A comparison of open treatment of seasonal major and minor depression with light therapy

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.     

Winter and summer outdoor light exposure in women with and without seasonal affective disorder

BACKGROUND: The annual decrease of daylight duration initiates a depressive phase in patients with seasonal affective disorder (SAD), and light therapy treats it. How much bright light exposure in winter and summer these patients actually receive may help understand the pathogenetic factors initiating SAD. METHODS: During a week in winter and summer, women with and without SAD kept daily logs of the time spent outdoors, subjective sleep, and self-ratings of mood and alertness. RESULTS: Compared with the winter depressive state, mood, alertness, and sleep of SAD patients improved in summer to control values, but did not correlate with the amount of light exposure. In summer, patients with SAD spent more time outdoors than controls. LIMITATION: Light logs--in comparison with light monitor measurements--may overestimate light exposure outdoors. CONCLUSION: Women with SAD do not spend less time outdoors in winter than controls, but spend more time outdoors in summer. CLINICAL RELEVANCE: Patients with SAD show a high amplitude seasonal difference in outdoor light exposure. The susceptibility to winter depression may arise not from behaviourally-related lack of sufficient light exposure, but an increased vulnerability to the amount of light received. They may require more light than controls to remain euthymic (higher light exposure in summer, light therapy in winter).     

Cognitive-behavioral therapy, light therapy, and their combination in treating seasonal affective disorder

Background: The need to develop supplementary or alternative treatments for seasonal affective disorder (SAD) is underscored by the significant minority (47%) of SAD patients that is refractory to light therapy, the persistence of residual symptoms despite light treatment, and poor long-term compliance with light use. Because preliminary studies suggest that cognitive and behavioral factors are involved in SAD, cognitive-behavioral therapy (CBT) warrants investigation as a possible treatment option. Methods: We piloted a 6-week randomized clinical trial to compare a standard light therapy protocol; a novel, SAD-tailored, group CBT intervention; and their combination in ameliorating and remitting a current SAD episode and as prophylaxis against episode recurrence. Depressive symptom severity and remission rates were assessed at post-treatment and at a 1-year follow-up visit to examine long-term treatment durability. Results: CBT, light therapy, and their combination all demonstrated significant reductions in depressive symptoms on two different outcome measures. Remission rates varied by measure, but did not reach statistical significance. During the subsequent winter, CBT, particularly in combination with light therapy, appeared to improve long-term outcome regarding symptom severity, remission rates, and relapse rates. No CBT-treated participant, with or without light, experienced a full SAD relapse compared to over 60% of those treated with light alone. Limitations: These results should be viewed as preliminary and are limited by the small sample size (n=23) and lack of a control group. Conclusions: The nearly half of SAD patients who do not remit with light alone may benefit from CBT as an adjunct or alternative treatment, especially as a prophylaxis against episode recurrence.     

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.     

Does neuroimmune dysfunction mediate seasonal mood changes in winter depression?

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.     

Characteristics of patients with otherwise typical winter depression, but with incomplete summer remission.

BACKGROUND: Seasonal affective disorder, winter depression type (WD-SAD), is characterized by recurring autumn/winter depression with full remission or hypomania/mania in summer. However, some patients have an otherwise typical WD but with incomplete summer remission. We wanted to elucidate in what other respects such patients differ from typical WD-SAD patients. METHODS: 14 patients meeting DSM-III-R criteria for Seasonal Pattern except for incomplete summer remission (ISR), were compared with 144 patients meeting the full criteria, including complete summer remission (CSR), with regard to demography, illness history, clinical symptoms, and response to light treatment. RESULTS: In comparison with the CSR group, the ISR group had a longer duration of illness, more often used antidepressants, and improved significantly less after treatment with bright light for 6 days, whereas the symptomatology in winter (Montgomery-Asberg Depression Rating Scale plus hypersomnia, hyperphagia, and carbohydrate craving) was similar in the two groups. LIMITATIONS: The ISR group was small, and the severity of their summer depression could only be assessed retrospectively. CONCLUSIONS: Patients with otherwise typical WD but with incomplete summer remission respond poorly to light treatment. Full summer remission should be retained as a criterion for WD-SAD.     

