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Seasonal affective disorder (SAD) is a
mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where a disturbance in the person's mood is the main underlying feature. The classification is in the '' Diagnostic and St ...
subset, in which people who have normal
mental health Mental health encompasses emotional, psychological, and social well-being, influencing cognition, perception, and behavior. It likewise determines how an individual handles stress, interpersonal relationships, and decision-making. Mental hea ...
throughout most of the year exhibit depressive symptoms at the same time each year. Common symptoms include sleeping too much, having little to no energy, and overeating. The condition in the summer can include heightened
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
.Seasonal affective disorder (SAD): Symptoms
MayoClinic.com (September 22, 2011). Retrieved on March 24, 2013.
In the ''
Diagnostic and Statistical Manual of Mental Disorders The ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM; latest edition: DSM-5-TR, published in March 2022) is a publication by the American Psychiatric Association (APA) for the classification of mental disorders using a common langua ...
'' DSM-IV and
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiatri ...
, its status was changed. It is no longer classified as a unique mood disorder, but is now a specifier, called "with seasonal pattern", for recurrent major depressive disorder that occurs at a specific time of the year, and fully remits otherwise. Although experts were initially skeptical, this condition is now recognized as a common disorder. However, the validity of SAD has been questioned by a 2016 analysis by the Center for Disease Control, in which no links were detected between depression and seasonality or sunlight exposure. In the
United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
, the percentage of the population affected by SAD ranges from 1.4% of the population in
Florida Florida is a state located in the Southeastern region of the United States. Florida is bordered to the west by the Gulf of Mexico, to the northwest by Alabama, to the north by Georgia, to the east by the Bahamas and Atlantic Ocean, and to ...
, to 9.9% in
Alaska Alaska ( ; russian: Аляска, Alyaska; ale, Alax̂sxax̂; ; ems, Alas'kaaq; Yup'ik: ''Alaskaq''; tli, Anáaski) is a state located in the Western United States on the northwest extremity of North America. A semi-exclave of the U.S., ...
. SAD was formally described and named in 1984, by Norman E. Rosenthal and colleagues at the
National Institute of Mental Health The National Institute of Mental Health (NIMH) is one of 27 institutes and centers that make up the National Institutes of Health (NIH). The NIH, in turn, is an agency of the United States Department of Health and Human Services and is the prima ...
. Marshall, Fiona. Cheevers, Peter (2003). "Positive options for Seasonal Affective Disorder", p. 77. Hunter House, Alameda, Calif. .


History

SAD was first systematically reported and named in the early 1980s, by Norman E. Rosenthal, M.D., and his associates at the National Institute of Mental Health (NIMH). Rosenthal was initially motivated by his desire to discover the cause of his own experience of depression during the dark days of the northern US winter, called
polar night The polar night is a phenomenon where the nighttime lasts for more than 24 hours that occurs in the northernmost and southernmost regions of Earth. This occurs only inside the polar circles. The opposite phenomenon, the polar day, or midni ...
. He theorized that the reduction in available natural light during winter was the cause. Rosenthal and his colleagues then documented the phenomenon of SAD in a placebo-controlled study utilizing light therapy. A paper based on this research was published in 1984. Although Rosenthal's ideas were initially greeted with skepticism, SAD has become well recognized, and his 1993 book, ''Winter Blues'' has become the standard introduction to the subject. Research on SAD in the United States began in 1979, when Herb Kern, a research engineer, had also noticed that he felt depressed during the winter months. Kern suspected that scarcer light in winter was the cause, and discussed the idea with scientists at the NIMH who were working on bodily rhythms. They were intrigued, and responded by devising a lightbox to treat Kern's depression. Kern felt much better within a few days of treatments, as did other patients treated in the same way.


Signs and symptoms

SAD is a type of
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
, and those with the condition may exhibit any of the associated symptoms, such as feelings of hopelessness and worthlessness, thoughts of suicide, loss of interest in activities, withdrawal from social interaction, sleep and appetite problems, difficulty with concentrating and making decisions, decreased libido, a lack of energy, or agitation. Symptoms of winter SAD often include falling asleep earlier or in less than 5 minutes in the evening, oversleeping or difficulty waking up in the morning, nausea, and a tendency to overeat, often with a craving for carbohydrates, which leads to weight gain. SAD is typically associated with winter depression, but springtime lethargy or other seasonal mood patterns are not uncommon. Although each individual case is different, in contrast to winter SAD, people who experience spring and summer depression may be more likely to show symptoms such as insomnia, decreased appetite and weight loss, and agitation or anxiety.


