Melatonin and jet lag syndrome: experimental model and clinical implications

What is the effect of melatonin on jet lag syndrome? Jet lag desynchronizes the internal sleep-wakefulness cycle with the environmental light/dark cycle. Advance (but not delay) of light onset is known to abolish pineal N-acetyltransferase activity and urine excretion of 6-sulphatoxymelatonin. Measurements of pineal serotonin, the substrate of melatonin biosynthesis; N-acetylserotonin (NAS), the immediate melatonin precursor; and melatonin (high-performance liquid chromatography-fluorimetric method) in the animal (rat) model of jet lag revealed that prolonged delay of dark-phase onset disrupted the rhytms in comparable ways as the advance of light-phase onset. Advance of dark phase onset resulted in less severe disturbances of rhythms as compared with the advance of light phase onset. Melatonin, but not NAS, injections at the beginning of a new dark period accelerated recovery of NAS and melatonin, but not serotonin, rhythms. Spontaneously hypertensive rats were more sensitive to advance of light onset and less responsive to melatonin injections than normotensive rats. NAS and methylene blue, an inhibitor of monoamine oxidase A, attenuated light-induced disruption of NAS but not melatonin rhythms. We draw the following conclusions from our data: the beginning of the dark period may be preferable to the beginning of light period as the arrival time on eastward flights; the efficacy of melatonin in alleviating jet lag may be enhanced by administering it before, during and after rapid transition through time zones; and hypertension may exaggerate jet lag syndrome.     

Melatonin rhythm abnormalities and sleep disorders in the elderly

Biological aging is often associated with sleep problems and daytime napping. Complaints of difficulty in initiating and maintaining sleep, as well as daytime drowsiness, are more common in the elderly than in any other age group. This report reviews evidence that impaired melatonin secretion is associated with sleep disorders in old age. Circulating melatonin levels have been found to be significantly lower and onset and peak times have been delayed in elderly insomniacs as compared to age-matched control subjects. In view of these findings, we investigated the effects of melatonin treatment on melatonin-deficient insomnia in the elderly. From the results of our study, it seems likely that melatonin replacement therapy may be beneficial in the initiation and maintenance of sleep in this population.     

REM sleep deprivation increases early morning pineal melatonin in castrated rats

Recently nighttime melatonin levels have been shown to be attenuated in depressive patients or patients with dementia of the Alzheimer type. On the other hand, depression can be transiently relieved by deprivation of rapid eye movement sleep. Since exogenous melatonin administration increases rapid eye movement sleep and slow wave sleep in the rat, could rapid eye movement sleep deprivation then inversely influence endogenous melatonin production? We found indices that in castrated Wistar rats 4 days of rapid eye movement sleep deprivation by the cuff pedestal method elevates the pineal content of melatonin by a factor of two at 1 to 2 h after light onset. Rapid eye movement sleep is thus suggested to influence pineal activity. This mechanism might be involved in the human depression-alleviating effect of rapid eye movement sleep deprivation.     

季节性情感障碍存在记忆损伤吗？

季节性情感障碍(Seasonal Affective Disorder, SAD)与轻度到中度的临床抑郁有类似的症状,它通常发生于季节性日照不足的地区。造成该障碍的一个可能原因是褪黑素分泌不足。与非季节性抑郁相比, 季节性抑郁的记忆损伤尚未得到充分研究。以往的研究也发现了一些类似于非季节性抑郁的记忆损伤, 但通常很少达到统计的显著性, 且其采用的测验任务也缺乏分辨力, 未能对损伤进行足够的细节描述。这里对有关文献做一个综述。     

