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PubMed2002

EMDR: a putative neurobiological mechanism of action.

Numerous studies have provided evidence for the efficacy of eye movement desensitization and reprocessing therapy (EMDR) in the treatment of posttraumatic stress disorder (PTSD), including recent studies showing it to be more efficient than therapist-directed flooding. But few theoretical explanations of how EMDR might work have been offered. Shapiro, in her original description of EMDR, proposed that its directed eye movements mimic the saccades of rapid eye movement sleep (REM), but provided no clear explanation of how such mimicry might lead to clinical improvement. We now revisit her original proposal and present a complete model for how EMDR could lead to specific improvement in PTSD and related conditions. We propose that the repetitive redirecting of attention in EMDR induces a neurobiological state, similar to that of REM sleep, which is optimally configured to support the cortical integration of traumatic memories into general semantic networks. We suggest that this integration can then lead to a reduction in the strength of hippocampally mediated episodic memories of the traumatic event as well as the memories' associated, amygdala-dependent, negative affect. Experimental data in support of this model are reviewed and possible tests of the model are suggested.

Affect↗
PubMed1989

Factitial leg ulcers associated with an unusual sleep disorder.

A 19-year-old woman presented with a 14-month history of multiple, factitially induced, full-thickness leg ulcers. Nocturnal polysomnography with video monitoring revealed a short sleep latency and frequent sleep stage changes. Rapid eye movement sleep was absent. All stages of non-rapid eye movement sleep were associated with leg rubbing. After treatment that included avoidance of daytime naps and administration of chlorpromazine at bedtime, affect, daytime behavior, nocturnal sleep, and the ulcers improved markedly. To our knowledge, there are no reports of factitial dermatosis associated with disordered sleep. Our findings suggest that abnormal sleep may play a role in initiating or perpetuating factitial dermatoses. This case illustrates that polysomnography and video monitoring may be indicated in the evaluation of patients with factitial dermatoses.

Adult↗
PubMed2006

Nocturnal eating: sleep-related eating disorder or night eating syndrome? A videopolysomnographic study.

STUDY OBJECTIVES: To describe the clinical and videopolysomnographic characteristics of nocturnal eating episodes in sleep-related eating disorder. DESIGN: Descriptive study of outpatients prospectively enrolled in 2 sleep centers. SETTING: Videopolysomnographic recordings done in the sleep laboratory. PATIENTS: Thirty-five consecutive drug-free patients with nocturnal eating. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Clinical interviews disclosed abnormal compulsory nocturnal eating episodes in all patients associated with a clinical report of sleepwalking (in 1), somniloquy (in 5), restless legs syndrome (in 8), and periodic limb movements during sleep (in 4). Videopolysomnography documented 45 episodes of nocturnal eating in 26 patients. Eating always occurred after complete awakenings from non-rapid eye movement sleep and only in 1 patient from REM sleep and was characterized by electroencephalographic alpha activity with no dissociated features of state-dependent sleep variables. Patients interviewed during the eating episodes were fully conscious and remembered the events the next day. Pathological periodic limb movements during sleep index was recorded in 22 and restless legs syndrome dyskinesias in 5 patients. Recurring chewing and swallowing movements during sleep were a feature in 29 patients, associated in about half of the events with electroencephalographic arousals. CONCLUSIONS: In our patients, eating episodes occurred with normal consciousness and recall. Chewing or swallowing movements during sleep occurred frequently, resembling rhythmic masticatory-muscle activity in bruxism patients. The presence of periodic limb movements during sleep and chewing activity, the reported efficacy of dopaminergic medications, and the compulsory food-seeking behavior all argue for a dopaminergic dysfunction underlying the pathogenesis of sleep-related eating disorder.

Adult↗
PubMed1987

Acetylcholine and affective disorder.