Bipolar disorder

''With seasonal pattern'' is a specifier for ''bipolar and related disorders'', including bipolar I disorder and bipolar II disorder. Most people with SAD experience
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
, but as many as 20% may have a
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
. It is important to distinguish between diagnoses because there are important treatment differences. In these cases, people who have the ''With seasonal pattern'' specifier may experience a depressive episode either due to major depressive disorder or as part of bipolar disorder during the winter and remit in the summer. Around 25% of patients with
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
may present with a depressive seasonal pattern, which is associated with bipolar II disorder, rapid cycling, eating disorders, and more depressive episodes. Differences in biological sex display distinct clinical characteristics associated to seasonal pattern: males present with more Bipolar II disorder and a higher number of depressive episodes, and females with rapid cycling and eating disorders.


Cause

In many species, activity is diminished during the winter months, in response to the reduction in available food, the reduction of
sunlight Sunlight is a portion of the electromagnetic radiation given off by the Sun, in particular infrared, visible, and ultraviolet light. On Earth, sunlight is scattered and filtered through Earth's atmosphere, and is obvious as daylight when t ...
(especially for diurnal animals), and the difficulties of surviving in cold weather. Hibernation is an extreme example, but even species that do not hibernate often exhibit changes in behavior during the winter. The preponderance of women with SAD suggests that the response may also somehow regulate
reproduction Reproduction (or procreation or breeding) is the biological process by which new individual organisms – "offspring" – are produced from their "parent" or parents. Reproduction is a fundamental feature of all known life; each individual or ...
. Various proximate causes have been proposed. One possibility is that SAD is related to a lack of serotonin, and
serotonin polymorphism Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...
s could play a role in SAD, although this has been disputed. Mice incapable of turning serotonin into N-acetylserotonin (by
serotonin N-acetyltransferase Aralkylamine ''N''-acetyltransferase (AANAT) (), also known as arylalkylamine ''N''-acetyltransferase or serotonin ''N''-acetyltransferase (SNAT), is an enzyme that is involved in the day/night rhythmic production of melatonin, by modification ...
) appear to express "depression-like" behavior, and antidepressants such as fluoxetine increase the amount of the enzyme serotonin N-acetyltransferase, resulting in an antidepressant-like effect. Another theory is that the cause may be related to melatonin, which is produced in dim light and darkness by the pineal gland, since there are direct connections, via the
retinohypothalamic tract In neuroanatomy, the retinohypothalamic tract (RHT) is a photic neural input pathway involved in the circadian rhythms of mammals. The origin of the retinohypothalamic tract is the intrinsically photosensitive retinal ganglion cells (ipRGC), wh ...
and the suprachiasmatic nucleus, between the retina and the pineal gland. Melatonin secretion is controlled by the endogenous circadian clock, but can also be suppressed by bright light. One study looked at whether some people could be predisposed to SAD based on personality traits. Correlations between certain personality traits, higher levels of neuroticism, agreeableness, openness, and an avoidance-oriented coping style, appeared to be common in those with SAD.


