Depressive mood and circadian rhythms disturbances as outcomes of seasonal affective disorder treatment: A systematic review.

BACKGROUND: The present systematic review was aimed at critically summarizing the evidence about interventions focused on circadian rhythms and mood symptoms in seasonal affective disorder (SAD). METHODS: A systematic search of the electronic databases PUBMED, PsycINFO and Web of Science was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Original papers reporting data about the effects of treatments on both mood and circadian rhythms disturbances in SAD patients were considered for inclusion. The quality of the evidence provided by the eligible studies was assessed using the Revised Cochrane Risk of Bias Tool (RoB 2.0) and the Cochrane Risk of Bias in Non-Randomized Studies of Interventions Tool (ROBINS-I). RESULTS: Forty papers were deemed eligible for the systematic review. The evidence of treatment outcomes referring to circadian disturbances was not robust. Despite this, bright light therapy (BLT) demonstrates to phase-advance delayed rhythms and to improve sleep-wake disorders. As for mood symptoms, both BLT and selective serotonin reuptake inhibitors (SSRIs) show evidence of efficacy. The possible connection between improvements of mood symptoms and changes in circadian outcomes seems controversial. LIMITATIONS: The included studies presented considerable methodological heterogeneity, small sample sizes and non-optimal sample selection. CONCLUSIONS: The effectiveness of BLT in depressive symptoms and circadian disturbances of SAD was outlined by the present systematic review. The evidence about other biological and pharmacological treatments, although promising, should be replicated. A multifactorial etiopathogenesis could explain the heterogeneous clinical presentations of SAD and the complex link between mood and circadian symptoms.

Enhanced inflammatory and T-helper-1 type responses but suppressed lymphocyte proliferation in patients with seasonal affective disorder and treated by light therapy.

BACKGROUND: Animals show seasonal changes in the endocrine and immune system in response to winter stressors. Even though increased inflammation has been implicated in the pathophysiology of depression, whether immune disorder is a key mediator in seasonal affective depression (SAD) is unknown. Here, we hypothesized that short photoperiods in winter may induce inflammatory response, which contributes to SAD, and that light treatments should normalize immune function and improve depressive symptoms. METHODS: Twenty patients with a diagnosis of SAD, and a score on the HAM-29 of 20 or higher were recruited for this study. Twenty-one healthy subjects with no personal and family history of psychiatric disorder were matched to patients according to age and sex. Patients and controls were sampled during winter between November and January, inclusive. A subset of SAD patients (N=13) was re-sampled after 4 weeks of light therapy. Blood samples were assayed for macrophage activity, lymphocyte proliferation and cytokine release. RESULTS: SAD patients showed significantly higher macrophage activity and lower lymphocyte proliferation in winter compared to healthy subjects. The concentrations of macrophage-produced proinflammatory cytokines interleukin-1ß and tumour necrosis factor-α, and T-helper (Th)-1 produced cytokine, interferon-γ were all significantly increased. In contrast, no significant changes in Th2-produced cytokines were observed. Light therapy significantly improved depressive scores, which was associated with attenuation of decreased lymphocyte functions, increased macrophage activity and level of proinflammatory cytokines. CONCLUSION: SAD patients have increased macrophage and Th1 type responses in winter, and light therapy normalized immune functions and depressive symptoms. These results support an inflammatory hypothesis for SAD and an immunomodulatory role of light therapy.

Short-term effects of bright light therapy in adults with chronic nonspecific back pain: a randomized controlled trial.