We reviewed the evidence for involvement of central cholinergic neurons in affective disorder. Cholinomimetics inhibit speech, thought, and activity in most subjects, decrease manic symptoms and, in some affective disorder patients, produce depressive symptoms. Cholinomimetics also cause ACTH and cortisol secretion and decrease latency to REM sleep. It is unclear whether cholinomimetics are specifically "antimanic" or "depressogenic" or whether their fundamental effect is nonspecific behavioral inhibition; whether the observed effects of cholinomimetics are mediated largely through cholinergic pathways, are secondary to changes in other neurotransmitters or are part of a nonspecific stress response. The suggestion that anticholinergic agents have mood elevating properties has not yet been subjected to controlled investigation. Although the proposal that affective disorders involve cholinergic neurons has received some support from clinical investigation further research is required to substantiate the intriguing observations to date and to clarify the physiologic and psychologic processes mediating them.

Acetylcholine↗
PubMedDate not supplied

The relationship between social alienation and disorganized thinking in normal subjects and localized cerebral glucose metabolic rates assessed by positron emission tomography.

This study investigated the relationships between the relatively mild manifestations in verbal behavior of social alienation and disorganized thinking in normal subjects and cerebral glucose metabolic rates measured by positron emission tomography (PET). Three groups of 10 young normal male subjects were injected with D-[18F]deoxyglucose (FDG) during either wakefulness, rapid eye movement (REM), or non-REM (NONREM) sleep, and 32 to 45 minutes later they were asked to report their thoughts, emotions, or dreams and free-associations to these mental events. Nonparametric correlations were obtained between measures of interpersonal social alienation, intrapsychic conflicts, and thought disorder derived from the typescripts of these reports by content analysis--using the Gottschalk-Gleser Social Alienation-Personal Disorganization Scale--and regional cerebral glucose metabolic rates obtained from PET scans. Total social alienation-personal disorganization scores obtained from the reports of wakeful, silent mentations showed significant positive correlations with glucose metabolic rates in the left temporal lobe. The patterns of significant correlations involving these verbal behavior measures derived from the content analysis of verbal reports of dreams or other mental events occurring during REM and non-REM sleep were in different cerebral locations from those found with these variables during silent, waking mentation. Previous observations suggesting that increased left temporal lobe glucose may typify chronic schizophrenia may instead be indicative of a wide range of thought disorder and/or social alienation manifestations occurring, at times transiently and minimally, in normal people.

Adult↗
PubMed1980

Narcotic abstinence in dependent rats: EEG and behavioral correlates.

The purpose of the study was to assess and compare EEG and behavioral correlates of abstinence from morphine, methadone, LAAM, NLAAM, and DNLAAM in dependent rats. Rats were initially trained to lever press for self-injections on a FR-20 schedule of reinforcement. Following substitution of saline for each of the narcotic agonists. REM sleep was significantly suppressed during morphine, methadone, and NLAAM abstinence, but not during LAAM and DNLAAM abstinence. Significant increases in lever pressing for saline during abstinence from morphine, methadone, and NLAAM emerged earlier than with LAAM and DNLAAM. Significant increases in head-shake behavior occurred during morphine, methadone, NLAAM, and DNLAAM abstinence, but not during LAAM abstinence. These results demonstrated further pharmacodynamic differences between the five narcotics studied. Our findings suggested that in dependent rats abstinence from LAAM was the least severe when compared with abstinence from any of the other four narcotic studied.

Animals↗
PubMed1984

Sleep and neuroendocrine disturbances in catatonia. A case report.

Sleep EEG investigations were performed in a 31-year-old catatonic male patient before and after electroconvulsive therapy and 3 months after recovery. The dexamethasone suppression test was also performed longitudinally together with measurements of CSF 5-HIAA, HVA and 24-h urinary MHPG. A normal male control aged 32 was also investigated. Sleep analysis showed reduced REM latency and increased REM activity and density during the catatonic phase before treatment when compared to the age-matched control. REM latency remained shortened after recovery following ECT treatment and 3 months after recovery. Dexamethasone suppression test, abnormal before treatment normalized with clinical improvement during ECT. Urinary MHPG values were low in the catatonic state and did not change after ECT treatment. CSF HVA and 5-HIAA were also low in the pretreatment period and increased during the 3 months follow-up period. There results indicate that some cases of catatonic behavior may be linked to affective disorders.

