Characterization of the sleep EEG in acutely depressed men using detrended fluctuation analysis.

OBJECTIVE: The aim of the present paper is to study the fluctuations of the sleep EEG over various time scales during a specific pathological condition: major depressive episode. Focus is made on scaling behaviour, which is the signature of the absence of characteristic time scale, and the presence of long-range correlations associated to physiological constancy preservation, variability reduction and mostly adaptability. METHODS: Whole night sleep electroencephalogram signals were recorded in 24 men: 10 untreated patients with a major depressive episode (41.70+/-8.11 years) and 14 healthy subjects (42.43+/-5.67 years). Scaling in these time series was investigated with detrended fluctuation analysis (time range: 0.16-2.00s). Scaling exponents (alpha) were determined in stage 2, slow wave sleep (stages 3 and 4) and during REM sleep. Forty-five epochs of 20s were chosen randomly in each of these stages. RESULTS: The median values of alpha were lower in patients during stage 2 and SWS. CONCLUSIONS: Major depressive episodes are characterized by a modification in the correlation structure of the sleep EEG time series. The finding which shows decreasing rate of the temporal correlations being different within the two groups in stage 2 and SWS provides an electrophysiologic argument that the underlying neuronal dynamics are modified during acute depression. SIGNIFICANCE: The observed modifications in scaling behaviour in acutely depressed patients could be an explanation of the sleep fragmentation and instability found during major depressive episode.     

Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls

The amplitude and time course of slow-wave activity (SWA) during NREM sleep were compared in 76 outpatients with depression and 55 healthy control subjects. Lower SWA amplitude was evident in the depressed group, especially among depressed men. For the most part, significant differences between patients and control subjects were restricted to the first NREM period and only in those 20-30 years of age. Significant age-related declines in SWA amplitude were evident in control subjects but not in depressed patients. In addition, sex differences in the depressed group were twice as large as those seen in control subjects. The time course of SWA amplitude, presumed to reflect homeostatic sleep regulation of SWA, was only abnormal in depressed men with lower accumulation and slower dissipation over NREM sleep. Depressed women showed no evidence of an abnormal SWA time course. Furthermore, no sex differences in the time course of SWA were evident in control subjects, and age-related changes in this aspect of regulation were not striking in any group. Thus, the amplitude of SWA showed strong age effects in healthy individuals but not in those with MDD whereas the time course showed very subtle age effects. It was suggested that men, but not women, with MDD show impaired SWA regulation that is evident from 20 to 40 years of age. These findings provide further support that the pathophysiology of depression differs for men and women and suggest that maturational effects on SWA in depression differ from those observed in healthy individuals.     

Endothelin-1 plasma concentrations in depressed patients and healthy controls.

Depression and cardiovascular morbidity are known to be associated. So far, however, the pathophysiological link between these conditions is unclear. We tested the hypothesis that in depressed hypercortisolemic patients endothelin-1 (ET-1) plasma concentrations are increased and contribute to the cardiovascular risk. Diurnal plasma concentrations of cortisol and ET-1 were measured in 29 healthy controls and 22 depressed patients. ANCOVA did not reveal a significant effect of diagnosis or age upon ET-1 concentrations. However, only in depressed patients, cortisol plasma concentrations tended to be positively related to ET-1 concentrations. We conclude that ET-1 is not increased in depressed patients, but within this group, hypercortisolemia may be associated with increased ET-1 concentrations.     

EEG sleep in outpatients with generalized anxiety: A preliminary comparison with depressed outpatients

To develop further perspective on the psychophysiology of generalized anxiety disorder and primary depression, all-night electroencephalographic (EEG) sleep measures in outpatients with diagnoses of generalized anxiety disorder and primary (nondelusional) depression were compared. Both groups had difficulty initiating and maintaining sleep, and diminished amounts of slow-wave sleep. Compared to patients with generalized anxiety disorder, depressive had a shorter rapid eye movement (REM) latency, greater REM sleep percent and eye movement activity, and a different temporal distribution of REM sleep. Anxious patients showed few changes from first to second night, whereas depressives showed increases in several REM sleep indexes. The combination of REM sleep latency and REM percent correctly classified 86.7% of patients. These data may provide a more direct measure of central nervous system arousal and sleep / wake function than previous studies in the psychophysiology of anxiety. They also lend support to the clinical distinction between generalized anxiety disorder and primary depression and to the classification of anxiety states as disorders of initiating and maintaining sleep.     

