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Did you know that depression can be influenced by DNA? In this article, we will discuss how mental health, depression, and genetics are related and how understanding these relationships can help you take action on optimizing your well-being.
Disclaimer: This article is for informational purposes only and is not intended to diagnose any conditions. LifeDNA does not provide diagnostic services for any conditions mentioned in this or any other article.
Depression or major depressive disorder (MDD) is a multifactorial psychiatric condition. Individuals with depression often find themselves in a persistently low mood, anhedonia (inability to feel pleasure), cognitive disturbances, and other symptoms that impair daily functioning.
Read our popular deep-dive on the Genetics of Depression
According to epidemiological data a lifetime prevalence of depression is approaching 15-20 % worldwide. Primary cause arises from complex interactions of genetics, neurochemical imbalance, dysregulated stress-axis activity, and environmental stress factors.
Brain research shows that depression is linked to fewer mood-related neurotransmitters, disrupted glutamate activity, a smaller hippocampus, and poor communication between brain areas that control emotion and thinking. Converging evidence also highlights inflammatory processes and neurotrophic deficits, particularly decreased brain-derived neurotrophic factor (BDNF) expression, as contributors to disease onset and progression.
Antidepressants help correct chemical imbalances in the brain that are linked to depression. Most work by increasing the levels of mood-related neurotransmitters such as serotonin, norepinephrine, or dopamine. By restoring these signals, the drugs can lift mood, improve sleep and appetite, and reduce anxiety. They usually take a few weeks to reach full effect and should be used under a doctor’s guidance.
Antidepressant prescribing still relies heavily on trial-and-error. Around one-third of patients achieve remission with the first drug they receive, while many experience delayed benefit or troublesome side-effects. Pharmacogenomics, the study of how genetic variation influences drug response, offers a path out of this uncertainty. Over the past decade, and especially since 2023, large-scale studies and guideline updates have clarified which genes are involved, how strongly they affect efficacy and tolerability, and when testing should guide routine care.
SSRIs are a common class of antidepressant medicines that raise the level of serotonin. Serotonin is a chemical that helps regulate mood, and SSRIs act by blocking its re-absorption (reuptake) into the brain’s nerve cells after it is released. With more serotonin remaining active in the synapse (the space between two nerve cells), communication between neurons improves, which over several weeks can lift mood, reduce anxiety, and ease other depressive symptoms.
Drugs such as fluoxetine, sertraline, and escitalopram belong to this group and are generally favored because they are effective, easy to dose, and safer than older antidepressants. However, they can still cause side effects like nausea, headache, or sleep changes and should be taken under medical supervision.
CYP2D6 and CYP2C19 are genes that encode specific liver-based cytochrome P450 enzymes critical for drug metabolism. Most SSRIs are metabolised by cytochrome P450 enzymes.
Alleles that reduce or stop the activity of CYP2D6 or CYP2C19 slow the serotonin clearance, leading to higher plasma levels, whereas increased-function alleles accelerate clearance and can lead to sub-therapeutic exposure.
Because these variants can markedly alter plasma drug levels, clinical pharmacogenomic guidelines (e.g., CPIC, DPWG) recommend genotype-guided dosing or drug selection for medications that are substantially cleared by either enzyme to improve efficacy and reduce adverse effects.
In April 2023 the Clinical Pharmacogenetics Implementation Consortium (CPIC) updated its guideline, expanding the genotypes covered and providing concrete dose or drug-switch recommendations for 18 antidepressants. For example, for the SSRI escitalopram, CPIC recommends a 50% dose reduction or an alternative agent in CYP2C19 poor metabolisers, and avoiding paroxetine in CYP2D6 poor metabolisers altogether.
Clinical impact is now supported by meta-analysis: patients whose treatment was guided by a multi-gene panel, including CYP2D6 and CYP2C19, were 41-78 % more likely to achieve remission than those treated as usual. Importantly, the benefit was confined to randomised controlled trials, underscoring the need for rigorous implementation rather than opportunistic testing.
Drug concentration at the synapse is only half the story; neuronal response is equally shaped by the receptor and transporter genes.
