Effects of mirtazapine on sleep polygraphic variables in major depression

Mirtazapine, a noradrenergic and specific serotonergic antidepressant(NaSSA), was administered on a flexible schedule in a sample of 17 drug-free patients meeting DSM-IV criteria for a major depressive episode. Sleep polygraphic recordings were performed before and during acute and chronic treatment. Severity of depression and subjective assessment of changes within different aspects of sleep were also evaluated. During the acute administration (first 2 days), mirtazapine significantly increased total sleep time, sleep efficiency, stage II, stage rapid eye movement and slow-wave sleep percentages, and decreased sleep latency and stage awake percentage. These effects persisted after 5 weeks of treatment. Subjectively, mirtazapine induced an improvement of sleep. This open, noncontrolled study suggests that mirtazapine ameliorates the sleep disturbances encountered in depressed patients both objectively and subjectively.     

Attentional bias training in depression: Therapeutic effects depend on depression severity

Depressed individuals show maintained attention to negative information and reduced attention for positive information. Selective biases in information processing are considered to have an important role in the origin, maintenance and recurrence of depressive episodes. In two experiments we investigated the effects of attentional bias manipulation on mood and depressive symptoms. In experiment 1 we investigated the effects of attentional bias manipulation compared to a control procedure in a sample of dysphoric students (N = 48) showing mild to severe levels of depressive symptoms. In experiment 2 we investigated the same attentional training procedure in a sample of depressed in- and outpatients (N = 35). Mild improvements on symptom severity were observed in students showing mild depressive symptoms. However, in students showing moderate to severe depressive symptoms, depressive symptoms increased after the training. No beneficial effects of training on top of therapy and/or medication were found in depressed patients. These results indicate that therapeutic effects of attentional bias modification might be dependent on depression severity.     

The link between sleep and depression: The effects of antidepressants on EEG sleep

The assumption that sleep dysregulation is more than a mere epiphenomenon of depression is based on several observations: sleep disturbances are strongly associated with the depressive state; a number of sleep manipulations can alleviate symptoms of depression in some patients; and the majority of antidepressants bring about remarkable changes in sleep polygraphic variables. An obvious question is whether changes in sleep physiological processes are intimately involved in the pathogenesis and recovery from depression. One way to elucidate the link between sleep and depression is to examine whether the influence of antidepressants on sleep is related to clinical improvement in depressives. For that purpose, the effects of antidepressants on EEG sleep and their importance for the treatment of depression are summarized against the background of two existing hypotheses concerning the link between sleep and depression: one hypothesis concerning the role of REM; the other concerning the role of non-REM sleep. EEG sleep studies on the use of antidepressants in depressives have not produced clear evidence of the involvement of REM sleep or non-REM sleep in the mechanisms underlying clinical change. Furthermore, the role of sleep physiological mechanisms during treatment with antidepressants is still unclear. To interpret the effects of antidepressants on EEG sleep in terms of sleep physiological processes more fundamental sleep research is necessary. Also, more comparative studies of antidepressants with similar therapeutic effects but different pharmacological profiles are needed in both healthy and depressed subjects to further quantify the impact of EEG sleep modification in the recovery from depression and to differentiate between pharmacological and sleep-related aspects.     

Predicting mortality in mixed depression and dementia using EEG sleep variables

The authors report a study of electroencephalographic (EEG) sleep predictors of two-year mortality in 26 elderly patients with mixed symptoms of depression and cognitive impairment. Patients who had died by two-year follow-up were characterized by significantly longer rapid eye movement (REM) sleep latencies at baseline, less robust REM sleep rebound following all-night sleep deprivation, and baseline apnea-hypopnea indexes greater than 3. Logistic regression analysis using the apnea-hypopnea index value and REM latency correctly predicted 77% of survivors and non-survivors. Survival time following initial measurements was significantly correlated with REM sleep time (r = 0.78, p less than .02) and duration of first REM sleep period (r = 0.75, p less than .02). The authors speculate that changes in these predictor variables may indicate impairment in the cholinergic control of cognitive function, REM sleep, and respiratory function.     