Aspects of aggression in formerly depressed patients and in healthy controls

Thirty former inpatients (14 male and 16 female) who had suffered from a nonpsychotic depressive syndrome were investigated by means of a new personality inventory--the KSP--when they had recovered from the depressive disorder, and their results were contrasted to those obtained from 53 healthy controls (19 male, 34 female). Attention was focused on the subscales of the KSP which refer to aspects of aggression. Former patients scored significantly higher than controls in the variables 'irritability,' 'suspicion,' 'guilt,' and 'inhibition of aggression.' The findings suggest a particular personality makeup for at least one subgroup of depression-prone subjects and closely resemble classical concepts of hostility and depression.     

Aspects of aggression in formerly depressed patients and in healthy controls

Summary Thirty former inpatients (14 male and 16 female) who had suffered from a nonpsychotic depressive syndrome were investigated by means of a new personality inventory—the KSP—when they had recovered from the depressive disorder, and their results were contrasted to those obtained from 53 healthy controls (19 male, 34 female). Attention was focused on the subscales of the KSP which refer to aspects of aggression. Former patients scored significantly higher than controls in the variables irritability, suspicion, guilt, and inhibition of aggression. The findings suggest a particular personality makeup for at least one subgroup of depression-prone subjects and closely resemble classical concepts of hostility and depression.Supported in part by a grant from the Swedish Medical Research Council (Grant No. 21X-5244)     

Detrended fluctuation analysis of short-term heart rate variability in late pregnant women

Spectral analysis of heart rate variability using short or long time series is a common method in the assessment of autonomic nervous activity. Nonlinear method such as detrended fluctuation analysis was proposed and proved to be useful for the possible non-stationary and nonlinear characteristics in the time series of heart period. In this study, we investigated the detrended fluctuation analysis and conventional heart rate variability measures in 16 late pregnant women before and 3 months after delivery and in 16 healthy controls. Global and discrete, short-term (≤ 11 beats, α1) and long-term (> 11 beats, α2), scaling exponent were calculated in detrended fluctuation analysis. We found that the late pregnant women have elevated global scaling exponent, elevated short-term scaling exponent and lower heart rate variability measures in the low and high frequency ranges than those of the healthy controls and 3 months after delivery. The deranged measures recovered 3 months after delivery. In addition, the detrended fluctuation scaling exponent did not correlate with most conventional time and frequency domain measures of heart rate variability. Our study suggested that the global and short-term detrended fluctuation scaling exponents might be new and independent measures of heart rate variability in late pregnancy, in addition to those conventional time and frequency domain measures.     

Niacin skin flushing in schizophrenic and depressed patients and healthy controls

This study compares the skin reactions to the niacin flushing test of 16 schizophrenic patients with those of 17 depressed patients and 16 healthy controls. Methyl nicotinate (niacin) in a concentration of 0.1 M was applied to the forearm for 5 min. Significant differences could be observed between the group of schizophrenic patients (less flushing) in comparison to the other groups. There were no statistical differences in niacin flushing between patients with depression and healthy controls. Gender, age and the use of antipsychotic agents did not appear to be confounders. The differences in flushing within the group of schizophrenic patients were striking, however. Most patients showed little or no flushing, but some patients reacted strongly. Although the three groups could be differentiated by the niacin flushing test, to develop a reliable clinical application of this test, further research is necessary.     