光照的警觉性作用

光照除了传统的视觉作用外, 还具有一定的非视觉效应, 包括调节昼夜节律、褪黑素分泌和警觉性等生理功能和行为表现。随着光照对生理节律影响研究的不断深入, 近来很多学者开始关注光照的警觉性作用。我们根据最新研究进展总结了：(1)警觉性的测量工具; (2)光照强度、时长、时间点、波长、色温等对光照警觉性作用的影响; (3)光照在治疗情绪障碍、调节生理节律、完善办公照明方面的应用; (4)提出了继续探讨光照警觉性作用的神经机制、优化参数特征和探讨混淆变量的研究方向。     

Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects

Bright light therapy for seasonal affective disorder (SAD) has been investigated and applied for over 20 years. Physicians and clinicians are increasingly confident that bright light therapy is a potent, specifically active, nonpharmaceutical treatment modality. Indeed, the domain of light treatment is moving beyond SAD, to nonseasonal depression (unipolar and bipolar), seasonal flare-ups of bulimia nervosa, circadian sleep phase disorders, and more. Light therapy is simple to deliver to outpatients and inpatients alike, although the optimum dosing of light and treatment time of day requires individual adjustment. The side-effect profile is favorable in comparison with medications, although the clinician must remain vigilant about emergent hypomania and autonomic hyperactivation, especially during the first few days of treatment. Importantly, light therapy provides a compatible adjunct to antidepressant medication, which can result in accelerated improvement and fewer residual symptoms.     

Melatonin and sleep qualities in healthy adults: pharmacological and expectancy effects

The impact of expectancy on melatonin's effects on sleep qualities was investigated. Both the pharmacological dose of 6 mg of melatonin and the expectation of receiving melatonin were predicted to improve subjective ratings of sleep qualities. The balanced placebo design varied 2 factors within-subjects: actual treatment and expected treatment. Adults (N = 53; 21 men and 32 women) between the ages of 26 and 71 years were administered either 6 mg of melatonin or a placebo for 8 nights. An instructional manipulation directed participants' expectations. Participants rated their nightly sleep experiences. Results revealed that feelings upon awakening differed between genders and that expecting melatonin increased ratings of sleep continuity. Most important, high ratings of "grogginess/tiredness" were associated with receiving melatonin, regardless of expectancy, as well as with receiving placebo when melatonin was expected. Overall, the findings underscore the need to consider expectancy and gender differences in research on melatonin and sleep experiences.     

Winter Depression Recurrence One Year After Cognitive-Behavioral Therapy, Light Therapy, or Combination Treatment

The central public health challenge in the management of seasonal affective disorder (SAD) is prevention of depression recurrence each fall/winter season. The need for time-limited treatments with enduring effects is underscored by questionable long-term compliance with clinical practice guidelines recommending daily light therapy during the symptomatic months each year. We previously developed a SAD-tailored group cognitive-behavioral therapy (CBT) and tested its acute efficacy in 2 pilot studies. Here, we report an intent-to-treat (ITT) analysis of outcomes during the subsequent winter season (i.e., approximately 1 year after acute treatment) using participants randomized to CBT, light therapy, and combination treatment across our pilot studies (N = 69). We used multiple imputation to estimate next winter outcomes for the 17 individuals who dropped out during treatment, were withdrawn from protocol, or were lost to follow-up. The CBT (7.0%) and combination treatment (5.5%) groups had significantly smaller proportions of winter depression recurrences than the light therapy group (36.7%). CBT alone, but not combination treatment, was also associated with significantly lower interviewer- and patient-rated depression severity at 1 year as compared to light therapy alone. Among completers who provided 1-year data, all statistically significant differences between the CBT and light therapy groups persisted after adjustment for ongoing treatment with light therapy, antidepressants, and psychotherapy. If these findings are replicated, CBT could represent a more effective, practical, and palatable approach to long-term SAD management than light therapy.     

