Antidepressants - Two Sides of the same coin Flashcards
Which theory (MA or Glucocorticoid) is correct?
Probably not either or, but rather two sides of the same coin.
i.e. stress hormones interact in complex ways with MA systems (5-HT, NE, DA).
What is an example of stress hormones interacting with a MA system?
DA and glucocorticoid receptors coexist in neurons of the VTA that project to the nucleus accumbens. Under chronic stress, heigthened cortisol levels encourage DA release and structural change within the mesolimbic DA system. One such change is an upregulation of DA receptors in the VTA.
Changes in glucocorticoid levels are also strongly associated with changes in what MA function?
5-HT (Serotonin).
High levels of HPA-axs stress hormones leads to a reduction in both number and function of postsynaptic 5-HTA1 receptors in the hippocampus.
Changes in 5-HT neurotransmission may be the result of what?
Hypersecretion of stress hormones, especially cortisol.
Chicken or the egg, which precedes what? Changes in 5-HT or changes in glucocorticoid release?
Research in patients with major depressive disorder suggests that abnormal HPA-axis function precedes the onset of clinical symptoms of depression. Probably due to a genetic vulnerability to HPA-axis hyperactivity.
Explain the evidence for genetic predisposition.
- Study that spanned 2 decades.
- Number of childhood and adolescent stressful experiences correlated with the development of depression and suicidal ideation.
- This correlation was strongest in individuals with the short form of the 5-HT transporter protein gene.
How does the short form of the 5-HT transporter protein gene affect depression development?
Possessing the short form of the 5-HT transporter protein gene also makes people more susceptible to depression resulting from childood maltreatment. The experience of tress, perhaps early in life, triggers and sensitizes the stress system so that when stressors occur later in life, the HPA axis overreacts.
How do antidepressant medications reduce stress?
They normalize HPA-axis functioning by increasing the number of cortisol receptors to create more efficient negative-feedback loops.
What does creating more efficient negative-feedback loops result in?
The stress induced rise in glucocorticoid levels is stunted and shortened, and decreases in 5-HTA1 receptor densities and binding that occur with elevated stress hormone levels are prevented.
This normalization of HPA-axis activity precedes the alleviation of depressive symptoms.
What happens when an individual shows improvement with antidepressants but HPA-axis function fails to normalize? What does this suggest?
They are more likely to relapse into depression. This suggests that normalizing the stress response may be necessary condition in order for antidepressants to work.