Controlled trial of bright light and negative air ions for chronic depression

BACKGROUND: This randomized controlled trial investigates the efficacy of two non-pharmacologic treatments, bright light and high-density negative air ions for non-seasonal chronic depression. Both methods have shown clinical success for seasonal affective disorder (SAD). METHOD: Patients were 24 (75%) women and 8 (25%) men, ages 22-65 years (mean age +/- S.D., 43.7 +/- 12.4 years), with Major Depressive Disorder, Single Episode (DSM-IV code, 296.2), Chronic (episode duration > or = 2 years). Patients were entered throughout the year and randomly assigned to exposure to bright light (10 000 lux, n = 10), or high-density (4.5 x 10(14) ions/s flow rate, n = 12) or low-density (1.7 x 10(11) ions/s, n = 10, placebo control) negative air ions. Home treatment sessions occurred for 1 h upon awakening for 5 weeks. Blinded raters assessed symptom severity weekly with the Structured Interview Guide for the Hamilton Depression Rating Scale--Seasonal Affective Disorder (SIGH-SAD) version. Evening saliva samples were obtained before and after treatment for ascertainment of circadian melatonin rhythm phase. RESULTS: SIGH-SAD score improvement was 53.7% for bright light and 51.1% for high-density ions v. 17.0% for low-density ions. Remission rates were 50%, 50% and 0% respectively. The presence or severity of atypical symptoms did not predict response to either treatment modality, nor were phase advances to light associated with positive response. CONCLUSIONS: Both bright light and negative air ions are effective for treatment of chronic depression. Remission rates are similar to those for SAD, but without a seasonal dependency or apparent mediation by circadian rhythm phase shifts. Combination treatment with antidepressant drugs may further enhance clinical response.     

Personality of seasonal affective disorder analyzed by Tri-dimensional Personality Questionnaire

BACKGROUND: Although there have been numerous reports in personality of mood disorders, there have been few reports in regard with personality of winter seasonal affective disorder (SAD). Furthermore, no reports have been published concerning summer SAD personality characteristics. Thus, this study was conducted to assess the personality of winter and summer SAD using Tri-dimensional Personality Questionnaire (TPQ) that have been used in a variety of mental disorders. METHODS: A total of 6135 Japanese were evaluated with TPQ, the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Self-rating Depression Scale (SDS). Winter, summer and non-SAD groups were classified by SPAQ. We compared the difference of personality trait among these three groups in consideration of gender, age and SDS score influence. RESULTS: Winter SAD demonstrated higher "Novelty Seeking" and "Harm Avoidance"; summer SAD showed higher "Harm Avoidance" than the non-SAD group. "Harm Avoidance" in both SAD groups was re-analyzed using SDS score as a covariate, and "Novelty Seeking" in winter SAD using age as a covariate. As a result, the significance of high "Novelty Seeking" and high "Harm Avoidance" in winter SAD was excluded. However, "Harm Avoidance" remained the significant difference between summer and non-SAD. LIMITATION: SAD was diagnosed only by SPAQ and not by interview. The state-dependency of "Harm Avoidance" was not confirmed in identical patients over lapse of time. CONCLUSION: Patients with winter SAD have high "Harm Avoidance" dependent on the depressive state that is in accordance with non-seasonal depression. Patients with summer SAD have high "Harm Avoidance" possibly independent from the depressive state.     

Sleep deprivation as a predictor of response to light therapy in major depression

BACKGROUND: While the majority of depressed patients benefit from total sleep deprivation (TSD), light therapy is regarded as a first-line treatment only for seasonal affective disorder (SAD). The results of light therapy in nonseasonal major depressive disorder have been non-conclusive. We examined the correlation of TSD response and light therapy response in major depressed patients. METHODS: 40 inpatients with major depressive disorder (seven with seasonal pattern, 33 without seasonal pattern) were deprived of a night's sleep. The TSD responders, as well as the TSD nonresponders, were randomly assigned to receive adjunct light therapy either with bright white light (2500 lux) or dim red light (50 lux) during 2 weeks beginning on the third day after TSD. RESULTS: The 20 TSD responders improved significantly better under the light therapy than the 20 TSD nonresponders (according to the Hamilton Depression Rating Scale and the self-rating depression scale Bf-S; v. Zerssen). LIMITATIONS: No significant difference could be found between the two light intensities. Since the patients were additionally treated with medication an interaction with the two adjunctive therapies cannot be excluded. CONCLUSION: Our results indicate that a positive TSD response in major depressed patients can be predicative of beneficial outcome of subsequent light therapy.     

Immune-inflammatory markers in patients with seasonal affective disorder: effects of light therapy

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.     

Light room therapy effective in mild forms of seasonal affective disorder--a randomised controlled study

BACKGROUND: The most common way to provide bright light therapy to Swedish patients with Seasonal Affective Disorder (SAD), is treatment in a light therapy room. Since few studies have evaluated treatment provided in this setting and few have evaluated the effect of bright light in sub-clinical SAD (S-SAD), such a study including a one-month follow-up was designed. METHODS: Fifty adults recruited from a previous prevalence study and clinically assessed as having SAD or S-SAD, were randomised to treatment in a light room or to a three-week waiting-list control group. The Hamilton Depression Rating Scale-Seasonal Affective Disorders Self-rating 29-items Version (SIGH-SAD/SR) was used to measure depressive mood at baseline, directly following treatment and at the one-month follow-up. RESULTS: ANCOVA with adjustment for baseline depression score, showed a significant main effect for the light room therapy group (p<0.001). Fifty-four percent (n=13/24) improved > or = 50% while no such improvement was seen in the control condition (n=0/24). After merging the two groups, repeated measures ANOVA confirmed the experimental analysis (p<0.001). At the one-month follow-up, 83.0% (n=39/47) had improved > or = 50% and 63.8% (n=30/47) had normal depression scores, i.e. < or = 8. CONCLUSIONS: Light room therapy was effective in reducing depressive symptoms in subjects with winter depressive mood. Results were maintained over a period of one month.     

