Morning vs evening light treatment of patients with winter depression

BACKGROUND: According to the phase-shift hypothesis for winter depression, morning light (which causes a circadian phase advance) should be more antidepressant than evening light (which causes a delay). Although no studies have shown evening light to be more antidepressant than morning light, investigations have shown either no difference or morning light to be superior. The present study assesses these light-exposure schedules in both crossover and parallel-group comparisons. METHODS: Fifty-one patients and 49 matched controls were studied for 6 weeks. After a prebaseline assessment and a light/dark and sleep/wake adaptation baseline week, subjects were exposed to bright light at either 6 to 8 AM or 7 to 9 PM for 2 weeks. After a week of withdrawal from light treatment, they were crossed over to the other light schedule. Dim-light melatonin onsets were obtained 7 times during the study to assess circadian phase position. RESULTS: Morning light phase-advanced the dim-light melatonin onset and was more antidepressant than evening light, which phase-delayed it. These findings were statistically significant for both crossover and parallel-group comparisons. Dim-light melatonin onsets were generally delayed in the patients compared with the controls. CONCLUSIONS: These results should help establish the importance of circadian (morning or evening) time of light exposure in the treatment of winter depression. We recommend that bright-light exposure be scheduled immediately on awakening in the treatment of most patients with seasonal affective disorder.     

Multivariate changes in coordination of postural control following spaceflight

BACKGROUND: Bright light therapy is the recommended treatment for winter seasonal affective disorder (SAD). However, the studies with the best placebo controls have not been able to demonstrate that light treatment has a benefit beyond its placebo effect. METHODS: Ninety-six patients with SAD completed the study. Patients were randomly assigned to 1 of 3 treatments for 4 weeks, each 1.5 hours per day: morning light (average start time about 6 AM), evening light (average start about 9 PM), or morning placebo (average start about 6 AM). The bright light (approximately 6000 lux) was produced by light boxes, and the placebos were sham negative-ion generators. Depression ratings using the Structured Interview Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) were performed weekly. RESULTS: There were no differences among the 3 groups in expectation ratings or mean depression scores after 4 weeks of treatment. However, strict response criteria revealed statistically significant differences; after 3 weeks of treatment morning light produced more of the complete or almost complete remissions than placebo. By 1 criterion (24-item SIGH-SAD score <50% of baseline and < or =8), 61% of the patients responded to morning light, 50% to evening light, and 32% to placebo after 4 weeks of treatment. CONCLUSIONS: Bright light therapy had a specific antidepressant effect beyond its placebo effect, but it took at least 3 weeks for a significant effect to develop. The benefit of light over placebo was in producing more of the full remissions.     

Neuromyopathy secondary to omeprazole treatment

We report a patient with non-24 h sleep-wake syndrome (non-24) whose free-running sleep-wake cycle was successfully treated with both scheduled bright light exposure and melatonin treatment. In the present study, morning bright light as well as evening melatonin phase-advanced sleep-wake cycles and melatonin rhythm. Both these procedures achieved appropriate entrainment to a 24 h day. However, the patient did not continue morning bright light therapy after the discharge. Rising at appropriate times in the morning for bright light therapy was difficult for him to continue. Melatonin treatment was better tolerated because of its ease of application.     

Effects of fluoxetine versus bright light in the treatment of seasonal affective disorder