Pathophysiology

Seasonal mood variations are believed to be related to light. An argument for this view is the effectiveness of bright-
light therapy Light therapy, also called phototherapy or bright light therapy is intentional daily exposure to direct sunlight or similar-intensity artificial light in order to treat medical disorders, especially seasonal affective disorder (SAD) and circad ...
. SAD is measurably present at latitudes in the
Arctic region The Arctic ( or ) is a polar region located at the northernmost part of Earth. The Arctic consists of the Arctic Ocean, adjacent seas, and parts of Canada (Yukon, Northwest Territories, Nunavut), Danish Realm (Greenland), Finland, Iceland, N ...
, such as northern
Finland Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of B ...
(64°00′N), where the rate of SAD is 9.5%. Cloud cover may contribute to the negative effects of SAD. There is evidence that many patients with SAD have a delay in their
circadian rhythm A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., Endogeny (biology), endogeno ...
, and that bright light treatment corrects these delays which may be responsible for the improvement in patients. The symptoms of it mimic those of
dysthymia Dysthymia ( ), also known as persistent depressive disorder (PDD), is a mental and behavioral disorder, specifically a disorder primarily of mood, consisting of similar cognitive and physical problems as major depressive disorder, but with lo ...
or even
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
. There is also potential risk of suicide in some patients experiencing SAD. One study reports 6–35% of people with the condition required hospitalization during one period of illness. At times, patients may not feel depressed, but rather lack energy to perform everyday activities. Subsyndromal Seasonal Affective Disorder is a milder form of SAD experienced by an estimated 14.3% (vs. 6.1% SAD) of the U.S. population. The blue feeling experienced by both those with SAD and with SSAD can usually be dampened or extinguished by exercise and increased outdoor activity, particularly on sunny days, resulting in increased solar exposure. Connections between human mood, as well as energy levels, and the seasons are well documented, even in healthy individuals.


Diagnosis

According to the American Psychiatric Association
DSM-IV The ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM; latest edition: DSM-5-TR, published in March 2022) is a publication by the American Psychiatric Association (APA) for the classification of mental disorders using a common langu ...
criteria, Seasonal Affective Disorder is not regarded as a separate disorder. It is called a "course specifier" and may be applied as an added description to the pattern of
major depressive episode A major depressive episode (MDE) is a period characterized by the symptoms of major depressive disorder. Those affected primarily have a depressed mood for at least two weeks or more, and a loss of interest or pleasure in everyday activities. Other ...
s in patients with
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Intro ...
or patients with
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
. The "Seasonal Pattern Specifier" must meet four criteria: depressive episodes at a particular time of the year; remissions or mania/hypomania at a characteristic time of year; these patterns must have lasted two years with no nonseasonal major depressive episodes during that same period; and these seasonal depressive episodes outnumber other depressive episodes throughout the patient's lifetime. The Mayo Clinic describes three types of SAD, each with its own set of symptoms.


Management

Treatments for classic (winter-based) seasonal affective disorder include
light therapy Light therapy, also called phototherapy or bright light therapy is intentional daily exposure to direct sunlight or similar-intensity artificial light in order to treat medical disorders, especially seasonal affective disorder (SAD) and circad ...
, medication, ionized-air administration,
cognitive-behavioral therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...
, and carefully timed supplementation of the hormone melatonin.


Light therapy

Photoperiod-related alterations of the duration of melatonin secretion may affect the seasonal mood cycles of SAD. This suggests that light therapy may be an effective treatment for SAD. Light therapy uses a
lightbox A lightbox is a translucent surface illuminated from behind, used for situations where a shape laid upon the surface needs to be seen with high contrast. Types Several varieties exist, depending on their purpose: * Various backlit viewing d ...
, which emits far more lumens than a customary incandescent lamp. Bright white "full spectrum" light at 10,000 lux, blue light at a wavelength of 480 nm at 2,500 lux or green (actually cyan or blue-green) light at a wavelength of 500 nm at 350 lux are used, with the first-mentioned historically preferred. Bright light therapy is effective with the patient sitting a prescribed distance, commonly 30–60 cm, in front of the box with her/his eyes open, but not staring at the light source, for 30–60 minutes. A study published in May 2010 suggests that the blue light often used for SAD treatment should perhaps be replaced by green or white illumination. Discovering the best schedule is essential. One study has shown that up to 69% of patients find lightbox treatment inconvenient, and as many as 19% stop use because of this.
Dawn simulation Dawn simulation is a technique that involves timing lights, often called wake up lights, sunrise alarm clock or natural light alarm clocks, in the bedroom to come on gradually, over a period of 30 minutes to 2 hours, before awakening to simulate da ...
has also proven to be effective; in some studies, there is an 83% better response when compared to other bright light therapy. When compared in a study to negative air ionization, bright light was shown to be 57% effective vs. dawn simulation 50%. Patients using light therapy can experience improvement during the first week, but increased results are evident when continued throughout several weeks. Certain symptoms like hypersomnia, early insomnia, social withdrawal, and anxiety resolve more rapidly with light therapy than with cognitive behavioral therapy. Most studies have found it effective without use year round, but rather as a seasonal treatment lasting for several weeks, until frequent light exposure is naturally obtained.
Light therapy Light therapy, also called phototherapy or bright light therapy is intentional daily exposure to direct sunlight or similar-intensity artificial light in order to treat medical disorders, especially seasonal affective disorder (SAD) and circad ...
can also consist of exposure to sunlight, either by spending more time outside or using a computer-controlled heliostat to reflect sunlight into the windows of a home or office. Although light therapy is the leading treatment for seasonal affective disorder, prolonged direct sunlight or artificial lights that don't block the ultraviolet range should be avoided, due to the threat of
skin cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC) ...
. The evidence base for light therapy as a preventive treatment for seasonal affective disorder is limited. The decision to use light therapy to treat people with a history of winter depression before depressive symptoms begin should be based on a person's preference of treatment.


