Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder.

Background: The development of a rapid-acting and sustainable treatment for bipolar disorder (BPD) depression has been a goal for decades. The most widely documented rapid-onset antidepressant therapy is sleep deprivation (SD), which acts within 24-48 hours in 40%-60% of depressed patients. Conventional antidepressants usually require 2-8 weeks to meet response criteria.

Sleep deprivation PET correlations of Hamilton symptom improvement ratings with changes in relative glucose metabolism in patients with depression.

Background: This PET study is a continuing investigation of the effects of antidepressant medication and one night of total sleep deprivation on cerebral metabolism in depressed patients. This study was undertaken to confirm previous correlations between symptom improvement ratings and regional changes in glucose metabolism, using a higher resolution scanner than in previous investigations. In addition, we also studied the effect of concomitant antidepressant medication in conjunction with sleep depression.

Frontal lobe metabolic decreases with sleep deprivation not totally reversed by recovery sleep.

We studied the effects of total sleep deprivation and recovery sleep in normal subjects using position emission tomography with 18F-deoxyglycose. Sleep deprivation resulted in a significant decrease in relative metabolism of the frontal cortex, thalamus, and striatum. Recovery sleep was found to have only a partial restorative effect on frontal lobe function with minimal reversal of subcortical deficits.

Improved anatomic delineation of the antidepressant response to partial sleep deprivation in medial frontal cortex using perfusion-weighted functional MRI.

This study used functional magnetic resonance imaging (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: 1) depressed responders' baseline ventral anterior cingulate (AC) perfusion will be greater than that of nonresponders and controls; 2) following partial sleep deprivation (PSD), ventral AC perfusion will significantly decrease in responders only. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD.

Does amygdalar perfusion correlate with antidepressant response to partial sleep deprivation in major depression?

This study used functional MRI (fMRI) to clarify the sites of brain activity associated with the antidepressant effects of sleep deprivation (SD). We hypothesized: (1) baseline perfusion in right and left amygdalae will be greater in responders than in nonresponders; (2) following partial sleep deprivation (PSD), perfusion in responders' right and left amygdalae would decrease. Seventeen unmedicated outpatients with current major depression and eight controls received perfusion-weighted fMRI and structural MRI at baseline and following 1 night of late-night PSD.

Similar sleep EEG topography in middle-aged depressed patients and healthy controls.

Objectives: One of the early hypotheses relating sleep disturbances in depression to a model of sleep regulation is the S-deficiency hypothesis. It is postulated that, in depressed patients, sleep propensity during wakefulness does not rise to the level attained by nondepressed subjects, resulting in altered sleep structure or changes in the electroencephalogram during sleep. We aimed to test this hypothesis by assessing topographic changes in the sleep electroencephalogram associated with depression.

TEMPS-A: validation of a short version of a self-rated instrument designed to measure variations in temperament.

Objective: To validate a short English-language version of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-autoquestionnaire version (TEMPS-A), a self-report questionnaire designed to measure temperamental variations in psychiatric patients and healthy volunteers. Its constituent subscales and items were formulated on the basis of the diagnostic criteria for affective temperaments (cyclothymic, dysthymic, irritable, hyperthymic, and anxious), originally developed by the first author and his former collaborators. Further item wording and selection were achieved at a later stage through an iterative process that incorporated feedback from clinicians, researchers, and research volunteers.

Temperament in the clinical differentiation of depressed bipolar and unipolar major depressive patients.

Objective: To examine differences in temperament profiles between patients with recurrent unipolar and bipolar depression.

Method: Depressed individuals with recurrent major depressive disorder (MDD) (n = 94) and those with bipolar (n = 59) disorders (about equally divided between types I and II) were recruited by newspaper advertisement, radio and television announcements, flyers and newsletters, and word of mouth. All patients were interviewed using the Structured Clinical Interview for DSM III-R (SCID) and had the severity of their depressive episode assessed by means of the 17-item Hamilton Rating Scale for Depression.