BACKGROUND: Disturbances of serotonergic neurotransmission appear to be particularly important for the pathophysiology of winter depression. This study investigated whether fluoxetine has antidepressant effects comparable to bright light in the treatment of seasonal affective disorder (winter type). METHOD: A randomized, parallel design was used with rater and patients blind to treatment conditions. One week of placebo (phase I) was followed by 5 weeks of treatment (phase II) with fluoxetine (20 mg per day) and a placebo light condition versus bright light (3000 lux, 2 h per day) and a placebo drug. There were 40 patients (20 in each treatment condition) suffering from seasonal affective disorder (SAD) according to DSM-III-R who had a total score on the Hamilton Depression Scale of at least 16. RESULTS: Forty patients entered phase II and 35 completed it (one drop-out in the fluoxetine group and four in the bright light group). Fourteen (70%) of the patients treated with bright light and 13 (65%) of those treated with fluoxetine were responders (NS). The remission rate in the bright light group tended to be superior (bright light 50%, fluoxetine 25%; P = 0.10). Light therapy improved HDRS scores significantly faster, while fluoxetine had a faster effect on atypical symptoms. Light treatment in the morning produced a significantly faster onset of improvement, but at the end of treatment the time of light application seemed not to be crucial. CONCLUSION: Both treatments produced a good antidepressant effect and were well tolerated. An apparently better response to bright light requires confirmation in a larger sample.     

Negative attributional style in seasonal and nonseasonal depression

OBJECTIVE: There is a substantial relationship between dysfunctional cognitions and the clinical course of major depression. This study examined whether this association extends to patients with seasonal affective disorder. METHOD: A revised version of the Attributional Style Questionnaire was used to assess negative attributional style and predict response to treatment in a group of depressed outpatients, 26 with seasonal depression and 30 with nonseasonal, unipolar major depression. RESULTS: Pretreatment scores on negative attributional style did not differ between the patients with seasonal affective disorder and those with nonseasonal depression. Negative attributional style predicted poor response to pharmacotherapy in the nonseasonal depression group but did not predict response to light therapy in the group with seasonal affective disorder. CONCLUSIONS: Dysfunctional cognitions may play a lesser role in seasonal affective disorder than in nonseasonal depression.     

Effects of bright light on sleepiness, melatonin, and 25-hydroxyvitamin D(3) in winter seasonal affective disorder

Sixteen patients with winter seasonal affective disorder and 13 healthy controls were exposed to 3300 lx of cool-white fluorescent light for either 1 hour or 15 min in the morning for 2 weeks during the winter. Subjective sleepiness, melatonin concentration in saliva, and serum 25-hydroxyvitamin D(3) concentration were measured before and after the 2-week trial as well as the following summer when the patients were well. There were no significant differences in the baseline values between the patients and healthy subjects. No significant differences in the outcome measures were observed in the patients or the controls in the two groups of each after the trial. The exposure to bright light resulted in a significant decrease in subjective sleepiness early in the evening in the patients but not in the control subjects. The reduction of depressive symptoms was associated with the decrease in subjective sleepiness but not with the changes in the melatonin or vitamin D concentrations.     

Phototherapy. An alternative for seasonal affective disorders or sleep disorders

Although clinicians have observed for centuries that som depressed patients become worse in the winter, it was first in 1984 that Norman Rosenthal and co-workers described a syndrome which they called seasonal affective disorder (SAD), characterised by winter depression, lethargy and a craving for carbohydrate. Phototherapy was proved to be an effective treatment right from the start. Recently it has been reported that not only depression, but also panic disorder and obsessive compulsive disorders may exhibit a seasonal pattern and thus benefit from phototherapy. Phototherapy may also benefit patients suffering from "sun-downing", a syndrome of confusion and agitation in the evening in persons with Alzheimer's disease. Based on the observation that bright light may both elevate brain serotonin and ameliorate sleep abnormalities, the authors report the results of phototherapy for treatment of non-seasonal depressions, either alone or in combination with antidepressants or sleep deprivation.     

