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Objectives: To determine the efficacy and safety of blue-light therapy in seasonal and non-seasonal major depressive disorder (MDD), by comparison to active and inactive control conditions., Methods: We searched Web of Science, EMBASE, Medline, PsycInfo, and Clinicaltrials.gov through January 17, 2022, for randomized controlled trials (RCTs) using search terms for blue/blue-enhanced, light therapy, and depression/seasonal affective disorder. Two independent reviewers extracted data. The primary outcome was the difference in endpoint scores on the Structured Interview Guide for the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD) or the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) between blue light and comparison conditions. Secondary outcomes were response (≥ 50% improvement from baseline to endpoint on a depression scale) and remission rates (endpoint score in the remission range)., Results: Of 582 articles retrieved, we included nine RCTs ( n  = 347 participants) assessing blue-light therapy. Seven studies had participants with seasonal MDD and two studies included participants with non-seasonal MDD. Four studies compared blue light to an inactive light condition (efficacy studies), and five studies compared it to an active condition (comparison studies). For the primary outcome, a meta-analysis with random-effects models found no evidence for the efficacy of blue-light conditions compared to inactive conditions (mean difference [MD] = 2.43; 95% confidence interval [CI], -1.28 to 6.14, P  = 0.20); however, blue-light also showed no differences compared to active conditions (MD = -0.11; 95% CI, -2.38 to 2.16, P  = 0.93). There were no significant differences in response and remission rates between blue-light conditions and inactive or active light conditions. Blue-light therapy was overall well-tolerated., Conclusions: The efficacy of blue-light therapy in the treatment of seasonal and non-seasonal MDD remains unproven. Future trials should be of longer duration, include larger sample sizes, and attempt to better standardize the parameters of 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-1β 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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We have earlier reported that season of birth interacts with the hypofunctional 7-repeat (7R) allele of the dopamine-4 receptor gene (DRD4) to promote weight gain and obesity in women with seasonal affective disorder (SAD). This study examined whether this gene-environment interaction influences body weight regulation in women with bulimia nervosa (BN). In 188 female probands with BN, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) using season-of-birth, DRD4 genotype (7R present/absent), and past history of anorexia nervosa (yes/no) as independent variables, and age at maximum weight as the co-variate. Consistent with our SAD study, the birth-season x DRD4 interaction was a significant predictor of maximal BMI. Although in SAD, the spring-birth/7R+ group had markedly elevated maximal BMIs and high rates of obesity, in this BN sample, the fall-birth/7R+ group exhibited the highest BMI values (N=17: mean maximal BMI=28.2 kg/m(2) (SE 0.9) vs 25.2 kg/ m(2) (SE 0.3) for all other probands combined (N=171); p=0.002). The lifetime rate of obesity (BMI>30) was also higher in the fall-birth/7R+ vs 'other' group (29.9 vs 8.8%, respectively, p=0.008). These data offer further evidence that season of birth interacts with the 7R allele of DRD4 to influence body weight regulation in female overeating populations.

Background: Retinal sensitivity anomalies have been reported in patients affected by seasonal affective disorder (SAD). We used the electroretinogram (ERG) to assess seasonal change in retinal function in patients with SAD and healthy participants, as well as in patients following 4 weeks of light therapy., Methods: ERG assessments were obtained in 22 SAD patients (2 men, 20 women, mean age 31 +/- 9 years) in the fall/winter season before and after 2 and 4 weeks of light therapy and in summertime. Matched healthy participants (2 men, 14 women; mean age 29 +/- 8 years) were evaluated once in the fall/winter and once in summer. The 29-item Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorder version was administered. Standard ERG parameters were derived from the photopic and scotopic luminance response functions. Salivary melatonin concentration during ERG was assessed in both groups but during fall/winter assessments only., Results: A significantly lower cone ERG maximal amplitude and lower rod sensitivity was found in SAD patients before light therapy compared with healthy participants. Following 4 weeks of light therapy, a normalization of cone and rod ERG function occurred. ERG parameters in the summer and melatonin concentrations in fall/winter were not significantly different between groups., Conclusions: Depressed patients with SAD demonstrate ERG changes in the winter compared with healthy comparison subjects with lower rod retinal sensitivity and lower cone maximal amplitude. These changes normalized following 4 weeks of light therapy and during the summer, suggesting that ERG changes are state markers for SAD.

Background: Seasonal affective disorder (SAD) consists of recurrent major depressive episodes in the fall/winter with remissions in spring/summer., Method: A Medline search was conducted to identify studies relating to clinical management of SAD using the Medical Subject Heading, seasonal affective disorder, and key words, depress* and season*, focusing on studies published in the past 10 years. The Cochrane library of systematic reviews was also searched for relevant studies., Results: A careful history is important to make the diagnosis and differentiate SAD from other similar conditions such as subsyndromal SAD and atypical depression. Seasonal patterns with winter worsening are also recognized in "nonseasonal" depression as well as many other psychiatric conditions, and comorbidity with SAD is common. The pathophysiology of SAD seems to be heterogeneous as research on circadian, neurotransmitter function and genetic hypotheses have shown discrepant results. A dual vulnerability model with differential loading on separate seasonal and depression factors has been proposed to explain these findings. Recent systematic reviews have shown that light therapy is an efficacious and well-tolerated treatment for SAD. There is also evidence for efficacy of pharmacotherapy to treat and prevent SAD. Clinical studies show equal effectiveness with light and antidepressants, so patient preference should be considered in the selection of initial treatment. Dawn stimulation, negative air ions, exercise and cognitve behaviour therapy are under investigation and may also be helpful treatments for SAD., Conclusions: SAD is a common condition with significant psychosocial impairment. Clinicians should be vigilant in recognizing seasonal patterns of depressive episodes because there are effective, evidence-based treatments for SAD.