Affective state and EEG sleep profile in response to rapid tryptophan depletion in recently recovered nonmedicated depressed individuals.

Background: The current study examines whether a tryptophan-free amino acid drink (TFD) causes a transient mood relapse in unmedicated patients recently recovered from major depression. TFD is thought to reduce cerebral serotonin, a neurotransmitter implicated in depression. Some studies report that TFD reverses the antidepressant and REM-suppression effects of selective serotonin reuptake inhibitors (SSRIs).

Increasing task difficulty facilitates the cerebral compensatory response to total sleep deprivation.

Study Objectives: To test the role of task difficulty in the cerebral compensatory response after total sleep deprivation (TSD).

Design: Subjects performed a modified version of Baddeley's logical reasoning task while undergoing functional magnetic resonance imaging twice: once after normal sleep and once following 35 hours of TSD. The task was modified to parametrically manipulate task difficulty.

A quantitative neuromotor predictor of antidepressant non-response in patients with major depression.

Predicting response to antidepressant medication has been a challenge to clinicians and researchers for decades. Attention has been paid to the role of motor retardation as a putative indicator of treatment response, yet previous findings have been mixed. One reason for this inconsistency may be related to the subjective nature of motor retardation and how it is assessed.

Rapid tryptophan depletion reverses phenelzine-induced suppression of REM sleep.

Treatment with the monoamine oxidase inhibitor phenelzine completely suppressed rapid eye movement (REM) sleep in five depressed patients. Hypothesizing that increased serotonergic neurotransmission eliminated REM sleep, we administered a tryptophan-free amino acid drink (TFD) known to reduce plasma tryptophan and brain levels of serotonin. The TFD reversed the REM sleep suppression, while the control drink (TFD plus tryptophan) had virtually no effect on sleep.

Effects of rapid tryptophan depletion on sleep electroencephalogram and mood in subjects with partially remitted depression on bupropion.

Serotonin has been implicated in both sleep and mood regulation. When central serotonin was depleted with a tryptophan-free amino acid drink (TFD), some studies have reported that the antidepressant benefits were reversed in partially remitted patients treated with SSRIs. Other studies showed that the TFD increased rapid eye movement (REM) sleep in both normal males and in remitted depression patients on selective serotonin reuptake inhibitors (SSRIs) without affecting mood.

Different effects of phenelzine treatment on EEG topography in waking and sleep in depressed patients.

A novel approach to investigate the relationship between depression and changes in sleep-wake regulatory mechanisms used the monoamine oxidase inhibitor (MAOI) phenelzine that is known to suppress rapid-eye-movement (REM) sleep. Sleep architecture and EEG topography during wakefulness and sleep were studied in eight depressed patients before and after five weeks of treatment with phenelzine (30-90 mg/day), which induced a significant alleviation of depressive symptoms. Theta power (4.

Sleep deprivation as a probe of homeostatic sleep regulation in primary alcoholics.

Background: Alcoholic patients show prominent disturbances of sleep electroencephalograms (EEGs) with a marked loss of slow wave sleep that is even more profound in African American alcoholics as compared to European Americans. Using partial sleep deprivation, this study examined the extent to which abnormal sleep is reversible in alcoholic subjects.

Methods: In a sample stratified on ethnicity, polysomnographic and spectral sleep EEG measures were compared in male primary alcoholic in patients (n=46) and age-matched comparison controls (n=32) at baseline-and recovery sleep following a night of partial sleep deprivation.

The effects of an orally administered cholinergic agonist on REM sleep in major depression.

Background: Centrally active cholinergic agents such as arecoline and physostigmine shorten rapid eye movement (REM) latency, reduce REM interval times, or both and do so preferentially in patients with depression. We tested an orally administered cholinergic agonist (donepezil HCL 10 mg [Aricept]) to determine whether this agent also alters REM timing in depressed patients (n = 8) compared with age- and gender-matched control subjects (n = 8).

Methods: All subjects were studied for 3 consecutive nights in the sleep laboratory.

