Functional brain asymmetry as a determinative factor in the treatment of depression: theoretical implications.

Depression is characterized by the functional insufficiency of both left and right hemispheres. Patients who respond to antidepressants are characterized by a relatively higher left hemisphere activity in comparison to non-responders, and successful treatment with antidepressants increases left hemisphere activity. Left hemisphere is responsible for the goal-oriented behavior that includes search activity as a state opposite to depression, which accounts for the positive outcome in depression following activation of the left hemisphere. However, it is not a pathogenetic but a palliative treatment, because the core reason for depression is the inability of the right hemisphere to correspond to the demands of the polydimensional environment. The article suggests that in order to achieve stability, treatment has to combine methods that restore left hemisphere activity with methods that restore right hemisphere efficiency.

Sleep deprivation in depression: An integrative approach.

The question as to whether the beneficial effect of sleep deprivation in depression is related to the increased wakefulness or to the sleep suppression by itself, is made moot by the search activity concept. According to this concept, rapid eye movement (REM) sleep is functionally deficient in depression and increases feelings of helplessness and hopelessness instead of restoring mood and search activity. Thus, REM sleep deprivation, either selective or not, is beneficial by breaking a vicious circle: depression in wakefulness…giving up (helplessness) in dream scenario…increased depression in the subsequent wakefulness. In addition, sleep deprivation is an important challenge for the depressed patient. The ability to confront this challenge and maintain wakefulness has a positive outcome on depression, especially when wakefulness is accompanied by active behavior.

First-night effect of melatonin treatment in patients with chronic schizophrenia.

The first-night effect (FNE) is the tendency for individuals to sleep worse than normal during their first night of polysomnographic sleep evaluation. FNE reflects the adaptive increase of alertness and perhaps the stress resulting from an unfamiliar sleeping environment. This effect is usually absent in patients with chronic schizophrenia. Melatonin (N-acetyl-5-methoxy-tryptamine), the hormone secreted by the pineal gland at night, has been found to improve sleep in elderly patients with insomnia and recently in patients with chronic schizophrenia. The authors used FNE as a marker to explore the neurobehavioral responses of patients with chronic schizophrenia to melatonin treatment. In a randomized, double-blind, crossover trial, 14 patients with chronic schizophrenia were administered melatonin (2 mg in a controlled-release formulation) or placebo for 3 weeks with a 1-week washout between treatment periods. Polysomnography was performed during the last two consecutive nights of each treatment period. The following significant FNEs were observed with melatonin treatment: (1) rapid eye movement sleep latency was longer; (2) sleep efficiency was lower; and (3) the duration of wakefulness during sleep was lower on the first night than on the second night. These effects were not found when the patients received a placebo. The FNE was manifested regardless of whether melatonin was administered before or after the placebo treatment period. For the first time, these results show that melatonin treatment exaggerates FNE in patients with chronic schizophrenia, thereby suggesting an improved ability of these patients to mobilize alertness in unfamiliar surroundings.

The relationship between subjective sleep estimation and objective sleep variables in depressed patients.

INTRODUCTION: To our knowledge there is no evidence in the literature about the relationship between subjective sleep estimation and objective sleep variables in depression. It is not known whether the subjective estimation of sleep quality and sleep duration is directly related to any objective sleep variable in depressed patients. METHODS: Thirty patients with major depression and 10 healthy subjects have been investigated in our sleep laboratory during 1 or 2 consecutive nights after 1 night for adaptation. Every subject, after final awakening in the laboratory, answered questions concerning the subjective feelings about sleep duration, number of awakenings and sleep depth. We compared the sleep estimation in both groups and calculated the correlation between objective and subjective sleep variables in depressed patients. RESULTS: The degree of a wrong sleep estimation in depressed patients is larger than in healthy subjects. Slow wave sleep (SWS) in depressed patients correlates positively with the subjective estimation of sleep duration. Eye movement density in REM sleep correlates with the subjective estimation of the number of awakenings. CONCLUSION: SWS in depression has a positive influence on the subjective feeling of sleep duration while phasic REM sleep activity has a negative influence.

Melatonin improves sleep quality of patients with chronic schizophrenia.