SLC6A4 (solute carrier family 6 member 4) is the gene that encodes the serotonin transporter (often abbreviated SERT or 5-HTT), a membrane protein responsible for pumping serotonin back into presynaptic neurons after it has been released into the synaptic cleft. SLC6A4 gene is highly polymorphic. The best-studied variant is the serotonin-transporter-linked polymorphic region 5-HTTLPR located at the gene’s promoter, which exists mainly as long (L) and short (S) alleles; the S allele reduces transcription, leading to fewer transporters and altered serotonin tone.
Variants in SLC6A4, notably the L and S promoter repeat alleles, influence transcription and thus transporter density. Some, but not all studies link the L allele to greater SSRI response, while the S allele heightens the risk of gastrointestinal side-effects.
A 2020 review of 49 studies found that people with major depression who carry the L form of the 5-HTTLPR variant in the SLC6A4 gene respond better to SSRI antidepressants than those with two S copies, but this benefit was clear only in Caucasian patients and did not appear in Asian groups or in studies using mixed drug classes.
CPIC now classifies the S/S genotype as “possible reduced benefit” but does not yet mandate a dose change.
A study published in May of this year (2025) of 302 European patients with depression or anxiety who failed previous SSRI treatment found that certain genetic combinations in the serotonin system were much more common than in the general population. Patients carrying at least one G allele of the HTR1A rs6295 variant together with the short/short (SS) form of the SLC6A4 promoter variant 5-HTTLPR had the highest over-representation among those with failed treatment—about 74 % above expectations—suggesting this pairing greatly increases the risk of SSRI non-response and associated disability. The findings indicate that genotyping both the serotonin transporter (SLC6A4) and its autoreceptor (HTR1A) could help predict treatment failure and guide more effective antidepressant choices.
Serotonin-2A receptor (HTR2A) polymorphisms, particularly rs7997012, and BDNF Val66Met (rs6265) have been repeatedly associated with differential remission rates, although effect sizes are modest. A 2024 genome-wide association study (GWAS) in an Indian cohort added weight by identifying HTR2A and other synaptic signalling loci among the top hits for inadequate treatment response.
Moreover, downstream stress-axis genes such as FKBP5, which regulates glucocorticoid receptor sensitivity, may explain why some patients develop early adverse reactions or emotional blunting. Evidence here is still emerging, and no prescribing guideline incorporates these variants yet.
Most pharmacogenomic evidence has historically been derived from European populations, but allele frequencies can diverge widely among others.
For instance, the CYP2C19*17 ultra-rapid allele is common in Northern Europeans yet rare in East Asians, whereas CYP2C19 loss-of-function alleles *2 and *3 occur in up to 20 % of Han Chinese. The 2024 Indian GWAS illustrates how locally generated data can uncover novel loci and improve predictive accuracy for the millions of patients in South Asia.
Genes that influence transporter affinity or membrane pumps such as ABCB1 (P-glycoprotein) modulate central nervous system exposure and have been linked to sedation and weight gain. Meanwhile, emerging evidence suggests genetic predisposition to a difficult withdrawal: a 2024 meta-analysis noted that 43 % of long-term users experience discontinuation symptoms, with risk rising in CYP2D6 poor metabolisers who accumulate active drugs. Personalised tapering schedules based on metabolic genotype may therefore reduce withdrawal burden.
International guidelines converge on three practical principles:
Health-system pilot studies show that pre-emptive panels integrated into electronic medical records are cost-effective, reducinghospitalisations from adverse reactions within two years of deployment. Some private insurances in the United States and several European countries now reimburse panel testing when guideline criteria are met.
The next frontier is adaptive prescribing algorithms that combine individual genotypes, Polygenic Risk Scores (PRS) , real-time mood rating and wearable-derived sleep data to adjust treatment weeks earlier than what is possible in today’s practice.