Background: Recent research has emphasized that the human circadian rhythm system is differentially sensitive to short wavelength light. Light treatment devices using efficient light-emitting diodes (LEDs) whose output is relatively concentrated in short wavelengths may enable a more convenient effective therapy for Seasonal Affective Disorder (SAD)., Methods: The efficacy of a LED light therapy device in the treatment of SAD was tested in a randomized, double-blind, placebo-controlled, multi-center trial. Participants aged 18 to 65 with SAD (DSM-IV major depression with seasonal pattern) were seen at Baseline and Randomization visits separated by 1 week, and after 1, 2, 3 and 4 weeks of treatment. Hamilton Depression Rating Scale scores (SIGH-SAD) were obtained at each visit. Participants with SIGH-SAD of 20 or greater at Baseline and Randomization visits were randomized to active or control treatment: exposure to the Litebook LED treatment device (The Litebook Company Ltd., Alberta, Canada) which delivers 1,350 lux white light (with spectral emission peaks at 464 nm and 564 nm) at a distance of 20 inches or to an inactivated negative ion generator at a distance of 20 inches, for 30 minutes a day upon awakening and prior to 8 A.M., Results: Of the 26 participants randomized, 23 completed the trial. Mean group SIGH-SAD scores did not differ significantly at randomization. At trial end, the proportions of participants in remission (SIGH-SAD less than 9) were significantly greater (Fisher's exact test), and SIGH-SAD scores, as percent individual score at randomization, were significantly lower (t-test), with active treatment than with control, both in an intent-to-treat analysis and an observed cases analysis. A longitudinal repeated measures ANOVA analysis of SIGH-SAD scores also indicated a significant interaction of time and treatment, showing superiority of the Litebook over the placebo condition., Conclusion: The results of this pilot study support the hypothesis that light therapy with the Litebook is an effective treatment for SAD., Trial Registration: Clinicaltrials.gov: NCT00139997.

Background: Although a host of studies have now examined the relationship between quality of life (QoL) and non-seasonal depression, few have measured QoL in seasonal affective disorder (SAD). We report here on results from the Can-SAD trial, which assessed the impact of treatment with either antidepressant medication or light therapy upon QoL in patients diagnosed with SAD., Method: This Canadian double-blind, multicentre, randomized controlled trial included 96 patients who met strict diagnostic criteria for SAD. Eligible patients were randomized to 8 weeks of treatment with either: (1) 10000 lux light treatment and a placebo capsule or (2) 100 lux light treatment (placebo light) and 20 mg fluoxetine. QoL was measured with the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Medical Outcomes Study (MOS) Short-Form General Health Survey (SF-20) at baseline and 8 weeks., Results: Both intervention groups showed significant improvement in QoL over time with no significant differences being detected by treatment condition. Q-LES-Q scores increased significantly in seven of eight domains, with the average scores rising from 48 x 0 (S.D.=10 x 7) at baseline to 69 x 1 (S.D.=15 x 6) at week 8. Treatment-related improvement in QoL was strongly associated with improvement in depression symptoms., Discussion: Patients with SAD report markedly impaired QoL during the winter months. Treatment with light therapy or antidepressant medication is associated with equivalent marked improvement in perceived QoL. Studies of treatment interventions for SAD should routinely include broader indices of patient outcome, such as the assessment of psychosocial functioning or life quality.

Non-adherence with antidepressant medication regimens is now recognised as a substantial problem when evaluating depression outcome. Given the behavioural demands of light treatment (LT), it might be expected that non-adherence would be even more pronounced in LT, a form of intervention for seasonal affective disorder (SAD). However, little research has focused upon the extent to which patients in light treatment protocols adhere to set regimens. Nineteen patients with SAD were allocated to either treatment with bright white light (intervention) or dim red light (control condition) in a four-week protocol. Light exposure was estimated automatically (without participants' knowledge) with elapsed time meters built into the light box. Daily diaries were also used to measure self-reported light box use. Participants were instructed to use the light box for 30 min each day during week 1, 45 during week 2 and one hour during weeks 3 and 4 (total duration of prescribed light exposure 1365 min). The results indicated that mean duration of light box operation for the entire sample was 59.3% of the prescribed 1365 min. Six of nineteen (31.6%) patients dropped out of treatment. Amongst those completing treatment, adherence to the prescribed duration of exposure averaged 83.3% (S.D.=31.4). A trend was found for the intervention condition to generate a lower dropout rate, as well as a trend for the degree of adherence to be greater in the intervention condition. Importantly, there was no association between adherence as measured automatically and the higher rates of self-reported adherence as measured in diaries. In summary, the results of this pilot study suggest that adherence with light treatment is of a similar order of magnitude to antidepressant medication adherence. Patient self-report was found to be unrelated to objectively estimated duration of light box use, a finding with significant research and clinical implications. Future research studies should routinely measure and evaluate adherence with light therapy and evidence-based techniques for maximising treatment adherence should be incorporated into routine clinical practice.

Recurrent major depressive disorder with regular seasonal patterns, commonly known as seasonal affective disorder (SAD), has evoked substantial research in the last two decades. It is now recognised that SAD is a common condition with prevalence rates between 0.4% and 2.9% of the general population, and that patients with SAD experience significant morbidity and impairment in psychosocial function. There is good evidence that bright light therapy and antidepressant medications are effective for the short-term treatment of SAD; however, given that SAD is characterised by recurrent major depressive episodes, long-term and maintenance treatment must be considered. Unfortunately, there are few studies of longer term (>8 weeks) and maintenance (preventative) treatments for SAD. The weight of evidence suggests that light therapy usually needs to be continued daily throughout the winter season because of rapid relapse when light is stopped too early in the treatment period. However, some studies support the use of antidepressants to continue the response from a brief (1-2 weeks) course of light therapy early in the depressive episode, as soon as the first symptoms emerge in autumn. Only small studies have examined preventative treatment (before onset of symptoms) with light therapy, all of which have methodological limitations. The best evidence for preventative treatment in SAD comes from antidepressant studies. Three large, randomised, placebo-controlled studies have shown that preventative treatment with bupropion XL reduces the recurrence rate of depressive episodes in patients with SAD. Given the limitations in the evidence base and the inconsistent recurrence rate of winter depressive episodes, clinical recommendations for long-term and preventative treatment must individualise treatment choices and weigh potential benefits against possible adverse effects.

We have recently described an association between the hypofunctional 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), weight gain, and obesity in women with seasonal affective disorder (SAD). In the current study, we examined whether season-of-birth might interact with the 7R allele to influence body weight regulation in SAD. In 182 female probands with SAD, we performed an analysis of covariance predicting maximum lifetime body mass index (BMI) with both the exon-3 variable number of tandem repeat polymorphism of DRD4 and season-of-birth as independent variables, and age as the covariate. The overall model was highly significant (F = 4.42, df = 8, 173, p < 0.0001) with season-of-birth predicting maximal lifetime BMI both on its own and in its interaction with the 7R allele. The latter finding was attributable to 7-repeat carriers born in the spring (N = 17), who had a mean maximal lifetime BMI of 33.7 kg/m2 (SD 8.6), compared to 26.7 kg/m2 (SD 5.4) for all other probands combined (N = 165) (F = 20.01, df = 1, 179, p < 0.0001). The lifetime rate of obesity (maximal BMI > 30 kg/m2) was also significantly higher in the 7R/spring birth group (9/17=52.9% vs 32/165=19.4%; chi2 = 9.94, df = 1, p = 0.002; odds ratio = 4.68, 95% CI = 1.67-13.07). These data may reflect a novel gene-environment interaction, during early brain development, which establishes an increased risk for obesity in women with SAD. Although the mechanism for season-of-birth effects in psychiatric disorders is unknown, a characteristic pattern of melatonin exposure during the second and third trimesters may be of particular relevance in this study population. We speculate that these data may reflect the vestigial expression of a seasonal thrifty phenotype that contributed to the positive selection of the 7R allele over the past 40,000 years.

