Genetic and environmental risk factors

Genetic and environmental risk factors

Genetic and environmental risk factors

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Genetic Factors - It's All Relative

  • Heritability: Major Depressive Disorder (MDD) is moderately heritable, with genetic factors accounting for ~40-50% of the risk. The remainder is attributed to unique environmental factors.

  • Family & Twin Studies:

    • First-degree relatives of individuals with MDD have a 2-3x higher risk of developing the disorder.
    • Concordance rates are higher in monozygotic (identical) twins (~46%) than in dizygotic (fraternal) twins (~20%), highlighting genetic influence.
  • Polygenic Nature:

    • There is no single "depression gene." Risk is conferred by multiple genes, each with a small effect.
    • A key area of research is the serotonin transporter gene (SLC6A4, 5-HTTLPR). Polymorphisms may increase susceptibility to depression, particularly in the context of stressful life events (gene-environment interaction).

⭐ The risk of developing MDD is approximately 2-3 times higher for individuals with an affected first-degree relative compared to the general population.

Environmental Factors - Life's Curveballs

  • Diathesis-Stress Model: A foundational concept where underlying genetic vulnerability (diathesis) is activated by environmental stressors, leading to depression.
  • Adverse Childhood Experiences (ACEs):
    • Includes abuse, neglect, and significant household dysfunction.
    • These experiences can lead to lasting changes in the HPA axis, increasing stress sensitivity.
  • Significant Life Stressors:
    • Events like bereavement (especially a spouse or child), job loss, divorce, or financial ruin are potent triggers.
  • Social & Support Factors:
    • Lack of a confiding, supportive social network is a major risk factor.
    • Conversely, strong social support is highly protective.

⭐ The loss of a parent before the age of 11 is one of the most significant environmental risk factors for the later development of Major Depressive Disorder.

Diathesis-Stress Model: Vulnerability vs. Resilience

Gene-Environment Interaction - The Perfect Storm

  • Diathesis-Stress Model: Posits that a genetic predisposition (diathesis) requires an environmental stressor to manifest as a disorder. Neither factor is sufficient alone.

  • Key Genetic Factor (Diathesis):

    • Serotonin Transporter Gene Polymorphism (5-HTTLPR):
      • Individuals with one or two copies of the short allele ('s') produce less serotonin transporter.
      • This leads to ↑ synaptic serotonin levels initially, but with chronic stress, it results in a blunted response and ↑ vulnerability to depression.
  • Key Environmental Factors (Stressors):

    • Childhood abuse or neglect
    • Major adverse life events (e.g., loss of a loved one, job loss)
    • Chronic medical illness

⭐ The link between childhood maltreatment and adult depression is significantly stronger in individuals with the short ('s') allele of the 5-HTTLPR gene.

Diathesis-Stress/Dual-Risk Model

High‑Yield Points - ⚡ Biggest Takeaways

  • Heritability for major depression is approximately 40%; risk is 2-4 times higher in first-degree relatives.
  • Key neurobiological factors include dysregulation of serotonin, norepinephrine, and dopamine pathways.
  • Adverse childhood experiences and significant life stressors are major environmental risk factors.
  • Chronic stress can lead to HPA axis hyperactivity and elevated cortisol levels.
  • Often comorbid with anxiety disorders, substance use disorders, and chronic medical illnesses.

Practice Questions: Genetic and environmental risk factors

Test your understanding with these related questions

A researcher is investigating whether there is an association between the use of social media in teenagers and bipolar disorder. In order to study this potential relationship, she collects data from people who have bipolar disorder and matched controls without the disorder. She then asks how much on average these individuals used social media in the 3 years prior to their diagnosis. This continuous data is divided into 2 groups: those who used more than 2 hours per day and those who used less than 2 hours per day. She finds that out of 1000 subjects, 500 had bipolar disorder of which 300 used social media more than 2 hours per day. She also finds that 400 subjects who did not have the disorder also did not use social media more than 2 hours per day. Which of the following is the odds ratio for development of bipolar disorder after being exposed to more social media?

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Flashcards: Genetic and environmental risk factors

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Depression is associated with _____ total REM sleep

TAP TO REVEAL ANSWER

Depression is associated with _____ total REM sleep

increased

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