Open-trial maintenance nortriptyline in geriatric depression: survival analysis and preliminary data on the use of REM latency as a predictor of recurrence.
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Aged↗
Biomedical subjects
C F Reynolds
Publications and source records attributed to C F Reynolds.
Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data.
Using electroencephalographic sleep data from a sample of 235 elderly subjects, discriminant function analyses of sleep alterations in depression and dementia were performed. Overall, 80% of patients were correctly classified using a backward discriminant function analysis, and 81% with a general stepwise discriminant function analysis. Four measures contributed to the separation of depressed and demented patients: rapid eye movement (REM) sleep latency (lower in depressives); REM sleep percent (higher in depressives); indeterminate non-REM sleep percent (higher in demented patients, reflecting greater loss of spindles and K complexes); and early morning awakening (more marked in depressives). When both discriminant functions were subjected to cross-validation in independent subsamples, both procedures correctly identified 78% of patients. The classification functions derived from nondemented depressed and nondepressed demented patients were applied to a mixed-symptom group (n = 42). Overall, 27 patients (64%) with either depressive pseudodementia or dementia with depressive features were correctly classified using the same four predictor variables. These findings suggest that sleep physiological alterations of depression and dementia reflect between-group differences in sleep continuity, sleep architecture, and REM sleep temporal distribution, and that the differences are statistically reliable, in both diagnostically pure and mixed clinical presentations. These findings are discussed in the context of current hypotheses of sleep regulation and its mechanisms.
Age Factors↗
Electroencephalographic sleep in depressive pseudodementia.
Twenty-six patients with mixed symptoms of depression and cognitive impairment were studied with serial clinical ratings and sleep electroencephalograms during a one-night sleep-deprivation procedure. A subgroup of these patients with depressive pseudodementia (n = 8) had less severe symptoms of dementia at baseline and showed significant improvements in both Hamilton Depression Rating Scale scores and Profile of Mood States tension scores following sleep deprivation, while another subgroup of patients having primary degenerative dementia with depression (n = 18) showed no change or worsening in Hamilton depression and Profile of Mood States tension ratings. Baseline sleep measures demonstrated significantly higher rapid eye movement (REM) percent and phasic REM activity/intensity in pseudodemented compared with demented patients. While both groups had increases in sleep efficiency, sleep maintenance, and slow-wave sleep following sleep deprivation, recovery night 2 was characterized by greater first REM period duration in depressive pseudodementia than in dementia. These differences in REM sleep rebound (using an REM period 1 cutoff of greater than or equal to 25 minutes) permitted correct identification of 88.5% of patients. Implications of these data for current theories regarding sleep, aging, and psychopathology are discussed.
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Platelet membrane fluidity and treatment response in cognitively-impaired, depressed elderly: initial results.
A prospective study of response to treatment with nortriptyline was carried out in a group of 14 inpatients with mixed symptoms of depression and dementia. Platelet membrane fluidity, as reflected by the fluorescence anisotropy of DPH labeled membranes, was determined for all 14 drug-free subjects prior to treatment by staff who were blind to clinical and demographic data. Patients who exhibited worsening of their cognitive impairment exhibited "increased" platelet membrane fluidity, an abnormally found in approximately 50% of patients with Alzheimer's disease.
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Nocturnal penile tumescence is diminished in depressed men.
