Gene/environment interactions in the development of mental health and illness

Question 1

What are gene-environment interactions?

Answer 1

• Gene-environment interaction (GxE) is a causal mechanism where one or more genetic variants and one or more environmental factors contribute to the causation of a condition in the same individual.
• In a GxE, the genetic factors influence the sensitivity to environmental exposures.
• GXE are distinguished from gene-environment correlations, where genetic factors influence the probability of environmental exposures.

Question 2

Are GxE important in the causation of mental illness?

Answer 2

Yes

• Individuals differ in their vulnerability to pathogens
• There is variably degeneracy of complex biological systems
• There is a paradox between heritable disorders and reproductive disadvantage
• Paradox of low shared environment estimates in twin studies and strong specific environmental risk factors
• These two paradoxes cause attributable risk of environment and genetic factors to sum up to more than 100%.
• There may be a large genetic risk for an illness, but it is imperceptible due to reproductive disadvantage (eg. autism)
• There are KNOWN environmental risk factor for mental illness (eg. cannabis use in adolescents)

Question 3

What are two good reasons for studying GxE?

Answer 3

• Dispeling myth of genetic (or social!) determinism

- Targeted/personalized interventions

Question 4

How does childhood maltreatment effect Monoamine oxidase A and antisocial behaviour?

Answer 4

Maltreatment leads to low MAO-A activity, which is associated with antisocial behaviour and adversity.

Question 5

How is serotonin transporter linked to stress and depression? Childhood maltreatment?

Answer 5

Serotonin transporter is upregulated with more stressful life events. This is also linked to a risk of developing major depression episodes.

Childhood maltreatment also linked with upregulated transporter and risk of major depression. Support attenuates this effect.

Question 6

How can childhood abuse and neglect lead to chronic depression?

Answer 6

Maltreatment leads to

• Reduced quality of intimate relationships
• Stressful life events and difficulties (affecting BDNF)
• Self esteem issues

These converge to cause onset depressive episodes. Perpetuation of onset depression can cause chronic depression. Through GxE childhood abuse and neglect facilitates this perpetuation (through increased 5-HT reuptake etc.)

Question 7

How does the amino acid sequence of BDNF correlate with depression onset?

Answer 7

ValVal: lower rates of depression. Seen with low stressful life events.

ValMet: Higher rates of depression

MetMet: Extremely high rates of depression. Seen with many stressful life events.