Sleep and body mass index in depressed children and healthy controls

ObjectiveHigher body mass index (BMI) has been associated with more sleep disturbance and depressive symptoms, but the combined effects of depression and BMI on sleep have not been studied in children. This study evaluated the relationship between BMI and polysomnography in children with major depressive disorder (MDD), compared to healthy controls (HCs).MethodThe sample of 104 subjects included 72 children, 8–17 years old, with MDD and 32 similarly aged HCs with no personal or family history of psychopathology. BMI was adjusted using the CDC formula for percentiles by age. Subjects were categorized as (1) normal weight (5–84th percentile) or (2) high weight, which included at risk of overweight and overweight (?85th percentile). All analyses were adjusted for sex and Tanner maturational stage scores.ResultsIn the MDD group only, higher BMI was significantly correlated with decreased sleep efficiency, decreased percentage of rapid eye movement sleep (REM%), and higher percentage of time spent awake and moving (TSPAM). In the HC group only, higher BMI correlated with higher total sleep time. Multivariate analyses revealed significant interactions between the BMI and diagnostic groups for several REM sleep parameters, such that high-weight children from the HC and MDD groups had increases and decreases in REM sleep, respectively. TSPAM increased in the high-weight MDD group, but decreased in the high-weight HC group.ConclusionsAlthough limited by small sample size, these findings suggest that children and adolescents with MDD and a high BMI have more fragmented sleep than other children. The increased REM sleep patterns observed with MDD in this and other studies normalized in high-weight children with MDD. Prevention and treatment strategies should target both sleep and weight as factors that can potentially influence the development and course of MDD.     

Comparison of personality beliefs between depressed patients and healthy controls

Introduction

According to the cognitive model, the common mechanism underlying all psychological disorders is distorted or dysfunctional thoughts that affect mood and behaviors. Dysfunctional thoughts predispose an individual to depression and are among the processes that form the basis of personality traits. Elucidating the personality beliefs associated with depression and dysfunctional thoughts is important to understanding and treating depression. The aim of the present study is to determine whether depressed patients exhibited pathological personality beliefs compared with healthy controls. Furthermore, we investigated which personality beliefs were more common among such depressed patients.

Methods

A total of 70 patients who were admitted to the Department of Psychiatry at Ankara Diskapi Yildirim Beyazit Training and Research Hospital (Ankara, Turkey) and diagnosed with major depressive disorder according to The Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) diagnostic criteria were included in the study. Additionally, 70 healthy controls matched for age, marital status, and education were included in the study. The Sociodemographic Data Form and Personality Belief Questionnaire-Short form (PBQ-SF) were administered to the participants.

Results

A comparison of the depression group with the healthy controls revealed higher scores in dependent, passive–aggressive, obsessive–compulsive, antisocial, histrionic, paranoid, borderline, and avoidant personality subscales in the depressive group.

Conclusions

These results suggest that personality beliefs at the pathological level are more common in depressive patients and that the detection of these beliefs would be useful for predicting the prognosis of the disease and determining appropriate treatment methods.     

EEG sleep in elderly depressed, demented, and healthy subjects

In a prospective study of EEG sleep patterns in 25 elderly depressives, 25 elderly demented patients, and 25 healthy, elderly control subjects, the sleep of depressives was characterized by reduced REM sleep latency, increased REM percent and first REM period density, and altered temporal distribution of REM sleep, as well as by diminished sleep maintenance (correlated significantly with Hamilton ratings of depression: multiple R = -0.42, p less than 0.05). In contrast, the sleep of demented patients showed reduced REM sleep percent, but normal REM temporal distribution, increased loss of spindles and K-complexes (the latter correlating significantly with severity of cognitive impairment as measured by the Folstein score: multiple R = -0.59, p less than 0.01), and less severe sleep maintenance difficulty than for depressives. An examination of REM latency demonstrated a skewed distribution in depression (i.e., 42% of nights with sleep-onset REM periods), but a normal distribution in the controls and demented subjects. A REM latency cut-off score of 30 min correctly classified 68% of all patients (kappa = 0.36; p less than 0.005), compared with 78% correctly identified in our retrospective study (Reynolds et al. 1983).     