Background: Personality factors have been implicated in seasonal affective disorder (SAD). The present study investigated the relationship between the five-factor model of personality (neuroticism, extraversion, openness, agreeableness, conscientiousness) and SAD., Methods: Ninety-five patients with SAD completed personality measures before and after treatment in a clinical trial and during the summer months. The personality scores of the SAD patients were compared with a matched group of non-seasonal depressed patients and published normative data. Stability and change in personality scores with changes in mood state were assessed. Personality dimensions were evaluated as possible predictors of treatment outcome., Results: SAD patients showed elevated openness scores relative to both non-seasonal depressed patients and norms. Their neuroticism scores were lower than non-seasonal depressed patients, but higher than norms. All personality dimensions showed large and highly significant test-retest correlations but several personality dimensions, particularly neuroticism and extraversion, also showed considerable change with changing mood state. None of the personality dimensions were significantly associated with treatment outcome., Limitations: Personality assessment relied on self-report., Conclusions: The personality profile of SAD patients differs from both non-seasonal depressed patients and norms. Elevated openness scores appear to be a unique feature of patients with SAD. Since mood state has a significant impact on personality scores, assessment of personality in SAD patients should ideally be conducted when they are in remission. Further investigation of the relationship between personality and SAD, especially the potential significance of elevated openness scores, is warranted.

Objective: Light therapy and antidepressants have shown comparable efficacy in separate studies of seasonal affective disorder treatment, but few studies have directly compared the two treatments. This study compared the effectiveness of light therapy and an antidepressant within a single trial., Method: This double-blind, randomized, controlled trial was conducted in four Canadian centers over three winter seasons. Patients met DSM-IV criteria for major depressive disorder with a seasonal (winter) pattern and had scores > or = 23 on the 24-item Hamilton Depression Rating Scale. After a baseline observation week, eligible patients were randomly assigned to 8 weeks of double-blind treatment with either 1) 10,000-lux light treatment and a placebo capsule, or 2) 100-lux light treatment (placebo light) and fluoxetine, 20 mg/day. Light treatment was applied for 30 minutes/day in the morning with a fluorescent white-light box; placebo light boxes used neutral density filters., Results: A total of 96 patients were randomly assigned to a treatment condition. Intent-to-treat analysis showed overall improvement with time, with no differences between treatments. There were also no differences between the light and fluoxetine treatment groups in clinical response rates (67% for each group) or remission rates (50% and 54%, respectively). Post hoc testing found that light-treated patients had greater improvement at 1 week but not at other time points. Fluoxetine was associated with greater treatment-emergent adverse events (agitation, sleep disturbance, palpitations), but both treatments were generally well-tolerated with no differences in overall number of adverse effects., Conclusions: Light treatment showed earlier response onset and lower rate of some adverse events relative to fluoxetine, but there were no other significant differences in outcome between light therapy and antidepressant medication. Although limited by lack of a double-placebo condition, this study supports the effectiveness and tolerability of both treatments for seasonal affective disorder and suggests that other clinical factors, including patient preference, should guide selection of first-line treatment.

This study investigated Lewy's Phase Shift Hypothesis (PSH) for winter Seasonal Affective Disorder, which asserts that the phase angle difference (PAD) between circadian and sleep rhythms is critical in the mechanism of light's therapeutic action. Specifically, we sought to test whether a euthymic "sweet spot" could be identified at a PAD (between temperature minimum and wake time) of circa 3 h. After a baseline week, symptomatic SAD patients (N = 43) received 8 weeks of morning light treatment. Analyses were based on SIGH-SAD ratings made at baseline and posttreatment. Also estimated pre- and posttreatment were T(min) (calculated from an algorithm based on Morningness-Eveningness self-report scores), and the phase of the sleep-wake rhythm (as assessed by daily sleep logs). It was predicted that a quadratic relationship would exist between PAD and depression ratings at baseline and posttreatment, with lowest levels around PAD = 3 h. It was further predicted that shift towards PAD = 3 h with treatment would be associated with decreases in depression with treatment. Although trends were in the expected direction, none of the three predictions were supported. Findings are discussed in terms of the study's limitations and the experimental challenge of parsing independent and interacting contributions of sleep and circadian phase.

The etiology and pathophysiology of seasonal affective disorder (SAD) has been linked to the seasons and to light since its first conceptualization. Aspects of SAD that make it particularly amenable to biological investigation include the predictable recurrent episodes, the rapid response to a nonpharmacologic treatment, the specific neurovegetative features, and the availability of rich animal models of seasonality. This paper reviews new findings for the major biological hypotheses for SAD, focusing on circadian rhythms, neurotransmitters, and molecular genetics. Integrative issues and future directions for the study of SAD, including the heuristic value of a dual-vulnerability hypothesis that conceptualizes seasonality as a dimensional construct and the importance of studying endophenotypes, will be discussed.

Objective: To compare perceived quality of life (QoL) in patients diagnosed with seasonal affective disorder (SAD) during the winter and summer months., Methods: Twenty-six patients who were enrolled in an ongoing multicentre study in Canada completed 2 measures of QoL (the 20-item Medical Outcomes Study Short-Form General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction Questionnaire, [Q-LES-Q]) during the winter, when suffering from depression, and again during the summer months., Results: Both general and health-related QoL scores were significantly improved in patients with SAD during the summer months, with scores for the most part falling within normal range., Conclusions: Perceived QoL in patients with SAD is markedly impaired during the winter months but shows a substantial rebound during the summer months. The findings of this study provide further evidence that SAD is a distinct diagnostic entity.