Photic entrainment of the mammalian rhythm in melatonin production

This review summarizes studies on the photic entrainment of the circadian rhythm in the rat pineal melatonin production, namely of the rhythm in N-acetyltransferase (NAT) activity, and compares the NAT rhythm resetting with preliminary results on the resetting of an intrinsic rhythmicity in the suprachiasmatic nucleus (SCN) of the hypothalamus, namely with the entrainment of the rhythm in the light-induced c-fos gene expression. Phase delaying of the NAT rhythm after various light stimuli proceeds within 1 day with almost no transients, whereas during phase advancing of the rhythm only the morning NAT decline is phase advanced within 1 day and the evening rise phase shifts through transients. A light stimulus encompassing the middle of the night may phase delay the evening NAT rise, phase advance the morning decline, compress the rhythm waveform, and eventually lower its amplitude. Similarly, a long photoperiod compresses the NAT rhythm waveform. The magnitude of phase shifts of the NAT rhythm, as well as their direction, depends on a previous photoperiod. Phase shifts of the evening rise in c-fos gene photoinduction in the SCN and of the morning decline are similar to those of the pineal NAT rhythm after all light stimuli studied so far. The data indicate that the resetting of the rhythm in melatonin production in the rat pineal gland reflects changes in the SCN functional state and suggest that the underlying SCN pacemaking system is complex.     

Cognitive-behavioral factors in seasonal affective disorder.

To longitudinally examine cognitive-behavioral correlates of seasonal affective disorder (SAD), the authors assessed women with a history of SAD and nondepressed, matched controls across fall, winter, and summer. SAD history participants reported more automatic negative thoughts throughout the year than controls and demonstrated a progression from decreased activity enjoyment during fall to reduced activity frequency during winter. Ruminative response style, measured in fall, predicted symptom severity during the winter. Across assessments, SAD history women endorsed greater depressive affect in response to low light intensity stimuli than to bright or ambiguous intensity stimuli, but less depressed mood to bright light stimuli than controls. These results suggest that the cognitive-behavioral factors related to nonseasonal depression may play a role in SAD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dawn simulation treatment of abstinent alcoholics with winter depression

BACKGROUND: Recent data suggest that winter depression (seasonal affective disorder [SAD]) may be a subtype of affective disorder that is closely related to alcoholism. Dawn simulation has been shown in controlled trials to be effective in SAD. The present study examined the effectiveness of dawn simulation in abstinent alcoholics who met DSM-III-R criteria for major depression, or bipolar disorder, depressed with seasonal pattern. METHOD: All 12 subjects with winter depression had a history of either alcohol dependence or alcohol abuse according to DSM-III-R and had been abstinent from alcohol for at least 6 months. They also fulfilled criteria for SAD according to Rosenthal and were hypersomnic and drug free. After a 1-week baseline period, the subjects were randomly assigned to a 1-week treatment period at home with either a white 1.5-hour dawn from 4:30 a.m. to 6:00 a.m. peaking at 250 lux or a red 1.5-hour dawn from 4:30 a.m. to 6:00 a.m. peaking at 2 lux. The subjects were told that they would receive daily either a red or a white dawn reaching the same illuminance, an illuminance that would be much dimmer than standard bright light treatment. At the end of each week, the subjects were blindly assessed by a psychiatrist using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorder version (SIGH-SAD). RESULTS: For the 6 subjects completing the white dawn treatment, the mean SIGH-SAD score decreased from 33.0 at baseline to 15.8 after treatment. For the 6 subjects completing the dim red dawn treatment, the mean SIGH-SAD score decreased from 34.3 to 32.7. The mean post-dawn SIGH-SAD score was significantly lower after the white dawn treatment than after the dim red dawn treatment (ANCOVA with baseline SIGH-SAD as the covariate, F = 12.95, p < .01). Superiority of the white dawn was also found by analogous analyses for the Hamilton Rating Scale for Depression (HAM-D) (p < .01) and the SAD Subscale (p < .05). CONCLUSION: The present study suggest that dawn simulation may be helpful in decreasing depression in abstinent alcoholics with SAD. Further study is necessary to confirm these preliminary findings and to determine whether dawn simulation might be helpful in preventing relapse in abstinent alcoholics who have SAD.     