Genetic insights are already refining antidepressant therapy, moving psychiatry toward the precision enjoyed in oncology and cardiology. Testing for CYP2D6 and CYP2C19 variants has immediate, guideline-backed utility, while accumulating evidence on transporter variants and advanced PRS models promise progressively finer tailoring. Widespread implementation will require equitable sequencing across ancestries, clinician education, and integration with clinical decision support. Yet the trajectory is clear: as our understanding of the genetic response to antidepressants deepens, the era of “fail first, switch later” is giving way to informed, patient-specific care—offering faster relief and fewer harms for millions living with depression.
Millions of individuals throughout the world have experienced or are currently experiencing depression, a prevalent mental condition that can significantly influence an individual’s quality of life and significantly reduce their ability to become functioning members of society.
According to the American Psychiatric Association, depression or major depressive disorder is a common and serious medical illness that negatively affects how you feel, think, and act. This condition can negatively impact a person’s feelings and emotions towards everything and everyone in their lives. People diagnosed with depression may frequently feel sadness or a loss of interest in things and people they once enjoyed and cared about.
There are tell-tale signs of depression but some of the common symptoms are feeling sad or down, changes in appetite, changes in sleeping patterns, increased fatigue, difficulty concentrating, and even thoughts of self-harm. While depression can affect a person of any age, experts have come to wonder, is there a genetic component to depression? Is depression purely influenced by a person’s environment, including their past traumas and current predicaments?
The truth is depression can be amplified by external variables such as stressful life events and stress, but DNA also has an important role in the development of this condition.
Environmental factors may also greatly contribute to developing depression. Chronic stress, traumatic childhood experiences, and recent life events are a few examples of environmental stressors linked to depression. A few other environmental factors may include:
It’s essential to understand how these elements can interact with one another and a person’s genetic makeup to affect how likely they are to experience depression.
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Untangling the complex web of causes for depression as a mental wellness issue requires an understanding of the genetics of depression. Can people be more predisposed to depression due to their unique genetic makeup? Is genetics just part of the puzzle and if so, how big of a part is it? If genetics has the potential to answer the long-standing questions of experts about how and why depression is developed, it is worth knowing more about the role of genetics even in the common person.
According to rigorous research, depression has a genetic component. People who have experienced depression in their families may be more likely to experience it themselves. Certain genetic differences may increase a person’s susceptibility to depression when they are subjected to particular environmental stressors or causes. Studies on twins and families have revealed that there is a hereditary component to depression. A person with close relatives, such as parents or siblings who have depression, may be more likely to experience depression than those who have no family history.
Scientists have identified specific genes that might be associated with an increased risk of this mental condition. However, no single gene has been found to be solely responsible for depression. It is also difficult to pinpoint a few specific genes with a significant effect on depression risk due to their polygenic character. There are likely several genes that together contribute to depression, each having an impact.
Moreover, genetics and environmental factors can interact and cause, trigger, or amplify depressive symptoms. People with a genetic predisposition may be more vulnerable to specific environmental triggers or aggravators of depression, such as traumatic experiences or long-term stress. In sum, depression results from the interaction of a person’s environment and genetic predisposition, and it is influenced by all of these elements at different stages of development.
Depression manifests in a variety of ways, each carrying its own distinct weight and being a complex and diverse emotional experience. There are several types of depression, some of which have symptoms that overlap. This is why the correct assessments of mental health professionals are needed when diagnosing depression in any individual.
A type of depressive disorder that can develop after childbirth is called postpartum depression (PPD), often referred to as postnatal depression. Mood swings, irritability, and feelings of sadness are common in new mothers shortly after giving birth and are commonly referred to as the “baby blues.” Postpartum depression is more severe and pervasive than the “baby blues,” and it can have a significant impact on a mother’s capacity to care for herself and her child. its prevalence is estimated to be between 10% and 15% among new mothers.
PPD symptoms might include ongoing melancholy, exhaustion, changes in eating and sleep patterns, trouble concentrating, feelings of guilt or worthlessness, and in extreme situations, thoughts of hurting oneself or the unborn child. Early identification and treatment of PPD are essential since it can affect a mother’s ability to carry out everyday tasks and form bonds with her child.