Adult↗
PubMed1990

A new animal model of endogenous depression: a summary of present findings.

In 1982 our laboratory proposed a new animal model of endogenous depression. The proposal was that in rats, neonatally administered clomipramine (CLI) will produce adult animals that model endogenous depression. We summarize here several tests of the validity of the model. Results were that after neonatal CLI, adult male rats showed behavioral abnormalities of the human disorder: decreased sexual, aggressive, and intracranial self-stimulation activities, as well as motor hyperactivity in a stressful situation. Preliminary evidence suggested that behavioral abnormalities in rats (sexual, aggressive, and motor) briefly treated with antidepressant treatments (imipramine, REM sleep deprivation) begin to normalize. Lastly, after neonatal CLI, the adult rats showed REM sleep abnormalities of endogenous depression, viz, low REM latency, frequent sleep onset REM periods, and abnormal temporal course of REM rebound after REM sleep deprivation. These results supported the hypothesis that in rats neonatal CLI produced adult animals that modelled endogenous depression.

Animals↗
PubMed2002

NREM sleep EEG frequency spectral correlates of sleep complaints in primary insomnia subtypes.

STUDY OBJECTIVES: To determine whether the frequency spectrum of the sleep EEG is a physiologic correlate of 1) the degree to which individuals with persistent primary insomnia (PPI) underestimate their sleep time compared with the traditionally scored polysomnogram (PSG) and 2) the sleep complaints in PPI subjects who have relatively long traditionally scored PSG sleep times and relatively greater underestimation of sleep time. DESIGN: We compared EEG frequency spectra from REM and NREM sleep in PPI subjects subtyped as subjective insomnia sufferers (those with relatively long total sleep time and relative underestimation of sleep time compared with PSG), and objective insomnia sufferers (those with relatively short PSG total sleep time) with EEG frequency spectra in normals. We also studied the correlation between these indices and the degree of underestimation of sleep. Further, we determined the degree to which sleep EEG indexes related to sleep complaints. SETTING: Duke University Medical Center Sleep Laboratory. PARTICIPANTS: Normal (N=20), subjective insomnia (N=12), and objective insomnia (N=18) subjects. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Lower delta and greater alpha, sigma, and beta NREM EEG activity were found in the patients with subjective insomnia but not those with objective insomnia, compared with the normal subjects. These results were robust to changes in the subtyping criteria. No effects were found for REM spectral indexes. Less delta non- REM EEG activity predicted greater deviation between subjective and PSG estimates of sleep time across all subjects. For the subjective insomnia subjects, diminished low-frequency and elevated higher frequency non- REM EEG activity was associated with their sleep complaints. CONCLUSIONS: NREM EEG frequency spectral indexes appear to be physiologic correlates of sleep complaints in patients with subjective insomnia and may reflect heightened arousal during sleep.

Adult↗
PubMed1998

[Sleep-arousal dissociation in a case of hypersomnia].

INTRODUCTION: Dissociated sleep-arousal states are clinical and experimental phenomena which represent mixed forms of the three stages of this cycle (arousal, NREM sleep and REM sleep). CLINICAL CASE: We describe the case of a man who presented with a history of excessive diurnal somnolence for the previous 5 years. He also had symptoms of sleep paralysis, hypnagogic hallucinations, automatic behavior and excessive movements during sleep. He had had no episodes of loss of muscle tone; MR was normal; HL DR2 and DQwl antigens were negative; two polisomnographic and a Multiple Latency Sleep test showed: 1. Absence of respiratory disorders. 2. Normal latency of REM sleep. 3. Periods of dissociated sleep (REM without atonia and arousal with atonia), and 4. An average sleep latency of 3.2 minutes and absence of REM periods. CONCLUSION: This case adds a new type of dissociated sleep state which may accompany the disorder known as hypersomnia without REM periods.