BACKGROUND: Accumulating evidence indicates decreased melatonin levels in patients with schizophrenia. Insomnia, mainly difficulty in falling asleep at night, is commonly reported in this population. Association of insomnia with low or abnormal melatonin rhythms has been repeatedly documented. Melatonin is an endogenous sleep promoter in humans. We hypothesized that insomnia in patients with schizophrenia may be partially due to diminished melatonin output. In this study, we measured melatonin output in patients with chronic schizophrenia and assessed the effects of melatonin replacement on their sleep quality. METHOD: In a randomized, double-blind, cross-over, clinically based trial, 19 patients with DSM-IV schizophrenia who were treated with the normal treatment regimen were given melatonin (2 mg, controlled release) or placebo for 2 treatment periods of 3 weeks each with 1 week washout between treatment periods (7 weeks total). For measuring endogenous melatonin production, urine was collected from each patient every 3 hours between 9:00 p.m. and 9:00 a.m. Actigraphy was performed for 3 consecutive nights at the end of each period. Activity- and rest-derived sleep parameters were compared for the whole population with treatment arm as the intervening variable. A separate analysis was performed for patients subgrouped into high versus low sleep efficiency. RESULTS: All patients had low melatonin output. Melatonin replacement significantly improved rest-derived sleep efficiency compared with placebo (83.5% vs. 78.2%, p = .038) in this population. Improvement of sleep efficiency was significantly greater (p < .0014) in low-efficiency (80% vs. 67%) than high-efficiency sleepers (88% vs. 90%). In addition, during melatonin therapy, tendencies toward shortened sleep latency (by 40 minutes, p < .056) and increased sleep duration (by 45 minutes, p < .078) were observed in low- but not high-efficiency sleepers. CONCLUSION: Melatonin improves sleep efficiency in patients with schizophrenia whose sleep quality is low.

Interrelationships between nocturnal sleep, daytime alertness, and sleepiness: two types of alertness proposed.

The authors studied daytime sleepiness and alertness (based on the Multiple Sleep Latency Test [MSLT] and Maintenance of Wakefulness Test [MWT]) and nocturnal sleep in 22 patients with depression/anxiety and in 47 nondepressed patients with sleep apnea. The patients underwent two overnight sleep studies followed by daytime tests. In depressed patients, MWT scores correlated negatively with total sleep time and stage 3. MSLT scores correlated negatively with total sleep time and with sleep efficiency. Apneic patients showed a negative correlation between MWT results and amount of stage 1 sleep. MSLT results correlated positively with sleep onset latency on the preceding overnight sleep study. Thus, in depressed patients, there is a paradox that with more disturbed sleep there is greater daytime alertness. In contrast, the more disturbed the sleep is in sleep apnea patients, the more difficult it is to maintain daytime alertness.

Sleep after immobilization stress and sleep deprivation: common features and theoretical integration.

The goal of the present paper is to elucidate and to resolve contradictions in the relationships among different forms of stress, sleep deprivation, and paradoxical sleep (PS) functions. Acute immobilization stress and the stress of learned helplessness are accompanied by an increase of PS, whereas the stress of defense behavior and the stress of self-stimulation cause PS reduction. Recovery sleep after total sleep deprivation performed on the rotating platform is marked by a dramatic rebound of PS although NREM (non-rapid eye movement) sleep deprivation is more prominent than PS deprivation. This PS rebound leads to a quick reversal of the pathology caused by prolonged sleep deprivation. The search activity (SA) concept presents an explanation for these contradictions. SA increases body resistance to stress and diseases, whereas renunciation of search (giving up, helplessness) decreases body resistance. PS and dreams contain covert SA, which compensates for the lack of the overt SA in the preceding period of wakefulness. The requirement for PS increases after giving up and decreases after active defense behavior and self-stimulation. Immobilization stress prevents SA in waking behavior and increases the need in PS. Sleep deprivation on the rotating platform, like immobilization stress, prevents SA, produces conditions for learned helplessness and, suppresses PS. Such a combination increases PS pressure and decreases body resistance.

Human memory, cerebral hemispheres, and the limbic system: a new approach.

