Anxiety, Depression, and Burnout: Is There a Link to Genetics?

You notice that you feel more anxious than colleagues or friends in similar situations. Or that after a difficult week, recovery takes far longer than it "should." Or that burnout sets in where others simply feel tired. None of this is a matter of willpower or character type.

Genetic predisposition to depression and anxiety is a real phenomenon that is actively studied. This doesn't mean someone is "destined" to experience certain conditions. But it explains why the same circumstances produce different responses in different people — and why standard advice sometimes simply doesn't work.

When the Stress Response Doesn't Match the Scale of the Stressor

Imagine two people with the same level of work pressure. One winds down by the end of the week and easily "sheds" the tension by evening. The other is still in a state of anxiety, poor sleep, and irritability three days later. The difference is not a weakness in either of them.

The issue lies in how the stress response is structured at the neurobiological level. Its central system is the HPA axis (hypothalamic-pituitary-adrenal axis), which regulates cortisol production in response to a stressor — and equally importantly, its "switch-off" once the threat has passed.

In some people, this system is more reactive: it activates faster and returns to baseline more slowly. Both experience and lifestyle contribute to this difference — as does genetics.

What Genetics Says: The Hereditary Component of Anxiety and Depression

For a long time, anxiety and depression were considered primarily reactions to circumstances. Twin studies revealed a more complex picture: the hereditary component of anxiety disorders is estimated at 20–60%, and of depression at 30–50%. This means that between a quarter and half of the variation in predisposition between people is explained by genetic variants (Tabrizi et al., Translational Psychiatry, 2025).

These figures are not an absolute individual prediction. They reflect the statistical contribution of genetics at the population level: if one twin has a depressive disorder, the monozygotic co-twin has a noticeably higher risk than a dizygotic co-twin. That is the hereditary component.

Particularly striking are data on comorbidity: when anxiety and depression occur together, the shared heritability of this combined state reaches 79% — significantly higher than for each condition separately. A 2025 study links this to shared genetic pathways regulating both conditions (Tabrizi et al., Translational Psychiatry, 2025).

A large-scale 2021 GWAS — a meta-analysis involving over 1.2 million participants — identified 178 independent genetic loci associated with depression. This confirmed that depression is polygenic, its genetic architecture spanning hundreds of variants each with small effect. None of them "resolves" the situation alone, but together they form a statistical predisposition (Levey D.F. et al., Nature Neuroscience, 2021).

How Genetics Influences Mood and Stress Resilience

Genetic influence operates through several distinct biological systems. They act at different levels and together shape how a person experiences stress, recovers from it, and how resilient they are to chronic load.

Serotonin Regulation

Serotonin is a neurotransmitter involved in regulating mood, anxiety, and emotional responses. After release into the synaptic cleft, it must be transported back into the neuron — and this transport is controlled by the protein encoded by the SLC6A4 gene.

Variants of this gene, including a polymorphism in the promoter region, are associated with reduced or increased efficiency of this transporter. In people with certain variants, serotonin "stays" in the synapse longer — or, conversely, is cleared faster than average. This influences how neurons respond to emotional stimuli. A 2023 meta-analysis confirms that these variants are associated with altered sensitivity to stressful events and are a factor in predisposition to depressive states in certain populations (Wang Y. et al., Frontiers in Psychiatry, 2023).

Neuroplasticity

The brain adapts to stressors — and this process depends significantly on the neurotrophic factor BDNF (brain-derived neurotrophic factor). BDNF supports neuron growth and survival, strengthens synaptic connections, and plays a key role in the brain's ability to recover from stress.

The BDNF gene has a well-studied variant: Val66Met (rs6265). A 2023 meta-analysis showed that in carriers of the Met allele, this variant is associated with elevated predisposition to depressive disorders in populations of predominantly European ancestry. The mechanism involves the Met variant reducing the secretory activity of BDNF — which affects the ability of neurons to form new connections in response to stress (Wang et al., Frontiers in Psychiatry, 2023).

The Stress Axis (HPA)

Third — the endocrine level. The FKBP5 gene encodes a protein that regulates cortisol receptor sensitivity. Effectively, it influences how efficiently the body "switches off" the stress response after it has ended.

