Genetics of Seasonal Affective Disorder

The Winter Blues… It’s often described as a low feeling, generally apathetic, blah, usually accompanied by changes in sleep. Officially called Seasonal Affective Disorder, the change in mood when the days grow short is a fairly common phenomenon in northern latitudes, affecting almost 10% of some populations. Interestingly, research shows that Seasonal Affective Disorder is driven by genetic variants in the genes that influence responsiveness to light and circadian rhythm.

This article dives into the science of why seasonal affective disorder occurs, which genetic variants increase susceptibility to it, and the personalized solutions that may work for specific genetic variants.

What is Seasonal Affective Disorder?

Seasonal Affective Disorder (SAD) is characterized by recurrent depression with a change in the season, usually in fall/winter for most. Scientists think this is possibly due to an aberrant or altered 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.[ref]  What is the other half of the equation here? Daylight exposure is a big one. Chronic inflammation may also increase the risk.

Looking at genes that increase the risk of a disease or disorder is how researchers figure out what is causing the disorder — the root cause.

Genes tied to the risk of seasonal affective disorder are mainly circadian rhythm genes that control our 24-hour rhythmic cycle.

Circadian rhythm and SAD:

Our circadian rhythm is controlled by genes that are set by light hitting the retina of our eyes.

During the daytime, light in the blue spectrum hits specific receptors in the retina and shuts off melatonin production from the pineal gland. At night, the lack of light in the blue wavelengths allows melatonin levels to rise again.

Both the suppression of melatonin during the daylight via exposure to bright light and the rise of melatonin at night due to darkness are integral to mental and physical health. The lack of light during the daytime may affect seasonal depression by not shutting off melatonin production enough during the day.[ref]

Interestingly, some of the genes associated with SAD also overlap with genetic variants that increase susceptibility to bipolar disorder and schizophrenia, but not to depressive disorders.[ref] For many, bipolar disorder is linked to circadian rhythm disruption.

Serotonin and SAD:

You may be wondering, but what about serotonin? Everyone thinks of serotonin for depression due to the popularity of SSRIs 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]

Interestingly, a couple of studies have found that a serotonin receptor, HTR2A, is significantly associated with seasonal depression in both winter and summer.  This receptor is involved in memory, mood, cognition, appetite, anxiety, perception, sleep, thermoregulation, and vasoconstriction. It is activated by serotonin, LSD, psilocybin, and DMT.

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.

Monoamine Oxidase (MAO-A)

MAO-A is an enzyme that breaks down neurotransmitters, and changes in MAO-A levels are linked to depressive disorders.

Recently, researchers discovered that most people normally have a seasonal change in MAO-A levels in the fall and winter. But people with SAD don’t have that normal, seasonal rhythm to MAO-A levels. Important here, the researchers also found that bright light therapy restored the normal MAO-A seasonal dynamics. [ref]


Genes involved in the risk for Seasonal Affective Disorder

Members: Log in and select your data file
Not a member? Join now to see your data below.

Details on the genetic variants:

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 genetic data for rs139315125 (23andMe v5):

  • A/A: typical
  • A/G: less PER3, higher risk of SAD
  • G/G: decreased PER3, higher risk of SAD, delayed sleep phase disorder[ref]

Members: Your genotype for rs139315125 is .

Check your genetic data for rs150812083 (23andMe v5 ):

  • C/C: typical
  • C/G: less PER3, higher risk of SAD
  • G/G: decreased PER3, higher risk of SAD, advanced sleep phase disorder[ref][ref]

Members: Your genotype for rs150812083 is .

Check your genetic data for rs228697 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/G: linked to evening preference; higher risk of anxiety disorders, SAD
  • G/G: linked to evening preference; higher risk of anxiety disorders, SAD[ref][ref][ref]

Members: Your genotype for rs228697 is .

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 involved in photo-entrainment, negative masking, and pupillary light reflex. Basically, it is excited by light in the blue-wavelengths (~480nm) and relays a signal to the brain that it is daytime.