Melatonin and Sleep Qualities in Healthy Adults: Pharmacological and Expectancy Effects

The impact of expectancy on melatonin's effects on sleep qualities was investigated. Both the pharmacological dose of 6 mg of melatonin and the expectation of receiving melatonin were predicted to improve subjective ratings of sleep qualities. The balanced placebo design varied 2 factors within-subjects: actual treatment and expected treatment. Adults (N = 53; 21 men and 32 women) between the ages of 26 and 71 years were administered either 6 mg of melatonin or a placebo for 8 nights. An instructional manipulation directed participants' expectations. Participants rated their nightly sleep experiences. Results revealed that feelings upon awakening differed between genders and that expecting melatonin increased ratings of sleep continuity. Most important, high ratings of “grogginess/tiredness” were associated with receiving melatonin, regardless of expectancy, as well as with receiving placebo when melatonin was expected. Overall, the findings underscore the need to consider expectancy and gender differences in research on melatonin and sleep experiences.     

Bright light treatment has limited effect in subjects over 55 years with mild early morning awakening

31 subjects, age 55 yr. or older, suffering from mild early morning awakening were randomized to either a bright light (10,000 lux) or to a red dim light placebo condition (200 lux). Light exposure took place in the evening in the patients' homes, 60 to 30 min. before bedtime and lasted for 3 wk. The subjects kept a sleep diary for 2 wk. and wore an actigraph for 1 wk. both before treatment and at post-treatment. Of the eight sleep diary outcome variables, significant effects that could be attributed to the light treatment were only detected for time spent in bed after final morning awakening. None of the six actigraph outcome variables yielded any significant effect of the light therapy. Explanations for the limited therapeutic effects of bright light treatment obtained in the present study are discussed, such as the criteria defining early morning awakening, the selection procedure, problems with compliance, age of the sample, and the dose of light. The lack of an objective circadian marker in this study could represent a problem concerning the timing of the light exposure. Despite the limited success of bright light therapy in this study, bright light therapy should still be considered as a treatment option for early morning awakening.     

Immune responses to lipopolysaccharide challenge in a tropical rodent (Funambulus pennanti): photoperiod entrainment and sex differences

Annual variation in day length (photoperiod) triggers changes in the immune system of seasonal breeders. The rationale behind this study was to delineate any sex differences in immune responses of photoperiodically entrained animals challenged against lipopolysaccharide (LPS)-induced inflammatory stress. We observed that photoperiodically entrained [short day, SD, 10?h light (L):14?h dark (D); long day, LD, 16?h L:8?h D; and natural day length, NDL, 12?h L:12?h D] male and female Indian palm squirrels, Funambulus pennanti, presented sexual dimorphism in immune status after LPS-induced stress. Females presented high humoral (anti-keyhole limpet hemocyanin immunoglobulin) and cellular immunity (lymphocyte proliferation) compared with the males of all photoperiodic conditions. Female squirrels showed reduced pro-inflammatory cytokine levels (interleukin-1β, interleukin-6, and tumor necrosis factor-α) than the males suggesting their high efficiency to recover from LPS-induced inflammatory stress. Increased duration of melatonin secretion and corticosterone concentration in squirrels experiencing SD evidently supported survival of squirrels as compared with control (NDL) and LD squirrels of both sexes. Decreased immune status in both sexes under LD condition might be due to a short melatonin signal mimicking the LDs of summer. Thus, we infer that photoperiodic entrainment via the levels of melatonin and corticosterone synergistically supported more the survival of female squirrels under LPS-induced stress.     

褪黑素受体MT1在骨肉瘤中的表达及临床意义

采用免疫组化法检测MT1在40例骨肉瘤及20例骨软骨瘤组织中的表达。结果显示MT1在骨肉瘤中的表达率（70％）明显高于骨软骨瘤（35％）（P〈0．05）。MT1的表达与骨肉瘤的Enneking分期、复发和转移相关（P〈0．05）,而与性别、年龄、肿瘤体积、Dahlin＇s组织学分型无关（P〉0．05）。因此,MT1可作...     

