Seasonal Affective Disorder

Abstract

Seasonal affective disorder (SAD), characterized by fall/winter major depression with spring/summer remission, is a prevalent mental health problem. SAD etiology is not certain, but available models focus on neurotransmitters, hormones, circadian rhythm dysregulation, genetic polymorphisms, and psychological factors. Light therapy is established as the best available treatment for SAD. Alternative and/or supplementary approaches involving medications, cognitive-behavioral therapy, and exercise are currently being developed and evaluated. Given the complexity of the disorder, interdisciplinary research stands to make a significant contribution to advancing our understanding of SAD conceptualization and treatment.

Description and Prevalence

Seasonal affective disorder (SAD) was first described as a syndrome involving depressive episodes that recur and remit annually in certain seasons.¹ The Diagnostic and Statistical Manual of Mental Disorders² includes a seasonal pattern specifier that can be applied to recurrent major depressive disorder or bipolar I or II disorder in cases where the major depressive episodes recur in a particular season and fully remit or change to mania or hypomania at a characteristic time of year.

An estimated 10 to 20 percent of recurrent depression cases follow a seasonal pattern.³ Although a summer pattern of recurrence is possible, the predominant pattern involves fall/winter depression with spring/summer remission. In U.S. community surveys, SAD prevalence ranges from 9.7 percent in New Hampshire to 1.4 percent in Florida.⁴ In North America, SAD prevalence increases with latitude, but the correlation is nonsignificant in other parts of the world.⁵

It is important to introduce the concept of seasonality and define it here. The construct of seasonality is relatively normally distributed in the general population, and the syndrome of SAD appears to represent an extreme along the seasonality continuum.⁶ Young adults and women are most likely to experience SAD with the reported gender difference ranging from 2:1 to 9:1.³

SAD also has been identified in children and adolescents.⁷ Not limited to the mood disorders, seasonal patterns have been identified in bulimia nervosa, anxiety disorders, and other psychiatric conditions.³

Etiological Theories

Pathogenic theories for SAD have focused on neurotransmitters, hormones, circadian rhythm dysregulation, genetic polymorphisms, and psychological factors. In humans, the rate of serotonin turnover in the brain is lowest in the winter season, and the rate of serotonin production increases with luminosity.⁸ Monoaminergic challenge and depletion studies implicate serotonergic systems in the pathogenesis of SAD.⁹ Individuals with SAD successfully treated with bright light therapy relapse when serotonin and catecholamine levels are depleted.^10,11 Efficacy of the serotonin reuptake inhibitors (SSRIs) in SAD treatment provides indirect evidence for the role of serotonin in SAD.¹² Taken cumulatively, research suggests that serotonin and catecholamines may play a role in both the pathophysiology of SAD and the antidepressant effect of light therapy.

The phase-shift hypothesis proposes that the body's sleep-wake cycle is phase-delayed in SAD with respect to the environmental light-dark cycle,¹³ and is based on observations of delayed onset of sleep, melatonin, body temperature, and cortisol rhythms in some SAD patients.¹⁴ Winter worsening of mood was associated with indirect measures of phase-delay in an Australian community sample.¹⁵ Light therapy administered in the morning can phase-advance circadian rhythms in individuals with SAD who are phase-delayed.¹⁶ The magnitude of the antidepressant response to morning light therapy has been related to the degree of phase-advance achieved.¹⁷ However, it remains unclear how a phase-delay may lead to depression.

The photon-count hypothesis suggests that shorter photoperiods (hours of daylight) and/or less intense light in the winter results in an insufficient dose of light (i.e., fewer photons) to the retina in SAD-vulnerable individuals.¹⁸ A prospective, longitudinal study found a positive correlation between depression severity and photoperiod and two measures of light intensity (minutes of sunshine and global radiation) in SAD patients.¹⁹ A recent light therapy meta-analysis found a dose-response relationship between light therapy intensity and degree of improvement in the typical, but not in the atypical, depressive symptoms.²⁰

Individuals with SAD may respond to longer nights in winter with an extended duration of nocturnal melatonin release, a hormone that can promote sleep.²¹ When measuring active melatonin secretion under constant dim light, Wehr, et al.,²¹ found that individuals with SAD had a longer duration of melatonin release during winter than summer whereas controls did not. This is analogous to the lengthened duration of melatonin release in some mammals that signals seasonal changes in reproductive activity.²¹ It is possible that only humans with SAD have retained the ability to track seasons in this way, which might explain the seasonal presentation of SAD.