Check your genetic data for rs2675703 P10L (23andMe v5; AncestryDNA):

  • C/C: typical
  • C/T: increased risk of SAD
  • T/T:  5.6x more likely to have SAD; heightened responsivity to daylength.[ref][ref]

Members: Your genotype for rs2675703 is .

Check your genetic data for rs1079610 I394T (AncestryDNA):

  • T/T: typical
  • C/T: response to light, earlier sleep/wake timing
  • C/C: increased response to blue light[ref]; earlier sleep/wake timing[ref], linked with SAD (small study)[ref]

Members: Your genotype for rs1079610 is .

CLOCK Gene:

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

Check your genetic data for rs1801260 (23andMe v4, v5: AncestryDNA)

  • A/A: typical
  • A/G: typical risk of SAD, increased evening activity
  • G/G: decreased risk of SAD; a higher level of activity in the evening.[ref][ref]

Members: Your genotype for rs1801260 is .

ARNTL gene: codes for BMAL1, which pairs with the CLOCK protein as part of the core circadian clock

Check your genetic data for rs2290035 (AncestryDNA):

  • A/A: lower risk of SAD
  • A/T: increased risk of SAD
  • T/T:  typical risk of SAD.

Members: Your genotype for rs2290035 is .

 

HTR2A gene: encodes the serotonin 2A receptor. This is the same receptor activated by psychedelics

Check your genetic data for rs731779 (23andMe v4; AncestryDNA):

  • C/C: significantly increased risk of SAD
  • A/C: typical risk
  • A/A: typical

Members: Your genotype for rs731779 is .


Lifehacks for Seasonal Affective Disorder

First and foremost: going outside first thing in the morning may help if you live at a middle latitude. The sun is powerful in resetting circadian rhythm.

Light Boxes for Full Spectrum Light:
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).[ref][ref]

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.[ref] (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 brains that regulate seasonal reproduction.[ref] Sunlight through the skull induces GABA release in rats.[ref]

Sleep in the dark: A mouse study looking at the effect of dim light at night found that for mice lacking in PER3 (similar to the above genetic variants), dim light at night caused an anhedonia-like effect.[ref] Anhedonia is the loss of pleasure or interest in things, feeling blah. Night-time light exposure has 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 ginkgo extract reverses depression in light-deprived mice.[ref]

Dietary links to seasonal affective disorder:
A recent study found that vegetarians in the Netherlands and in Finland are 3 to 4 times more likely to have seasonal affective disorder.[ref] 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 vegetarians.

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).[ref] Not sure that high cholesterol is really a ‘lifehack’, but this is interesting.

What doesn’t work: 

A review that looked at studies of melatonin for mood disorders (including SAD) found no benefit to melatonin supplementation.[ref]

Another review looked at omega-3 supplements for seasonal affective disorder and found no evidence of clinical efficacy.[ref]

Even though these studies don’t show much benefit, on average, everyone is unique. So if you feel that fish oil or melatonin are benefiting you for SAD, then keep taking it.  (Read more about melatonin research)


Extras for Members:

Member Content:

An active subscription is required to access this content.

Join Here for full access to this article, genotype reports, and much more!


Already a member? Log in below.


Related Genes and Topics:

Is inflammation causing your depression or anxiety?
Research over the past two decades clearly shows a causal link between increased inflammatory markers and depression. Genetic variant in the inflammatory-related genes can increase the risk of depression and anxiety.

Serotonin: Genetic variants that impact serotonin levels and serotonin receptors
Serotonin is a neurotransmitter that is important in depression, sleep, and many other aspects of health. Learn how your genetic variants in the serotonin receptor genes impact their function.

COMT Gene: Neurotransmitters, estrogen metabolism, and more
Wondering why your neurotransmitters are out of balance? It could be due to your COMT genetic variants. The COMT gene codes for the enzyme catechol-O-methyltransferase which breaks down (metabolizes) the neurotransmitters dopamine, epinephrine, and norepinephrine.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.