Although depressed individuals commonly report decreased libido, it was not known if such changes are accompanied by neurophysiological alterations. Preliminary studies suggest that some depressed men may manifest diminished nocturnal penile tumescence (NPT), an objective measure of erectile capacity. We report NPT findings in 34 male outpatients with major depression (SADS/RDC) and an age-matched group of 28 healthy controls. A 3-night electroencephalographic (EEG) sleep/NPT protocol was utilized, with penile rigidity (buckling force) determined on night 3. Analysis of night 2 data by MAN-COVA revealed significant effects for age, the covariate (F = 2.86, p = 0.002), and diagnosis (F = 2.32, p = 0.02). Depressed men had significantly diminished NPT time (F = 16.8, p less than 0.001), even when adjusted for sleep time (F = 13.4, p less than 0.001) or rapid eye movement (REM) time (F = 7.2, p less than 0.01). NPT time was reduced by greater than or equal to 1 SD below the control mean in 40% of depressives and was comparable to the level seen in 14 nondepressed patients with a clinical diagnosis of organic impotence. An intermediate proportion of depressed patients (38%) had maximum buckling forces less than or equal to 500 g, indicating diminished penile rigidity, when compared to controls (16%) and men with presumed organic impairment (93%) (p less than 0.001). Diminished NPT time and low buckling force were associated with a history of erectile dysfunction within the index depressive episode (p less than 0.001). These findings suggest that depression in men is associated with a potentially reversible decrease in erectile capacity, which may be associated with significant sexual dysfunction.
Adult↗
Age of illness onset and sleep EEG variables in elderly depressives.
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Age Factors↗
Diagnostic efficacy of computerized spectral versus visual EEG analysis in elderly normal, demented and depressed subjects.
Computerized spectral and visual EEG analyses were performed in 35 patients with Alzheimer's disease (AD) and compared to 23 patients with major depression and to 61 healthy elderly controls. In particular, we were interested in the diagnostic efficacy of these two techniques in the identification of cases of AD with only mild cognitive impairment (as measured by the Folstein Mini-Mental State score). For the computer analyzed data, in differentiating AD patients from controls, the spectral pooled parasagittal mean frequency was used. In comparing AD patients to depressed subjects, a combined parasagittal delta and theta spectral score was employed. Visual analysis criteria were based on the severity of generalized EEG abnormalities (with or without focal features). We found that spectral analysis afforded only modest advantages over visual EEG analysis in differentiating AD patients from elderly controls as well as from those with major depression. Since the degree of spectral and visual EEG abnormalities correlated with the severity of dementia, both tests more often correctly classified those AD patients with lower Folstein scores. Also, both tests identified primarily the same patients. We did not find the computer to be more sensitive than the eye in the identification of AD patients with mild impairment. However, computerized spectral data was derived from only 4 channels, while 16 channels and a longer recording time were used for visual analysis. In addition, some areas which have been reported to show EEG abnormalities in AD were not included in the computerized data.
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Diagnostic performance of nocturnal penile tumescence studies in healthy, dysfunctional (impotent), and depressed men.
Nocturnal penile tumescence (NPT) studies were evaluated in 17 men with a clinical diagnosis of organic erectile dysfunction in comparison to age-matched healthy controls (n = 17) and depressed men (n = 17). The dysfunctional group had significantly fewer NPT episodes and reduced maximal penile tip changes when compared to healthy controls and depressed patients. Further, the dysfunctional group had significantly diminished erectile fullness and reduced penile rigidity. Diagnostic performance of polygraphic (night 1) and visual inspection (nights 2 or 3) components of the NPT protocol were examined in these criterion groups. A diagnostic classification based on polygraphic measures successfully discriminated 73.5% of dysfunctional and healthy control subjects, but classified 47% of depressives in the dysfunctional range. Use of visual inspection indices correctly identified 88% of the dysfunctional sample and 94% of normal controls, and reduced the "false-positive" rate in depression to only 18%. Results support the diagnostic utility of NPT studies, particularly when enhanced by visual inspection procedures. Nevertheless, the presence of major depression may confound interpretation of such studies.
Circadian Rhythm↗
Assessment of sexual function in depressed, impotent, and healthy men: factor analysis of a Brief Sexual Function Questionnaire for men.
We report a study of sexual function in outpatient men with major depressive disorder (n = 42), compared with healthy control men (n = 37) and a clinic sample complaining of erectile dysfunction (n = 13). A principal-components factor analysis of the Brief Sexual Function Questionnaire confirmed differences in the clinical dimensions of sexual activity/performance, interest, satisfaction, and physiological competence. The four factors accounted for 72% of the variance in the analysis. Acceptable test-retest reliability, construct validity, and concurrent validity (with the Derogatis Sexual Function Inventory and a self-report behavioral log) were demonstrated. Parallel observations with findings from previous nocturnal penile tumescence studies in these same men are discussed.
