Your mood shifts with the seasons. Your genes may be why.

COMT is your brain’s cleanup crew for dopamine, norepinephrine, and epinephrine. These are the neurotransmitters that drive focus, motivation, emotional stability, and stress resilience. After a stressful moment passes, COMT breaks down these hormones so your nervous system can calm down. If COMT works normally, stress hormones spike during a threat and then clear quickly. Your mood stabilizes. You recover.

The Val158Met variant, carried by roughly 25% of people with European ancestry in homozygous form, makes COMT work slowly. When COMT moves slowly, dopamine and norepinephrine linger in your synapses longer than they should. You stay stuck in a state of alertness and emotional reactivity even after the stressor is gone. Combine slow COMT with seasonal light reduction and your baseline anxiety climbs. Small annoyances feel like catastrophes. You feel wired but exhausted.

In winter, when light is low and your nervous system is already more reactive, slow COMT keeps stress hormones elevated. You feel jumpy, irritable, unable to unwind at night. Your mood swings become sharper because your brain can’t clear the very chemicals that create emotional intensity.

SLC6A4 codes for the serotonin transporter, the protein that pulls serotonin back out of the space between brain cells after it’s been used. This recycling is crucial. Your brain doesn’t have unlimited serotonin production. Recycling is how you maintain stable mood across the day and across seasons. If your transporter works efficiently, serotonin gets reused quickly and you maintain emotional baseline.

The 5-HTTLPR short allele, carried by roughly 40% of the population in at least one copy, impairs this recycling process. Your brain reuses less serotonin, so available serotonin drops and mood destabilizes more easily. You become more sensitive to mood triggers. In winter, when natural serotonin production already declines due to reduced light exposure, the short allele makes the problem worse. Your baseline mood drops further than it would if you had the long allele.

You notice this as a subtle but persistent lowness in winter. Not necessarily depression, but a flatness. Colors seem duller. Socializing feels effortful. Energy dips. Your emotional resilience shrinks. Things that wouldn’t normally bother you in summer feel overwhelming. By February you’re wondering if something is wrong.

MAOA (monoamine oxidase A) is the enzyme that breaks down serotonin, dopamine, and norepinephrine once they’ve done their job. Proper degradation is essential. If neurotransmitters aren’t cleared efficiently, they accumulate and create overstimulation. If they’re cleared too quickly, you run low. The balance matters.

The MAOA-L variant (low activity), present in roughly 30 to 40% of males, slows the breakdown of these neurotransmitters. Serotonin and dopamine linger in your brain longer, causing mood and energy to fluctuate unpredictably. You don’t get the steady, regulated state other people experience. Instead, you swing between peaks of agitation and valleys of depletion. In winter, when light reduction naturally lowers serotonin, the MAOA-L variant amplifies the swing. Your mood becomes more reactive to seasonal changes.

You experience this as emotional turbulence. You feel intense one day and flat the next. Your mood doesn’t feel stable. Seasonal transitions hit harder because the underlying neurotransmitter swings are already more dramatic. You might have difficulty with emotional regulation or find yourself reacting more strongly to minor frustrations.

MTHFR is the enzyme that processes folate into its active form, methylfolate. This active form is essential for dozens of reactions in your body, including the synthesis of serotonin, dopamine, and norepinephrine. Your brain cannot manufacture mood-regulating neurotransmitters without adequate methylfolate. MTHFR also supports the methylation cycle, which is critical for stress hormone regulation and gene expression in your brain.

The C677T variant, carried by roughly 40% of people with European ancestry, reduces MTHFR enzyme activity by 35 to 70%. You experience functional folate deficiency at the cellular level, even if your serum folate levels look normal on standard blood tests. Your brain cannot synthesize serotonin, dopamine, and norepinephrine at full capacity. During winter, when you might already be managing lower serotonin from reduced light, the MTHFR variant makes the deficit worse.

You notice this as persistent low mood, difficulty concentrating, and reduced ability to manage stress. You might feel foggy in winter even though you’re sleeping. Your mood baseline is lower than it should be given your life circumstances. You might have tried standard antidepressants with limited effect, because the problem at the root is neurotransmitter synthesis capacity, not just reuptake.

BDNF (brain-derived neurotrophic factor) is a protein that supports the survival of existing neurons and encourages the growth of new neurons and synapses. This is neuroplasticity: your brain’s ability to rewire itself in response to experience and treatment. BDNF is essential for mood regulation, learning, and recovery from depression. Higher BDNF means your brain is more adaptive and resilient. Lower BDNF means your mood is more rigid and less responsive to interventions.

The Val66Met variant, carried by roughly 30% of the population, reduces BDNF secretion. Your brain has less capacity to build new neural connections and adapt to mood regulation strategies. This shows up as reduced antidepressant response and difficulty bouncing back from mood episodes. In seasonal mood swings, the Met allele means your brain is less able to compensate for seasonal neurotransmitter shifts. The mood changes stick around longer because your brain can’t rewire out of the pattern.

You experience this as mood changes that feel entrenched. When winter mood drops hit, they last longer and feel harder to shift. You might try therapy, exercise, light therapy, and they help less than you’d expect. Standard antidepressants might work partially but not fully. Your brain’s plasticity is reduced, so recovery from seasonal mood swings takes longer and requires more deliberate intervention.

FKBP5 codes for a protein that regulates cortisol receptor sensitivity. This protein sits on the glucocorticoid receptor and determines how sensitive your cells are to cortisol. When you face a stressor, your body releases cortisol to mobilize energy and focus. When the stressor passes, cortisol should drop and your nervous system should calm. FKBP5 helps reset this system. Normal FKBP5 means your cortisol response is proportional and recovery is quick.

The rs1360780 variant, present in roughly 30% of the population, impairs glucocorticoid receptor sensitivity. Your body takes longer to register that the stressor is gone, so cortisol stays elevated longer than it should. Your HPA axis (the brain’s stress regulation system) stays activated. You stay in a state of heightened vigilance even after the threat has passed. Seasonal stress compounds this: winter darkness itself is a mild stressor, so cortisol creeps up and stays up.

You feel this as persistent tension, difficulty relaxing, and a sense of underlying dread that doesn’t match your current situation. Sleep is difficult because your nervous system won’t downregulate at night. Your mood feels reactive and fragile. You might notice that you recover poorly from small stressors. By midwinter, your baseline cortisol is higher than it was in summer, and your resilience is lower.