Effects of rapid tryptophan depletion in patients with seasonal affective disorder in natural summer remission

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.     

Cognitive therapy for depressed adults with comorbid social phobia

BACKGROUND: Evidence suggests that comorbid depression influences the outcome of cognitive-behavioral treatment for patients presenting with social phobia. Little is known, however, about the influence of comorbid social phobia on the response to cognitive therapy (CT) for depression among adults presenting with recurrent major depressive disorder (MDD). These analyses seek to clarify this relationship. METHODS: Patients (N=156) with recurrent DSM-IV MDD entered CT (20% also met DSM-IV criteria for social phobia). Every week during the course of CT, clinicians assessed depressive symptoms and patients completed self-report instruments measuring severity of depression and anxiety. RESULTS: At presentation, outpatients with comorbid social phobia reported greater levels of depressive symptoms and clinicians rated their impairment as more severe, compared to their counterparts without social phobia. Patients with or without comorbid social phobia did not differ significantly in (1) attrition rates; (2) response or sustained remission rates; (3) time to response or sustained remission; or (4) rate of improvement in symptoms of depression or anxiety. LIMITATIONS: The lack of domain-specific measures limits inference with respect to the improvements in social anxiety that occur with CT of depression. CONCLUSIONS: These findings introduce the hypothesis that CT for depression may be flexible enough to treat the depressive symptoms of patients presenting with MDD who also suffer from social phobia.     

Seasonality and affective disorders: a report from North India

Case records of the patients with major affective disorders (ICD-10 criteria), seen over a 5 year period in a busy clinic in North India were examined for Seasonal Affective Disorder (SAD) as per DSM-III-R criteria. In addition, seasonality of episodes of all affective disorders was also studied. Around 5.67% of the cases (n=44) retrospectively met the DSM-III-R criteria of SAD and predominant pattern was that of summer depression (n=18). There was also a consistent pattern of seasonal mania either in conjunction with seasonal depression (n=18) or in form of seasonal recurrent mania (n=11). None of the cases of depression showed any atypical vegetative features. In cases not meeting criteria for SAD (n=731), there was a trend for peaks for depressive episodes in winter followed by a smaller peak in summer months while manic episodes had peaks towards rainy and winter months. As compared to seasonal patterns of affective disorders in temperate zones, there was a general trend for opposite patterns of seasonality in SAD as well as in non-SAD. The findings are discussed in context of the climatic conditions of North India.     

Psychic and somatic anxiety differentially predict response to light therapy in women with seasonal affective disorder

OBJECTIVE: To examine whether psychic and/or somatic anxiety predict responsiveness to light therapy in women with winter Seasonal Affective Disorder (SAD). DESIGN: Eighty-one women with SAD were administered a standard 10-day trial of light therapy administered for one-half hour in the early morning. Using a multiple regression model, baseline somatic and psychic anxiety item scores were used to predict percentage change scores on the 29-item SIGH-SAD post treatment. Baseline scores for weight gain, hypersomnia and the total SIGH-SAD were also included as predictor variables. RESULTS: The regression model was highly significant (F=4.63, df=5,75; p=.001; model R(2)=.236), with both psychic anxiety and somatic anxiety contributing significantly to the model. Consistent with prior work using anti-depressant medication in non-seasonal depression, psychic anxiety was positively correlated with outcome, while somatic anxiety negatively predicted outcome. CONCLUSIONS: In SAD, psychic and somatic anxiety scores at baseline appear to be independent and opposite predictors of light therapy response. These effects were independent of baseline scores for weight gain and hypersomnia, two previously established predictors of response to light. These findings may be an important consideration in the design and interpretation of light therapy studies 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.     