Variants of FKBP5 are associated with altered HPA axis function: in carriers of certain polymorphisms, cortisol declines more slowly after a stress episode — keeping the system in an active state for longer. A 2023 review describes this mechanism as one of the key factors in the pathogenesis of stress-induced psychiatric disorders — from anxiety to PTSD (Malekpour et al., Frontiers in Psychiatry, 2023).

Burnout Is Not Just "Too Much Work"

In the current ICD-11 classification, burnout is described as a phenomenon associated with chronic workplace stress. It is not a psychiatric diagnosis in the formal sense, but mechanistically it is closely linked to prolonged HPA axis activation, reduced neuroplasticity, and disrupted serotonin balance.

This is where the genetic context becomes especially relevant. A person with a genetically modulated HPA axis response — for instance through FKBP5 variants — may enter a state of exhaustion faster and at a lower load threshold than someone with a different genetic profile. This means their stress system is structured differently and requires a different recovery approach.

Similarly, variants of SLC6A4 and BDNF influence how quickly and completely a person recovers from prolonged load. Where one person "recharges" over a weekend, another — with a different set of genetic features — needs significantly more time and a more structured recovery approach.

Self-Observation Markers: What to Pay Attention To

The following list is not a set of diagnostic criteria. These are signs that may indicate elevated sensitivity of the stress system. If several of them are a consistent part of your daily life, this is a reason to speak with a specialist.

• You notice that after conflicts or difficult situations, the tension doesn't release for hours or even days.

• An anxious response arises even in situations you yourself assess as minor.

• After a stressful week, you need significantly more time to recover than seems like it "should" be necessary.

• Your mood depends heavily on sleep: one bad night and the next day you can't get into your usual rhythm.

• You are prone to anxious anticipation — and begin to panic well before anything has actually happened.

• Burnout sets in at a load level that others seem to handle calmly.

• After a vacation or extended rest, you have the sense that even more time is needed to recover.

Once more: these are signs you may notice in yourself — not a diagnosis or grounds for conclusions about a disorder. They are a starting point for a conversation with a mental health professional, and a reason to consider whether there is a genetic component to your stress response.

Genetic Context: What It Provides in Practice

Knowing that you have a genetic predisposition to a more intense stress response is not the same as "finding your diagnosis."

A person who knows their genetic profile in the context of stress resilience can:

• better explain to a doctor why standard recommendations may not be a good fit;

• understand why certain recovery approaches are more effective for them personally;

• plan their workload in accordance with their actual threshold — not an imagined "average."

To discover how your body responds to stress and what genetic basis may influence mood and recovery → DNA test "Mental Health & Brain".

It turns out that the state a person describes as "I'm just very sensitive" or "I can't let things go" is often connected to specific features of the neurobiological regulatory systems. And yet no standard laboratory test or routine examination reveals this.

Stress Resilience Is Not a Character Trait

The capacity to tolerate stress, recover from it, and not "get stuck" in anxiety is shaped at the intersection of genetics, experience, and lifestyle. Genetics here is neither a verdict nor the sole cause — but meaningful context that explains why the same situations produce different responses in different people.

Knowing your genetic profile matters not to find a problem — but to better understand how your body is structured and how to most effectively support your mental health.

Genetic test results are not a diagnosis and do not replace a physician's consultation. The Apixmed Prism report provides genetic context that complements examination results and supports decision-making together with a doctor.

References

• Levey, D. F., Stein, M. B., Wendt, F. R., et al. (2021). Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions. Nature Neuroscience, 24(7), 954–963. https://doi.org/10.1038/s41593-021-00860-2

• Tabrizi, F., et al. (2025). Heritability and polygenic load for comorbid anxiety and depression. Translational Psychiatry, 15(1), 98. https://doi.org/10.1038/s41398-025-03325-3

• Wang, Y., Li, O., Li, N., et al. (2023). Association between the BDNF Val66Met polymorphism and major depressive disorder: a systematic review and meta-analysis. Frontiers in Psychiatry, 14, 1143833. https://doi.org/10.3389/fpsyt.2023.1143833

• Malekpour, M., et al. (2023). Role of FKBP5 and its genetic mutations in stress-induced psychiatric disorders: an opportunity for drug discovery. Frontiers in Psychiatry, 14, 1182345. https://doi.org/10.3389/fpsyt.2023.1182345

• Coombes, B. J., et al. (2023). The genetic contribution to the comorbidity of depression and anxiety. Psychological Medicine, 53(15), 7368–7374. https://pubmed.ncbi.nlm.nih.gov/38078748/