OBJECTIVE: The present trial evaluated incorporation of bright light therapy in the treatment of chronic nonspecific back pain (CNBP). DESIGN: A prospective, randomized, controlled, multicenter, open design with three parallel trial arms was used. SETTING: Subjects received a novel therapeutic, an expected therapeutic ineffective low dose, or no light exposure at three different medical centers. PATIENTS: A total of 125 CNBP patients reporting pain intensity of ≥3 points on item 5 of the Brief Pain Inventory (BPI) were included. INTERVENTION: Over 3 weeks, 36 active treatment, 36 placebo controls, and 33 controls received 3 or no supplementary light exposures of 5.000 lx or 230 lx, respectively. OUTCOME MEASURES: Changes in self-reported scores of pain intensity (BPI sub-score 1) and depression (Hospital Anxiety and Depression Questionnaire) were the primary outcome measures. Secondary outcome measures were changes in self-reported overall pain sensation (BPI total score), grade of everyday life impairment (BPI sub-score 2), mood (visual analog scale), and well-being (World Health Organization-Five Well-Being Index). RESULTS: Changes in pain intensity were higher (1.0 [0.8-1.6]) in the bright light group compared with controls (0.3 [-0.1-0.8]; effect size D = 0.46). Changes in the depression score were also higher in the intervention group (1.5 [0.0-2.5]) compared with controls (0.0 [0.0-2.0]; effect size D = 0.86). No differences were seen in change scores between intervention vs sham group. CONCLUSION: The present randomized controlled trial shows that light therapy even in low dose could improve depressive symptoms and reduce pain intensity in CNBP patients. Further research is needed for optimizing parameters of frequency, dose, and duration of therapeutic light exposure.

Recognizing emotions in faces: effects of acute tryptophan depletion and bright light.

In healthy never-depressed individuals, acute tryptophan depletion (ATD) may selectively decrease the accurate recognition of fearful facial expressions. Here we investigated the perception of facial emotions after ATD in more detail. We also investigated whether bright light, which can reverse ATD's mood-lowering effect, can also reverse its effect on the perception of facial emotions. On two separate test days, spent in a room that was either bright (n = 14) or dim (n = 16), healthy never-depressed women completed a facial emotion perception task six hours after ingesting tryptophan-deficient and balanced amino acid mixtures. Treatments were administered double blind and in randomized order using a crossover design. In dim light ATD decreased recognition accuracy of anger, disgust, and surprise. The labeling of fear and sadness was not affected. In bright light no effects of ATD were seen. Bright light was identified as a potential confounding factor in task performance. The effects of ATD on facial emotion perception may be less emotion-specific than thought previously, and occurred in a direction opposite to what might be expected based on theories of mood-congruent bias.

[Less need for insulin, a surprising effect of phototherapy in insulin-dependent diabetes mellitus]. / Verminderde insulinebehoefte; een verrassend effect van lichttherapie bij insulineafhankelijke diabetes mellitus.

A 40-year-old woman with insulin-dependent diabetes mellitus was treated successfully with phototherapy for a seasonal affective disorder. Following sessions of phototherapy she developed hypoglycaemias and required less insulin. A review of the literature showed that melatonin has an inhibiting effect on insulin sensitivity. The melatonin secretion, which is suppressed by phototherapy, may cause an immediate decrease in the plasma glucose levels. This decrease may well be important for patients with insulin-resistant diabetes mellitus and seasonal affective disorder.

Enhanced serotonin transporter function during depression in seasonal affective disorder.

Decreased synaptic serotonin during depressive episodes is a central element of the monoamine hypothesis of depression. The serotonin transporter (5-HTT, SERT) is a key molecule for the control of synaptic serotonin levels. Here we aimed to detect state-related alterations in the efficiency of 5-HTT-mediated inward and outward transport in platelets of drug-free depressed patients suffering from seasonal affective disorder (SAD). 5-HTT turnover rate, a measure for the number of inward transport events per minute, and tyramine-induced, 5-HTT-mediated outward transport were assessed at baseline, after 4 weeks of bright light therapy, and in summer using a case-control design in a consecutive sample of 73 drug-free depressed patients with SAD and 70 nonseasonal healthy controls. Patients were drug-naive or medication-free for at least 6 months prior to study inclusion, females patients were studied in the follicular phase of the menstrual cycle. All participants were genotyped for a 5-HTT-promoter polymorphism (5-HTTLPR) to assess the influence of this polymorphism on 5-HTT parameters. Efficiency of 5-HTT-mediated inward (p=0.014) and outward (p=0.003) transport was enhanced in depressed patients. Both measures normalized toward control levels after therapy and in natural summer remission. Changes in outward transport showed a clear correlation with treatment response (rho=0.421, p=0.001). Changes in inward transport were mediated by changes in 5-HTT transport efficiency rather than affinity or density. 5-HTTLPR was not associated with any of the 5-HTT parameters. In sum, we conclude that the 5-HTT is in a hyperfunctional state during depression in SAD and normalizes after light therapy and in natural summer remission.

[Association of obesity and depression]. / Az elhízás és a depresszió kapcsolatai.