Greater improvement in summer than with light treatment in winter in patients with seasonal affective disorder

OBJECTIVE: The authors sought to compare the degree of mood improvement after light treatment with mood improvement in the subsequent summer in patients with seasonal affective disorder. METHOD: By using the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale, the authors rated 15 patients with seasonal affective disorder on three occasions: during winter when the patients were depressed, during winter following 2 weeks of light therapy, and during the following summer. They compared the three conditions by using Friedman's analysis of variance and the Wilcoxon signed ranks test. RESULTS: The patients' scores on the depression scale were significantly higher after 2 weeks of light therapy in winter than during the following summer. CONCLUSIONS: Light treatment for 2 weeks in winter is only partially effective when compared to summer. Further studies will be necessary to assess if summer's light or other factors are the main contributors to this difference.     

Effect of melatonin on 24-hour rhythms of ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats

Young (50 days old) and old (18 months old) Sprague-Dawley rats were injected with mycobacterial Freund's adjuvant to produce an inflammatory disease of the joints and were studied the day before, and on days 6, 12 and 18 after injection. At every postinjection interval examined, old rats had significantly lower circadian amplitudes of pineal melatonin content. On day 18 of arthritis development, decreased levels of pineal melatonin were also seen in young rats. A second study, carried out 18 days after the injection of Freund's complete adjuvant and after 17 daily injections of 10 or 100 microg of melatonin in the evening, indicated that melatonin treatment restored the inflammatory response in old rats (assessed plethysmographically in hind paws) to the level found in young animals. In young rats, an inflammation-promoting effect of 100 microg melatonin could be demonstrated. As a consequence of the immune reaction, submaxillary lymph node and splenic ornithine decarboxylase activity (an index of lymph cell proliferation) augmented significantly, with acrophases of 24-hour rhythms in the afternoon for lymph nodes or in the morning for spleen. Mesor and amplitude of ornithine decarboxylase rhythm were lowest in old rats, while melatonin injection generally augmented its amplitude. Lymph node and splenic tyrosine hydroxylase activity (a presynaptic adrenergic marker) reached maximal values during early night hours while maximal values of [3H]acetylcholine synthesis (a presynaptic cholinergic marker) occurred during the afternoon in lymph nodes. Amplitude and mesor of these rhythms were lowest in old rats, an effect generally counteracted by melatonin treatment. The results suggest that inflammation is accompanied by an age-dependent, significant depression of pineal melatonin synthesis during adjuvant-induced arthritis and a decreased amplitude of the circadian rhythm of immune cell proliferation and autonomic activity in lymph nodes and spleen. These effects are counteracted by injection of melatonin, mainly in old rats.     

Exposure to long summer days affects the human melatonin and cortisol rhythms

Exposure of 8 human subjects in summer to a natural 16 h bright light photoperiod phase advanced the morning salivary melatonin decline and cortisol rise and shortened the nocturnal melatonin signal by 2 h relative to the winter patterns of the same subjects followed under a combined artificial and natural light 16 h photoperiod. The data suggest that summer days experienced from sunrise till sunset and not winter days with a combined artificial and natural light long photoperiod evoke a true long day response of the human circadian system.     

Winter depression and phototherapy. The state of the art

Winter depression (seasonal affective disorder, SAD) is characterised by a seasonal major depressive episode in the last 2 years. Hypersomnia, carbohydrate-craving and weight-gain are specific traits. These patients preferentially seek help from their General Practitioner. Current research on the aetiology of SAD covers fields such as retinal deficiency, phase-disturbance of the internal circadian rhythms given by internal oscillators and neuro-endocrinologically expressed disorders, assuming that melatonin is the main mediator of human circadian systems in the CNS. Disorders of neurotransmitters (serotonin) are another cue. Recent longitudinal studies show a prevalence of seasonal depressive symptoms in up to 10% of the general population. Among patients treated for depression, the prevalence of SAD is even higher. The SAD sex-ratio of women to men of 3 to 1 is found repeatedly. SAD becomes rare above the age of 50. Effectiveness of phototherapy is showed in nearly all controlled studies. Bright light appears to be most effective for patients with mild SAD. Hypersomnia and hyperphagia seem to be predictors of response to bright light therapy. To enable evaluation of unspecific therapeutic factors in phototherapy a true placebo for bright light-studies is still to be found. Possible new indications for photo therapy are currently being explored. Bright light for non- seasonal depression has been tested with encouraging results; panic disorders seem to have features in common with SAD; effectiveness in bulimia has been suggested and recently sleep disorders in elderly patients have been successfully and substantially diminished.     

