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Genetics & Depression: How Polygenic Risk Scores Predict Mood Over Long-Term (2024 Study)

A recent study examined how our genetic makeup influences our temperament traits, particularly in relation to depression.

By analyzing the polygenic risk for depression (PRS) and its correlation with various temperament traits over time, this research provides significant insights into the complex interplay between genetics and mood.


  • High PRS Linked to Increased Persistence: Individuals with a high polygenic risk for depression showed higher levels of Persistence from early adulthood to middle age.
  • No Direct Link to Novelty Seeking or Reward Dependence: The study found no significant relationship between PRS and the temperament traits of Novelty Seeking or Reward Dependence.
  • Stronger Association with Anticipatory Worry in Depressive Individuals: For individuals with high PRS, the connection between Anticipatory Worry (a subtrait of Harm Avoidance) and depressive symptoms was notably stronger.
  • Results Independent of Affective Disorders: The observed associations remained consistent even when excluding participants with diagnosed affective disorders, emphasizing the genetic influences on temperament independent of clinical conditions.

Source: Journal of Affective Disorders (2024)

Genetics & Mood: Understanding the Connection

The interplay between genetics and mood, particularly in the context of mood disorders like depression, is a rapidly evolving area of scientific inquiry.

Mood and emotional responses are complex traits influenced by a myriad of factors, including genetics.

While everyone experiences mood fluctuations, a person’s baseline mood and their vulnerability to mood disorders can be significantly shaped by their genetic makeup.

  • Genes & Neurotransmitters: Certain genes are involved in the production and regulation of neurotransmitters like serotonin, dopamine, and norepinephrine, which play crucial roles in mood regulation. Variations in these genes can affect neurotransmitter levels and activity, influencing an individual’s mood stability.
  • Heritability of Mood Disorders: Studies, particularly those involving twins, have consistently shown that mood disorders have a significant heritable component. For instance, if one identical twin has a mood disorder like major depression, the other twin has a higher probability of developing the disorder compared to fraternal twins or the general population.
  • Genetic Overlap Between Different Mood Disorders: Research has also uncovered genetic links between various mood disorders, suggesting shared genetic factors. For example, genes that influence the risk for major depression may also affect the likelihood of developing other conditions like bipolar disorder.

Specific Genes Linked to Depression

Recent advances in genetic research have identified several specific genes that appear to be implicated in the development and progression of depression.

Understanding these genes is crucial for unraveling the complex genetic architecture of depression and for the development of targeted treatments.

Serotonin Transporter Gene (SLC6A4)

  • Function: SLC6A4 is responsible for the reuptake of serotonin, a neurotransmitter crucial for mood regulation.
  • 5-HTTLPR Polymorphism: Research has focused on a specific polymorphism in SLC6A4 known as 5-HTTLPR. It’s been suggested that the short allele of this polymorphism may be associated with an increased risk of depression, particularly in the context of stressful life events.

Brain-Derived Neurotrophic Factor (BDNF)

  • Role in Neuroplasticity: BDNF plays a key role in neuroplasticity, the brain’s ability to change and adapt.
  • Val66Met Variant: The Val66Met polymorphism in BDNF has been linked to depression. This variant may influence the activity of BDNF, affecting neuronal resilience and psychiatric vulnerability.

Dopamine Receptor Genes (DRD4 and DRD2)

  • Dopamine System: Dopamine receptors, especially DRD4 and DRD2, are part of the dopamine system, which is involved in reward and pleasure mechanisms.
  • Associations with Depression: Variations in these genes have been associated with susceptibility to depression, possibly due to their influence on reward-related brain circuits.

FK506 Binding Protein 5 (FKBP5)

  • Stress Response: FKBP5 is involved in regulating the stress response system in the body.
  • Gene-Environment Interaction: Certain variants of FKBP5 have been shown to interact with environmental stressors, increasing the risk of developing depression, particularly after childhood trauma.


  • Metabolism of Neurotransmitters: The COMT gene plays a role in the metabolism of dopamine and other neurotransmitters.
  • Val158Met Polymorphism: The Val158Met polymorphism in this gene has been studied for its potential impact on mood and depression, although findings have been mixed.

Genome-Wide Association Studies (GWAS)

  • Discovery of New Genes: GWAS have identified numerous additional genetic variants associated with depression. These studies have significantly expanded our understanding of the genetic basis of depression, highlighting its polygenic nature.

Polygenic Risk Scores & Depression

The concept of polygenic risk scores (PRS) has emerged as a crucial tool in understanding the genetic predisposition to complex disorders like depression.