Drug effects on REM sleep and on endogenous depression

In earlier work REM sleep deprivation (RSD) by arousals improved endogenous depression. This suggested that drugs producing a similar RSD would have antidepressant activity. The arousal RSD was large, persisted for weeks, and was followed by a REM rebound. We call RSD with these properties arousal-type RSD. The present study reviewed literature from 1962 to 1989 on drug REM sleep effects to examine the hypothesis that drugs producing arousal-type RSD improve endogenous depression. The literature reviewed concerned the REM sleep effects of amine precursors, antidepressants, antihistamines, antipsychotics, barbiturates, benzodiazepines, other hypnotics, drugs affecting cholinergic and noradrenergic neurotransmission, ethanol, lithium and narcotics. Four hundred and sixty-eight relevant papers were read and 215 contributed information that could be used in the review. The findings indicated that all drugs producing arousal-type RSD improved endogenous depression. Four drugs that improved endogenous depression did not produce arousal-type RSD.     

Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables

In an attempt to determine the relative contributions to adrenocortical hyperactivity in depression of agitation, delusions, and melancholic subtype, we measured cortisol levels before and after dexamethasone in 93 unipolar major depressed inpatients. Stepwise multiple regression showed that agitation predicted 22% of the variance in a.m. cortisol level after dexamethasone. Addition of the variables melancholia and delusionality to the regression model accounted for 27% and 34%, respectively, of the variance in the same cortisol variable. Age, illness severity, and weight loss added no further significant predictive value. Age, weight loss, and illness severity did affect cortisol levels when examined separately from the other variables. Rate of nonsuppression on the dexamethasone suppression test (DST) differed between the nonmelancholic major depressive group and any other group with melancholia. These results suggest why some discrepancies may exist between studies of the DST in delusional depression and indicate that agitation merits careful assessment in future studies of DST response.     

Major depressive disorder and immunity. Role of age, sex, severity, and hospitalization

An association between depression and altered immunity has been suggested but has not been consistently demonstrated. We have studied 91 patients with unipolar major depressive disorder, and no mean differences were found between the patients and concurrently studied matched controls in mitogen-induced lymphocyte proliferation, lymphocyte subsets, and natural killer cell activity. There were, however, significant age-related differences between the depressed patients and controls in mitogen responses and in the number of T4 lymphocytes. In contrast to age-related increases in mitogen response and in T4 cells in controls, depressed patients did not show increased lymphocyte responses or numbers of T4 lymphocytes with advancing age. Severity of depression and hospitalization status were also associated with immune system changes. Altered immunity does not appear to be a specific biologic correlate of major depressive disorder but may occur in subgroups of depressed patients.     

MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males

We investigated whether the genetic variants of the MAO-A gene were associated with major depression and/or the clusters of depressive symptoms. The EcoRV and the uVNTR polymorphisms were studied in a population of 191 patients with major depression and 233 control subjects. The EcoRV polymorphism was found to be associated with depression in males but not in females. Haplotype analysis revealed that one of the haplotypes (EcoRV2-uVNTR1) was significantly more frequent among male patients than male controls. Among the HAMD symptom clusters, insomnia scores were significantly higher in male patients carrying allele 2 of the EcoRV polymorphism. These data suggest that the EcoRV and uVNTR polymorphisms may be involved in the pathogenesis of major depression and associated with insomnia in depressed patients.     

Agreement between physicians and liaison psychiatrists on depression in old age patients of a general hospital: influence of symptom severity,age and personality

Objective: Comorbid depressive episodes are common among general hospital inpatients. However, existing evidence shows that depression is often poorly recognized in patients aged over 60 years. The aim of the study was first to determine the degree of agreement between primary care physicians' and liaison psychiatrists' evaluation of depression, and second, to analyze how patients' clinical presentation and personality traits influence this degree of agreement.

Methods: Agreement was defined as the matching of the physicians' initial referral for depressive mood and the actual diagnosis of a major depressive disorder evaluated by the consultation–liaison service in 148 inpatients aged 60+ years. Nature and severity of psychiatric symptoms were rated on the HoNOS65+ scale and patients' personality traits were assessed with the Big Five Inventory.

Results: Forty percent of the patients referred for depressive mood were indeed diagnosed with major depression. Agreement between physicians and psychiatrists was most likely in patients with more severe depressive symptoms and younger age. In contrast, risk for non-agreement was increased for patients with more open personalities, yet lower levels of neuroticism, who were referred for depressive mood even though they presented another or even no psychiatric disorder.

Conclusion: These data reveal that the detection of late-life depression in general hospitals may be critically influenced by age, symptoms severity and personality traits.     

Letter matching: effects of age, Alzheimer's disease, and major depression.

