Seasonal Affective
Disorder: A Future for
SAD
Prepared for the Global Life Sciences Institute
Investigator: Lex Gomez
3/25/2014
Seasonal Affective Disorder: A Future for SAD
1
Summary
This white paper focuses on the mood disorder known as Seasonal Affective Disorder
(SAD). This paper has been prepared for and funded by the Global Life Sciences Institute
(GLSI), in compliance with the schedule and budget dictated in the proposal dated February
27, 2014. The topic of this paper has been selected to identify with GLSI interests as stated
in the GLSI Request for Proposal, particularly those regarding human disease and disorder.
This paper includes multiple sections, listed below:
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Summary
Background
State of the Science
Future Research Needs
This document will discuss the nature of SAD as a mood disorder; it will also describe the
symptoms most commonly associated with SAD and those characteristics considered in
making a diagnosis of the disorder. The main focus of this white paper is to review and
elucidate the proposed biological mechanisms that may cause SAD, and to determine which
hypothesis is best supported by the amounting literature evidence. This paper also seeks to
competently review methods of treatment for SAD, the efficacy and longevity of treatment
methods, what this implies regarding the current ability of physicians to treat SAD, and
potential insights to underlying biological mechanisms. Lastly, this document will suggest
future research needs for this topic, and give one recommendation for GLSI to consider in
their future research.
Seasonal affective disorder has provided an interesting puzzle for the scientific and medical
communities. Though both scientists and physicians have conducted studies monitoring
symptoms, treatment methods, etc., the disorder remains poorly understood. Determining
the cause of SAD has presented a particular problem, and subsequently has been the main
focus of research. Most literature investigating the cause of SAD has focused on the effect
of seasonal changes in light exposure, and the biological mechanisms that this change could
influence. Despite the multitude of literature devoted to SAD, scientists have not
successfully reached definite conclusions about its cause. Not knowing the cause may prove
detrimental to developing effective treatment methods. Scientists have developed
treatments with varying levels of success; however, an obvious deficit exists concerning
concrete knowledge of SAD.
Investing into future research of this topic would benefit scientists by providing insight into
biological systems; it would also pave the way for refining and improving treatment
methods, which serves to benefit doctors and, more importantly, those afflicted with the
disorder. This paper is designed to discuss SAD and identify areas of future research that
would contribute most benefit to all, particularly by increasing SAD sufferers’ quality of life.
Seasonal Affective Disorder: A Future for SAD
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Background
What is Seasonal Affective Disorder?
Scientists classify seasonal affective disorder (SAD) as a mood disorder subtype that entails
a yearly cycle where the onset and remission of depression symptoms coincide with
changes in season. The term “seasonal affective disorder” was first used in a research
paper by Rosenthal et al. in 1984. The Diagnostic and Statistical Manual of Mental Disorders
first included SAD as a clinical condition and subtype of depression in 1987. Scientists have
identified two types of SAD: winter SAD, in which patients experience depression in the
fall-winter months with remission in the spring-summer; and summer SAD, in which
patients experience depression symptoms in the spring-summer months, with remission in
the fall-winter. Winter SAD is the most prevalent type; consequently, the majority of SAD
research focuses on this variety (Partonen and Lonnqvist 1998). Scientists propose that
seasonal changes in light exposure (or photoperiod variation) may contribute in part to
winter depression. This theory is popular in explaining winter depression, but it does not
effectively address the occurrence of summer SAD. Scientists do not understand the cause
or mechanism of SAD very well (Lee et al. 1997).
Symptoms, Diagnosis, and Prevalence
Symptoms of SAD include many of the hallmark symptoms of both typical and atypical
depression. Typical symptoms associated with SAD include lack of motivation, fatigue,
sluggishness, and feelings of sadness or melancholy. Atypical symptoms include excessive
eating associated with carbohydrate craving, weight gain, and excessive sleeping.
Symptoms manifest in varying degrees of severity, ranging from mild to severe (Iwaki et al.
2006, Rohan et al. 2013). SAD diagnostic criteria entails reoccurring depressive episodes
that present in the fall-winter and may last up to 5 months or approximately 40% of the
year (Rohan et al. 2013). Diagnosis of SAD can pose problems for doctors because they may
first diagnose it as non-seasonal depression unless they are aware of the seasonal changes.