Adult↗
PubMed1996

Autism, Asperger's syndrome and the Crick-Mitchison theory of the biological function of REM sleep.

Autism, Asperger's syndrome and other autistic syndromes are developmental brain disorders that cause serious impairments in communication, social interaction, empathy, mood and play. In addition to such deficits, the autistic syndromes involve pathologically high levels of repetitive, stereotypic, ritualistic, compulsive or obsessive behavior, together with extreme resistance to change. According to the Crick-Mitchison theory of the biological function of rapid eye movement sleep, normal brain development in the fetus and infant depends on undisrupted function of a 'reverse learning' mechanism during rapid eye movement sleep. Could abnormalities in this hypothetical reverse learning during rapid eye movement sleep in the fetus explain some aspects of the autistic syndromes? Does the Crick-Mitchison theory suggest if a drug could interfere with rapid eye movement sleep and cross the placental barrier, then that drug might cause developmental brain disorders in the fetus? Should all pregnant women completely avoid caffeine or any agent that might disrupt serotonergic or cholinergic systems?

Autistic Disorder↗
PubMed1998

Brief paradoxical sleep deprivation impairs reference, but not working, memory in the radial arm maze task.

Selective deprivation of paradoxical sleep after learning results in memory deficits in a variety of tasks. The present experiment was designed to examine the effects of paradoxical sleep deprivation (PSD) upon spatial working and reference memory. Adult male Sprague-Dawley rats were trained for 10 days in an eight-arm radial maze. Food rewards were available in four of the arms, while the other four arms were never baited. After each daily training session, different groups of rats were given 4 h of PSD, beginning either immediately, 4 h, or 8 h after the training experience. An additional group received PSD during the period 13-24 h following daily training. The group that received PSD for 4 h immediately following daily training showed significant impairment compared to the other groups, but the deficit was limited to the reference component of the task. This result suggests that PSD causes deficits only in long-term forms of spatial memory.

Animals↗
PubMed1999

Is psychotherapy an effective treatment for melancholia and other severe depressive states?

The treatment of severe depression with psychotherapy, alone, is controversial. In this paper, we review the historical, conceptual, and empirical contexts of this controversy. In addition to work by others, we review recent work from our institute which has examined the psychobiological substrates of response to treatment in depressive subtypes. We examine the traditional categories that describe severe depressions. The features and psychobiological correlates of melancholia are discussed, as is the relationship between melancholia and aging. Research on treatment of melancholia and other severe depressive states with psychotherapies such as cognitive behavior therapy (CBT) and interpersonal psychotherapy (IPT) is reviewed in detail. We conclude that although some melancholic patients are responsive to IPT or CBT, there is not yet compelling evidence that melancholic patients respond to psychotherapy as well as they do to medications. The potentially mediating effects of hypercortisolism, alterations of sleep neurophysiology, and disturbances of information processing and regional cerebral metabolism represent fertile grounds for future investigation. We discuss the practical implications of the literature reviewed.

Aging↗
PubMedDate not supplied

Memory scores in middle-aged rats predict later deficits in memory, paradoxical sleep, and blood glucose regulation in old age.

Age-related deficits in memory are correlated with deficits in paradoxical sleep and poor glucose tolerance in rats. The present experiment used a longitudinal design to determine whether memory or glucose tolerance in middle-aged rats could predict deficits in memory, sleep, and glucose tolerance in old age. Correlations were obtained between spontaneous alternation scores and glucose tolerance levels in middle age (14 months) and inhibitory avoidance, daytime sleep, and glucose tolerance levels in old age (24 months). Spontaneous alternation scores, but not glucose tolerance levels, predicted performance on all 3 behavioral and biological measures in old age. Measures of functional integrity, such as memory, may be sensitive predictors of subsequent age-related change in specific cognitive and neurobiological systems.

Aging↗