Change in Seasonal Beliefs Mediates the Durability Advantage of Cognitive-Behavioral Therapy Over Light Therapy for Winter Depression

In treating an acute episode of winter depression, cognitive-behavioral therapy for seasonal affective disorder (CBT-SAD) and light therapy are comparably efficacious, with improvement in depression symptoms during CBT-SAD mediated by reduced seasonal beliefs (i.e., maladaptive thoughts about the seasons, light availability, and weather). Here, we tested whether the enduring benefit of CBT-SAD over light therapy following treatment is associated with offsetting seasonal beliefs during CBT-SAD. Currently depressed adults with Major Depression, Recurrent with Seasonal Pattern (N = 177) were randomized to 6 weeks of light therapy or group CBT-SAD and followedup one and two winters after treatment. Outcomes measured during treatment and at each follow-up included depression symptoms on the Structured Clinical Interview for the Hamilton Rating Scale for Depression—SAD Version and Beck Depression Inventory—Second Edition. Candidate mediators measured at pre-, mid-, and posttreatment were SAD-specific negative cognitions (Seasonal Beliefs Questionnaire; SBQ); general depressogenic cognitions (Dysfunctional Attitudes Scale; DAS); brooding rumination (Ruminative Response Scale-Brooding subscale; RRS-B); and chronotype (Morningness-Eveningness Questionnaire; MEQ). Latent growth curve mediation models found a significant positive path from treatment group to the slope of SBQ during treatment, with CBT-SAD showing larger improvements in seasonal beliefs with overall change in seasonal beliefs in the medium-effect range, and significant positive paths from SBQ slope to depression scores at the first and second winter follow-ups, indicating greater change towards more flexible seasonal beliefs during active treatment was associated with less severe depression symptoms following treatment. Estimated indirect effects (treatment group → SBQ change * SBQ change → outcome) were also significant at each follow-up for each outcome with β_indirect ranging from .091 to .162. Models also found significant positive paths from treatment group to the slope of MEQ and RRS-B during treatment, with light therapy showing a greater increase in “morningness” and CBT-SAD showing a greater decrease in brooding during active treatment; however, neither construct emerged as a mediator of follow-up depression scores. Change in seasonal beliefs during treatment mediates both the acute antidepressant and long-term effects of CBT-SAD and explains lower depression severity following CBT-SAD relative to light therapy.     

照明的非视觉作用及其脑神经机制

照明在人类生活、工作和学习中发挥着举足轻重的作用, 除了提供基本的视觉作用(对周围事物的大小、颜色、形状等方面的视觉感知)外, 还会对人的生理、心理功能产生显著影响, 如调节褪黑素分泌、影响生物节律, 促进认知加工、调节由季节变化引起的情绪情感障碍(SAD)等。这种对生理、心理活动产生直接或间接的影响即为照明的非视觉作用。近年来, 照明的非视觉作用及其背后的神经机制得到了研究者的广泛关注和大量实证研究, 并取得了丰硕成果。未来研究需从模型建构、动态照明等角度入手进一步探索照明的非视觉作用及其脑神经机制。     

Depression and its relation to light deprivation

The absence or diminution of light is potentially an anxiety-arousing situation for, perhaps, all of us. Even a cursory look at the origin myths of many cultures reveals the chaotic, destructive, and dangerous aspects of darkness. Additionally, language reflects the same qualities metaphorically and symbolically. Developmentally, the arrival of the darkness of evening potentially signals object loss and ego regression. But factors other than ubiquitous references to a consideration of light and darkness are relevant. Can it be that we are all at least prone to depression due in part to this factor? Questions regarding possible biological causes of depression are perhaps unanswerable at this time. Is the seratonin level really associated with depression and light deprivation? Research is as yet inconclusive. If a relationship exists, another question must be asked: Will certain psychological situations affect a person's seratonin production? The answer to this question of how depression is associated with biological causes is certainly beyond the scope of this paper. Yet the preceding case history reveals at least some psychological causes of depression that were initially seen as biologically based. The SAD proponents would have treated Mr. B with light therapy. The quick solution of light therapy, based on a shaky theoretical base and lacking sturdy research, has too often replaced the psychoanalytic approach. In all too many situations psychoanalysts are being replaced by lightbulbs.     