Adult↗
Red blood cell/plasma choline ratio in elderly depressed and demented patients.
In further study of red blood cell (RBC) and plasma choline concentrations in 160 elderly subjects, we found no significant differences in RBC/plasma choline ratios among depressed, demented, and healthy subjects. On the basis of a smaller sample, we had earlier reported that a significantly higher proportion of Alzheimer patients had RBC/plasma choline ratios greater than 1.9. Thus, it now appears that static RBC choline levels cannot be recommended as a specific marker of Alzheimer's dementia. However, within subgroups of these diagnostic categories, determined by RBC/plasma choline ratios less than or equal to 1.9 or greater than 1.9, consistent differences in electroencephalographic (EEG) sleep measures were found. The subgroup of demented patients with a RBC/plasma choline ratio greater than 1.9 was more impaired on the Blessed Dementia Rating Scale and had less rapid eye movement (REM) sleep than the subgroup with a choline ratio less than or equal to 1.9. Similarly, depressives with a choline ratio less than or equal to 1.9 had a lower REM latency than depressives with a choline ratio greater than 1.9. Finally, depressed-demented (i.e., mixed-symptom) patients with a choline ratio greater than 1.9 showed less sleep continuity disturbance but more indeterminate non-REM sleep (reflecting loss of spindles and K-complexes) than those with lower choline ratios. These differences parallel those previously reported for diagnostically "pure" depressed and demented patients, and they suggest a possible link between peripheral RBC/plasma choline measures and central nervous system function as reflected in sleep physiological alterations.
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Stability of EEG sleep and sleep quality in healthy seniors.
When the electroencephalogram-recorded (EEG) sleep of 19 healthy seniors (9 men, 10 women) aged 60-82 years was restudied after an average interval of 2.2 years, most measures of EEG sleep and sleep quality were stable over time. Both elderly men and women showed more awakenings during the second recording series, but no change in visual or computer-scored delta activity. Furthermore, gender-dependent sleep changes were noted only in phasic rapid eye movement (REM) measures (increasing in men, decreasing in women). Reports of sleep quality were also stable over time despite the increase in awakenings, with women reporting a lower sleep quality than men.
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The role of polysomnography in the differential diagnosis of chronic insomnia.
The authors examined the accuracy of the differential diagnosis of chronic insomnia with and without sleep laboratory studies in a consecutive series of 123 patients. All patients were evaluated by means of a sleep/wake log, a sleep habits questionnaire, structured psychiatric and clinical interviews, and a minimum of two consecutive nights of polysomnography. Notwithstanding a high rate of Research Diagnostic Criteria (RDC)-diagnosed psychopathology (63%) in this sample, the major finding was that in 49% of the patients laboratory results added to, refuted, and/or failed to support the clinical impression. This resulted in substantial modification of the initial diagnostic formulation and therefore in increased specificity of diagnosis.
Chronic Disease↗
Bedside differentiation of depressive pseudodementia from dementia.
The authors analyzed the pretreatment clinical presentations of 14 patients with depressive pseudodementia and 28 patients with primary degenerative dementia as measured by the Mini-Mental State, the Blessed Dementia Rating Scale, and the Hamilton Rating Scale for Depression. They found that patients with pseudodementia showed significantly greater pretreatment early morning awakening, higher ratings of psychological anxiety, and more severe impairment of libido. Patients with dementia, however, showed significantly more disorientation to time, greater difficulty finding their way about familiar streets or indoors, and more impairment with dressing. The authors suggest that these findings be considered preliminary.
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Sleep patterns in Alzheimer, depressed, and healthy elderly.
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The nature and management of sleep/wake disturbance in Alzheimer's dementia.
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Alzheimer Disease↗
Pretreatment systolic orthostatic blood pressure (PSOP) and treatment response in elderly depressed inpatients.