Mood-worsening with high-pollen-counts and seasonality: a preliminary report

BACKGROUND: Because aeroallergens produce inflammation in the respiratory airways, and inflammation triggers depression in vulnerable individuals, we hypothesized that mood sensitivity to pollen, the most seasonal aeroallergen, will be associated with a greater seasonality of mood. Since pollen is absent during winter, we specifically predicted that mood sensitivity to tree pollen will predict non-winter SAD but not winter SAD. METHODS: A convenience sample of African and African American college students who lived in the Washington DC metropolitan area for at least the past 3 years completed the Seasonal Pattern Assessment Questionnaire (SPAQ), from which the Global Seasonality Score (GSS) was calculated, a diagnosis of cumulative SAD (syndromal or subsyndromal SAD) was derived, a seasonal pattern (winter vs non-winter) identified, and self-reported mood changes during high pollen counts obtained. A Mann-Whitney test was used to compare GSS between participants with vs without mood worsening during high pollen counts. The capability of mood worsening with high pollen counts, gender, ethnicity, and age to predict non-winter SAD was analyzed with logistic regressions. RESULTS: GSS was greater (z=5.232, p<0.001) in those who reported mood worsening with high pollen counts. Mood sensitivity to pollen predicted non-winter SAD (p=0.017), but not winter SAD. LIMITATIONS: The SPAQ is not a definitive tool to assess seasonality, and self-reported mood worsening with high pollen counts relies on recollection. No direct measures of depression scores or pollen counts were collected. The non-winter SAD concept has not been previously established. CONCLUSIONS: Our study, which should be considered preliminary in light of its limitations, suggests that self-reported mood-worsening with high pollen count is associated with a greater seasonality of mood, and predicts SAD of non-winter type.     

Multi-center study of seasonal affective disorders in Japan. A preliminary report

A multi-center study on seasonal affective disorder (SAD) was conducted from the autumn of 1988 to the spring of 1989 with the cooperation of 16 facilities in Japan. Forty-six SAD patients were identified among 1104 respondents to our advertisements in mass media, or patients seen at the outpatient clinics. Essentially similar findings to other previous reports were obtained in terms of onset age of the first episode, duration of episode, high proportion of depression in first-degree relatives and atypical vegetative symptoms. However, a nearly equal sex ratio, together with a high proportion of unipolar depression, is characteristic of the present study. Increased appetite and carbohydrate craving were predominant only in female patients, whereas hypersomnia was prominent in both sexes. Effective response to light therapy was found in 17 SAD patients. However, a controlled study on a large number of patients is required to allow final conclusions on the efficacy of light therapy in Japanese SAD patients.     

Correlates of symptomatic, minor and major depression in the elderly

BACKGROUND: Associations between different types of depression with clinical characteristics and putative vulnerability factors from several domains (health, disability, personality, familial psychopathology) were studied in a sample of elderly subjects, in order to find arguments that support or discard the notion of discontinuity in correlates of depression. METHODS: Subjects were 183 depressed elderly persons from the general population, general practitioners and mental health care outpatient clinics, and a random elderly control group (n=74). Depression was subdivided into symptomatic (n=45), DSM-IV minor (n=73), and DSM-IV major (n=65) depression. The groups were compared with respect to a variety of variables from different domains. RESULTS: Most variables showed a marked difference between the control group and the depressive groups, and smaller or no differences between depressive subtypes. Limitations: The data were collected cross-sectionally. CONCLUSIONS: With a few notable exceptions, all subtypes of depression were significantly different from the control group, while differences between depressive subtypes were generally smaller. Depressive subtypes showed no discontinuum with respect to the associated variables. Similar associations in different subtypes of depression may indicate common vulnerability factors.     

Monorhinal odor identification and depression scores in patients with seasonal affective disorder

BACKGROUND: Visual and olfactory pathways are interconnected. Olfactory deafferentation unmasks photoperiodic responsiveness in some nonphotoperiodic animals such as laboratory rats. By analogy, we hypothesized that olfactory deficits may unmask seasonal rhythms in certain individuals, namely those with seasonal affective disorder (SAD). Since previous studies suggest lateralized hemispheric dysfunction in SAD, and since olfactory neurons' primary projections are largely ipsilateral, we assessed olfactory identification performance on both the right and left side of the nose. METHODS: Twenty-four patients with SAD and 24 matched controls were studied using a phenyl ethyl alcohol detection threshold test bilaterally and the University of Pennsylvania Smell Identification Test unilaterally. Subjects rated their mood using the Self Assessment Mood Scale for SAD. Patients' testing was done in both 'depressed' and 'improved on light' states. RESULTS: No difference in olfactory performance was found between patients and controls or between patients before and after light treatment. However, right-side identification scores were negatively correlated with 'typical' depression scores (r = -0.56, P = 0.006), while left-side olfactory scores were not. Atypical depression scores were unrelated to olfactory performance. Similar correlations emerged between the olfactory identification laterality quotient (Right - Left)/(Right + Left) and typical depressive scores (r = - 0.64, P < 0.001) and total depression scores (r = - 0.59, P < 0.004). LIMITATIONS: We studied a demographically heterogeneous sample and did not control for menstrual factors. DISCUSSION: Our results add to previous evidence of lateralized hemispheric involvement in SAD and suggest that olfaction may be related to seasonal emotional rhythms in humans.