Medication

SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs increase the extracellul ...
(selective serotonin reuptake inhibitor) antidepressants have proven effective in treating SAD. Effective antidepressants are fluoxetine,
sertraline Sertraline, sold under the brand name Zoloft among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. The efficacy of sertraline for depression is similar to that of other antidepressants, and the differ ...
, or
paroxetine Paroxetine, sold under the brand names Paxil and Seroxat among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used to treat major depressive disorder, obsessive-compulsive disorder, panic disorder ...
. Both fluoxetine and light therapy are 67% effective in treating SAD, according to direct head-to-head trials conducted during the 2006 Can-SAD study. Subjects using the light therapy protocol showed earlier clinical improvement, generally within one week of beginning the clinical treatment. Bupropion extended-release has been shown to prevent SAD for one in four people, but has not been compared directly to other preventive options in trials. In a 2021 updated Cochrane review of
second-generation antidepressant The second-generation antidepressants are a class of antidepressants characterized primarily by the era of their introduction, approximately coinciding with the 1970s and 1980s, rather than by their chemical structure or by their pharmacological ...
medications for the treatment of SAD, a definitive conclusion could not be drawn, due to lack of evidence, and the need for larger randomized controlled trials. Modafinil may be an effective and well-tolerated treatment in patients with seasonal affective disorder/winter depression. Another explanation is that
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
levels are too low when people do not get enough Ultraviolet-B on their skin. An alternative to using bright lights is to take vitamin D supplements. However, studies did not show a link between vitamin D levels and depressive symptoms in elderly Chinese, nor among elderly British women given only 800IU when 6,000IU is needed. 5-HTP (an amino acid that helps to produce serotonin, and is often used to help those with depression) has also been suggested as a supplement that may help treat the symptoms of SAD, by lifting mood, and regulating sleep schedule for those with the condition. However, those who take antidepressants are not advised to take 5-HTP, as antidepressant medications may combine with the supplement to create dangerously high levels of serotonin – potentially resulting in '
serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain serotonergic medications or drugs. The degree of symptoms can range from mild to severe, including a potentiality of death. Symptoms in mild cases include high ...
'.


Other treatments

Depending upon the patient, one treatment (e.g., lightbox) may be used in conjunction with another (e.g., medication). Negative air ionization, which involves releasing charged particles into the sleep environment, has been found effective, with a 47.9% improvement if the negative ions are in sufficient density (quantity). Physical exercise has shown to be an effective form of depression therapy, particularly when in addition to another form of treatment for SAD. One particular study noted marked effectiveness for treatment of depressive symptoms, when combining regular exercise with bright light therapy. Patients exposed to exercise which had been added to their treatments in 20 minutes intervals on the aerobic bike during the day, along with the same amount of time underneath the
UV light Ultraviolet (UV) is a form of electromagnetic radiation with wavelength from 10 nm (with a corresponding frequency around 30  PHz) to 400 nm (750  THz), shorter than that of visible light, but longer than X-rays. UV radiation i ...
were seen to make a quick recovery. Of all the psychological therapies aimed at the prevention of SAD, cognitive-behaviour therapy, typically involving thought records, activity schedules and a positive data log, has been the subject of the most empirical work. However, evidence for CBT or any of the psychological therapies aimed at preventing SAD remains inconclusive.


