Chronic Stress & Depression Flashcards
What is Stress?
Stress is defined as the psychological and physiological responses generated in the face of, or in anticipation of, a perceived threat.
The body produces a very robust, non- specific response to each and every stressor.
For example, a lion chasing a zebra for lunch: - Very different situations for the two animals;
- Both have identical stress responses.
Stressors
Something that causes an organism to be stressed is called a stressor.
Stressors:
- Stimulus that threatens an animal’s physiological homeostasis (e.g. exercise);
- Physical vs. psychological;
- Environmental vs. internal;
- Real vs. perceived;
- Predictability matters.
Stress response can be considered an automatic (i.e. ANS) reaction to actively maintain physiological homeostasis.
The Stress Response
The stress response consists of two separate sequences (arrow) fast & slow response.
Fast response:
- Sympathetic division of ANS produces “fight or flight” response;
- Adrenal medulla stimulates the release of epinephrine;
- Epinephrine surge (adrenaline rush) prepares body for
sudden burst of energy.
Slow response:
- Hypothalamic-Pituitary-Adrenal Axis (HPA axis);
- Ultimately, adrenal cortex secretes cortisol in response to a stressor;
- Cortisol turns off insulin secretion to increase energy supply, turns off reproductive function, inhibits production of growth hormone, shuts off immune function, etc.
- Strategically directs energy resources to adequately respond to a stressor.
Fast Response Activation of sympathetic division of ANS.
Activation of sympathetic division of ANS.
- Epinephrine release from adrenal medulla
and locus coeruleus;
- Increase heart rate & breathing, constricting blood vessels;
Induces rapid physiological changes
- Catecholamines, CRH, neurosteroids all released;
- Increases vigilance, alertness, arousal and attention;
- Facilitates spontaneous behaviors related to fight or flight.
Slow Response Controls “slow” changes throughout, and following, a stress response:
Controls “slow” changes throughout, and following, a stress response:
- Changes to gene expression;
- Suppresses immune system;
- Increases blood pressure;
- Decreases sensitivity to pain;
- Increases blood pressure;
- Increases blood sugar (arrow) gluconeogenesis in the liver;
- Consolidation of memories (related to stressor);
- Preparation for future responses.
Mediated by glucocorticoids.
- Secreted by the adrenal glands (specifically the adrenal cortex);
Glucocorticoids
Glucocorticoids (GCs) are a form of steroid hormone that belong to the corticosteroid family.
- Gluco = glucose
- Cort = cortex
- As the name implies, GCs regulate circulating glucose levels, and are synthesized in the adrenal cortex.
Cortisol (arrow) humans Corticosterone (arrow) rodents
GCs bind to corticosteroid receptors which are expressed in many tissues.
Corticosteroid Receptors
There are two main types of corticosteroid receptors in the body:
1. Mineralocorticoid Receptor (MR)
- Glucocorticoid Receptor
Both MR and GR responds to glucocorticoid secretion during a stress response.
Mineralocorticoid Receptor (MR)
Mineralocorticoid Receptor (MR)
- Appraisal, initial (fast) stress response;
- Important in gene transcription;
- More sensitive to corticosteroids (~10X).
Glucocorticoid Receptor
Glucocorticoid Receptor
- Terminates stress response;
- Increased sensitivity to corticosteroids during stress;
- High density in the paraventricular nucleus of the hypothalamus (PVN) and hippocampus;
- Promotes stressor-related memory storage.
Terminating a Stress Response
Normally, a stress response is brief.
- Alert, vigilant and aware of surroundings;
- Body will mobilize appropriate energy resources;
- Organism deals with stressor (fight or flight);
- The end (arrow) stress response needs to be turned off.
Negative Feedback Loop
- There is a built in mechanism that turns off the HPA axis (arrow) negative feedback loop; - Cortisol travels back to the anterior pituitary, hypothalamus and hippocampus to shut down any further activation of HPA axis.
The Maladaptive Stress Response
Chronic stress can lead to a dysfunctional HPA axis and leads to detrimental changes (arrow) all of a sudden the stress response is working against us, rather than for us.
- Continuous mobilization of energy results in muscle wasting and fatigue;
- Growth hormone inhibition prevents body from growing/repairing itself;
- GI tract is shut off, therefore reduced food intake and processing of nutrients to replace spend resources;
- Reproductive functions are inhibited;
- Immune system is suppressed, therefore organism is vulnerable to infection/disease;
- Hypertension, Type-II diabetes, ulcers, etc.
The negative feedback loop becomes desensitized and therefore creates a vicious cycle.
Chronic Stress & Depression
The hippocampus contains a high density of GRs - Projects directly to the hypothalamus;
- Exerts control over HPA axis activity.
Elevated cortisol stimulate GRs, and activates inhibitory projections to CRH neurons of the hypothalamus.
Chronically elevated cortisol levels overstimulate GRs and damage hippocampal neurons.
- Hippocampal cells eventually display atrophy (arrow) wasting away.
- Over time, damaged hippocampus loses control over the HPA axis;
- Hippocampal atrophy is closely related to depressive symptoms.