In the context of Lewy's phase delay hypothesis, the present study tested whether effective treatment of winter Seasonal Affective Disorder (SAD) is mediated by advancing of circadian phase. Following a baseline week, 78 outpatients with SAD were randomized into 8 weeks of treatment with either fluoxetine and placebo light treatment or light treatment and placebo pill. Depression levels were measured on the Ham17+7 and the BDI-II, and circadian phase was estimated on the basis of daily sleep logs and self-reported morningness-eveningness. Among the 61 outpatients with complete data, both treatments were associated with significant antidepressant effect and phase advance. However, pre- and post-treatment comparisons found that the degree of symptom change did not correlate with the degree of phase change associated with treatment. The study therefore provides no evidence that circadian phase advance mediates the therapeutic mechanism in patients with SAD. Findings are discussed in terms of the limitations of the circadian measures employed.

Evidence-based treatments for seasonal affective disorder (SAD) include light therapy and pharmacotherapy. We briefly review the diagnosis and treatment of SAD, focusing on clinical and treatment differences between patients with unipolar and bipolar illness. Special considerations for the management of SAD in patients with bipolar disorder are discussed, including the need to monitor for emergence of manic and hypomanic mood switches, to use mood stabilizers in patients with bipolar I disorder, and to be aware of potential interactions between bright light and medications used in treating bipolar disorder. Chronobiological treatments such as bright light therapy may be combined with pharmacotherapy to enhance therapeutic effects, reduce adverse side effects, and optimize treatment in patients with seasonal and nonseasonal bipolar disorder.

Background: We recently described a preliminary association between the hypofunctional seven-repeat allele of the dopamine-4 receptor gene (DRD4) and increased maximal lifetime body mass index in women with seasonal affective disorder (SAD). In this study, we examined whether binge eating behavior mediated this putative association., Methods: The study sample consisted of 131 women with winter SAD who reported increased intake of high-carbohydrate/high-fat foods during depressive episodes. We compared rates of binge eating behavior in the two genotypic groups defined by the presence or absence of the seven-repeat allele of DRD4., Results: Consistent with our working hypothesis, the proportion of binge eaters was significantly greater in probands with the seven-repeat allele (18 of 46, 39.1%) than in probands without this allele (14 of 85, 16.5%) [chi(2)(1)= 8.32, p = .004; odds ratio = 3.25, 95% confidence interval 1.43, 7.41]., Conclusions: Pending replication in other samples, these results point to a genetic factor that could help in the early identification and treatment of women at higher risk for seasonal weight gain associated with binge eating behavior. At a theoretic level, the current results suggest a novel link between evolutionary models of seasonal weight gain on the one hand and the DRD4 gene on the other.

Although a relatively large body of research has now accumulated concerning the relationship between quality of life (QoL) and nonseasonal depression, there is a dearth of information about QoL in seasonal affective disorder (SAD). The aim of this study was to compare perceived levels of broad ('generic') and health-related QoL in patients with seasonal and nonseasonal depression. Participants were 72 patients with SAD enrolled in an on-going multicentre study in Canada, and 72 patients with nonseasonal major depressive disorder (MDD) matched for severity of depression attending an outpatient psychiatric clinic in Vancouver, British Columbia. All participants completed two measures of QoL (the 20-item Medical Outcomes Study [MOS] Short-Form General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q]) at baseline prior to treatment. The results of the study indicated that both generic and health-related QoL were compromised in patients with SAD compared with general population norms. For example, mean Q-LES-Q scores (range 0-100, where higher scores indicate better QoL) were 44%, compared with scores of 83% reported for the general population. Patients with nonseasonal depression showed significantly poorer functioning in several domains on the SF-20, but no significant differences in Q-LES-Q scores emerged. Perceived QoL is impaired in patients with SAD. Degree of impairment between seasonal and nonseasonal depressives is equivalent when assessed using the Q-LES-Q, but significant inter-group differences are apparent in SF-20 domain scores. Future research is required to determine whether perceived QoL is improved by treatment interventions for seasonal depression such as light therapy or antidepressant medication.

Although a large body of research has accumulated concerning the relationship between nonseasonal depression and personality, comparatively few studies have examined the relationship between seasonal affective disorder (SAD) and personality. This study compared dimensional aspects of personality in patients diagnosed with SAD (N = 60), nonseasonal depression (N = 273), and nonclinical controls (N = 297) using the Dimensional Assessment of Personality Pathology (DAPP-BQ; Livesley & Jackson, in press). Analysis by ANCOVA indicated that significant between-group differences occurred in several of the 18 DAPP-BQ dimensions, with patients with SAD exhibiting personality psychopathology that was intermediate between the nonclinical sample and patients with nonseasonal depression. The results demonstrated that the traits associated with seasonal and nonseasonal depression differ in degree, not kind.

A retinal sensitivity abnormality has been hypothesized in seasonal affective disorder (SAD). To explore this hypothesis, the electroretinogram (ERG) was used to assess retinal sensitivity at the level of the rod photoreceptor system. We examined 27 depressed patients who met DSM-III-R criteria for major depression, recurrent, with a seasonal (winter) pattern and 23 normal control subjects who were age-paired and sex-matched as much as possible with the SAD patients. ERG testing was performed in dark-adapted, dilated eyes in winter between 10:00 and 15:00 h. Retinal sensitivity was based on the light stimulus intensity necessary to reach a 50-microV amplitude threshold. We found that retinal sensitivity was significantly lower (0.21 log units) in SAD patients compared with normal control subjects and that 55% of the patients had a retinal sensitivity value one standard deviation lower than the mean value of the control subjects. These results are consistent with a retinal hyposensitivity hypothesis for SAD, but the explanation for lower rod photoreceptor sensitivity in SAD is not known. We hypothesize that brain neurotransmitter dysregulation may be at the origin of both the mood disorder and retinal sensitivity change., (Copyright 2004 Elsevier Ireland Ltd.)

Objective: Although a relatively large body of research has now accumulated concerning the relation between negative life events, social support, and major depressive disorder (MDD), little is known about the relation between seasonal affective disorder and these psychosocial variables. This study aimed to compare baseline levels of negative life events (NLEs) and perceived social support (SS) in patients with seasonal and nonseasonal depression., Method: Canadian patients with winter seasonal affective disorder (SAD) (n = 26) and nonseasonal recurrent MDD (n = 66) completed measures of recent NLEs (the List of Threatening Experiences) and perceived SS (the Social Support Survey) prior to treatment., Results: No significant between-group differences were observed in mean number of NLEs experienced or in quality of SS. Perceived SS was impaired in both groups, compared with patients with chronic medical conditions., Conclusions: The results of this study complement those of previous research reporting increased incidence of NLEs and decreased SS in primary care patients with high seasonality in the UK. Future research is required to determine the causal relation between these psychosocial risk factors and SAD and to assess whether they have an effect on, or are affected by, treatment interventions for SAD.