The chance of having PPD may have a hereditary component, according to research studies. Women who have family members who have experienced postpartum depression may be more likely to develop depression themselves. Genetics, however, is not the only cause; hormonal changes, psychological factors, lack of social support, and other life stressors all significantly contribute to the development of PPD.
There is still a chance that you could develop postpartum depression even if no women in your family have ever experienced it. Environmental elements also have an impact. For instance, a difficult childbirth could result in postpartum depression. Recognize the danger indicators and risk factors so you can seek assistance as soon as feasible. Risk elements consist of:
Although having a genetic predisposition may raise the risk, PPD is not a given. Many women with a family history of depression may not experience PPD. Contrarily, some women without a family history of depression may get PPD. Complex interactions exist between environmental and genetic risk factors.
While undoubtedly a challenging and often scary battle for mothers, having PPD does not equate to being a bad parent. Therapy, support groups, lifestyle modifications, and in certain situations, medication, are all possible treatment choices. Early intervention can help moms regain their emotional health and capacity to care for their children while also dramatically improving outcomes.
Both depression and bipolar disorder are mental health conditions that are related to one another but also have crucial differences. While mood disruptions are present in both illnesses, there are differences in the types and patterns of these changes. Both conditions have similar symptoms such as:
The key differences between bipolar disorder and major depressive disorder (sometimes also referred to as unipolar disorder) may include the lengths of episodes, varying degrees of symptoms, and the manic episodes that are more commonly attributed to bipolar disorder.
It is crucial to remember that a mental health professional must do a complete evaluation in order to diagnose and distinguish between these disorders. People who think they might have either ailment should have a proper evaluation so they can get a proper diagnosis and the right care.
Seasonal Affective Disorder (SAD), often referred to as seasonal depression, is a type of depression that follows a seasonal pattern. It frequently happens during certain seasons of the year, most frequently in the fall and winter when there are fewer daylight hours. Although less frequently, some people may have SAD in the spring and summer.
Low mood, loss of interest in activities, exhaustion, changes in sleep and appetite, difficulties focusing, and feelings of worthlessness or hopelessness are just a few of the symptoms that SAD and major depressive illness share. But what distinguishes SAD is its predictable pattern of onset and remission depending on the cyclical nature of the seasons.
Research suggests that there is a genetic component to seasonal affective disorder, although the genetic links are not as well-established as they are for some other types of depression. Studies have shown that individuals with a family history of mood disorders, including SAD, might be at a higher risk of developing the condition themselves.
It’s crucial to remember that, although genetics may play a part in a propensity for SAD, environmental circumstances can have a big impact. It is believed that one of the main causes of SAD is diminished exposure to natural sunlight during particular seasons. Incorrect levels of neurotransmitters like serotonin and melatonin can cause circadian cycles to be disrupted, which can affect mood and sleep.
Seasonal affective disorder is more common in people with bipolar disorder. Mania episodes in some bipolar patients may be connected to a particular season. For instance, spring and summer might trigger mania symptoms or a milder type of mania (hypomania), as well as worry, agitation, and impatience. They could also go through periods of depression in the fall and winter.
Can SAD be treated? Much like other types of depression, SAD has varying treatment options. Experts believe that focusing on addressing the disruption in sleeping patterns and increasing the body’s exposure to natural light may help treat or manage SAD. Some of the more common treatments include:
According to research, the neurological underpinnings and pathogenesis of depressive illnesses are still unclear, despite extensive research over the past few decades. Based on family, twin, and adoption studies, genetic variables play significant roles in the onset of MDD and may provide crucial insights into the disease’s pathophysiology.
While there isn’t a single “strongest” genetic link connected to depression, scientists have discovered a number of genetic markers and candidate genes that are thought to contribute to its onset. It’s crucial to remember that no single gene can entirely explain depression, which is likely affected by a mix of several genetic variants.
However, the most studied single nucleotide polymorphisms (SNPs) are SNP rs782212 (gene: Intergenic), SNP rs4810896 (gene: LOC105372648-ARFGEF), and SNP rs7973260 (gene: KSR2). The most prevalent form of genetic variation in people is called an SNP. They entail a single nucleotide alteration at a specific location in the genome’s DNA sequence. These differences are what give people their unique characteristics, and they also have an impact on different traits, illnesses, and susceptibilities.
