Elsevier

Medical Hypotheses

Volume 83, Issue 5, November 2014, Pages 517-525
Medical Hypotheses

Possible contributions of skin pigmentation and vitamin D in a polyfactorial model of seasonal affective disorder

https://doi.org/10.1016/j.mehy.2014.09.010Get rights and content

Abstract

Seasonal affective disorder (SAD) is a polyfactorial and polygenetic disorder that involves biological and psychological sub-mechanisms that differentially involve depression, seasonality, circadian rhythms, retinal sensitivity, iris pigmentation, sleep factors, and the neurotransmitters involved with these systems. Within the framework of the polyfactorial conceptualization of SAD, we review the possible contributions of vitamin D3 with respect to the aforementioned sub-mechanisms. We hypothesize that rather than functioning primarily as a proximal or direct sub-mechanism in the etiology of SAD, vitamin D likely functions in a more foundational and regulative role in potentiating the sub-mechanisms associated with the depressive and seasonality factors. There are several reasons for this position: 1. vitamin D levels fluctuate in the body seasonally, with a lag, in direct relation to seasonally-available sunlight; 2. lower vitamin D levels have been observed in depressed patients (as well as in patients with other psychiatric disorders) compared to controls; 3. vitamin D levels in the central nervous system affect the production of both serotonin and dopamine; and 4. vitamin D and vitamin D responsive elements are found throughout the midbrain regions and are especially concentrated in the hypothalamus, a region that encompasses the circadian timing systems and much of its neural circuitry. We also consider the variable of skin pigmentation as this may affect levels of vitamin D in the body. We hypothesize that people with darker skin pigmentation may experience greater risks for lower vitamin D levels that, especially following their migration to regions of higher latitude, could contribute to the emergence of SAD and other psychiatric and physical health problems.

Section snippets

Seasonal affective disorder

Major depressive episodes that follow a seasonal pattern are commonly referred to as seasonal affective disorder (SAD) [1], [2]. SAD involves depressed mood or loss of interest in daily activities, and may include feelings of worthlessness, recurrent thoughts of death, sleep disturbances, fatigue, decreased ability to think, concentrate or make decisions, appetite changes, and/or changes in psychomotor activity level that arise in response to a shorter photoperiod in the fall and winter

Polyfactorial model of SAD

The etiology of SAD is complex and appears to be both polyfactorial and polygenetic [13], [14], [15]. Earlier research suggested that seasonality and depression vulnerability factors, occurring in various combinations may underlie the observed spectrum of seasonal affective symptoms [16], [17]. For example, a preponderance of the seasonality factor along with a minor component of the depression factor was hypothesized to explain sub-syndromal SAD. The converse, predominant depression

Vitamin D

Vitamin D is a pre-steroid hormone that is photosynthesized in the epidermis from 7-dehydrocholesterol through exposure to ultraviolet radiation in the 260–320 nm wavelength range, the UV-B section of the solar ultraviolet (UV) spectrum [32], [33], [34], [35], [36]. The liver metabolizes vitamin D to 25(OH) D3, which is the principal form of vitamin D that circulates in the blood on the key measure of vitamin D status. Further, the kidney converts 25(OH) D3 to the hormone, 1,25 dihydroxyvitamin D

Vitamin D, dopamine and serotonin

Evidence exists that both the dopamine and serotonin neurotransmitter systems are involved in the pathophysiology of SAD. The positive emotion effects of 10,000 lux daily light therapy for people with SAD were reversed comparably by the depletion of serotonin and dopamine in a cross-over study of 16 patients [52]. Similarly, other researchers evaluated the depletion of dopamine in a sample of women with mild seasonality under two different lighting environments (3000 versus 10 lux). Regardless

Vitamin D and the circadian timing system

Gominak and Stumpf [59] maintain that vitamin D is probably one of the phylogenetically oldest steroid hormones in that it links the presence or absence of the sun to the availability of food, to activity levels, and to cycles of rest and sleep. Changes in vitamin D levels according to latitude appear to work at the level of individual genes to affect the adaptation to environmental conditions [63]. The circadian system in mammals regulates activity cycles according to the timing of dawn and

Vitamin D status and depression symptoms

Given its contribution to the dopamine and serotonin neurotransmitter systems and its likely involvement in the circadian system, it is logical to inquire about the relationship of vitamin D status with depression symptoms. In patients with nonseasonal depression or SAD, does the administration of vitamin D provide symptomatic relief? Several cross-sectional studies have reported significantly greater depressive symptoms in groups of older people with varying levels of hypovitaminosis D [69],

Skin pigmentation and vitamin D

Melanin is a derivative of tyrosine and exists in two forms within humans: pheomelanin (red-yellow) and eumelanin (black-brown). Melanin is synthesized in melanosomes that are present in several human tissues that include the epidermis, hair follicles, and the iris. Human skin pigmentation most likely represents the outcome of two antagonistic clines that have evolved through natural selection to adapt human constitutive skin pigmentation to the UV radiation levels that occur as a function of

Summary

Seasonal affective disorder possesses a complex etiology that involves several causal and contributory mechanisms [13], [19]. Vitamin D is a phylogenetically old steroid hormone whose presence researchers have documented in at least 36 tissues and 900 genes as of this writing. Rather than functioning as a causally proximal sub-mechanism in SAD, our review of the literature suggests that the role of vitamin D may be more basic and distal in its contributions to SAD, and to the emergence of other

Hypotheses

We propose a dual-vulnerability conceptualization for the emergence of SAD among people with greater pigmentation who migrate to higher-latitude areas, similar in form to Dealberto’s and McGrath’s approaches for conceptualizing the role of vitamin D in the emergence of schizophrenia and atypical psychoses among first and second-generation immigrants. [56], [82], [83]. Specifically, the first generation of people with dark skin to migrate to high latitude areas may be more likely to exhibit

Conflict of interest statement

None.

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