There is significant evidence that altered dopamine activity plays a role in seasonal affective disorder (SAD). The current study examined three separate genetic hypotheses for SAD related to the 7-repeat allele (7R) of the dopamine-4 receptor gene (DRD4), a variant associated with decreased affinity for dopamine. We examined the possible contribution of 7R to the overall expression of SAD, attention deficit disorder (ADD) comorbidity, and body weight regulation. As part of an ongoing genetic study of increased eating behavior and mood in female subjects, 108 women with winter SAD and carbohydrate craving/weight gain were administered the Wender-Utah Rating Scale to measure childhood ADD symptomatology, and a questionnaire to assess maximal lifetime body mass index (BMI). To test for an association between 7R and the categorical diagnosis of SAD, the transmission disequilibrium test (TDT) was used in a subsample of probands providing familial DNA. Standard parametric tests were used to compare childhood ADD symptoms and maximal lifetime BMI across the two genotypic groups defined by the presence or absence of 7R. The TDT found no initial evidence for an association between 7R and the categorical diagnosis of SAD. However, 7R carriers reported significantly greater inattention and dysphoria in childhood (p=0.01 and 0.001, respectively) and a higher maximal lifetime BMI (p=0.007) than did probands without this allele. Furthermore, excluding probands with extreme obesity (maximal BMI >40), a strong correlation was found linking childhood inattentive symptoms and maximal lifetime BMI (r=0.35, p=0.001). In overeating women with SAD, the 7R allele of DRD4 may be associated with a unique developmental trajectory characterized by attentional deficits and dysphoria in childhood and mild to moderate obesity in adulthood. This developmental course may reflect different manifestations of the same underlying vulnerability related to central dopamine dysfunction. Given the possibility of population stratification when studying genotype/phenotype relationships, future use of genomic controls and replication of our findings in other overeating and/or ADD populations are needed to confirm these initial results.

Background: Animal studies have demonstrated seasonal changes in immune function mediated by nocturnal melatonin duration as a biological signal for photoperiod. Recent research has highlighted the potential role of neuroimmune dysfunction in depressive disorders. The etiology of winter depression (seasonal affective disorder, or SAD) is not known, but a number of studies have provided support for both photoperiod and neurotransmitter hypotheses., Hypothesis: A new hypothesis is presented that links the SAD data on melatonin, photoperiod, and neurotransmitters by proposing that seasonal increases in proinflammatory cytokines are critical in the pathophysiology of winter SAD., Testing the Hypothesis: In SAD patients, but not healthy subjects: proinflammatory cytokines will be increased and the Th1/Th2 balance will be shifted to the left in winter compared to summer; neuroimmune function will be correlated with nocturnal melatonin duration in SAD patients; and light treatment will correct neuroimmune dysfunction., Implications of the Hypothesis: Diagnostic tests for SAD may be developed using cytokine assays; neuroimmune dysfunction may be predictors of response to treatments; new treatments for SAD (immune or anti-inflammatory treatment) may be developed., (Copyright 2004 Elsevier Ltd.)

Introduction: Several lines of research point to a possible overlap between seasonal affective disorder (SAD) and attention deficit hyperactivity disorder (ADHD), particularly in females. There is also emerging evidence that variation of the 5-HT2A receptor gene (HTR2A) contributes to both SAD and ADHD. The current study investigated whether variation in HTR2A was associated with symptoms of childhood ADHD in adult women with SAD., Method: Sixty-six women with SAD were administered the Wender-Utah Rating Scale (WURS), which retrospectively assesses childhood ADHD, as part of an ongoing genetic study of SAD. WURS scores were compared across the three genotypic groups defined by the T102C polymorphism of HT2RA., Results: Analysis of variance indicated a significant difference in mean 25-item WURS scores across the three genotypic groups (p = 0.035). Post-hoc tests revealed that the C/C genotypic group had a significantly higher mean score than both the T/T group and T/C group. Based on previously established WURS criteria, 38% of subjects with the C/C genotype, and none with the T/T genotype, had scores consistent with childhood ADHD., Limitations: The current sample size is small, and childhood ADHD diagnoses were based on retrospective recall., Conclusion: These preliminary results suggest a possible association between variation in HTR2A, childhood ADHD, and the later development of SAD in women.

Background: Although several investigators have described a milder form of seasonal affective disorder (SAD), called subsyndromal SAD, little is known about the effect of light therapy in this group. The current study evaluates 3 weeks of open treatment with light therapy in SAD and subsyndromal SAD patients., Methods: Subjects with major or minor depression according to DSM-IV with a seasonal pattern were recruited during the winter of 1998-1999 from clinic patients and media advertising. Subjects were commenced on open treatment of morning light therapy, for 30 min daily using a new fluorescent light therapy unit that produced approximately 5,000 lux at a distance of 12 inches. The treatment lasted 3 weeks and at the end of the first and second week of treatment the duration of exposure could be increased to a maximum of 60 min at the discretion of the clinician. The Structured Interview Guide for the Hamilton Depression Rating Scale-SAD version (SIGH-SAD) was administered weekly to evaluate outcome. Response was defined in a variety of ways to reflect the fact that subsyndromal SAD subjects had milder symptoms., Results: Forty-six subjects entered treatment and 44 (SAD, n = 29, subsyndromal SAD, n = 15) completed at least 2 weeks. Response rates were generally similar in SAD subjects (64-69%) and subsyndromal SAD (40-67%) patients. There was a trend for longer exposure to be associated with better outcome., Conclusions: Light therapy may be an effective treatment for subjects with both major and minor depression with a seasonal pattern. Optimal duration, for the light therapy unit used in this study, is likely 45-60 min daily.

Noradrenergic and dopaminergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder (SAD). We investigated the effects of catecholamine depletion using alpha-methyl-para-tyrosine (AMPT), an inhibitor of tyrosine hydroxylase, in patients with SAD in natural summer remission. Nine drug-free patients with SAD by DSM-IV criteria, in summer remission for at least eight weeks, completed a double-blind, crossover study. Behavioral ratings and serum HVA and MHPG levels were obtained for 3-day sessions during which patients took AMPT or an active control drug, diphenhydramine. The active AMPT session significantly reduced serum levels of HVA and MHPG compared with the control diphenhydramine session. The AMPT session resulted in higher depression ratings with all nine patients having significant clinical relapse, compared with two patients during the diphenhydramine session. All patients returned to baseline scores after drug discontinuation. Catecholamine depletion results in significant clinical relapse in patients with SAD in the untreated, summer-remitted state. AMPT-induced depressive relapse may be a trait marker for SAD, and/or brain catecholamines may play a direct role in the pathogenesis of SAD.

