Your nervous system is stuck in overdrive. Your genes may be why.

Your COMT gene produces an enzyme that breaks down catecholamines: dopamine, norepinephrine, and epinephrine. These are your stress hormones. The moment a threat passes, COMT clears them so your nervous system can return to baseline. It’s the off switch.

The Val158Met variant changes how efficiently this enzyme works. Roughly 25% of people with European ancestry carry the slow version (homozygous Met). If you have slow COMT, your stress hormones linger in your bloodstream for hours after the stressor is gone. Your body experiences an artificial extended threat signal. Your nervous system never fully recovers.

You notice this as restlessness, racing thoughts at night, sensitivity to caffeine, difficulty unwinding after work, and a constant low-level anxiety that doesn’t match your actual circumstances. You might feel jumpy or reactive. Loud noises startle you. Small frustrations trigger big responses. Sleep is light and fragmented because your nervous system is still primed.

FKBP5 is a protein that attaches to your cortisol receptor. When cortisol binds to this complex, it sends a feedback signal: ‘the threat has passed, shut down the stress response.’ This is your nervous system’s natural brake. FKBP5 makes that brake work efficiently.

The rs1360780 variant impairs this feedback loop. Roughly 30% of people carry the risk allele. If you have this variant, cortisol stays elevated for hours after a stressor ends because the brake signal is weak. Your nervous system doesn’t get the all-clear message. It keeps running at high speed even after the danger is gone. Recovery is slow and incomplete.

You experience this as difficulty unwinding, racing thoughts that continue long after a stressful event, hypervigilance that feels automatic, and a sense of dread that lingers. You might feel exhausted but wired: too tired to function but too activated to sleep. Your baseline cortisol may creep higher and higher over time, locking you into burnout.

SLC6A4 produces the serotonin transporter, a protein that recycles serotonin back into nerve cells after it’s been released. Serotonin is your mood buffer: it reduces anxiety, supports emotional resilience, and helps you recover from stress. Recycling it efficiently keeps the buffer charged.

The 5-HTTLPR short allele reduces how much transporter protein you make. Roughly 40% of people carry at least one short allele. If you have the short allele, serotonin gets recycled slowly, leaving you with lower available serotonin during stress. Your emotional buffer depletes faster. Your anxiety reactivity increases. You become more vulnerable to mood crashes under workload.

You notice this as racing thoughts under pressure, difficulty finding calm even in quiet moments, heightened sensitivity to rejection or criticism, and low mood that arrives suddenly. You might feel more anxious around crowds, during social stress, or when facing uncertainty. Minor stressors trigger disproportionate anxiety. Your nervous system feels more reactive than others’ seem to be.

MAOA produces monoamine oxidase A, an enzyme that breaks down serotonin, dopamine, and norepinephrine once they’ve done their job. It’s a cleanup enzyme. When MAOA works efficiently, neurotransmitter levels stay balanced. When it works slowly, neurotransmitters accumulate and fluctuate unpredictably.

The MAOA-L variant (low activity) is carried by roughly 30 to 40% of males. If you have MAOA-L, neurotransmitters accumulate and clear slowly, causing dramatic mood and anxiety swings throughout the day. You might feel fine one moment and intensely anxious the next with no external trigger. Your emotional baseline is unstable. Stress hits harder because you’re starting from a higher baseline of activation.

You experience this as sudden waves of anxiety, irritability that feels disproportionate, emotional volatility, and difficulty maintaining calm. You might have strong impulses that surprise you. Your nervous system feels like it’s running on high with the throttle stuck. Stimulants like caffeine make this much worse.

BDNF is brain-derived neurotrophic factor. It’s a protein that repairs brain cells damaged by stress, creates new neural connections, and helps your brain adapt to challenges. BDNF is your biological resilience factor: with enough of it, stress bounces off. Without it, stress accumulates as damage.

The Val66Met variant reduces how much BDNF your brain produces, especially in response to stress. Roughly 30% of people carry the Met allele. If you have the Met allele, your brain has reduced capacity to repair stress damage and adapt to challenges. You recover more slowly from burnout. Your nervous system stays sensitized longer. You’re more vulnerable to the cumulative wear of chronic stress.

You notice this as difficulty bouncing back from stressful events, a feeling that stress accumulates over time, depression or low mood that deepens with repeated stress, and a sense that your brain feels ‘sticky’ or burned out. Learning feels harder under pressure. Your mental flexibility decreases. You might feel cognitively slower after periods of high stress.

NR3C1 produces the glucocorticoid receptor, a protein that sits on your cells and responds to cortisol. When cortisol binds to this receptor, it triggers a cascade of stress responses: raised heart rate, blood sugar mobilization, inflammatory suppression, and heightened vigilance. The sensitivity of this receptor determines how much cortisol is needed to trigger these responses.

Several NR3C1 variants reduce the sensitivity of the glucocorticoid receptor. Roughly 25 to 30% of people carry these variants. If you have NR3C1 variants, your cells require higher cortisol levels to register ‘stress’ and respond. This means you need more cortisol circulating to trigger appropriate responses. Over time, chronically elevated cortisol becomes your baseline. Your nervous system recalibrates to this higher level as normal.

You experience this as constant mild anxiety even in neutral situations, difficulty recognizing when you’re actually stressed until you’re completely overwhelmed, persistent low-level agitation, and a sense that your nervous system is running hot all the time. You might have high energy but it feels jittery rather than purposeful. Relaxation feels foreign.