Studies of twins, families with a SAD proband, and other relatively homogeneous groups indicate that SAD may be, in part, an inherited disorder.²² Candidate genes related to serotonin and dopamine and molecular components of the circadian clock have been investigated.

Polymorphisms in the serotonin transporter promoter region (5-HTTLPR) and in the serotonin 2A receptor (5-HT2A-1483G/A) have been associated with SAD in some studies^23,24 but not others.^25–26 The dopamine-4 receptor gene (DRD4) seven-repeat allele was associated with binge eating behavior in a sample of women with SAD.²⁸ Neuronal PAS domain protein 2 (NPAS2), a transcription factor expressed in the circadian clock, was implicated in diurnal variation (preference for morning or evening) in a SAD case-control study.²⁹ These results suggest that SAD and specific SAD symptoms may be regulated by different genetic factors, each contributing a small-to-moderate amount of risk.³⁰

Recent etiological models have attempted to integrate biological and psychological mechanisms in explaining SAD onset and maintenance. Young's dual vulnerability model proposes two separate vulnerabilities among individuals with history of SAD: 1) a physiological vulnerability to experience atypical symptoms during the winter and 2) a psychological vulnerability to develop cognitive and affective symptoms of depression in reaction to the vegetative symptoms.³¹ Young devised this hypothesis based on his finding that individuals with SAD retrospectively recounted onset of fatigue, hypersomnia, and increased appetite prior to developing cognitive and affective symptoms.³² Different pathophysiological mechanisms may account for the different vulnerabilities proposed, leading to heterogeneity of findings from studies addressing the etiology and treatment of SAD.³³

Evidence is growing that cognitive and behavioral models of depression may apply to SAD. In two cross-sectional studies, individuals with SAD and nonseasonal depression reported similarly negative attributional styles³⁴ and similar negative automatic thoughts and dysfunctional attitudes.³⁵ A prospective, longitudinal study found that women with a SAD history endorsed more frequent negative automatic thoughts than nondepressed controls across all seasons, with peak negative automatic thought frequency in the winter.³⁶ Two studies found that ruminative coping (i.e., focusing on the causes and consequences of depressed mood,) as assessed in the fall, predicted the severity of SAD symptoms during the subsequent winter.^36,37 Behavioral disengagement is underscored by the progression of decline in SAD from reduced potential for enjoyment in fall to decreased frequency of response-contingent positive reinforcement in the winter.³⁶

Treatment Approaches

The most widely used and extensively investigated treatment for SAD is light therapy (i.e., daily exposure to a box containing fluorescent lamps during the symptomatic months). Certain activities, such as reading, are not prohibited as long as the user can maintain the appropriate position and distance from the unit. Regarding the optimal dose, 10,000-lux of full spectrum or cool white fluorescent lights set behind an ultraviolet shield is the standard.³⁸ The recommended daily duration varies from 30 minutes to two hours per day, and two to four weeks is typically adequate to determine responsiveness.³⁸

The greatest controversy surrounds the optimal timing of light therapy. Head-to-head comparisons suggest that morning light may be more efficacious than evening light, but one meta-analysis found the largest mean effect size for morning-plus-evening light.³⁹ A growing variety of portable, head-mounted light visors, smaller desk lamp units, dawn stimulators, and light fixtures with light-emitting diodes (LEDs) have also been developed. More research is needed to determine whether these devices are as effective as standard light boxes for SAD.

Available guidelines recommend administering light therapy under the supervision of a qualified professional.³⁸ In clinical settings, the specific light therapy prescription is often tailored to the individual's sleep-wake patterns, side effects, and preferences. Side effects to light therapy are generally mild and ameliorated by dose manipulations, but can include headache, eyestrain, and psychomotor agitation. Relative contraindications for light therapy include certain retinal diseases, medications that increase retinal sensitivity to light, and a history of mania or hypomania.

A pooled analysis of light therapy studies⁴⁰ concluded that 53.3 percent of individuals with SAD met criteria for full remission with light therapy. However, only 43 percent of individuals with moderate to severe SAD symptoms remitted with light therapy.⁴¹ Supplementary and alternative treatments have been developed because light therapy is not sufficient for all SAD patients.