An open-label, 12-week clinical and sleep EEG study of nefazodone in chronic combat-related posttraumatic stress disorder.

Background: We examined the effects of nefazodone on polysomnographic sleep measures and subjective reports of sleep quality and nightmares. as well as other symptoms, in patients with chronic combat-related posttraumatic stress disorder (PTSD) during a 12-week, open-label clinical trial. To our knowledge, this is the first polysomnographic study of treatment in patients with PTSD.

Sleep deprivation as a model experimental antidepressant treatment: findings from functional brain imaging.

This paper reviews the functional brain imaging studies in depressed patients treated with sleep deprivation. Sleep deprivation is an excellent experimental model of antidepressant treatments which offer new opportunities to understand the basic neural mechanisms. Its antidepressant effects are efficacious and rapid; sleep deprivation is easy to administer, inexpensive, and relatively safe; it can be studied in patients, normal controls, and animals; and it may lead to new treatments and new paradigms for antidepressant therapies.

Sleep abnormalities during abstinence in alcohol-dependent patients. Aetiology and management.

Virtually every type of sleep problem occurs in alcohol-dependent patients. Typically, these individuals take a longer time to fall asleep and show decreased sleep efficiency, shorter sleep duration and reduced amounts of slow wave sleep when compared with healthy controls. Their sleep patterns are fragmented, and the typical time course of electroencephalogram (EEG) delta wave activity is severely disrupted.

Ultradian rhythms of alternating cerebral hemispheric EEG dominance are coupled to rapid eye movement and non-rapid eye movement stage 4 sleep in humans.

Objective: To replicate the left minus right (L-R) hemisphere EEG power shifts coupled to rapid eye movement (REM) and non-rapid eye movement (NREM) sleep observed in 1972 by Goldstein (Physiol Behav (1972) 811), and to characterize the L-R EEG power spectra for total EEG, delta, theta, alpha and beta bands.Background: Ultradian alternating cerebral hemispheric dominance rhythms are observed using EEG during both waking and sleep, and with waking cognition. The question of whether this cerebral rhythm is coupled to the REM-NREM sleep cycle and the basic rest-activity cycle (BRAC) deserves attention.

Increased cerebral response during a divided attention task following sleep deprivation.

We recently reported that the brain showed greater responsiveness to some cognitive demands following total sleep deprivation (TSD). Specifically, verbal learning led to increased cerebral activation following TSD while arithmetic resulted in decreased activation. Here we report data from a divided attention task that combined verbal learning and arithmetic.

Relationship of mood disturbance to cigarette smoking status among 252 patients with a current mood disorder.

Background: The relationship between cigarette smoking and mood has received increasing attention. This retrospective study evaluated the relationship between mood disturbance and cigarette smoking status among patients with a current mood disorder. The association between level of nicotine dependence and severity of mood disturbance was also evaluated among current smokers.

Health-related quality-of-life measure enhances acute treatment response prediction in depressed inpatients.

Background: Many nonbiological variables are reported to predict treatment response for major depression; however, there is little agreement about which variables are most predictive.

Method: Inpatient subjects (N = 59) diagnosed with current DSM-IV major depressive disorder completed weekly depressive symptom ratings with the Hamilton Rating Scale for Depression (HAM-D-17) and Beck Depression Inventory (BDI), and weekly health-related quality-of-life (HRQL) ratings with the Quality of Well-Being Scale (QWB). Acute responders were identified by a 50% decrease in HAM-D-17 score from baseline within 4 weeks of medication treatment.

Sleep and sleep electroencephalogram in depressed patients treated with phenelzine.

Background: The beneficial effect of antidepressant interventions has been proposed to depend on suppression of rapid eye movement (REM) sleep or inhibition of electroencephalographic (EEG) slow-wave activity (SWA) in non-REM sleep. Use of the monoamine oxidase inhibitor phenelzine sulfate can eliminate REM sleep. We studied the relation between REM sleep suppression and antidepressant response and the effect of phenelzine therapy on sleep EEG power spectra.