This study evaluated the utility of morning pretreatment systolic orthostatic blood pressure (PSOP) in predicting clinical response to treatment with nortriptyline (N = 11) or electroconvulsive therapy (N = 6) in 17 depressed geriatric inpatients (mean age, 70.4 +/- 5.1). Morning PSOP showed a significant inverse correlation with percent change in Hamilton depression ratings (rho = -0.59, p less than 0.01; r = -0.52, p less than 0.02). In nortriptyline-treated patients (N = 10, excluding one outlier), PSOP was significantly correlated with percent change in Hamilton ratings (rho = -0.55, p less than 0.05); a similar association was also found in the subsample of electroconvulsive therapy-treated patients (N = 6, rho = -0.77, p less than 0.05). Patients with PSOP less than or equal to 10 mm Hg averaged 83% improvement in Hamilton depression ratings versus 64% improvement in patients with PSOP less than or equal to 10 mm Hg (p less than 0.05). In an age-equated contrast group of 15 inpatients with mixed clinical pictures of depression and cognitive impairment (11 with primary degenerative dementia with depressive features and four with major depressive disorder with cognitive impairment), no relation between PSOP and treatment response (as measured by Hamilton ratings) was found. The current findings extend earlier work in medically healthy, nonsuicidal geriatric depressed outpatients and suggest that PSOP may also be useful in predicting treatment response in older, cognitively intact depressed inpatients (many with concurrent medical illness and/or suicidal) but not in mixed depression-dementia.
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Electroencephalographic sleep in young, never-medicated schizophrenics. A comparison with delusional and nondelusional depressives and with healthy controls.
Electroencephalographic (EEG) sleep characteristics of young, never-medicated, nonschizoaffective schizophrenics were compared with the EEG sleep of patients with major depressive disorders (delusional and nondelusional) and with that of healthy controls. Schizophrenics had decreased sleep continuity comparable to delusional depressives. Slow-wave sleep percent was similar to that seen in healthy controls, as was the intranight temporal distribution of EEG delta activity. However, schizophrenics showed diminished delta counts per minute of non-rapid eye movement (NREM) sleep and a decreased total delta wave count. In contrast, depressives showed diminished slow-wave sleep percent compared with controls, greatly decreased delta activity (more so than did the schizophrenics), and an altered temporal distribution of delta activity, as evidenced by a shift of delta activity from the first to the second NREM period. Minutes of slow-wave sleep in the schizophrenics was inversely correlated with the severity of negative symptoms independent of the effects of age and the presence of depression. The schizophrenics showed normal REM latency and first REM period duration, in contrast to the depressives. These findings, reviewed in the historical context of sleep physiologic studies of schizophrenia over the past 30 years, suggest that young, never-medicated schizophrenics do not show the characteristic constellation of abnormalities in the first NREM-REM cycle seen in patients with major depression. However, decreased slow-wave sleep should be investigated as a possible marker for negative symptoms in schizophrenia.
Adult↗
Sleep deprivation as a probe in the elderly.
Decreased slow-wave sleep (SWS) and sleep continuity are major effects of healthy aging and of associated psychopathological states. Using sleep deprivation, we studied the extent to which age- and psychopathology-related sleep "decay" is reversible in aged normal, depressed, and demented subjects. Depression or probable Alzheimer's dementia compromised the augmentation of sleep continuity and SWS seen in healthy elderly following sleep deprivation. Rapid eye movement (REM) latency decreased during recovery sleep in the controls but increased in both patient groups. Compared with demented patients, depressed elderly had greater severity of sleep continuity disturbance both before and after sleep deprivation, a more protracted course of recovery sleep, and increased slow-wave density in the second non-REM (NREM) sleep period (during recovery). The REM sleep time was diminished in dementia compared with depression both at baseline and during recovery sleep. These differential effects of age, health, and neuropsychiatric disease on recovery from sleep loss are relevant to recovery or reversal theories of sleep and have implications for daytime well-being in the elderly.
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