Intergenic Gene (SNP rs782212). SNP rs782212 is situated in an area of the genome that does not code for a particular protein, which is referred to as an “intergenic” region of DNA. Although research has demonstrated that intergenic areas can still perform regulatory roles, altering the expression of nearby genes or contributing to the three-dimensional folding of chromosomes, they were previously thought to be non-functional and were not given much attention. Numerous genetic variations for major depressive disorder (MDD) have been discovered through genome-wide association (GWA) research, however, the majority of these variations are intergenic. The intergenic regions have been shown to contain about 54% of long non-coding RNAs (lncRNAs).
LOC105372648-ARFGEF Gene (SNP rs4810896). The gene identification LOC105372648-ARFGEF has a long non-coding RNA (lncRNA) component and a mention of the “ARFGEF” gene. A family of RNA molecules known as long non-coding RNAs (lncRNAs) are those that are longer than 200 nucleotides yet do not code for proteins. Instead, they participate in a number of cellular regulatory processes including chromatin remodeling, gene expression regulation, and interaction with other cellular elements. Some lncRNAs have been linked to particular illnesses and cellular functions. ADP-ribosylation factor guanine nucleotide-exchange factor (ARFGEF) is a protein that is encoded by the “ARFGEF” gene. ADP-ribosylation factors (ARFs), which are GTPases that participate in intracellular membrane trafficking and vesicle formation, are regulated by this protein. By enabling the exchange of GDP for GTP, ARFGEFs activate ARFs, and as a result, regulate their activity.
KSR2 Gene (SNP rs7973260). Obesity and metabolic characteristics are linked to the KSR2 gene and the SNP rs7973260. On chromosome 12, the KSR2 (Kinase Suppressor of Ras 2) gene produces a protein that participates in intracellular signaling pathways. KSR2 is a component of the Raf-MEK-ERK pathway, which plays a crucial role in the communication of signals from cell surface receptors to the cell nucleus, ultimately influencing functions like cell proliferation, differentiation, and survival. The KSR2 gene contains the single nucleotide polymorphism (SNP) rs7973260. SNPs, such as rs7973260, are variations in the DNA sequence that may affect how a gene functions or how it is expressed. Some SNPs have links to specific traits, illnesses, or drug reactions.
Regardless of genetic markers, anyone can experience depression, and most people may experience depression at least briefly in their lifetimes. If you think you have a unique genetic makeup that is susceptible to depression, a DNA test is your best bet. Experts believe that while Major Depressive Disorder (MDD) is yet to be scientifically proven to be hereditary, there are similar mental health conditions to MDD that are passed down from one generation to the next.
If you want to take genetic testing for mental well-being, LifeDNA can give you insights into genetic inclination towards depression, loneliness, and other unique traits based on your DNA. Check out our personalized DNA plans to learn more.
Aside from depression, one other important trait that can impact your well-being is Neuroticism. Neuroticism is one of the Big Five personality traits. It is a long-term and relatively stable tendency to be in a negative or anxious emotional state, especially in response to threats, frustration, or loss.
Individuals who score high in this trait tend to experience mood swings, anxiety, irritability, and sadness. Neuroticism can also be damaging to the quality of your life and reduce your lifespan.
Depending on your DNA, you may have an increased likelihood of being moody and experiencing feelings such as anxiety, worry, fear, anger, frustration, envy, jealousy, guilt, depression, and loneliness.
Get your mental health DNA test today for Neuroticism and unlock LifeDNA’s Personality & Cognition Report.
If you or a loved one are struggling with mental wellness challenges, consider exploring the potential benefits of genetic testing.
By gaining a deeper understanding of your unique genetic makeup, you can better understand your genetic inclination towards mental wellness issues, and ultimately, make more informed decisions about your well-being.
Take charge of your mental wellness journey today and see what genetic testing can do for you.
*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.
Our reports and suggestions do not diagnose or treat any health conditions or provide any medical advice. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results.
*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.
Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.
