement (REM) sleep percentages in the lowest 15% or highest 15% of the total sample’s distribution (percentage of REM <16.1 or >25.7) were at 1.71 times greater risk (p = .045, CI = 1.01–2.91). Percentage of slow-wave sleep was associated with time to death at the bivariate level, but not after controlling for potential confounders. Conclusions Older adults with specific EEG sleep characteristics have an excess risk of dying beyond that associated with age, gender, or medical burden. The findings suggest that interventions to optimize and protect older adults’ sleep initiation, continuity, and quality may be warranted.

Daytime Sleepiness Predicts Mortality and Cardiovascular Disease in Older Adults

INTRODUCTION: As part of the baseline examination in the Cardiovascular Health Study, sleep disturbance symptoms including snoring and daytime sleepiness, were assessed as potential risk factors or precipitants of cardiovascular disease (CVD). Because of the association of sleep disturbance with poorer health and the possible associations of sleep apnea with CVD, we hypothesized that those with poorer sleep or daytime sleepiness may be at increased risk of mortality or incident CVD.

The Pittsburgh Sleep Diary

SUMMARY  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).

Circadian rhythms in human performance and mood under constant conditions

This study explored the relationship between circadian performance rhythms and rhythms in rectal temperature, plasma cortisol, plasma melatonin, subjective alertness and well‐being. Seventeen healthy young adults were studied under 36 h of «unmasking» conditions (constant wakeful bedrest, temporal isolation, homogenized «meals») during which rectal temperatures were measured every minute, and plasma cortisol and plasma melatonin measured every 20 min. Hourly subjective ratings of global vigour (alertness) and affect (well‐being) were obtained followed by one of two performance batteries. On odd‐numbered hours performance (speed and accuracy) of serial search, verbal reasoning and manual dexterity tasks was assessed. On even‐numbered hours, performance (% hits, response speed) was measured at a 25–30 min visual vigilance task. Performance of all tasks (except search accuracy) showed a significant time of day variation usually with a nocturnal trough close to the trough in rectal temperature. Performance rhythms appeared not to reliably differ with working memory load. Within subjects, predominantly positive correlations emerged between good performance and higher temperatures and better subjective alertness; predominantly negative correlations between good performance and higher plasma levels of cortisol and melatonin. Temperature and cortisol rhythms correlated with slightly more performance measures (5/7) than did melatonin rhythms (4/7). Global vigour correlated about as well with performance (5/7) as did temperature, and considerably better than global affect (1/7). In conclusion: (1) between‐task heterogeneity in circadian performance rhythms appeared to be absent when the sleep/wake cycle was suspended; (2) temperature (positively), cortisol and melatonin (negatively) appeared equally good as circadian correlates of performance, and (3) subjective alertness correlated with performance rhythms as well as (but not better than) body temperature, suggesting that performance rhythms were not directly mediated by rhythms in subjective alertness.

Computerized EEG spectral analysis in elderly normal, demented and depressed subjects

Computerized spectral analysis of the EEG was performed in 35 patients with Alzheimers disease and compared to patients with major depression (23) and healthy elderly controls (61). Compared to controls, demented patients had a significant increase in the theta and alpha 1 bandwidths as well as an increased theta-beta difference. The parasagittal mean frequency, beta 1 and beta 2 activity were significantly decreased. Depressed patients differed from demented patients, particularly at the lower end of the spectrum, having significantly less delta and theta activity. Like the demented group, depressed patients also had a decreased parasagittal mean frequency, beta 1 and beta 2 when compared to controls. In demented patients, there was a high correlation between several spectral parameters (parasagittal mean frequency, delta and theta activity, and the theta-beta difference) and the Folstein score, EEG measures used for discriminant analysis were more accurate in identifying demented patients who had lower Folstein scores.