Clinically, the SSRIs and other psychotropic medications are frequently used as an adjunct or alternative to light therapy.^42,43 A preliminary study found that light therapy plus pill placebo (50%) had a higher remission rate than fluoxetine plus dim light placebo (25%).⁴⁴ Most recently, a five-center Canadian study found comparable remission rates for light therapy plus pill placebo (54%) and fluoxetine plus dim light placebo (50%).⁴⁵ In a retrospective analysis of SAD outpatients in Finland, 73 percent of eight patients treated with moclebemide and 61 percent of 11 patients treated with fluoxetine responded over six weeks.⁴⁶ A study that randomized eight women with SAD to combined light therapy and citalopram or light therapy and pill placebo found no difference in the two conditions at post-treatment, but greater efficacy for combination treatment 34 weeks later.⁴⁷ A randomized trial comparing sertraline to pill placebo for eight weeks demonstrated greater improvements with setraline on measures of depression severity.⁴⁸

In addition to antidepressants, other pharmacologic agents show promise in treating SAD. One open-label study found that modafinil, a novel wake-promoting agent, demonstrated a 67-percent response rate, defined as a 50- percent or greater reduction in SAD symptoms, indicating that randomized, controlled studies may be warranted.⁴⁹ Propranolol, administered in the morning in open treatment for two weeks, produced a 73-percent response rate in a sample of 33 SAD patients, although not all treatment gains were maintained over the subsequent two weeks in the active drug continuation group versus placebo.⁵⁰ Future studies should examine propranolol's melatonin-suppressing effects as a mediator of antidepressant response in SAD.⁵⁰

Our group has recently developed and pilot-tested a SAD-tailored version of cognitive-behavioral therapy (CBT), modeled upon Beck's cognitive therapy,⁵¹ which is an empirically validated treatment for non-seasonal depression. The CBT for SAD protocol involves 90-minute sessions twice a week over six weeks (total of 12 sessions) delivered in group format. The behavioral component uses pleasant activity scheduling to counteract “hibernation” by developing wintertime interests. Negative cognitions are identified and challenged, including thoughts related to winter, light availability, seasonal environmental cues, and weather. Relapse-prevention emphasizes using CBT skills during subsequent fall/winter seasons in response to anticipatory negative thoughts about winter or SAD-related behavior changes.

Our feasibility study found that CBT, light therapy, and their combination were equally effective in the acute treatment of SAD.⁵² At a naturalistic one-year follow up, individuals treated with CBT, with or without adjunct light therapy, evidenced less severe depression on patient- and interviewer-rated measures. No CBT-treated participant met criteria for a full SAD episode recurrence relative to 62.5 percent of participants treated with light therapy alone. We have completed a larger sample, multiyear trial comparing CBT, light therapy, and combination therapy to a wait-list control with manuscript preparation underway.

Aerobic exercise interventions, which have demonstrated efficacy in the treatment of nonseasonal major depression,^53,54 are being explored in SAD. Pinchasov, et al., compared light therapy to aerobic exercise (i.e., two daily sessions on a stationary bicycle separated by five minutes of rest, each involving a 5-minute warm up followed by 10 minutes of basic pedaling and 10 minutes of pedaling at 75-percent maximal heart rate), with both treatments administered for one week during the afternoon, in a small sample of women with SAD.⁵⁵ Exercise and light therapy were associated with similar and significant reductions in depression severity and an increased rate of oxygen consumption relative to an untreated control group, suggesting that normalization of daily energy expenditure may underlie the efficacy of both treatments.

Although morning exercise might be beneficial in the treatment of SAD, based on the assumption that it would induce a phase-advance, these results suggest that the timing of exercise may not be important to the antidepressant effects of exercise on SAD. However, exercise late at night might be contraindicated in SAD because it can lead to a phase-delay in the onset of melatonin release the following night in humans.⁵⁶

In healthy controls, aerobic exercise performed under bright (2,500- to 4,000-lux) lights appears to be more beneficial than either exercise under typical indoor lighting or no exercise for atypical symptoms and vitality.⁵⁷ Therefore, outdoor exercise or combining aerobic exercise with light therapy might have utility for SAD, but has not yet been tested. Larger controlled trials are needed to further test exercise as an alternative or adjunctive treatment strategy in SAD.

Conclusions

Given its predictable pattern of recurrence and remission, SAD provides a “natural laboratory” for studying depression vulnerability, onset, maintenance, recurrence, and treatment response. SAD is likely to result from a complex interplay between environmental, biological, and psychological factors. Therefore, interdisciplinary research is needed to advance scientific knowledge regarding SAD etiology, treatment, and reasons behind the widely documented increased incidence of SAD among women. The established efficacy of light therapy and a variety of newly emerging treatment approaches to SAD affords providers with flexible options that can be tailored to individuals, keeping in mind patient compliance and perceived palatability of the treatment plan as important considerations.