Cerebrospinal fluid and urinary biogenic amines in depressed patients and healthy controls

The National Institute of Mental Health-Clinical Research Branch Collaborative Study investigated 132 drug-free, severely depressed patients and 80 healthy controls. Forty-five percent of the depressed patients excreted markedly elevated levels of urinary epinephrine (E) and metanephrine (MET), while only 5% of healthy controls did so. Using gaussian mixture distributions, we identified two subgroups of depressed patients: one excreting normal levels and the other excreting high levels of urinary E, MET, norepinephrine, and normetanephrine. Cerebrospinal fluid homovanillic acid levels were low in a subgroup of depressed patients. When analyzed by subgroup, the elevated E + MET group had markedly lower cerebrospinal fluid homovanillic acid levels than controls, whereas depressed patients with normal catecholamine levels did not. Since it has been postulated that there are two subgroups of depressed patients, those with low 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and normal 5-hydroxyindoleacetic acid (5-HIAA) levels and those with normal MHPG levels and low 5-HIAA levels, several analyses were performed to see if such a group could be identified. Our analysis failed to find evidence of a subgroup of depressives with low MHPG and normal 5-HIAA levels or normal MHPG and low 5-HIAA levels.     

Prolactin response to thyrotropin-releasing hormone in schizoaffective depressed compared to depressed and schizophrenic men and healthy controls

Biological tests may help clarify the relationship of schizoaffective disorder to major depressive disorder (MDD) and schizophrenia (SCZ). Thyrotropin-releasing hormone (TRH), 500 micrograms, was administered intravenously to eight schizoaffective depressed (SD), ten SCZ, 23 MDD patients and 43 healthy controls (HC), all males, ages 20-66 years and drug-free. Research Diagnostic Criteria (RDC) were utilized for establishing diagnoses, Hamilton Rating Scale for Depression (HRSD) total scores were used for assessing depressive symptoms. There were no differences in dmax PRL (post-TRH prolactin peak minus baseline, mean +/- SD) amongst SD, SCZ and HC groups (27.3 +/- 5.2, 28.8 +/- 5.4 and 31.5 +/- 5.6 ng/ml respectively). Mean dmax PRL in MDD was significantly lower than each of the other three groups (17.1 +/- 2.2 ng/ml, P less than 0.05 for all). The essentially normal PRL response to TRH in SD, significantly different from MDD but similar to SCZ parallels our previous observations on the pattern of thyrotropin (TSH) response to TRH in the same diagnostic groups. These biological findings may be taken to indicate that schizoaffective disorder, depressed subtype, is closer to schizophrenia than to major depressive disorder. However, they cannot be considered definitive evidence to that effect since schizoaffective disorders are known to be quite heterogeneous, and since the utilized biological tests lack specificity.     

Interpersonal psychotherapy of depressed HIV-positive outpatients.

In an open pilot study, 23 depressed adults infected with human immunodeficiency virus were treated using interpersonal therapy. Twenty subjects recovered from depression after a mean of 16 sessions. The authors discuss six aspects of interpersonal therapy that make it useful with depressed HIV-infected persons: psychoeducation about the sick role; a here-and-now framework; formulation of problems from an interpersonal perspective; exploration of options for changing dysfunctional behavior patterns; identification of focused interpersonal problem areas (grief, role transition, interpersonal disputes, and interpersonal deficits); and the confidence therapists gain from a systematic approach to problem formulation and treatment. Results suggest that mental health professionals should consider interpersonal therapy as a treatment for depressed HIV-positive patients.     

From early to late adulthood. Changes in EEG sleep of depressed patients and healthy volunteers

In order to evaluate the impact of aging on EEG sleep patterns we investigated the polysomnograms of 74 patients with major depression and 51 healthy volunteers aged 18-65 years. In most of the EEG sleep parameters, age-related changes were obvious in both the depressives and the normals. In the patients, some of these alterations occurred earlier and were more pronounced. The amount of slow-wave sleep decreased with age, but no differences were found between the depressives and the healthy volunteers at any particular age. Rapid-eye-movement (REM) latency was clearly affected by age, but there were no significant differences between patients and controls until the middle of the fourth decade of life. On the other hand, REM density measures did not vary with age and were increased in the depressives. Therefore, REM density appears to be a more likely candidate for a biologic marker for major depression than is REM latency.     

