Seasonal affective disorder
Synonyms and keywords: SAD, seasonal disorder, seasonal depression, winter blues, winter depression

# Overview
Seasonal affective disorder (SAD), also known as winter depression, is a form of depression that is related to changes in the season. In the most common form of SAD, an individual experiences more frequent depressive periods between the late fall and early spring, with a return to normal baseline mood in the late spring and summer months. Less commonly, patients may experience depressive episodes in the summer; this type of disorder is known as reverse seasonal affective disorder (Reverse-SAD). The management options for SAD are phototherapy, medications, psychotherapy, or a combination of these.

# Historical Perspective
- The seasonal variation in mood is observed since ancient times.
- Hippocrates circa (400 BC) first explained seasonal depression. 
- The Greco-Roman physicians managed depression by focusing the sunlight toward the affected individual's eyes.
- In 1894, Cook described a disorder characterized by depressed mood, low energy, fatigue, and loss of libido, which Cook related to the seasonal loss of sunlight. 
- Esquirol(1845) and Kraplein (1921) also described the seasonal variability in the mood.
- In the 1980s, SAD was systematically described for the first time and named by South African physician Normal Rosenthal. He noticed that he felt significantly less energetic during the winters and returned to his normal state during the spring.
- In 1984, a paper was published based on Rosenthal's idea of treating depression with artificial light therapy. 
- Wehr's (1989) contribution in the form of a chapter in the book seasonal affective disorder and phototherapy is well-acknowledged. 
- Wehr et al have also described a variant with the opposite pattern, depression in the summers and non-depressed phases in the winters. This condition is termed reverse-SAD.
- The Seasonal Pattern Assessment Questionnaire (SPAQ), developed by Rosenthal in 1984, is a self-administered screening tool for SAD.

# Classification
- First in 1984, Rosenthal  et  al. proposed a diagnostic criteria in the form of Seasonal Pattern Assessment Questionnaire (SPAQ).
- Diagnostic criteria for SAD was included in DSM-III-R in 1987. 
- According to the Diagnostic and Statistical Manual of Mental Disorders (DSM), SAD does not exist as a separate disorder.
- In DSM-5, the seasonal variation in mood is mentioned as a specifier for both major depressive disorder (recurrent episodes) and bipolar disorder (bipolar I and bipolar II). 
- The International Classification of Diseases, Tenth Edition (ICD-10) includes SAD under the category of recurrent depressive disorder. The characteristic of this condition is that the symptomatology appear in winter and remit during the spring season.

# Pathophysiology
- The pathophysiologic basis of SAD is not completely understood.
- There is a combined effect of circadian, neurotransmitter, and genetic modulations.
- The circadian phase shift and retinal phototransduction of light are also hypothesized to be involved in the pathophysiology.
- The individuals with SAD have some of the following hormonal/neurotransmitter imbalances:
- Serotonin: Studies have shown that individuals with winter-occurring SAD produce more serotonin transporter proteins in the winters than in the summers, causing the lesser effect of serotonin in winters.
- Norepinephrine: Catecholamine levels are also found to be low in these patients.
- Melatonin: In the winters, as days become shorter, and periods of darkness increase. The levels of melatonin that is produced during the night increases. This interferes with the circadian rhythm and induces lethargy.
- Vitamin D: Patients with SAD tend to have lower levels of vitamin D than controls. This deficiency plays a role in exacerbating depression through interference with serotonin action.

# Differential Diagnosis
SAD must be differentiated from diseases that present with similar symptoms, including:
- Major depressive disorder
- Atypical depression
- Bipolar Disorder
- Hypothyroidism
- Seasonal occupational stressors
- Seasonal psychosocial stressors

# Epidemiology and Demographics
- The prevalence of SAD ranges from 1.5% to 9%, depending on latitude.
- A higher positive correlation has been found with latitude and prevalence of winter SAD. This finding is prominent in the age groups over 35 years.