Epidemiology


Nordic countries

Winter depression is a common slump in the mood of some inhabitants of most of the
Nordic countries The Nordic countries (also known as the Nordics or ''Norden''; literal translation, lit. 'the North') are a geographical and cultural region in Northern Europe and the Atlantic Ocean, North Atlantic. It includes the sovereign states of Denmar ...
.
Iceland Iceland ( is, Ísland; ) is a Nordic island country in the North Atlantic Ocean and in the Arctic Ocean. Iceland is the most sparsely populated country in Europe. Iceland's capital and largest city is Reykjavík, which (along with its s ...
, however, seems to be an exception. A study of more than 2000 people there found the prevalence of seasonal affective disorder and seasonal changes in anxiety and depression to be unexpectedly ''low'' in both sexes. The study's authors suggested that propensity for SAD may differ due to some genetic factor within the Icelandic population. A study of Canadians of wholly Icelandic descent also showed low levels of SAD. It has more recently been suggested that this may be attributed to the large amount of fish traditionally eaten by Icelandic people. In 2007, about 90 kilograms of fish per person was consumed per year in Iceland, as opposed to about 24 kilograms in the US and Canada,Fishery and Aquaculture Statistics: SECTION 2 – Food balance sheets and fish contribution to protein supply, by country from 1961 to 2007
. Rome: Food and Agriculture Organization of the United Nations (2008)
rather than to genetic predisposition; a similar anomaly is noted in Japan, where annual fish consumption in recent years averages about 60 kilograms per capita. Fish are high in
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
. Fish also contain
docosahexaenoic acid Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-lin ...
(DHA), which help with a variety of neurological dysfunctions.


Other countries

In the United States, a diagnosis of seasonal affective disorder was first proposed by Norman E. Rosenthal, M.D. in 1984. Rosenthal wondered why he became sluggish during the winter after moving from sunny
South Africa South Africa, officially the Republic of South Africa (RSA), is the southernmost country in Africa. It is bounded to the south by of coastline that stretch along the South Atlantic and Indian Oceans; to the north by the neighbouring countri ...
to (cloudy in winter) New York. He started experimenting increasing exposure to artificial light, and found this made a difference. In
Alaska Alaska ( ; russian: Аляска, Alyaska; ale, Alax̂sxax̂; ; ems, Alas'kaaq; Yup'ik: ''Alaskaq''; tli, Anáaski) is a state located in the Western United States on the northwest extremity of North America. A semi-exclave of the U.S., ...
it has been established that there is a SAD rate of 8.9%, and an even greater rate of 24.9% for subsyndromal SAD. Around 20% of
Irish people The Irish ( ga, Muintir na hÉireann or ''Na hÉireannaigh'') are an ethnic group and nation native to the island of Ireland, who share a common history and culture. There have been humans in Ireland for about 33,000 years, and it has been c ...
are affected by SAD, according to a survey conducted in 2007. The survey also shows women are more likely to be affected by SAD than men.One in five suffers from SAD
Irish Examiner (November 10, 2007). Retrieved on March 24, 2013.
An estimated 3% of the population in the
Netherlands ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...
experience winter SAD.


See also

*
Diurnal Cycle A diurnal cycle (or diel cycle) is any pattern that recurs every 24 hours as a result of one full rotation of the planet Earth around its axis. Earth's rotation causes surface temperature fluctuations throughout the day and night, as well as we ...
* Seasonal effects on suicide rates *
Seasonal Pattern Assessment Questionnaire The Seasonal Pattern Assessment Questionnaire, or SPAQ, is a simple, self-administered screening test for Seasonal Affective Disorder, first developed in 1984. Though some aspects of its accuracy have been questioned since then, it is widely used t ...
*
Vitamin D deficiency Vitamin D deficiency or hypovitaminosis D is a vitamin D level that is below normal. It most commonly occurs in people when they have inadequate exposure to sunlight, particularly sunlight with adequate ultraviolet B rays (UVB). Vitamin D defic ...


References


External links

* * USA National Institute of Mental Health webpages https://www.nimh.nih.gov/health/topics/seasonal-affective-disorder/index.shtml {{Medical resources , ICD10 = {{ICD10, F, 33, , f, 33 , MedlinePlus = 001532 Mood disorders Circadian rhythm Major depressive disorder Weather and health