PRS involves assessing the cumulative effect of numerous small genetic variations, each contributing to the overall risk.

  • Polygenic Nature of Depression: Depression is not typically caused by a single gene mutation but rather arises from the combined effect of many genetic variants. Each variant contributes a small amount to the overall risk, and their cumulative impact is assessed using PRS.
  • Calculating PRS for Depression: PRS for depression is derived from large-scale genome-wide association studies (GWAS) that identify common genetic variants associated with the disorder. By aggregating the effects of these variants, PRS provides an individualized estimate of genetic susceptibility to depression.

Why it helps to know PRS in depression

  • Predicting Risk: PRS can help identify individuals at a higher genetic risk for depression, enabling early intervention and tailored treatment strategies. It’s particularly useful in understanding why some individuals are more susceptible to depression than others, even under similar environmental conditions.
  • Personalized Medicine: In the future, PRS could be instrumental in personalized medicine. Healthcare providers could use an individual’s PRS to guide decisions about prevention and treatment strategies for depression, potentially improving outcomes.
  • Research & Prevention: PRS also offers valuable insights for researchers studying depression. It helps in understanding the biological underpinnings of the disorder and in developing preventive strategies targeting individuals at high genetic risk.

The Young Finns: The Role of Genetics in Temperament & Depression (2024 Study)

Lavonius et al. analyzed data from The Young Finns Study, to explore the intricate relationship between genetics, temperament, and the risk of developing depression.

The primary goal of the Young Finns Study was to examine how the polygenic risk score (PRS) for major depression influences the trajectory of various temperament traits from early adulthood to middle age.

The study focused on determining whether individuals with a higher genetic risk for depression exhibited different patterns in temperament traits compared to those with a lower risk.


  • Participant Demographics: The study involved 2212 participants from the population-based Young Finns Study, encompassing a diverse range of ages and backgrounds.
  • Measuring PRS: The PRS for depression was calculated based on data from the latest genome-wide association study (GWAS), providing a comprehensive genetic risk profile for each participant.
  • Temperament Traits: Temperament traits, including Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence, were measured using the Temperament and Character Inventory. These assessments were conducted at four different points over the study period (1997, 2001, 2007, and 2012).
  • Covariates: The study accounted for various covariates, such as depressive symptoms, family environment during childhood, and socioeconomic factors in adulthood, to isolate the influence of genetic risk.


  • Persistence & PRS: One of the most significant findings was that individuals with high PRS exhibited higher levels of Persistence over time, indicating a potential genetic underpinning for this temperament trait.
  • Lack of Association with Other Traits: The study found no direct relationship between PRS and other temperament traits like Novelty Seeking or Reward Dependence.
  • Stronger Anticipatory Worry in High PRS Individuals: There was a notable interaction between PRS and depressive symptoms in predicting the Harm Avoidance subscale, Anticipatory Worry. This suggests that individuals with a higher genetic risk for depression might experience stronger associations between anticipatory worry and depressive symptoms.
  • Consistent Results Independent of Clinical Conditions: Interestingly, the observed patterns remained consistent even when excluding participants with diagnosed affective disorders, highlighting the influence of genetics on temperament outside of clinical depression.


While the Young Finns Study offers valuable insights, it is not without limitations:

  • Attrition Over Time: The long duration of the study led to some participant dropout, which could potentially bias the results.
  • Modest Predictive Power of PRS: The PRS used in the study, while based on the most recent GWAS data, still had a limited ability to predict depression-related outcomes, reflecting the complexity of the disorder.
  • Generalizability of Findings: The findings, while robust, are based on a Finnish population and may not be directly applicable to other populations due to genetic and environmental differences.
  • Complex Interplay of Factors: The multifaceted nature of depression and temperament, influenced by a combination of genetic, environmental, and psychosocial factors, makes it challenging to isolate the impact of genetics alone.

Details of Results: Genetics, Temperament, Depression Risk (2024)

The Young Finns Study yielded complex and insightful results that deepen our understanding of the relationship between genetics, temperament, and depression.

Temperament Traits

Persistence & PRS

A notable discovery was the positive correlation between high polygenic risk scores for depression and increased levels of Persistence.

This finding was consistent even after adjusting for factors like socioeconomic status and depressive symptoms.

Interestingly, the link between PRS and Persistence became evident only after controlling for adulthood socioeconomic factors, suggesting an intricate interplay between genetic predisposition and environmental factors.

No Significant Association with Novelty Seeking & Reward Dependence

Contrary to Persistence, PRS did not significantly predict changes in Novelty Seeking or Reward Dependence across different models.