## Age
- The age of onset of SAD is generally between 18 and 30 years.
- In most of the studies, SAD has been diagnosed in younger adults.
- Compared to high-school students, SAD is found to be less prominent in adults. Winter type SAD is related to latitude in adults whereas sociocultural factors play a role in adolescents.

## Gender
- SAD is more common in women as compared to men. Women are four times as likely as men to be diagnosed with SAD.
- The gender differences in SAD are the same as in non-seasonal depression.
- For assessing the gender-based prevalence of SAD, importance should be given to case criteria such as diagnosis (unipolar vs. bipolar), and birth cohort.

## Race
- SAD has no specific racial predilection.

# Risk Factors
Risk factors for SAD include: 
- Female gender
- Age less than 40 years
- Higher latitude
- Family history of depression
- 5-HTTLPR gene polymorphism
- Sociocultural factors (for adolescents)

# Screening
- The Seasonal Health Questionnaire (SHQ) was found to be more sensitive and specific than SPAQ. It also had higher positive and negative predictive values. 
- Other screening tools that can be used are
Seasonal Pattern module of the Structured Clinical Interview for DSM Disorders (SCID)
Hypomania Interview Guide for Seasonal Affective Disorder (HIGH-SAD)
Structured Interview Guide for the Hamilton Depression Rating ScaleSeasonal Affective Disorder
- Seasonal Pattern module of the Structured Clinical Interview for DSM Disorders (SCID)
- Hypomania Interview Guide for Seasonal Affective Disorder (HIGH-SAD)
- Structured Interview Guide for the Hamilton Depression Rating ScaleSeasonal Affective Disorder

# Natural History, Complications, and Prognosis
- SAD can be a very serious disorder and may require hospitalization.
- There is also a risk of suicide in some patients experiencing SAD.
- The symptoms mimic those of clinical depression, with seasonal variability.
- The prognosis of SAD is generally good. However, it has been observed that an index episode with a short duration and the illness course with high frequency showed a seasonal relapse pattern. 
- If appropriate treatment is started early with phototherapy, the prognosis is generally better in patients with predominant atypical symptoms than those having typical melancholic symptoms.

# Comorbidities
Commonly comorbid conditions include:
- Major depressive disorder
- Bipolar disorder
- ADHD
- Alcoholism
- Eating disorders
- Hypothyroidism

# Diagnosis

## Diagnostic Criteria
A diagnosis of SAD is used for patients who meet all the criteria for major depression and have depression corresponding to the onset of specific seasons for a minimum duration of two years.

## Symptoms
General symptoms of major depression are:
- Feeling depressed
- Feeling hopeless
- Lethargy
- Lack of interest in activities enjoyed earlier
- Having trouble sleeping
- Changes in appetite or weight
- Difficulty concentrating
- Frequent thoughts of death or suicide
Symptoms of winter-occurring SAD are:
- Lethargy
- Hypersomnia
- Overeating and weight gain
- Craving carbohydrates and sugars
- Social withdrawal
Symptoms of summer-occurring SAD are:
- The decreased appetite and weight loss
- Insomnia
- Agitation and restlessness
- Anxiety
- Episodes of violence

## Diagnostic and Statistical Manual of Mental Disorders (DSM)
- DSM-5 criteria for the diagnosis of SAD specifier requires 
Two or more episodes fulfilling the DSM-5 criteria of major depressive episode in bipolar I, bipolar II, or major depressive disorder (recurrent), with the last two episodes being consecutive.
Onset and remission of episodes must occur in the same season.
Seasonal episodes must outnumber the non-seasonal ones.
Non-seasonal episodes should be absent over the last two episodes.
Seasonal psychosocial stressors should be excluded.
- Two or more episodes fulfilling the DSM-5 criteria of major depressive episode in bipolar I, bipolar II, or major depressive disorder (recurrent), with the last two episodes being consecutive.
- Onset and remission of episodes must occur in the same season.
- Seasonal episodes must outnumber the non-seasonal ones.
- Non-seasonal episodes should be absent over the last two episodes.
- Seasonal psychosocial stressors should be excluded.