In addition, because SAD is seasonal and might therefore seem ephemeral to uninformed
sufferers, those affected by SAD may not seek help for some time (Partonen and Lonnqvist
1998).
Studies estimate that SAD affects approximately 5% of Americans. As with major
depression, SAD tends to affect females more commonly than males. The majority of studies
suggest that SAD is three to four times more common in women than men, though other
studies implicate higher ratios between the sexes (Johnson 2000). One study found that half
of the subjects suffering from SAD began experiencing symptoms in early childhood or
adolescence; subjects reported that their symptoms during this time were mild and
increased in severity as they aged (Partonen 2010).
Seasonal affective disorder has received increased attention and scrutiny from the scientific
and medical communities in the last four decades. It presents a particular puzzle for
scientists; many aspects of the disorder, including mechanism, cause, prevalence,
successful treatment, and remission remain elusive. This presents very real problems for
the medical community and those affected by SAD.
Seasonal Affective Disorder: A Future for SAD
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State of the Science
Biological Clocks and Rhythms
Currently, scientists have proposed several mechanisms for winter SAD. These include:
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The Melatonin Hypothesis
The Photoperiod Hypothesis
The Phase Shift Hypothesis (PSH)
Abnormal Serotonin Transport Activity
Most explanations have something to do with biological clocks and rhythms.
Many factors and elements may control or influence biological rhythms. Scientists have
identified external/environmental cues as well as internal/biological cues that allow living
organisms to regulate their biological rhythms in ways that best suit their survival needs.
Scientists believe that the circadian (day-night) rhythm is somehow involved in SAD. They
propose that this rhythm is thrown off in SAD patients. Most SAD researchers think that SAD
symptoms result from irregular or improperly synchronized biological rhythms (Partonen 2010).
Scientists have studied several internal and external factors that may cause or influence the
onset of SAD. Because the circadian rhythm is entrained to function in tandem with lightdark cycles, and light input from eyes is one of the main external factors that help regulate
circadian rhythms, scientists study SAD by observing light exposure in subjects with SAD.
They have also studied several hormones thought to be involved with sleep-wake cycles,
such as melatonin, serotonin, and noradrenaline (Partonen 2010). The hypotheses formed to
explain the mechanism of SAD have revolved around these internal and external influences,
particularly those concerning light.
Melatonin Hypothesis
Melatonin is a hormone secreted at night by a brain structure known as the pineal gland; its
main function is thought to be regulation of sleep. The melatonin hypothesis posits that
melatonin secretion in SAD sufferers is distinctly different from healthy control subjects,
and that melatonin levels directly relate or correlate to the onset of SAD symptoms. Since
the nights are longer in the winter than in the summer, the pineal gland will secrete more
melatonin in the winter, coinciding with winter SAD symptoms. However, studies that have
monitored melatonin levels in SAD and control groups have found that melatonin levels are
not significantly different in SAD sufferers as compared to unaffected controls. Studies have
also found that attempts to treat SAD with melatonin-suppressing drugs have proved
relatively ineffective (Lee et al. 1997).
Photoperiod Hypothesis
The term “photoperiod’ refers to the time amount of light present in a 24-hour cycle. The
photoperiod hypothesis of SAD postulates that SAD is “caused by abnormal body response
to seasonal change in day length”. This hypothesis works with the notion that many
biological rhythms and behaviors are greatly influenced by the amount of daylight present;
in animals, the behaviors affected include but are not limited to sleeping, foraging, mating,
Seasonal Affective Disorder: A Future for SAD
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and metabolism. An observation of animals showed that they tend to experience
hypersomnia, weight gain, decreased energy, and decreased mating drive in periods of the
year when the photoperiod is shorter. Thus, the photoperiod hypothesis also implies that
these symptoms of SAD may be residual ancestral behavior. To test this hypothesis,
researchers exposed subjects to long and short-period light, and determined that the
amount of light exposure was not directly related to therapeutic effect. They concluded that
it unlikely that SAD is caused by variations in the seasonal photoperiod length (Lee et al. 1997).