Cross-reactivity between Ficus benjamina (weeping fig) and natural rubber latex

The efficacy of hydroxyzine and buspirone, controlled by placebo, was investigated in a double-blind, parallel group, multicentre study conducted in France and the UK. A total of 244 patients with generalised anxiety disorder in primary care was allocated randomly to treatments with hydroxyzine (12.5 mg morning and mid-day, 25 mg evening), buspirone (5 mg morning and mid-day, 10 mg evening) or placebo (three capsules/day) for 4 weeks, preceded by a 1-week single-blind placebo run-in and followed by 1-week single-blind placebo administration. Rating scales were applied on days -7,0,7,14, 12,28 and 35. Seventy percent of the patients were female, the average age was 41 +/- 11 years, and the mean Hamilton Anxiety Score at day 0 was 26.5 +/- 4.2. Only 31 of the 244 patients dropped out, but equally in the three groups. Intention-to-treat LOCF analyses on the primary variable showed a significant difference only between hydroxyzine and placebo with respect to improvement on the Hamilton Anxiety Scale (10.75 versus 7.23 points, respectively). Secondary variables such as CGI and self-ratings (HAD scale) showed both hydroxyzine and buspirone to be more efficacious than placebo. Thus, hydroxyzine is a useful treatment for GAD.     

Disorders of the sleep-wake cycle in adults

Adults have an intrinsic body clock which regulates a complex series of rhythms including sleep and wakefulness, fatigue and cognitive ability. This endogenous clock naturally runs more slowly than the solar day and is entrained to a 24-h rhythm primarily by the alternation of light and darkness. Jet lag, shift-work sleep disorder, and some of the chronic insomnias are caused by a temporal discrepancy of the body clock relative to the surrounding environment and social network. The underlying mechanisms and general management are described. Both bright light and melatonin therapy have potential in the management of these disorders. Traditionally, bright light therapy has been used to alleviate the depression associated with seasonal affective disorder. Melatonin has received much ill-formed publicity, it being claimed that it is a panacea and an 'antiageing' treatment. Both of these treatment approaches are reviewed.     

Involvement of trihydroxyconjugated bile salts in cholesterol assimilation by bifidobacteria

BACKGROUND: We assessed diurnal variation in the direction of mood switches in a sample of outpatients with rapid-cycling bipolar disorder who were on stable medication regimens. We predicted that patients would be more likely to switch from depression into mania or hypomania during the daytime hours and from mania/hypomania into depression overnight. METHOD: Fifteen patients with rapid-cycling bipolar disorder completed self-rated mood scales twice a day: once shortly after awakening and once at bedtime. Using 3 months of data for each patient, we performed categorical analyses (McNemar chi-square) to study the direction of mood switches between each day's morning and evening rating and between each evening rating and the subsequent morning rating. RESULTS: As predicted, switches that occurred between the morning and evening ratings were more likely to be from depression into mania/ hypomania or euthymia (64.3%) than in the opposite direction (35.6%; p < .0001). Similarly, switches that occurred between the evening rating and the next morning's ratings were more likely to be from mania/hypomania or euthymia into depression (64.8%) than in the opposite direction (35.2%; p < .0001). CONCLUSION: Extended wakefulness, exposure to light, increased activity, and/or endogenous rhythms could contribute to the elevation of mood during the course of the day. Sleep, darkness, reduced activity, and/or endogenous rhythms could contribute to the tendency to switch into depression overnight. Clinicians should attend to the time of day that clinical assessments are performed in patients with rapid-cycling bipolar disorder. Potential therapeutic implications include the use of light or activity during depression and use of induced sleep or exposure to darkness during mania/hypomania.     