Enhancing Family Therapy with Analytical Psychology

In a postmodern era of changing values and competing world views this article suggests that analytical psychology can enter the epistemological debate and speak to contemporary family therapy. Key concepts and contributions are examined and highlighted with an emphasis on their relevance for enhancing the field of family therapy. Individuation is discussed in light of Jung's analytical treatment stages, which include confession, explanation, education, and transformation. The relevance for family therapy is illustrated throughout the article as each treatment stage is explicated. Jung's emphasis on the spiritual is also discussed with implications for the importance of recognizing and attending to issues of spirituality in family therapy.     

Behavioral effects of chronic melatonin and pregnenolone injections in a myelin mutant rat (taiep)

The taiep (tremor, ataxia, immobility, epilepsy, and paralysis) myelin mutant displays a number of locomotor deficits. Taiep rat gait is characterized by shorter stride and step lengths as well as by larger stride widths. Thirty-day-old taiep mutants were placed under a regimen of daily hormone injections for 60 days. Animals in Condition 1 received melatonin, those in Condition 2 received pregnenolone sulfate, and those in a third control condition received injections of saline. Following the injections, each taiep mutant's gait was analyzed. The animals that received melatonin and pregnenolone displayed significantly larger stride and step lengths than did the controls. In addition, the animals that received hormones displayed shorter stride widths than did the controls. These experimental effects are consistent with a normalization of gait. Possible cellular mechanisms of this behavioral effect are discussed.     

Alzheimer病褪黑素假说的哲学思考

Ａｌｚｈｅｉｍｅｒ病（Ａｌｚｈｅｉｍｅｒ’ｓ Ｄｉｓｅａｓｅ,ＡＤ）正日益人类健康,而其发病机理至今尚不清楚,治疗也无特效药物。褪黑素（Ｍｅｌａｔｏｎｉｎ,ＭＴ）假说直到近几年有大量研究支持后才得到人们的重视,该假说为ＡＤ的研究与治疗打开发了一个全新的视解。ＡＤ在ＭＴ方面的研究历程揭示了人类科学发现及科学认识的普遍规律。     

Values in Family Therapy Practice and Research: An Invitation for Reflection

Values have been shown to be a pervasive part of both marriage and family therapy (MFT) clinical practice and research. Yet, many therapists and researchers remain unclear about how values affect their work. This article examines the influence of Western philosophical assumptions and therapy traditions in light of current understandings of values in therapy. The influence of values in MFT research processes is similarly examined. Implications for how family therapy professionals can be more reflective and sophisticated in their understanding of values in clinical practice and scientific inquiry are discussed. Suggestions for addressing values in MFT training also are given.     

Moderate versus light pressure massage therapy leads to greater weight gain in preterm infants

Sixty-eight preterm infants (M GA = 30 weeks) were randomly assigned to a moderate or to a light pressure massage therapy group to receive 15 massages three times per day for 5 days. Behavior state, stress behaviors and heart rate were recorded for 15 min before and during the first 15-min therapy session. Weight gain was recorded over the 5-day therapy period. The moderate versus light pressure massage group gained significantly more weight per day. During the behavior observations the moderate versus light pressure massage group showed significantly lower increases from the pre-session to the session recording on: (1) active sleep; (2) fussing; (3) crying; (4) movement; and (5) stress behavior (hiccupping). They also showed a smaller decrease in deep sleep, a greater decrease in heart rate and a greater increase in vagal tone. Thus, the moderate pressure massage therapy group appeared to be more relaxed and less aroused than the light pressure massage group which may have contributed to the greater weight gain of the moderate pressure massage therapy group.