Lecture 2.5: Genetic and Biological Etiology of Mood Disorders

Prefrontal cortex

the front-most part of the frontal lobe. It acts as the brain’s "CEO," orchestrating higher-level cognitive functions, emotional regulation, and complex behaviors.

Among individuals struggling with depression, we see lower level. levels of activity in the ____________.

Interior cingulate

The _____________ refers to an area of the brain that is broadly responsible for emotional expression and social behavior. We often see differential functioning, not consistently higher levels or lower levels of activity, but notably different across individuals with depression.

Hippocampus

The _______ is responsible for memory processing and also fear-related learning. We see the size of the _________ among individuals who struggle with depression tends to be smaller. This may be the result of higher levels of cortisol, which is a stress hormone that is often seen at higher levels among individuals with depression. Cortisol is known to damage the __________ at excessive levels.

Amygdala

The __________, which is responsible for emotional awareness and attention, tends to be larger and tends to have more activity going on with depression. This may indicate cases in which an individual experiences stronger or more powerful levels of low mood.

Epinephrine/Norepinephrine

another term for adrenaline or fight/flight. Seen in lower levels in depressed individuals.

Why does depression cause lower levels of norepinephrine, serotonin and dopamine

• Unclear whether this is due to:

  • Certain neurotransmitters not being synthesized correctly,

  • Not being released correctly, or

  • Not being absorbed correctly (re-uptake)

Neurotransmitters

chemicals that creates experiences of awareness, of emotion, of cognition. These are the chemicals that are released between neurons that allow neurons to communicate. Examples include: norepinephrine, serotonin and dopamine

Serotonin

a neurotransmitter that is responsible for reducing anxiety. This gives a person a sense of calm or serenity.

Dopamine

________is a neurotransmitter responsible for feelings of pleasure or reward. And so this is the neurotransmitter that's activated most often when you do something that you really enjoy. This is also the neurotransmitter that's implicated most often in experiences of addiction.

Which concordance rate shows a higher genetic influence?

Unipolar depression concordance rates:

MZ = .54 DZ = .24

Bipolar disorder concordance rates:

MZ = .43, DZ = .06

Bipolar disorder concordance rates:

MZ = .43, DZ = .06

(The ratio of .43 to .06 is larger than .54 to .24)

Family studies and twin studies suggest a mild genetic influence for unipolar depression and a stronger one for bipolar disorder.

However, no strong evidence of a single gene responsible for mood disorders.

Holism

outcome > the sum of its parts

ex. We know that stress leads to depression in some people, but not others.

This reality may reflect an interaction of genes and environment:

• Interaction – outcome greater than the sum of its parts

Reductionism

outcome = the sum of its parts

What did Caspi et al., (2003) tell us about the genes that effect seretonin?

Two major findings:

• The effect of stressful life events on depression symptoms was significantly stronger among those with genetic vulnerability.

• Stressful life events predicted major depressive disorder as well as suicidal ideation/attempts only among those with the genetic vulnerability.

Caspi et al., (2003) assessed level of genetic risk based on the serotonin transporter gene in 1000+ subjects:

• 2 short alleles (ss) = highest genetic vulnerability (low serotonin level)

• 1 short & 1 long allele (sS) = medium genetic vulnerability (medium serotonin level)

• 2 long alleles (SS) = lowest genetic vulnerability (high serotonin level)

What kind of person are mood disorders symptoms the most severe among?

Mood disorder symptoms tend to be more severe among individuals with both genetic vulnerabilities and major life stressors.