It has been long known that the frequency of overweight and obese people is higher among depressed and bipolar patients than in the general population. The marked alteration of body weight (and appetite) is one of the most frequent of the 9 symptoms of major depressive episode, and these symptoms occur during recurrent episodes of depression with a remarkably high consequence. According to studies with representative adult population samples, in case of obesity (BMI over 30) unipolar or bipolar depression is significantly more frequently (20-45%) observable. Since in case of depressed patients appetite and body weight reduction is observable during the acute phase, the more frequent obesity in case of depressed patients is related (primarily) not only to depressive episodes, but rather to lifestyle factors, to diabetes mellitus also more frequently occurring in depressed patients, to comorbid bulimia, and probably to genetic-biological factors (as well as to pharmacotherapy in case of medicated patients). At the same time, according to certain studies, circadian symptoms of depression give rise to such metabolic processes in the body which eventually lead to obesity and insulin resistance. According to studies in unipolar and bipolar patients, 57-68% of patients is overweight or obese, and the rate of metabolic syndrome was found to be between 25-49% in bipolar patients. The rate of metabolic syndrome is further increased by pharmacotherapy. Low total and HDL cholesterol level increases the risk for depression and suicide and recent studies suggest that omega-3-fatty acids possess antidepressive efficacy. Certain lifestyle factors relevant to healthy metabolism (calorie reduction in food intake, regular exercise) may be protective factors related to depression as well. The depression- and possibly suicide-provoking effect of sibutramine and rimonabant used in the pharmacotherapy of obesity is one of the greatest recent challenges for professionals and patients alike.

Evolving applications of light therapy.

The psychiatric intervention, light therapy, grew from an intensive 25-year research focus on seasonal affective disorder (SAD). Dosing and timing strategies have been honed to optimize the antidepressant effect, and efficacy relative to placebo has provided the evidence base for widespread implementation. A persistent question has been whether the model system for SAD has wider utility for psychiatric disturbance, even beyond depression. The circadian phase-shifting capacity of timed light exposure is universal, and chronobiological factors are at play across the disease spectrum. Recent promising initiatives extend to light treatment for nonseasonal major depressive disorder and bipolar depression, including drug- and electroconvulsive therapy-resistant cases. With light therapy, patients with antepartum depression may find an alternative to medication during pregnancy. Cognitive improvement under light therapy has been noted in adult attention deficit hyperactivity disorder. Motor function in Parkinson's disease has improved in parallel with the antidepressant effect of light therapy. The rest-activity disturbance of elderly dementia has been partially allayed under light therapy. In a new initiative, three major chronotherapeutic inventions-light therapy, sleep deprivation (wake therapy) and sleep time displacement (sleep phase advance therapy) are being combined to snap hospitalized patients out of deep depression and maintain long-term improvement.

Co-occurring SAD symptomatology and schizophrenia at high latitude: a pilot study.

OBJECTIVES: Recent research investigates major depression with seasonal pattern, also called seasonal affective disorder (SAD), depression in schizophrenia and seasonality in schizophrenia, but there exits limited research investigating SAD in schizophrenia. This study documents co-occurring SAD symptomatology in patients with schizophrenia at high latitude. STUDY DESIGN: Clinical cross-sectional study of patients with schizophrenia attending treatment centres in Alaska. METHOD: Twenty-eight patients completed a structured interview assessing seasonal patterns in mood, depression, negative symptoms of schizophrenia and alcohol use. RESULTS: Thirty-six percent of patients with schizophrenia met the criteria for SAD used in previous general population research on SAD in Alaska. When a presence of major depressive episode was confirmed using a structured clinical interview for depression in schizophrenia, the rate was 25%. Severity of SAD symptoms was greatest among patients with alcohol-abuse history. CONCLUSIONS: Co-occurring SAD symptomatology was identified in this extreme latitude sample of patients with schizophrenia. The frequency and severity of symptomatology was greater than found in a general population study of SAD conducted in Alaska using identical criteria. SAD may be under-diagnosed in schizophrenia at moderate and extreme latitudes, highlighting clinical assessment considerations, potential utility of bright light therapy and the need for additional research.

Changes in allergy symptoms and depression scores are positively correlated in patients with recurrent mood disorders exposed to seasonal peaks in aeroallergens.