Modafinil as adjunctive therapy in depressed outpatients.

The wake-promoting agent modafinil (PROVIGIL) may prove useful as an adjunctive treatment in patients with suboptimal responses to antidepressant regimens. This retrospective chart review describes the use of modafinil as an adjunct to antidepressant therapy in 78 outpatients in a general psychiatric practice and discusses in detail treatment outcomes for 3 patients. Statistically significant improvements in mean Carroll Depression Rating Scale scores (p < 0.01), Visual Analog Scale scores for overall feeling (p < 0.003), and Clinical Global Impression of Severity ratings (p < 0.001) were demonstrated following treatment with modafinil. Treatment with modafinil rapidly improved wakefulness, fatigue, and everyday functioning in individual cases. Modafinil was well tolerated in combination with antidepressants and other medications. These findings suggest that adjunctive modafinil may improve treatment outcomes when used with antidepressant therapy in depressed patients, particularly in those with problematic sleepiness or fatigue.     

Sexual functioning in depressed outpatients taking mirtazapine.

OBJECTIVES: One-third of patients with untreated depression have sexual difficulties manifested by decreased libido, erectile dysfunction or delayed ejaculation. This dysfunction may be exacerbated by stimulation of post-synaptic serotonin 5HT2 receptors, a side-effect of most widely-used antidepressant medications, especially the selective serotonin reuptake inhibitors (SSRIs). Mirtazapine is an atypical antidepressant with alpha 2 adrenergic antagonist and serotonin 5-HT2 and 5-HT3 receptor-blocking activity. In theory, it should not worsen and perhaps may improve sexual function. This pilot study investigated sexual functioning and antidepressant activity in depressed patients taking mirtazapine. EXPERIMENTAL DESIGN: Twenty-five (F = 18, M = 7) sexually active adult outpatients with a DSM-IV-diagnosis of major depressive episode entered a 12-week, flexible-dosing, open-label pilot study. The Arizona Sexual Experiences Scale (ASEX) assessed sexual functioning and the Hamilton Depression Rating Scale (HAM-D) assessed depressive symptoms on a bimonthly basis. PRINCIPAL OBSERVATIONS: Desire, arousal/lubrication, and ease/satisfaction of orgasm improved (by 41%, 52%, and 48%, respectively) in the depressed women. In men, desire, arousal/erection, and ease/satisfaction of orgasm also improved (by 10%, 23% and 14%, respectively) but much more modestly. HAM-D, Clinical Global Impression (CGI) Sheehan Disability Scale (SDS), and Symptom Checklist-90 (SCL-90) scores improved in both groups. There was a 50% dropout rate among women before six weeks of treatment. However, the ASEX and HAM-D scores of the groups terminating before and after six weeks of treatment showed similar rates of improvement. CONCLUSIONS: Mirtazapine has a beneficial effect on sexual functioning in both depressed women and men. Longer-term double-blind research assessing sexual function during the administration of mirtazapine as well as other antidepressants is recommended.     

Relationship between objective and subjective sleep measures in depressed patients and healthy controls

The purpose of this study was to correlate subjective sleep characteristics based on questionnaire response, and objective sleep EEG features based on polysomnography, in 52 patients with major depressive disorders (MDD) and 49 healthy controls. With the exception of the number of awakenings, subjective and objective sleep measures were strongly correlated in both groups. Patients and controls were able to accurately judge time in bed, total sleep time and sleep latency. However, sleep quality, depth, and how rested participants felt upon awakening were not strongly correlated with objective sleep characteristics, particularly in those with MDD The findings suggest that estimates such as total sleep time and sleep latency, obtained from questionnaire data, bear a strong resemblance to objective polysomnographic characteristics in both those with MDD and healthy controls. Patients with MDD do not show sleep-state misperceptions although depressed women are more accurate in estimating sleep characteristics than depressed men. Depression and Anxiety 5:97–102, 1997. © 1997 Wiley-Liss, Inc.