Effects of light treatment on sleep structure in seasonal affective disorder

Twelve outpatients with seasonal affective disorder (depression, winter type) were treated by 1 h of bright light exposure for five mornings. The intervention produced a significant reduction in depression scores, but no change was seen in the sleep electroencephalographic variables recorded after light treatment. Significant changes were seen, however, in ratings of subjective sleepiness. The acrophase of the circadian sleepiness rhythm was phase advanced, the mean level of the sleepiness rhythm was diminished, and the mean values of sleepiness scores were reduced at 8 and 10 a.m. This minimal influence of bright light on sleep structure is unlikely to explain the well-documented antidepressant effect.     

Effects of meta-chlorophenylpiperazine infusions in patients with seasonal affective disorder and healthy control subjects. Diurnal responses and nocturnal regulatory mechanisms

BACKGROUND: Multiple lines of evidence suggest that brain serotonergic systems may be disturbed in seasonal affective disorder (SAD). Previously, we found that the serotonergic agent meta-chlorophenylpiperazine (m-CPP) produced increases in activation and euphoria in depressed patients with SAD, but not in patients with SAD following light treatment or in the summer, nor in healthy control subjects in any condition. In the present study, we attempted to replicate and extend this finding using better methods. METHODS: Seventeen outpatients with SAD and 15 control subjects underwent successive 3-week periods of bright light treatment and light avoidance in a randomized order. During the third week of each condition, on 2 different occasions, subjects were admitted to the hospital for a night of sleep (core temperatures were recorded), followed by infusions of m-CPP (0.08 mg/kg) or placebo the next morning. Dependent measures included the 24-item National Institute of Mental Health Self-Rating Scale, plasma corticotropin, cortisol, prolactin, growth hormone, and norepinephrine concentrations, and core temperatures. RESULTS: Meta-chlorophenylpiperazine produced (1) significant increases in "activation-euphoria" ratings only in depressed patients with SAD in the untreated condition and (2) blunted corticotropin and norepinephrine responses in patients with SAD compared with controls across both light treatment conditions. In both groups, light treatment was associated with significant reductions in nocturnal core temperatures, which were correlated with similarly significant reductions in mean diurnal growth hormone concentrations. In patients with SAD, (1) the reductions in nocturnal core temperatures also were correlated with the reductions in baseline depression ratings and (2) the reductions in mean growth hormone concentrations were significantly smaller compared with controls. CONCLUSIONS: The abnormal m-CPP-induced activation-euphoria responses represent a replicated state marker of winter depression in patients with SAD. The blunted m-CPP-induced responsiveness of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system may represent traitlike abnormalities. The improvements in mood following light treatment in patients with SAD seem to be associated with the lowering of nocturnal core temperatures. The findings, although not easily explained based on a uniform abnormality of serotonin receptors, are nonetheless compatible with the notion that selected regions of the central nervous system are deficient in serotonin transmission during winter depression.     

Adjustment of the human melatonin and cortisol rhythms to shortening of the natural summer photoperiod

Fifteen human subjects were exposed to natural outdoor summer light from 0415 h until 2000 h for 4 days and then from 0800 h until 1600 h for another 4 days. Following shortening of the natural summer photoperiod, times of the morning salivary melatonin decline and cortisol rise did not change whereas the time of the evening melatonin rise phase advanced by about 1.5 h within 1 day and further did not change significantly. Consequently, the melatonin signal duration extended markedly within 1 day. The data show that the compressed melatonin rhythm waveform in humans experiencing a long natural summer photoperiod from sunrise until sunset may change rapidly following a shortening of the photoperiod.