Although growing evidence supports an association between allergy, allergens and depression, it remains unknown if this relationship is between "states" (possible triggers) or "traits" (possible vulnerabilities). We hypothesized that patients with recurrent mood disorders who are sensitized to tree pollen (as determined by allergen specific IgE antibodies), in comparison to those who are not sensitized, would report larger negative changes in mood during exposure to tree pollen in spring. We also hypothesized that differences between high and low tree pollen periods in self reported allergy symptoms would correlate positively with differences in self reported depression scores. We present 1-year preliminary data on the first 51 patients with unipolar or bipolar disorder (age: 19-63 years, 65% female, twelve patients were tree-pollen IgE positive). Ratings of mood and allergic disease status were performed once during the peak airborne pollen counts and once during the period of low airborne pollen counts, as reported by two local pollen counting stations. Linear regression models were developed to examine associations of changes in depression scores (dependent variable) with tree pollen sensitization, changes in the allergy symptom severity score, adjusted for gender and order of testing. We did not confirm the hypothesized relationship between a specific tree pollen sensitization and changes in mood during tree pollen exposure. We did confirm the hypothesized positive relationship between the changes in allergy symptoms and changes in subjects' depression scores (adjusted p<0.05). This result is consistent with previous epidemiological evidence connecting allergy with depression, as well as our recent reports of increased expression of cytokines in the prefrontal cortex in victims of suicide and in experimental animals sensitized and exposed to tree pollen. A relationship between changes in allergy symptom scores and changes in depression scores supports a state-level rather than only trait-level relationship, and thus lends optimism to future causality-testing interventional studies, which might then lead to novel preventative environmental interventions in mood disorders.

Sleep in seasonal affective disorder patients in forced desynchrony: an explorative study.

The majority of winter-type seasonal affective disorder (SAD) patients complain of hypersomnia and daytime drowsiness. As human sleep is regulated by the interaction of circadian, ultradian and homeostatic processes, sleep disturbances may be caused by either one of these factors. The present study focuses on homeostatic and ultradian aspects of sleep regulation in SAD. Sleep was recorded polysomnographically in seven SAD patients and matched controls subjected to a 120-h forced desynchrony protocol. In time isolation, subjects were exposed to six 20-h days, each comprising a 6.5-h period for sleep. Patients participated while being depressed, while remitted after light therapy and in summer. Controls were studied in winter and in summer. In each condition, the data of each subject were averaged across all recordings. Thus, the influence of the effects of the circadian pacemaker on sleep was excluded mathematically. The comparison of patients with controls and with themselves in the various conditions revealed no abnormalities in homeostatic parameters: sleep stage variables, relative power spectra and time courses of power in various frequency bands across the first three non-rapid eye movement-rapid eye movement (NREM-REM) cycles showed no differences. The data suggest that homeostatic processes are not involved in the disturbance of sleep in SAD.

Is dawn simulation effective in ameliorating the difficulty awakening in seasonal affective disorder associated with hypersomnia?

BACKGROUND: Patients with winter depression, (seasonal affective disorder, SAD) frequently complain of difficulty awakening in the morning. Dawn simulation has been found effective in treating SAD, but its effect on difficulty awakening has not been assessed. METHODS: Fifty medication-free patients with SAD associated with hypersomnia were randomized to receive either 1 week of dawn simulation (250 lux) or a dim (0.2-2 lux) placebo signal. The patients assessed their level of drowsiness upon awakening during the baseline week and during the treatment week using the Stanford sleepiness scale (SSS). A psychiatrist rated difficulty awakening after the baseline week and after the treatment week. RESULTS: Dawn simulation lowered both the difficulty awakening score (P<0.05) and the SSS score (P<0.05) compared to the placebo dawn signal. LIMITATIONS: Replication is necessary. No biological markers of circadian phase were measured. CONCLUSIONS: Compared to a placebo condition, dawn simulation appears effective in decreasing both prospectively assessed morning drowsiness and retrospectively assessed difficulty awakening. The symptom of difficulty awakening is consistent with the phase delay hypothesis of SAD. Assessment of difficulty awakening could prove useful in the evaluation of SAD.

Prevalence of premenstrual dysphoric disorder in female patients with seasonal affective disorder.