We compared Alzheimer's disease (AD) patients and Major Depressive Disorder (MDD), Aged normal, and Young normal controls on a letter-matching task designed to measure the time needed to access overlearned linguistic information in long-term memory. Name identity (NI) and physical identity (PI) reaction time and the NI-PI difference were compared for ADs, MDDs, and Aged normals and separately for Aged and Young normal groups. AD subjects had slower NI and PI reaction times and a bigger NI-PI difference than Aged normal and MDD subjects, suggesting that speed of access to overlearned letter-name information in long-term memory is slowed for ADs. There were no reliable differences between Aged normal and MDD subjects. Aged normals had slower NI and PI reaction times and a bigger NI-PI difference than Young normals, suggesting that the highly practiced operations needed to access letter-name information slow with age. A discriminant analysis was used to evaluate the usefulness of the "easy to perform" letter-matching task for diagnostic purposes. Ninety percent of normal and MDD subjects but only 68% of AD subjects were classified correctly.     

Differential effects of trimipramine and fluoxetine on sleep in geriatric depression

The effects of trimipramine, a tricyclic antidepressant (TCA) with atypical pharmacological properties, and fluoxetine, a selective serotonine reuptake inhibitor (SSRI), were compared in an exploratory analysis using mood and polysomnographic parameters during a six-week double-blind trial in 19 depressed geriatric patients. In sleep EEG measures, trimipramine demonstrated clear-cut effects on sleep measures resulting in higher values for sleep efficiency, total sleep time, stage 2 sleep, and shorter wake time. Under fluoxetine treatment, the proportion of REM sleep was decreased and REM latency was lengthened, whereas no change in REM sleep parameters was observed in the trimipramine group. The present data suggest that early antidepressant effects of medication occur independently of drug-induced changes in objective measures of sleep, i.e. suppression of REM sleep.     

Differential effects of age on sequence learning and sensorimotor adaptation

Although many studies have documented declines in the ability of the elderly to learn new manual motor skills, studies have not directly compared the capacity of older adults to learn sequences versus adapt to sensorimotor perturbations within the context of the same task paradigm, despite differences in the underlying neural mechanisms and strategic processes supporting the two types of learning. The purpose of the current study was to exploit these task differences in an effort to determine whether aging results in a generalized or more specific skill learning deficit. Groups of young and older adult subjects learned to make a sequence of actions, adapted to one of two visuomotor rotations, or adapted to an altered gain of display, all while performing the same basic manual joystick aiming task. While the older adults exhibited normal sequence learning in comparison to the young adults, they exhibited impairments in all three of the adaptation tasks. These deficits in adaptation for the older adults were associated with hypometric movements and reduced velocity modulation in comparison to that seen in the younger adults. These data suggest that older adults may have greater difficulty with learning cerebellar-mediated motor skills.     

Differential effects of age on sequence learning and sensorimotor adaptation

Although many studies have documented declines in the ability of the elderly to learn new manual motor skills, studies have not directly compared the capacity of older adults to learn sequences versus adapt to sensorimotor perturbations within the context of the same task paradigm, despite differences in the underlying neural mechanisms and strategic processes supporting the two types of learning. The purpose of the current study was to exploit these task differences in an effort to determine whether aging results in a generalized or more specific skill learning deficit. Groups of young and older adult subjects learned to make a sequence of actions, adapted to one of two visuomotor rotations, or adapted to an altered gain of display, all while performing the same basic manual joystick aiming task. While the older adults exhibited normal sequence learning in comparison to the young adults, they exhibited impairments in all three of the adaptation tasks. These deficits in adaptation for the older adults were associated with hypometric movements and reduced velocity modulation in comparison to that seen in the younger adults. These data suggest that older adults may have greater difficulty with learning cerebellar-mediated motor skills.     

REM sleep reduction effects on depression syndromes.

Thirty-four endogenous and 18 reactive, depressed patients (hospitalized and nonschizophrenic) were treated in a double-blind, crossover study of the hypothesis that rapid eye movement (REM) sleep reduction (by awakenings) relieves depression. In the endogenous group-but not in the reactive group-subjects deprived of REM sleep for three weeks improved significantly more than control subjects awakened from non-REM sleep. Therapeutic efficacy of REM sleep reduction appeared similar to reported efficacy of imipramine hydrochloride treatment of depression. Eight of nine endogenous patients, unimproved by REM sleep deprivation, did not improve with imipramine. Results suggested (1) that substantial REM sleep reduction has antidepressant activity, and (2) since imipramine and other drug antidepressants reduce REM sleep much more so than nonantidepressant drugs, that an antidepressant "mechanism" of drugs resides in their capacity to substantially reduce REM sleep.