This outcome suggests that the genetic underpinnings of these temperament traits might be distinct from those influencing Persistence and depression.

Harm Avoidance Subscales

The study also delved into the subscales of Harm Avoidance, finding a stronger association between Anticipatory Worry and depressive symptoms in individuals with higher PRS.

This result indicates a potential genetic vulnerability in the stress response mechanisms linked to depression.

Interaction Effects

Age & PRS

The study explored the potential interaction between age and PRS in influencing temperament traits but found no significant effects.

This suggests that the impact of genetic risk on temperament traits is relatively stable across the age range of the participants (24-50 years).

Depressive Symptoms Modification

Another intriguing aspect was how depressive symptoms modified the relationship between PRS and temperament traits, particularly the Harm Avoidance subscale, Anticipatory Worry.

This finding could indicate that individuals with higher genetic risk may experience a magnified impact of depressive symptoms on certain aspects of their temperament.

(Related: 2 Gene Clusters & Anxiety Disorders: Serotonin & Dopamine)

What are the potential implications of this study?

The findings of the Young Finns Study have many potential implications, particularly in the fields of psychology, psychiatry, and genetic counseling.

Depression & Temperament

  • Genetic Basis of Temperament: The study underscores the significance of genetic factors in shaping key aspects of temperament. This could lead to a better understanding of personality development and its connection to mental health conditions.
  • Targeted Interventions: For individuals with high PRS, especially those showing higher levels of Persistence and Anticipatory Worry, tailored intervention strategies could be developed. These might include focused therapy and counseling aimed at managing perfectionism and anxiety, potentially reducing the risk of developing depression.

Clinical & Therapeutic Applications

  • Personalized Medicine: The results could inform personalized approaches in treating and preventing depression. Understanding an individual’s genetic risk could help clinicians in developing more effective, customized treatment plans.
  • Preventive Mental Health Strategies: The study could also aid in the development of preventive mental health strategies targeting individuals at higher genetic risk for depression. Early intervention programs could focus on resilience-building and coping mechanisms.

Future Research

  • Further Genetic Studies: The results pave the way for more detailed genetic studies exploring the links between PRS, various temperament traits, and other mental health disorders.
  • Longitudinal Studies: Long-term studies could provide additional insights into how these relationships evolve over different life stages, particularly in relation to changing environmental and psychosocial factors.

Ethical & Social

  • Genetic Counseling: As genetic testing becomes more prevalent, there is a growing need for genetic counseling to help individuals understand and manage their risk for conditions like depression.
  • Public Awareness and Stigma: Increasing public awareness about the genetic aspects of mental health could help in reducing stigma and misconceptions about mental health disorders.

(Related: Genetics of Anxiety Disorders: 2023 Research)

The Future of Depression Treatment: Targeting Genes

In the realm of depression treatment, the future holds promising potential for targeting specific genes, a concept stemming from advances like those demonstrated in the Young Finns Study.

With the growing understanding that depression is influenced by a complex network of genetic factors, treatments could become more precise and effective.

Identifying specific genes that contribute to the risk of depression can lead to the development of new pharmaceuticals designed to target these genetic pathways directly.

This approach could be especially beneficial for individuals with a high genetic predisposition to depression, as identified by polygenic risk scores.

Furthermore, gene-targeted treatments might offer fewer side effects and higher efficacy, as they would be tailored to the individual’s genetic profile.

Ultimately, this shift towards genetic targeting in depression treatment heralds a new era of personalized medicine, where therapy is adapted to the unique genetic makeup of each individual, promising more successful outcomes in managing this complex and multifaceted disorder.

(Read: Gene Therapy for Depression)

Takeaway: Genetics, Mood, Depression Risk

The Young Finns Study offers groundbreaking insights into the complex interplay between genetics, temperament, and depression, highlighting the nuanced roles of polygenic risk scores (PRS).

Its findings, particularly the association between high PRS and increased Persistence, along with the interaction between PRS and Anticipatory Worry, underscore the significance of genetic factors in personality development and mental health.

The study’s methodology, which accounted for a range of covariates, enhances the robustness of its conclusions, despite challenges like participant attrition and the modest predictive power of PRS.

These findings have far-reaching implications for personalized medicine, potentially guiding more targeted interventions and preventive strategies for mental health disorders.

Moreover, they pave the way for future research to further explore and validate these connections, with the potential to transform clinical practices in psychiatry and psychology.

As our understanding of these genetic influences deepens, we move closer to a future where mental health treatment and prevention are more tailored and effective than ever before.


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