BACKGROUND: Both seasonal affective disorder/winter type (SAD) and premenstrual dysphoric disorder (PMDD) are cyclical disorders characterized by so-called atypical depressive symptoms. In the present study we compared the point prevalence rates of PMDD between a sample of premenopausal female patients suffering from SAD and healthy female controls. METHODS: Forty-six female patients with SAD and 46 healthy controls were included in our study. All subjects underwent a semistructured clinical interview according to DSM IV criteria and completed the Seasonal Pattern Assessment Questionnaire. PMDD was diagnosed in a self-rating interview for PMDD according to DSM IV criteria. To verify the diagnosis of PMDD, all patients were followed up in stable summer remission using daily self-rating scales for two full menstrual cycles. RESULTS: Patients with SAD fulfilled significantly more often the diagnostic criteria for PMDD than female healthy controls (46% vs. 2%, respectively; chi-square: P<0.001). CONCLUSIONS: These results provide preliminary evidence for a high point prevalence rate of PMDD in premenopausal females with SAD. CLINICAL IMPLICATIONS: It would be worthwhile to investigate whether an additional diagnosis of PMDD has an impact on the clinical outcome and the response to bright light therapy in female patients with SAD.

Seasonal affective symptoms in adults with residual attention-deficit hyperactivity disorder.

There is evidence from clinical, epidemiological, and neuroimaging studies that attention-deficit hyperactivity disorder (ADHD) and seasonal affective disorder (SAD) may have several features in common. To assess seasonal affective symptoms in adults with ADHD, 115 individuals attending an adult ADHD clinic in Toronto, Ontario, Canada were asked to complete the Seasonal Pattern Assessment Questionnaire (SPAQ). From this clinic population of 115, a total of 56 completed SPAQs were returned. Assuming that all individuals failing to complete the SPAQ were nonseasonal and depending on which case-finding criteria were used, the rate of SAD in the overall clinic sample was estimated at either 10.4% (Terman criteria) or 19.1% (criteria of Kasper et al.). These prevalence rates are significantly greater than the rates reported in large population surveys at similar latitudes. There was an apparent relationship between female gender, impulsive-subtype ADHD, and seasonality. Future studies to examine whether core symptoms of ADHD fluctuate across the seasons and to assess the efficacy of light therapy in "seasonal" ADHD patients would be of great theoretical and clinical interest.

Hypericum in seasonal affective disorder (SAD).

Volunteers from the membership of the SAD Association took part in a postal survey, before and after eight weeks' treatment with Hypericum (Kira), using an 11-item rating scale. The maximum score is 44 and the mean score in 168 patients using Kira alone was 21.3. This fell to 13 at endpoint (p < 0.001). The corresponding figures for 133 patients using Kira + light therapy were 20.6 and 11.8, respectively (p < 0.001). In both groups, there was significant improvement in anxiety, loss of libido and insomnia. There were no significant between-group differences on any measure except that improvement in sleep was greater in the Kira + light group (p < 0.01). On the results of this survey, Hypericum would appear to be an effective treatment for SAD.

Cluster headache and periodic affective illness: common chronobiological features.

Many of the seasonal changes occurring in animals appear to be associated with photoperiodic modifications, and particularly with the duration of the phases of exposure to light and dark. The integration of these processes is made possible by the normal functioning of biological oscillators or synchronizers, presumably located at the hypothalamic level. Cluster headache (CH), seasonal affective disorder (SAD) and bipolar mood disorders are conditions bearing numerous analogies, particularly as regards the temporal pattern of disturbances, the nature of predisposing or precipitating factors, the peculiar relationship with sleep, the neuroendocrine findings, and the clinical response to current treatments. The secretion of melatonin, which is influenced by the light/dark cycle, displays a bimodal pattern, which is likely to be dictated by the activity of distinct synchronizers for light and dark. Changes in the secretory pattern of this neurohormone have also been documented in both CH and SAD. The possibility of normalizing the secretory rhythm of melatonin by means of phototherapy in SAD, and the therapeutic use of the hormone to prevent the recurrence of active phases in CH, represent further interesting similarities between these two disorders. Melatonin, acting as a unique neuroendocrine transductor of photic inputs, may therefore be viewed as a marker of dyschronic disease to be used in patients suffering from CH and affective illness, for both diagnostic purposes and to assess the response to pharmacological and non pharmacological treatments.