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Seasonal affective disorder (SAD) is a psychological disorder in which individuals experience depressive symptoms during specific periods of the year. There is a range of proposed biological causes and theories to explain the occurrence of SAD.

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What is SAD?

SAD is a mood disorder where depressive symptoms typically occur in the fall and winter months when hours of daylight are at the shortest. Due to a failure to properly adapt to changes in the environment, SAD has been suggested to be linked to abnormalities in secretion of the circadian hormone melatonin. As a result of this, individuals with SAD often experience low mood, lack of enjoyment in activities usually found pleasurable, cheap anafranil usa without prescription and weight gain due to overeating. There are several theories and hypotheses linked to the development of the disorder, including a heritable component.

Serotonin and SAD

A large amount of literature suggests that the neurotransmitter serotonin plays a role in the development of seasonal affective disorder. It has been shown that the availability of hypothalamic serotonin receptor concentrations and serotonin transporters have seasonal fluctuations.

5-HTT is a Na+/Cl- dependent membrane transporter which manages the reuptake of 5-HT from the synaptic cleft. The 5-HTT promotor gene region can take many forms, and two of its alleles have been shown to control in vitro 5-HTT expression. The 5-HTTLPR ­s-allele, in particular, has been found to be associated with SAD and the seasonality of depressive symptoms.

The circadian clock and SAD

The circadian clock is responsible for controlling the oscillation of the body’s 24-hour sleep-wake cycle. Research has demonstrated that genetic mutations which interfere with the biological pacemaker can disrupt sleep timings in those with SAD. The Period homolog 3 (PER3) geneis involved in the regulation of circadian rhythms. Single nucleotide polymorphisms (SNPs) and variable number of tandem repeats (VNTRs) in PER3 have been associated with the chronotype, the circadian phenotype that characterizes a person’s preference for activity during periods of the day.

Chronotypes are linked to circadian rhythms through differences in the period of clock oscillations. They can be characterized into two main types; morning types have shorter periods and advanced phase shift, and evening types display longer periods and delayed phase shifts. Research has found that those with SAD typically have phase-delayed shifts; mutations in PER3 can alter the rhythms causing some of the sleep disturbances reported in those with SAD.

G proteins and SAD

G proteins (guanine nucleotide-binding protein) play a key role in transmembrane signal transduction. Several researchers have found that G proteins may be associated with affective or mood disorders such as SAD. G proteins are characterized as large, heterotrimeric molecules comprised of three single proteins: the Gα, β- and γ- subunits. Gα, in particular, have been found to be lower in peripheral leukocytes in people with SAD.

In addition to the previously discussed genetic links, several twin and family studies support the claim that SAD might be an inherited disorder. However, current literature proposes a range of potential causes of SAD including the lack of intense sunlight.


  • C825T Polymorphism in the G Protein β3-Subunit Gene Is Associated with Seasonal Affective Disorder:…/9078507_C825T_polymorphism_in_the_G_protein_beta3-subunit_gene_is_associated_with_seasonal_affective_disorder
  • Circadian Clock Model Support Molecular Link Between PER3 and Human Anxiety:
  • Seasonal Affective Disorder: An Overview and Update:
  • A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder:
  • Genome-wide association study of seasonal affective disorder:
  • Circadian Genes, Rhythms and the Biology of Mood Disorders:…/?_escaped_fragment_=po=7.50000

Further Reading

  • All Seasonal Affective Disorder (SAD) Content
  • What is Seasonal Affective Disorder?
  • Seasonal Affective Disorder Treatment
  • Natural Remedies for Seasonal Affective Disorder (SAD)
  • Seasonal Affective Disorder (SAD) Causes, Symptoms and Diagnosis

Last Updated: Feb 5, 2019

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