Objective: In DSM-IV, winter seasonal affective disorder (SAD) is classified as a seasonal pattern of recurrent major depressive episodes in winter with full remission of symptoms in summer. However, other groups with "winter depression" have been identified, including patients with incomplete summer remission (ISR) and subsyndromal SAD (sub-SAD, winter depressive symptoms that do not meet criteria for major depression). In this study, we compare the clinical characteristics of these three seasonal groups and their response to light therapy., Method: 558 patients assessed at a specialized SAD Clinic were diagnosed using DSM-III-R or DSM-IV criteria. Clinical information was recorded using a checklist at index assessment. A subset of patients (N=192) were treated with an open, 2 week trial of light therapy using a 10000 lux fluorescent light box for 30 min per day in the early morning. Patients were assessed before and after treatment with the 29 item modified Hamilton Depression Rating Scale and clinical response was defined as greater than 50% improvement in scores., Results: The rates of some melancholic symptoms, anxiety, panic, suicidal ideation, and family history of mood disorder were lowest in the sub-SAD group. The clinical response rates to light therapy were highest in the sub-SAD group (N=32, 78%), intermediate in the SAD group (N=113, 66%), and lowest in the ISR group (N=47, 51%)., Limitations: This was a retrospective study of patients seen in a specialty clinic, although information was obtained in a standardized format. The light therapy trial had an open design so that placebo response could not be determined., Conclusions: There are differences in both the patterns of clinical symptoms and the response to light therapy in these three groups with winter depression. These results are consistent with a dual vulnerability hypothesis that considers these groups to result from interaction of separate factors for seasonality and depression.

Background: There is increasing evidence that an activation of the immune-inflammatory system is involved in the pathophysiology of depressive disorders. The purposes of this study were to (1) compare immune-inflammatory markers in patients with seasonal affective disorder (SAD) with those in matched normal controls; and (2) examine the effects of light therapy on the immune-inflammatory markers in patients with SAD., Methods: Plasma concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and soluble IL-2 receptor (sIL-2R) were measured in 15 patients with SAD and 15 age- and sex-matched normal controls. Of the 15 patients, 14 had repeated blood sampling for these variables following 2 weeks of light therapy., Results: We found that patients with SAD had significantly increased IL-6 levels compared to normal controls (P<0.0005). There was a trend toward increased sIL-2R in patients with SAD (P=0.09). There was no significant difference in sIL-6R level between the two diagnostic groups (P=0.18), but the product term (IL-6xsIL-6R) was significantly higher in patients with SAD than that in normal control controls (P<0.0003). Furthermore, all 14 patients who completed the study improved with 2 weeks of light therapy and nine of them (64%) had 50% reduction in score of the Hamilton Depression Rating Scale-SAD version post-treatment compared to baseline. However, the initially increased immune markers in SAD patients were not significantly altered by the therapeutic light therapy., Limitations: This study was limited to a small sample size and other immune inflammatory markers should be measured for further evidence of immune activation in seasonal depression., Conclusions: Our results of increased IL-6, IL-6xsIL-6R, and sIL-2R in patients with SAD suggest an activation of the immune-inflammatory system in winter depression, which is not altered by 2 weeks of successful light therapy.

Objective: Many patients with seasonal affective disorder (SAD) have dysfunctional eating behaviors. Conversely, many women with bulimia nervosa have marked winter worsening of mood and bulimic symptoms. Controlled studies of light therapy in SAD and in bulimia nervosa have shown beneficial effects on mood and binge/purge symptoms. We explored the clinical use of light therapy in women with SAD who also had comorbid bulimia nervosa., Method: Twenty-two female patients diagnosed using DSM-IV criteria with both bulimia nervosa and major depressive disorder with a seasonal (winter) pattern were treated with an open design, 4-week trial of light therapy (10,000 lux fluorescent light box with an ultraviolet filter, 30 to 60 minutes per day in the early morning). Patients were assessed before and after treatment with depression scales and with binge/purge diaries., Results: Light therapy resulted in significant improvement in mood, with a mean 56% reduction in 29-item Hamilton Rating Scale for Depression scores following treatment (p < .001). The frequency of binges and purges per week also significantly decreased (p < .001) from baseline by a mean of 46% and 36%, respectively. Two (9%) of 22 patients became abstinent of binge/ purge episodes, compared with 10 (45%) of 22 patients who met criteria for remission of depressive symptoms. The light therapy was well tolerated by patients., Conclusion: These results suggest that therapeutic effects of light therapy on mood and bulimic symptoms in patients with SAD and comorbid bulimia nervosa are sustained over at least 4 weeks. However, the low abstinence rate in bulimic symptoms indicates that light therapy may be most effectively used as an adjunctive treatment to medications and/or psychotherapy for bulimia nervosa.

The study of the pathophysiology of seasonal affective disorder (SAD, also known as winter depression) has historically been intimately linked to investigations into the mechanisms of action of light therapy. This paper reviews the studies on the pathophysiology of SAD with emphasis on circadian, neurotransmitter, and genetic hypotheses. There is substantial evidence for circadian phase shift and serotonergic hypotheses, but conflicting results may indicate that SAD is a biologically heterogeneous condition. Recent progress in defining the molecular mechanisms of the human circadian clock and retinal phototransduction of light will provide important new directions for future studies of the etiology and pathophysiology of SAD.

Background: Recent case reports suggest that some patients with seasonal affective disorder (SAD) may become suicidal after initial treatment with light therapy. This retrospective study sought to determine the effects of light therapy on suicidal ideation in patients with SAD., Method: The cases of 191 depressed patients with SAD by DSM-III-R or DSM-IV criteria treated with an open trial of morning light therapy using cool white fluorescent light boxes (2500 lux for 2 hours per day or 10,000 lux for 30 minutes per day) for 2 weeks were retrospectively analyzed. Patients had been rated before and after treatment with the expanded Hamilton Depression Rating Scale (SIGH-SAD)., Results: Sixty-seven percent of patients were rated as clinical responders to light therapy. There was significant improvement in the SIGH-SAD suicide item score, with 45% of patients showing a reduction in score. Only 6 patients (3%) had slight worsening of suicide scores. No patients attempted suicide or discontinued light therapy because of emergent suicidality., Conclusion: Light therapy relieves suicidal ideation in patients with SAD consistent with overall clinical improvement. Emergence of suicidal ideas or behaviors is very uncommon with light therapy.