Phase Shift Hypothesis
The Phase Shift Hypothesis (PSH) first constructed by Lewy et al. is concerned with the
entrainment of circadian rhythms to the 24-hour day-night cycle. Like the photoperiod
hypothesis, the PSH is also concerned with exposure to light, but it less concerned with
length than alignment of internal and external rhythms. Circadian rhythms such as
sleep/wake cycles and melatonin levels are measured by phase-response curves. “Phase
shift” refers to a change in the wavelength or frequency of the circadian rhythm. The
circadian entrainment of the PSH is realized by advancing or delaying the phase shift that
occurs as a consequence of exposure to light. In SAD patients, this entrainment occurs
improperly, causing biological rhythms to become deregulated, unsynchronized, or show
abnormal phase change (Murray et al. 2003). Of the three hypotheses mentioned, PSH is
most widely supported by scientists (Lee et al. 1997). Researchers have studied the use of
light therapy at specific times of day to try and correct the abnormal phase-shifting in SAD
patients; results show that exposure to light in the morning has more effect on alleviating
SAD symptoms than evening exposure. However, some studies have also given evidence
against the PSH, with suggestions that SAD patients do not exhibit abnormal delay or
advance in phase-shifting (Partonen 2010).
Abnormal Serotonin Transport Activity
Research into a genetic model for SAD has lead scientists to examine genes that code for
serotonin transport systems. Serotonin influences sleep, appetite, and mood, and decreased
availability of serotonin is commonly seen in depressed subjects. Serotonin levels also vary
throughout the year, indicating some aspect of seasonality. Some SAD research has pointed
to a genetic abnormality that may result in hyperactivity of serotonin transport, which would
decrease the amount of available serotonin. Scientists proposed that this genetic abnormality
was more prevalent in SAD subjects; however, a genotyping study by Johansson et al. found no
significant link between these serotonin transporters and SAD (Johansson et al. 2001).
Current Treatments
Treatment for SAD may involve both homeopathic and pharmacological elements. Current
treatment methods include:
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Bright light therapy (BLT)
Medication
Exercise
Cognitive-behavioral therapy (CBT)
Seasonal Affective Disorder: A Future for SAD
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All treatments vary in effectiveness, and are often used in combination with one another. Of
the treatments, scientists have only used light therapy or drug therapy as effective standalone treatments (Iwaki et al. 2006).
Bright Light Therapy
Bright light therapy (BLT), also called phototherapy, is a popular method for treating SAD
and it lends credibility to the PSH. Subjects receive light therapy at specific times of day in
attempt to correct abnormal phase-shifting; this treatment appears to work for the slight
majority of SAD patients, with 53-57% success rate in treatment reported from
experimental studies (Rohan et al. 2008, Rohan et al. 2013). BLT has become the standard
first treatment for SAD; however, the reason why light therapy works for some patients and
not others is not understood. Scientists find it difficult to differentiate between light
therapy’s therapeutic and placebo effects, which makes understanding the mechanism even
more obscure. BLT has also proven to be ineffective as a long-term treatment strategy,
since many subjects may cease light therapy treatment post-study, when they are not under
supervision (Lam and Westrin 2007, Rohan et al. 2004).
Medication
If light therapy proves to be ineffective in treating a particular patient, physicians may
prescribe antidepressants and anti-anxiety drugs as a second form of treatment. Both
selective serotonin reuptake inhibitors and noradrenaline have shown some effectiveness in
reducing SAD symptoms, though with adverse side effects (Pjerk et al. 2009). A study
comparing the effects of a serotonin precursor, tryptophan, and light therapy found that both
were equally effective in treating depression symptoms in SAD (Ghadirian et al. 1998).
Scientists have also implicated melatonin and melatonergic agonists in the treatment of SAD,
but were mainly effective in regulating sleep patterns (Leppämäki et al. 2003).
Exercise
Physicians commonly advise depressed patients to participate in physical activity as a
method of elevating mood. While usually not the only form of treatment prescribed, exercise
can help improve subjects’ mood (Iwaki et al. 2006). A study published in Psychiatric
Research compared the effects of light therapy and exercise therapy in treating both nonseasonal depressive and seasonal depressive patients; the study measured effects mainly by
differences in mood and oxygen consumption before and after the treatments. The results of
this study showed that light therapy and exercise therapy were equally effective in
improving mood and increasing oxygen consumption in the seasonal depressive patients
(Pinchasov et al. 2000). Combining light therapy and exercise may significantly alleviate
atypical depression symptoms that accompany SAD (Leppämäki et al. 2002).
