Genetics of Seasonal Affective Disorder

The Winter Blues… described as a low feeling, generally apathetic, blah, usually accompanied by changes in sleep.  It is fairly common in northern latitudes, affecting almost 10% of some populations.

Seasonal Affective Disorder (SAD) is characterized by a recurrent depression with a change in the season usually in fall/winter for most. Scientists think this is possibly due to an aberrant response to light – either not enough brightness to the sunlight or not enough hours of light.

SAD is considered to be “heritable” with twin studies indicating that about 50% of the risk factors are genetic.

Genes that have been found in studies to be tied to the risk of seasonal affective disorder are mainly circadian rhythm genes that function to control our 24-hour rhythmic cycle. Our circadian rhythm is controlled by genes that are set by light hitting the retina of our eyes. Interestingly, some of the genes associated with SAD also overlap with genetic variants that increase susceptibility to bipolar disorder and schizophrenia but not depressive disorders.[ref]

You may be wondering, but what about serotonin?  Everyone thinks of serotonin for depression due to the popularity of SSRI’s as an antidepressant. Several studies for seasonal affective disorder have looked into the link to serotonin. Most of the studies didn’t find a big link to serotonin genes, but the way serotonin is used by the brain may play a role in SAD.[ref] [ref] [ref] And how people react to SAD, for example, by overeating, may be related to serotonin.[ref]

While genes do play a major role in increasing the risk of SAD, there is not one specific gene mutation that causes seasonal affective disorder. Rather, there are multiple genetic variants that add to the risk, along with latitude, length of daylight, and possibly dietary factors.

Genes involved in the risk for Seasonal Affective Disorder

PER3 Gene
The PER3 gene has been tied to the seasonal effect from shorter daylight hours in a number of studies. All of the PER (Period) genes (PER1, PER2, and PER3) play a central role in our body’s circadian rhythm. PER1 and PER2 genetic variants may cause disruptions in sleep and a shift in circadian rhythm. PER3 genetic variants have been linked specifically to mood changes due to shorter daylight hours in the winter. The slight shift in circadian rhythm from the PER3 genetic variant coupled with the change in daylight may be what causes SAD for some people.[ref][ref] [ref] [ref][ref]

Check your 23andMe results for rs139315125 P415A (v.5 only):
AA: normal
AG: less PER3, higher risk of SAD
GG: decreased PER3, higher risk of SAD, delayed sleep phase disorder [ref]
Check your 23andMe results for rs150812083 H417R (v.5 only):
CC: normal
CG: less PER3, higher risk of SAD
GG: decreased PER3, higher risk of SAD, delayed sleep phase disorder [ref]
Check your 23andMe results for rs228697 (v4, v5):
CC: normal
CG: linked to evening preference; higher risk of anxiety disorders, SAD
CG: linked to evening preference; higher risk of anxiety disorders, SAD [ref][ref][ref]

OPN4 – melanopsin gene
Melanopsin is the non-visual photopigment in your retina that sets the circadian clock. It is thought that lower levels of melanopsin may contribute to the risk of SAD because of the lower light levels in the winter.
Melanopsin is the photopigment involved in photoentrainment, negative masking, and pupillary light reflex.

Check your 23andMe results for rs2675703 (v5 only) P10L:
CC: normal
TT:  5.6x more likely to have SAD; heightened responsivity to daylength.[ref] [ref]

The Circadian Locomotion Output Kaput (CLOCK) gene is one of the core genes that set our daily rhythms.

Check your 23andMe results for rs1801260 (v. 4, v5)
AA: normal
GG: decreased risk of SAD; a higher level of activity in evening. [ref] [ref]


If you can’t get outside for enough sunlight during the daylight hours for whatever reason (working, living too far north, etc), there are full spectrum lights made specifically for SAD. Studies have found 30 minutes of 10000 lux in the early morning to be effective.

New studies show that narrow spectrum blue light (100 lux) may be as effective as bright full wavelength light (10,000 lux).

Putting a blue light in your ear may sound a bit ‘out there’, but there are a few studies that indicate this might just be something worth trying. A clinical trial of transcranial blue light through the ear canal reduced depression by half in more than 75% of participants. (I’m not sure how great this clinical trial is, though, since there is no sham or control group, just comparisons of different strengths of light.)  Transcranial light isn’t as crazy as it seems. Animal studies have shown that extra-ocular light (i.e. through the ear canal) has an effect on the brain. Birds are known to have photoreceptors in their brain that regulate seasonal reproduction.  Sunlight through the skull induces GABA release in rats.

A mouse study looking at the effect of dim light at night found that for mice lacking in PER3 (similar to above genetic variants), dim light at night caused an anhedonia-like effect. Anhedonia is the loss of pleasure or interest in things, feeling blah. Night-time light exposure had become a huge problem around the world, with far-reaching health effects on people and animals. If you have PER3 genetic variants (or even if you don’t!), blocking light at night is important for healthy sleep. Blackout curtains are not that expensive, and you can block all the little LED lights from chargers, etc by just putting a piece of dark tape over them.

A gingko extract reversed depression in light-deprived mice.

A recent study found that vegetarians in the Netherlands and in Finland are 3 to 4 times more likely to have seasonal affective disorder.  I’m not sure if this means that vegetarians are more susceptible to SAD, or if people who have SAD are more likely to be vegetarian.

Another study found that SAD is more likely to affect people with lower total cholesterol levels (<230 mg/dl) than with higher cholesterol levels (>230 mg/dl).  Not sure that this is really a ‘lifehack’ but it is another reason that higher cholesterol may not be as bad as the statin-producers make it sound like.

Several studies found that commonly suggested supplements, such as melatonin and fish oil, may not have much benefit for SAD. Keep in mind that these studies are looking at a general population and individual results could vary. (In other words, if fish oil or melatonin makes your SAD go away, keep taking it :-)
A review that looked at studies of melatonin for mood disorders (including SAD) found no benefit to melatonin supplementation. Another review looked at omega-3 supplements for seasonal affective disorder and found no evidence of clinical efficacy.

More to read:

Will Norway Ever Beat the Winter Blues?


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