Background: Serotonergic mechanisms have been proposed for the pathophysiology of seasonal affective disorder (SAD) and the therapeutic effect of bright-light treatment. Previously, we showed that SAD patients, in clinical remission with light therapy during the winter, experienced transient depressive relapses after a rapid tryptophan depletion (RTD) technique, which results in decreased brain serotonin levels. The objective of this study was to investigate the effect of RTD in SAD patients who were in natural summer remission., Methods: Twelve drug-free patients with SAD by DSM-IV criteria and 10 normal subjects participated in this double-blind, placebo-controlled, crossover study. SAD patients were in natural summer remission for at least 8 weeks. Behavioural ratings and plasma tryptophan levels were obtained before, and 5 h after, ingesting an amino acid (AA) mixture +/- tryptophan. Experimental RTD and control sessions were scheduled 1 week apart., Results: The RTD session resulted in significant reduction in total and free plasma tryptophan levels compared to the control session. The behavioural data were analysed using repeated measures analysis of variance. This analysis found significant main effects of time (higher scores after AA ingestion) and diagnosis (higher scores in SAD patients), but no main effect of session or significant interaction effects between the three factors. Thus, there were no significant behavioural effects of RTD compared to the sham depletion control session., Conclusions: The summer remission experienced by SAD patients is not dependent on plasma tryptophan levels (and presumably brain serotonin function) in the same manner as that of remission after light therapy. These results conflict with those of other laboratories, perhaps because of differences in study samples.

There is evidence for gamma-aminobutyric acid (GABA) dysfunction in the pathophysiology and treatment response of patients with major depression, but this has not been studied in seasonal affective disorder (SAD). Growth hormone (GH) response to a challenge with a GABAB receptor agonist, baclofen, is considered an in vivo index of hypothalamic GABAB receptor function in humans. To explore the role of GABAB receptor function in SAD, we compared the GH response to baclofen challenge in 15 patients with SAD and 20 matched healthy controls. Of the 15 patients with SAD, 14 had repeat baclofen challenge following 2-week treatment with light therapy. The results showed that baclofen administration led to a significant increase in GH release both in patients with SAD and normal controls. There was no significant difference in the GH response to baclofen between the two groups. Furthermore, 2-week treatment with light therapy did not significantly alter the baclofen-induced GH response in patients with SAD, in spite of a clear therapeutic effect. The results of this study suggest that hypothalamic GABAB receptor function, as measured by baclofen induced GH release, is not altered in patients with SAD or by light therapy.

Clinical observations and empirical studies suggest that Seasonal Affective Disorder (SAD) is related to personality. The present study estimates the genetic and environmental correlations between the Global Seasonality Score (GSS) from the Seasonal Pattern Assessment Questionnaire and personality measures, assessed using the NEO Five Factor Inventory (NEO-FFI) and the Dimensional Assessment of Personality Pathology (DAPP) in a volunteer sample of 163 monozygotic (MZ) pairs (102 female and 61 male pairs) and 134 dizygotic (DZ) pairs (70 female, 38 male and 26 opposite-sex pairs). Large genetic correlations were found between the GSS and NEO-FFI Neuroticism (0.52: 95% CI = 0.36-0.71) and DAPP-BQ Cognitive Dysregulation (0.50: 95% CI = 0.30-0.71), Affective Lability (0.49: 95% CI = 0.29-0.77), Anxiousness (0.37: 95% CI = 0.18-0.55) and Stimulus Seeking (0.45: 95% CI = 0.25-0.64) scales. The genetic correlations with the remaining scales, such as Extraversion (0.06: 95% CI = -0.16-0.26), Compulsivity (-0.09: 95% CI = -0.31-0.12) and Submissiveness (0.15: 95% CI = -0.05-0.34) were uniformly small. All environmental correlations between the GSS and personality scales were < or = 0.19. These results provide evidence that the observed correlations between these seasonality and personality dimensions are attributable to common genetic factors and that environmental influences are domain specific.

To explore the role of serotonergic system in seasonal affective disorder (SAD), we compared growth hormone (GH) responses to a challenge with a novel 5-HT1D receptor agonist sumatriptan between 11 patients with SAD and nine healthy controls. Of the 11 patients with SAD, nine had repeat sumatriptan challenge following treatment with light therapy. The results showed that GH responses were significantly blunted during winter depression in patients with SAD compared to healthy controls. The GH responses normalized following treatment with light therapy to similar levels in controls. The results of this study provide a support for the role of serotonergic system in pathophysiology of SAD and in the mechanism of action of light therapy.

The authors examined the rates of atypical depression and prevalence of specific atypical symptoms in patients with seasonal versus non-seasonal depression. Fifty-three patients with seasonal affective disorder (SAD) were compared to 54 patients with non-seasonal major depressive disorder (MDD) using the atypical depression diagnostic scale (ADDS). SAD patients scored significantly higher than non-seasonal MDD patients in hyperphagia and hypersomnia, and significantly lower in interpersonal sensitivity and other rejection avoidance. There was no difference in the rate of ADDS diagnosis of atypical depression. Differences between atypical depression and SAD suggest that they are separate subtypes of depression with an overlapping symptom picture.

A number of recent research reports have reported significant relationships between seasonal mood change (seasonality) and personality. However, some of the results are difficult to interpret because of inherent methodological problems, the most important of which is the use of samples drawn from the southern as opposed to the northern hemisphere, where the phenomenon of seasonality may be quite different. The present study examined the relationship between personality and seasonality in a sample from the northern hemisphere (minimum latitude = 49 degrees N). A total of 297 adults drawn from the general population (112 male and 185 female subjects) completed the Seasonal Pattern Assessment Questionnaire, and the results obtained confirmed most of the previously reported relationships and showed that these are reliable across (i) different hemispheres, (ii) different measures of personality and (iii) clinical and general population samples. However, the impact of the relationship seems to be more apparent than real, with personality accounting for just under 15% of the total variance.

The study estimated gender differences in the magnitude of genetic and environmental influence in seasonal mood change. The self-report Seasonal Pattern Assessment Questionnaire (SPAQ) was completed by 339 volunteer reared-together twinpairs (187 monozygotic pairs, 152 dizygotic pairs) and analysed using biometric genetic models. The SPAQ yields a global seasonality score (GSS) which is an index of change in sleep patterns, social activities, mood, weight, appetite, and energy level. The GSS was significantly heritable among males and females, estimated to account for 69% and 45% of the total variance, respectively. For the individual symptoms, changes in sleep patterns, social activities, mood, appetite, and energy levels were accounted for primarily by additive genetic effects in both males (median, 45.5%) and females (median, 30.5%). For both sexes, weight changes were not heritable. Sex-by-genotype analyses suggested that the genetic factors influencing female seasonality may not be the same as those influencing male seasonality.