Cognitive Behavioral Therapy
Scientists have used cognitive-behavioral therapy (CBT) to treat SAD and prevent relapse
of depression symptoms. One study examined the effectiveness of combining CBT with light
therapy, and found significance improvement in patients (Rohan et al. 2004). Another
experiment compared the relative effectiveness of light therapy and CBT. This study found
that both treatments were equally efficient in palliating depression, though CBT-treated
subjects were less likely to experience a relapse in the next winter (Iwaki et al. 2006).
Seasonal Affective Disorder: A Future for SAD
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Future Research Needs
This review has revealed that a substantial amount of research exists dedicated to the
treatment and study of seasonal affective disorder. The scientific and medical communities’
understanding of SAD has vastly increased in the last four decades. However, areas of
study exists that researchers have not explored thoroughly, and the fact remains that,
despite recent efforts, SAD continues to dwell in some amount of obscurity. Gaps endure in
the research that scientists must strive to fill so that doctors are able to better combat SAD
in the future.
Treatment Efficacy
Treatment of SAD is lacking in several areas. One of those areas concerns efficacy. As
outlined in the previous section, scientists and physicians have developed several different
forms of therapy to treat SAD; of those, bright light therapy has received the most attention
regarding amount of research devoted to it. However, bright light therapy is not effective
for treating all SAD patients, and the extent of its antidepressant effects may vary. Bright
light therapy on its own is generally not enough to fully treat SAD patients (Pjerk et al.
2004). The same can be said for pharmacological therapy. Antidepressant drugs are
generally employed in the event that light therapy is not effective, and they themselves may
be only partially effective in alleviating SAD (Iwaki et al. 2006). More importantly,
pharmacological treatments mainly aim to treat the mood symptoms of SAD rather than the
underlying cause; this means that not all symptoms may be treated or treated equally.
Scientists need to conduct more work in order to understand how to effectively alleviate all
symptoms.
Treatment Duration
Another area in which SAD treatment is lacking concerns long-term treatment strategies.
SAD presents particular problems in this area because its onset is not chronic, but seasonal,
which may indicate that the treatment should be also. As mentioned, light therapy is difficult
to maintain as a long-term treatment method. Patients tend to discontinue self-treatment by
light therapy after participation in studies or doctor-supervision because it is very timeconsuming and sometimes difficult to work into every day routine. Very few studies that
examine long-term treatment of SAD with medication or light therapy are available for
review (Lam and Westrin 2007). Exercise is a sustainable form of therapy that can be
continued year-round; but, as mentioned, it does not fully palliate effects of SAD and is
better used as an add-on form of treatment (Iwaki et al. 2006). Physicians and scientists
alike would be well-advised to work on devising long-term treatment strategies that can be
tailored to suits individual patients’ needs.
Mechanism
The third area concerns understanding the underlying cause and mechanism of SAD. This
area is not necessarily lacking in research; the majority of research found during the
literature review search focused either on determining the mechanism of SAD or bright light
therapy. However, determining a mechanism has proven difficult for researchers. Most of
the research that attempts to identify the biological mechanism underlying SAD is unable to
make a definitive conclusion; instead, the literature is filled with observations of what might
Seasonal Affective Disorder: A Future for SAD
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cause SAD. A broad review of all hypotheses seems to indicate that multiple factors may
contribute to SAD, not all of which may have a biological basis. One study has suggested
that socio-environmental factors and climate (though not necessarily latitude) may
contribute to the occurrence and prevalence of SAD (Mersch et al. 1999). However, as
previously stated, researchers have not made any definite conclusions.
Recommendation
Based on the literature reviewed and presented for this white paper, future research
regarding SAD should focus on increasing the efficacy of treatment methods and treatment
strategies for subjects with SAD. Though all of the research areas presented bear
considerable merit, increasing treatment efficacy has several distinct advantages.
Improving treatment efficacy is currently the most relevant area of research for sufferers of
SAD. Improving efficacy would offer the most immediate and direct positive impact on the
lives of SAD sufferers. Whereas research geared towards finding the SAD mechanism would
eventually lead to better understanding of treatment, discovering the mechanism may take
considerable time. The current state of research shows that discovering or even narrowing
down a cause or mechanism is, and will most likely continue to be, a difficult task. It is
unclear how fast research in this area will progress, and this uncertainty does not bode well
for SAD sufferers. In addition, treatment efficacy should also seek to benefit summer SAD
sufferers, which research has neglected in comparison to winter SAD.
