Etiology
Familial studies suggest a higher incidence of seasonal affective disorder (SAD) among first-degree relatives, with genetic factors accounting for at least 29% of variance in seasonal mood symptoms among twins.[20][21] Vulnerability to seasonal mood fluctuations may be influenced by multiple genes related to biologic rhythms.[22] Candidate regions have been investigated at serotonergic and dopaminergic receptors, as well as certain clock-related genes.[23] A 2018 genome-wide association study identified ZBTB20 as a candidate susceptibility gene for SAD.[24]
Diminished light during winter months and increased light during summer months may contribute to risk for seasonal mood variations.[23] Rates of SAD may be slightly higher among people living in more northern latitudes.[3][6] However, although the latitude-SAD association has been demonstrated in North American samples, this finding has not been reliably replicated in European cohorts. This suggests the influence of other factors, such as genetic variability, cultural differences, and climate.[7]
Pathophysiology
Circadian and neurotransmitter factors likely contribute to the pathophysiology of SAD, although the exact mechanism of action remains ill-understood.[25][26] The suprachiasmatic nucleus (SCN) of the hypothalamus is being increasingly recognized as the "master regulator" of several systems implicated in seasonal mood regulation.[22] The impact of environmental changes, stress, diet, and genetic expression on the SCN circuitry are being investigated in animal models to better understand the pathophysiology in SAD.[27] Diminished light during the fall and winter may cause a phase shift in various circadian rhythms, including sleep-wake cycle, body temperature, hormone levels, and melatonin secretion.[28][29][30] An abnormality in melatonin rhythms during seasonal changes may be particularly implicated in SAD.[31]
Decreased serotonergic activity also appears common among SAD patients.[32][33] Studies have speculated the shared neuroanatomical pathways and genetic features between the serotonergic and the circadian systems that underlie SAD risk.[34] Studies suggest lower cortisol secretions among SAD patients in the morning during winter months compared with nondepressed controls. Cortisol secretion levels appear similar between the groups during the summer months.[35] Genetic disruptions in circadian rhythm gene functions may partially account for an association between SAD and alcohol-use disorders.[36] Individuals with SAD may have reduced retinal sensitivity during the winter months relative to people without SAD. Specifically, genetic variation in the retinal photopigment melanopsin may be a potential biologic marker for increased SAD risk.[37]
Classification
Season of onset of symptoms
Onset of depressive symptoms during the fall and winter, with full remission or hypomanic or manic symptoms during spring or summer months (most common presentation of SAD).
Onset of depressive symptoms during the summer, with remission or hypomanic or manic symptoms during the winter months (less common than fall- or winter-onset depression).
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