## International Classification of Diseases, Tenth Edition (ICD-10)
- ICD-10 does not include specific clinical guidelines for diagnosing SAD.
- Specific criteria are present in the research-version of ICD-10. These are 
These criteria can be applied to affective disorders category F30-33, the episodes must fulfill the diagnostic criteria for major depression.
Three or more affective episodes must occur within 90 days period of the year for 3 or more consecutive years.
Remission also occurring within 90 days period of the year.
Seasonal episodes outnumber the non-seasonal ones.
- These criteria can be applied to affective disorders category F30-33, the episodes must fulfill the diagnostic criteria for major depression.
- Three or more affective episodes must occur within 90 days period of the year for 3 or more consecutive years.
- Remission also occurring within 90 days period of the year.
- Seasonal episodes outnumber the non-seasonal ones.

# Treatment
- The main options for the treatment of SAD include light therapy, medication, and psychotherapy.
- Any of these therapies can be used alone or in combination. Combination therapies are useful if the patient is unresponsive to a single treatment modality. 

### Light Therapy
- SAD has been treated primarily with light therapy. It is also called bright light therapy (BLT) or phototherapy.
- The rationale behind the use of light therapy is that the depressive effect of decreased sunlight during the winter months can be counteracted through daily exposure to bright light. Phototherapy acts through the change in the amplitude and timing of melatonin secretion as well as serotonergic system modulation. 
- Patients who undergo light therapy typically use a lightbox each morning from early fall until the start of spring.
- The use of lightboxes generally requires 20 to 60 minutes of exposure to 10,000 lux of cool-white fluorescent light, which is approximately 20 times brighter than the standard light.
- Common side effects of light therapy include eye strain, insomnia, and headaches.
- If patients experience side effects, the therapy should be split multiple times a day or administered earlier in the day in case of insomnia. 
- Light therapy is contraindicated if the patient is on photosensitizing medications.
- Light therapy is used daily and it may take up to two weeks for the complete therapeutic response. Maintenance treatment is usually needed daily for the rest of the winter. The treatment should be discontinued on remission otherwise may result in hypomania.
- Precipitation of hypomanic episodes with phototherapy is commonly seen with bipolar cases. These can be controlled by reducing the therapy dose.
- Patients with atypical symptoms of depression respond better to light therapy. 

### Medications
- SAD may be treated with selective serotonin reuptake inhibitors (SSRIs) such as sertraline, and fluoxetine. Like phototherapy, SSRIs should be discontinued on remission to avoid hypomania. 
- Common side effects of SSRIs are nausea, diarrhea, constipation, vomiting, dry mouth, weight changes, sexual dysfunction,  and headaches.
- Bupropion, a norepinephrine dopamine reuptake inhibitor (NDRI), has been specifically approved by the FDA for the treatment of SAD. It can also be used prophylactically in these patients to prevent another episode. 
- Common side effects of bupropion are drowsiness, anxiety, insomnia, dry mouth, dizziness, weight loss, and sore throat.
- Although studies have variable results with the use of vitamin D in patients with SAD, researchers have postulated that it may be helpful due to low vitamin D levels in these patients.
- Agomelatine (melatonergic (MT1 and MT2) receptor agonist and serotonin-2C receptor antagonist) has also shown improvement in SAD symptomatology.
- Other treatment modalities with limited evidence in the management of seasonal affective disorder are high-density negative ionizer, Moclobemide (Monoamine oxidase A Inhibitor), Duloxetine (Serotonin Norepinephrine Reuptake Inhibitor), Modafinil, and hypericum extract.  

### Psychotherapy
- The use of psychotherapy, specifically cognitive behavioral therapy (CBT), to treat SAD is common.
- CBT, in combination with light therapy, has shown promising results. 
- The use of psychotherapy for the prevention of a new depressive episode in individuals with a history of SAD is inconclusive. 
- Seasonal affective disorder is surrounded by treatment options with inadequate evidence. The prophylaxis and management measures warrant thorough long-term research to optimize patient well-being.