An integrative approach to human memory is presented in the context of brain asymmetry. The results of psychophysiological investigations suggest that right-hemisphere functioning is closely associated with the limbic system; that association leads to the formation of a polysemantic context. Polysemantic context is determined by multiple interconnections among its elements; each element bears the stamp of the whole context. That context sustains episodic, personal, and emotionally laden memories. Left-hemisphere functioning leads to the formation of a monosemantic context, which is responsible for the maintenance of semantic memories. That distinction--in terms of general organization of material by hemispheres--explains such phenomena as memory disturbances among the very old, the influence of emotions on memory, and confabulations.

Change of mood during sleep and REM sleep variables.

Polysomnography was performed during two consecutive nights in 23 patients with major depression. After every final awakening patients estimated the change of their mood from evening to morning: 1. Mood worse in the morning than in the evening; 2. Mood does not change; 3. Mood better in the morning. When mood was estimated as being better in the morning (20% of all nights), eye movement density in REM sleep increased from the first to the fourth cycle. In all other nights eye movement density was slightly higher in the first than in subsequent cycles. Mood improvement correlated positively with eye movement density in the fourth cycle and negatively with REM sleep duration in the first cycle. Eye movement density in the first cycle correlated positively with the subjective estimation of sleep latency. A possible functional difference between initial and final REM sleep periods is proposed.

First night effect in depression: new data and a new approach.

Polysomnography was performed in 20 depressed patients and 8 normal controls for 2 consecutive nights. A subset of patients had 3 consecutive nights. Patients were assigned to groups according to the presence (group I) or absence (group II) of a first night effect (REM sleep latency on the first night in the laboratory was at least 30 min longer than on the second night). The groups were equivalent with regard to gender distribution, age, and severity of depression. In group I, REM sleep latency on nights 2 and 3 was significantly shorter than in group II. REM sleep percentage on the second night in group I was increased compared to the first night. A shift of REM sleep to the first cycle was prominent on the first night only in patients with a first night effect. On average, delta sleep was preserved in group I compared to group II. We suggest that the first night effect reflects a physiological system with greater capacity to respond adaptively and to preserve homeostasis when confronted with environmental stressors.

REM sleep in depressed patients: different attempts to achieve adaptation.

Twenty-seven depressed patients and 10 healthy subjects were investigated in the sleep laboratory during two to three consecutive nights. Eleven of the 27 patients demonstrated the "first night effect" (group I) and 11 other patients demonstrated a clear absence of the "first night effect" (group II). Five of the 27 depressed patients were omitted from the study because they did not fit criteria for first night effect. The 10 healthy controls demonstrated a first night effect. In group I, the duration of the first rapid eye movement (REM) sleep episode was increased on the first night and on the second night the REM sleep latency was decreased, whereas REM sleep duration and eye movement (EM) density was increased. The number of the short sleep cycles (less than 40 minutes) was greater in group I versus group II and the percentage of slow-wave sleep (SWS) was also higher in group I. In depressed patients with the "first night effect" the enhanced REM sleep requirement is satisfied not only by an increased REM sleep duration but also by the improved REM sleep quality that is crucial for adaptation. The adaptive role of the increased first REM period and the increased EM density in this period is very limited.

To inform or not to inform--a decision with psychobiological implication.

A patient, being informed about his dangerous or even fatal disease, like cancer, has a higher chance to give up and display a renunciation of search activity. Such renunciation decreases body resistance and makes the overall situation hopeless. Thus a person has the right to be not informed about such diseases, because he has the right to use all his inner resources for survival.

Psychoneuroimmunology: searching for the main deteriorating psychobehavioral factor.

Psychoneuroimmunology has become an independent science with a broad experimental basis. However, its theoretical basis is still very vague and ambiguous. There are many contradictions in the experimental data that have not been integrated into a united conception, and some accepted paradigms that remain doubtful. The present critical review suggests a conceptual approach to the problem based on the proposition of two opposite types of behavior (search activity and renunciation of search) with attempts to integrate experimental results by avoiding contradiction. The analysis of the literary data confirms that every behavior that includes search activity prevents psychoimmunological disorders, whereas renunciation of search displays a general predisposition to such disorders. Such an approach makes possible new solutions of paradoxes and broadens the possible interpretations of the alteration of immune functions in depression, anxiety, and stressful events.