Research that focuses on the effectiveness of treatment will not only provide more
immediate and useful results for SAD patients, but it will gradually lead to the two other
areas of research alluded to. Focusing on efficacy will also necessitate focus on long-term
and preventative treatment in the management of SAD. If scientists and physicians can
figure out what is and is not effective, they will gain more insight into potential biological
mechanisms of the disorder.
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References
Ghadirian, A., Murphy, B.E.P., and Gendron, M. (1997). Efficacy of light versus tryptophan
therapy in seasonal affective disorder. Journal of Affective Disorders. 50: 23-27
Iwaki, R., Kasper, S., Pjrek, E., and Winkler, D. (2006). Treatment of seasonal affective
disorder. Expert Review of Neurotherapeutics. 6.7: 1039.
Johansson, C., Smedh, C., Partonen, T., Pekkarinen, P., Paunio T., Ekholm, J., Peltonen L.,
Lichtermann, D., Palmgren, J., Adolfsson R., and Schalling M. (2001). Seasonal
affective disorder and serotonin-related polymorphisms. Neurobiology of Disease.
8: 351-357.
Johnson, R. (2000). Diagnosing and managing seasonal affective disorder. Nurse
Practitioner. 25.8: 56, 59-62, 68-70 passim.
Lam, R. and Westrin, A. (2007). Long-term and preventative treatment for seasonal
affective disorder. CNS Drugs. 21.11: 901
Lee, T., Blashko, C., Paterson, J., and Chan, C. (1997). Pathophysiological mechanism of
seasonal affective disorder. Journal of Affective Disorders. 46(1), 25-30.
Lee, Tatia; Chen, Eric. (2006). Seasonal affective disorder. Clinical Psychology: Science and
Practice. 5 (3), 275-290.
Leppämäki, S., Partonen, T., and Lonnqvist, J. (2002). Bright light exposure combined with
physical exercise elevates mood. Journal of Affective Disorders. 72 (2): 139-144.
Leppämäki, S., Partonen, T., Vakkuri, O., Lonnqvist, J., Partinen, Ma., and Laudon, M. (2003).
Effect of controlled-release melatonin on sleep quality, mood, and quality of life in
subjects with seasonal or weather-associated changes in mood and behavior.
European Neuropsychopharmacology. 13 (3): 137-145.
Mersch, P., Middendorp, H., Bouhuys, A., Beersma, D., and Hoofdakker, R. (1999). Seasonal
affective disorder and latitude: a review of the literature. Journal of Affective
Disorders. 53 (1), 35-48.
Murray, G., Allen, N.B., and Trinder, J. (2003). Seasonality and circadian phase delay:
prospective evidence that winter lowering of mood is associated with a shift towards
Eveningness. Journal of Affective Disorders. 76, 15-22.
Partonen, T. (2010) Seasonal Affective Disorder: Practice and Research. New York, USA:
Oxford University Press.
Partonen, T. and Lonnqvuist, J. (1998) Seasonal affective disorder. The Lancet: 1369-1374.
Seasonal Affective Disorder: A Future for SAD
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Peiser, B. (2009). Seasonal affective disorder and exercise treatment: a review. Biological
Rhythm Research. 40(1): 85-97.
Pinchasov, B.B., Shurgaja, A.M., Grischin, O.V., and Putilov, A.A. (2000). Mood and energy
regulation in seasonal and non-seasonal depression before and after midday
treatment with physical exercise or bright light. Psychiatry Research. 94: 29-42.
Pjerk, E., Konstantinidis, A., Assem-Hilger, E., Praschak-Rieder, N., Willeit, M., Kasper, S.,
and Winkler, D. (2009). Therapeutic effects of escitalopram and reboxetine in
seasonal affective disorder: a pooled analysis. Journal of Psychiatric Research. 43:
792-797.
Pjerk, E., Winkler, D., Stastny, J., Konstantinidis, A., Heiden, A., and Kasper, S. (2004).
Bright light therapy for seasonal affective disorder: does it suffice? European
Neuropsychopharmacology. 14: 347-351.
Rohan, K., Evans, M., Mahon, J., Sitnikov, L., Ho, S., Nillni, Y.I., Postolache, T.T., and Vacek,
P.M. (2013). http://www.trialsjounral.com/content/14/1/82
Rohan, K., Lindsay, K., Roecklein, K., and Lacy, T. (2008). Cognitive Behavioral therapy,
light therapy, and their combination in treating seasonal affective disorder. Journal of
Affective Disorder. 80: 273-283.