Objective: Up to one-third of patients with seasonal affective disorder (SAD) do not have a full response to light therapy. Given the evidence for serotonergic dysregulation in SAD, we examined the possible role of l-tryptophan as an augmentation strategy for nonresponders and partial responders to light therapy., Method: Eligible drug-free patients meeting DSM-IV criteria for SAD were treated for 2 weeks using a standard morning light therapy regimen (10,000 lux cool-white fluorescent light for 30 minutes). Partial and nonresponders were treated for 2 weeks with open-label l-tryptophan (1 g 3 times daily) while light therapy was continued. Ratings at baseline and follow-up included the 29-item Structured Interview Guide for the Hamilton Depression Rating Scale, SAD version (SIGH-SAD) and the Clinical Global Impression (CGI) scale., Results: Sixteen patients began the l-tryptophan augmentation phase. Two patients discontinued medications within 3 days because of side effects. In the 14 patients completing treatment, the addition of l-tryptophan resulted in significant reduction of mean depression scores. Nine of 14 patients (64%) showed very good clinical responses to combined treatment and minimal side effects., Conclusion: This open-label study suggests that l-tryptophan may be an effective augmentation strategy for those patients with SAD who show limited or poor response to bright ligh therapy. Further placebo-controlled studies are warranted to demonstrate efficacy.

Background: Previous studies show that rapid tryptophan depletion reverses the effects of therapy with serotonergic, but not noradrenergic, antidepressant drugs in patients with remitted nonseasonal depression. The objective of this study was to investigate the effects of rapid tryptophan depletion in patients with seasonal affective disorder (SAD) that was in clinical remission after light therapy., Methods: Patients who met DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern (equivalent to SAD), were treated with a standard course of light therapy. Ten patients with SAD in clinical remission after light therapy underwent rapid tryptophan depletion in a placebo-controlled, double-blind crossover study. Behavioral ratings and plasma tryptophan levels were obtained before and after rapid tryptophan depletion., Results: Plasma total and free tryptophan levels were significantly reduced to 20% of normal levels by the rapid tryptophan depletion. The depletion session resulted in significant increases in depression scores compared with the sham control session. Six of 10 patients had a clinically significant relapse of their depression following the tryptophan depletion session., Conclusions: Rapid tryptophan depletion appears to reverse the antidepressant effect of bright light therapy in patients with SAD. This suggests that the therapeutic effects of bright light in SAD may involve a serotonergic mechanism.

Objective: The authors investigated the efficacy and safety of fluoxetine in the treatment of winter seasonal affective disorder., Method: Sixty-eight outpatients who met the DSM-III-R criteria for recurrent major depressive episodes, seasonal (winter) pattern, were randomly assigned to 5 weeks of treatment with fluoxetine, 20 mg/day (N = 36), or placebo (N = 32). The outcome measures included the 29-item modified Hamilton Depression Rating Scale, administered by experienced clinicians, and the self-rated Beck Depression Inventory; adverse events and safety data were also recorded. Clinical response was defined as a greater than 50% reduction in depression score between baseline and study termination., Results: Both groups showed significant improvement. The fluoxetine group had lower depression scores at termination than the placebo group, but these differences did not achieve statistical significance. However, the rate of clinical response in the fluoxetine group (59%) was superior to that in the placebo group (34%). Post hoc analyses showed that the greatest fluoxetine responses were in the most markedly depressed patients and that overall response was greater for patients studied later in the season. Fluoxetine was well tolerated, and few subjects dropped out because of adverse events., Conclusions: On the basis of clinical response rate, fluoxetine appears to be an effective, well-tolerated treatment for seasonal affective disorder. Because the differences between fluoxetine and placebo in the continuous outcome measures did not reach statistical significance, further studies with larger study groups and longer treatment periods are required to conclusively demonstrate efficacy of fluoxetine for seasonal affective disorder.

Objective: To review the status of current treatment of seasonal affective disorder (SAD)., Method: Treatment studies of SAD published between January 1989 and March 1995 were identified using a computerized MEDLINE literature search. Additional citations were obtained from the reference sections of these articles. Studies included in this review were selected using operational methodologic criteria., Results: Many studies support the efficacy of bright light therapy using a fluorescent light box. The best studied protocol is > 2500 lux white light for 2 hours per day, but newer protocols using 10,000 lux for 30 minutes have comparable response rates. Studies of light visors and other head-mounted devices also report similar response rates, but have not yet shown superiority over putative control conditions. There are fewer medication studies in SAD, but controlled studies suggest that fluoxetine, d-fenfluramine and propranolol are effective. Other treatments such as dawn simulation require further study. No studies of psychological treatments for SAD were found. Many studies had methodologic limitations, including brief treatment periods, small sample sizes, and lack of replication, that limit the generalizability of findings., Conclusion: There are several well-studied, effective treatments for SAD, including light therapy and medications. However, further research must be done to demonstrate sustained treatment response over time, to clarify the intensity-response relationship of light therapy, to clarify the role of light therapy and medications, and to assess combination treatments.

Bright-light therapy is widely regarded as an effective treatment for winter seasonal affective disorder (SAD). We attempted to identify predictors of light therapy response in 54 depressed, drug-free outpatients diagnosed with SAD by DSM-III-R criteria. After a baseline week, patients were treated for 2 weeks with 2500-lx cool-white fluorescent light exposure from 0600 to 0800 daily. The results showed that light therapy significantly reduced depression scores. Several indices of atypical and typical symptoms correlated with response, but none was clearly superior to the pre-treatment depression score. A multiple regression analysis identified 3 factors (hypersomnia, increased eating and younger age) that predicted light-therapy response. These results suggest that specific symptoms of hypersomnia and hyperphagia are predictors of response to morning bright-light therapy in SAD.

Markedly increased appetite and eating are commonly found in seasonal affective disorder (SAD) and bulimia nervosa (BN). To investigate dysfunctional eating attitudes, we administered the Eating Disorders Inventory (EDI), a self-rating questionnaire that assesses abnormal eating attitudes and behaviours, to 30 female SAD patients, 30 matched BN patients, and 30 non-clinical subjects. The SAD patients had higher scores on most EDI subscales compared to the non-clinical subjects; the BN patients had higher scores than the SAD patients on only two of three EDI subscales that are specific to eating disorders. These data add to the evidence supporting a clinical overlap between SAD and BN.