Psychosocial problems faced during absorption of Russian-speaking new immigrants into Israel: a systematic approach.

The problems faced by immigrants during the absorption process are multidimensional and require a systematic approach. According to the authors' theoretical perspective and clinical experience, two main principles determine the "facets" of absorption: search activity and self-esteem. The paper begins with a definition of search activity and its relationship to self-esteem and then discusses intrapsychic and environmental blocks to search activity and their effect on self-esteem. The paper concludes with a therapeutic approach toward restoration of search activity and self-esteem.

The revised monoamine hypothesis: mechanism of antidepressant treatment in the context of behavior.

The temporal restoration of brain monoamines in the synaptic cleft due to MAO inhibition or by blocking catecholamine reuptake is only the first step on the way to recovery from depression. The second and crucial step represents the feedback system, which can provide the continuous restoration of brain monoamines in the context of free search behavior. This feedback system on the one hand helps to overcome depression and on the other hand causes the hyposensitivity of the postsynaptic catecholamine (CA) receptors, due to the increased activity of the brain CA system. According to the search activity concept, REM sleep in the healthy subject, being a part of the same feedback system, restores brain monoamines. The mechanism of REM sleep deprivation in the treatment of depression is discussed in the context of this feedback system.

An integrative psychophysiological approach to brain hemisphere functions in schizophrenia.

The present paper proposes a new psychophysiological approach to the genesis of positive and negative schizophrenic symptoms. According to this approach, the initial factor in schizophrenic disorders is a functional insufficiency of the right hemisphere which can be determined by early emotional experience in combination with subtle brain damage. This functional insufficiency causes (a) the inability to grasp and select information before its realization; and (b) the inability to produce a polysemantic context which is crucial for creativity, psychological defense, and the restoration of search activity, all of which determine psychophysiological adaptation to the environment. Right hemisphere insufficiency causes left hemisphere hyperactivity as an ineffective attempt to compensate for this functional deficiency. As a result, normal search activity is replaced by artificial search activity which is represented by "positive" symptoms, and which uses the predisposition of the left hemisphere's catecholamine system for its increased activity. The suggestion is made that cognitive impairment in schizophrenia (the inability to use appropriate previous information in relation to current perceptual input) is related to the competition between information processing which requires left hemisphere activity, and the formation of positive symptoms, also based on left hemisphere activity.

Adaptive versus maladaptive emotional tension.

The problem of emotional tension is usually discussed only with regard to its negative (maladaptive) aspects. The positive (adaptive) function of emotional tension, however, is as important as its negative function. In this article, we have examined psychophysiological outcomes of adaptive versus maladaptive emotional tension with respect to opposite forms of behavior (search activity and renunciation of search) that have an opposite outcome on body resistance and performance. Some traditional psychophysiological problems, for example, the law of initial values (Wilder, 1931), the difference between orienting and defensive reaction, or between anxiety and panic behavior, are revised on the basis of the assumption of adaptive and maladaptive emotional tension.

Sleep and memory. I: The influence of different sleep stages on memory.

A new approach to the sleep stages role in memory is discussed in the context of the two opposite patterns of behavior-search activity and renunciation of search. Search activity is activity designed to change the situation (or the subjects attitudes to it) in the absence of a definite forecast of the results of such activity, but with the constant consideration of these results at all stages of activity. Search activity increases general adaptability and body resistance while renunciation of search decreases adaptability and requires REM sleep for its compensation. Unprepared learning, which is often accompanied by failures on the first steps of learning, is suggested to produce renunciation of search, which decreases learning ability, suppress retention, and increase REM sleep requirement. A prolonged REM sleep deprivation before training causes learned helplessness and disturbs the learning process, while short REM sleep deprivation cause the "rebound" of the compensatory search activity that interferes with passive avoidance. REM sleep deprivation performed after a training session can increase distress caused by a training procedure, with the subsequent negative outcome on retention.