Neuroendocrinology and Stress Flashcards by Georgia Elouise

The brain is key in the _________________ and ____________ to potential stressors

Interpretation
Response

How well did you know this?

Not at all

Perfectly

What are the consequences of short-term, everyday stress?

▪️ Altered brain function
▪️ Adaptation to environmental challenges

How well did you know this?

Not at all

Perfectly

What are the consequences of long-term stress?

▪️ Mal-adaptation
▪️ Psychiatric disorders

How well did you know this?

Not at all

Perfectly

What are the key messengers for communication between the endocrine systems and the nervous system?

▪️ Hormones
▪️ Neurotransmitters

How well did you know this?

Not at all

Perfectly

What are the key messengers used for communication between the immune system and the nervous/endocrine system?

Cytokines

How well did you know this?

Not at all

Perfectly

What is the pituitary gland?

The master gland - produces hormones that control for many different processes, sending signals to other organs and glands to regulate function and homeostasis

How well did you know this?

Not at all

Perfectly

What are the main pituitary hormones?

▪️ TSH
▪️ ACTH
▪️ FSH and LH
▪️ Growth hormone
▪️ Prolactin
▪️ Endorphins

How well did you know this?

Not at all

Perfectly

What are hormones?

Chemical messengers, produced by glands, that are transported via blood to target organs to coordinate physiology and behaviour

How well did you know this?

Not at all

Perfectly

What activities are regulated by hormones?

▪️ Digestion
▪️ Metabolism
▪️ Growth and development
▪️ Reproduction
▪️ Maintenance of body temperature
▪️ Cognitive function and mood etc

How well did you know this?

Not at all

Perfectly

How do hormones relate to the circadian rhythm?

Secretion and action usually follows it
▪️ Follows the particular needs of the body at a particular time of day
▪️ Not always secreted in the same way throughout the day

How well did you know this?

Not at all

Perfectly

How does transmission in the nervous system differ to the endocrine system?

▪️ Neurotransmitters
▪️ Rapid and brief duration
▪️ “wired”
▪️ Anatomical proximity

(Hormones as slower, have longer action, can go anywhere in the body)

How well did you know this?

Not at all

Perfectly

What condition first led to the appreciation of psychiatric problems in patients with endocrine disorders?

Cushing’s syndrome:
▪️ Increased glucocorticoid secretion
▪️ Depression, irritability, loss of recent memory

How well did you know this?

Not at all

Perfectly

How does stress relate to psychosis?

▪️ Stressful events associated with onset
▪️ Vulnerability stress model
▪️ Childhood trauma as a risk factor

How well did you know this?

Not at all

Perfectly

How does stress relate to depression?

Adverse experience, especially during childhood, associated with significant increase in risk

How well did you know this?

Not at all

Perfectly

What is the Hypothalamus-Pituitary-Adrenal (HPA) Axis?

In response to stress:
▪️ CRF stimulates pituitary gland to produce ACTH
▪️ ACTH stimulates adrenal gland to produce cortisol
▪️ Cortisol induces physiological changes supporting fight or flight response
▪️ Negative feedback loop - cortisol can feedback to pituitary and hypothalamus when too much to stop production

How well did you know this?

Not at all

Perfectly

What are the two main types of corticosteroid receptor?

▪️ Mineralocorticoid receptor (type I/MR)
▪️ Glucocorticoid receptor (type II/GR)

How well did you know this?

Not at all

Perfectly

What does the mineralocorticoid receptor do?

▪️ Binds endogenous glucocorticoids (e.g., cortisol) with HIGH AFFINITY (thus good even when levels are low)
▪️ Leads to regulation of circadian fluctuations of these hormones

How well did you know this?

Not at all

Perfectly

What does the glucocorticoid receptor do?

▪️ Binds to endogenous glucocorticoids with LOWER AFFINITY
▪️ Leads to regulation of the response to stress when levels of glucocorticoids are high enough

How well did you know this?

Not at all

Perfectly

What needs to detach from corticosteroid receptors before they can be activated?

HSP complex

How well did you know this?

Not at all

Perfectly

What happens if the HSP complex does not detach from the corticosteroid receptor?

▪️ Translocation to the nucleus cannot occur
▪️ Receptors don’t get activated despite potentially very high levels of cortisol

Why might individuals with depression have increased levels of cortisol?

▪️ GR receptors not working properly
▪️ No negative feedback to the PG/HT to stop cortisol production

(Glucocorticoid resistance due to high levels)

How can you test for overproduction of cortisol/glucocorticoid resistance?

Dexamethasone Suppression Test

▪️ Potent synthetic glucocorticoid
▪️ Activates negative feedback, suppressing cortisol production in non-depressed people
▪️ If depressed/high cortisol, will have no effect staying high throughout the day, indicating negative feedback isn’t working

What can the low dose dexamethasone suppression test be used for?

Differentiating healthy individuals from those who produce too much cortisol

What can the high dose dexamethasone suppression test be used for?

Determining whether the abnormality is in the pituitary gland (i.e., Cushing’s disease)

Are HPA axis abnormalities as consequence of depression?

Possibly but there is also evidence that is PRECEDES depression, increasing risk of developing it

What are the consequences of sustained increased cortisol levels?

▪️ HPA axis alterations correlate with impaired cognitive function in depression ▪️ More common and more pronounced in severely depressed patients with melancholic and/or psychotic features ▪️ Damaging to brain and neurogenesis?

How does chronic stress affect neuroplasticity in rats?

▪️ Dendrites become shorter in CA3 (hippocampus) ▪️ BUT reversible within several weeks

Why might HPA axis dysfunction increase risk or psychosis?

Glucocorticoids increase dopaminergic activity in the mesolimbic system

What stress/HPA-related changes are evident in both depression and psychosis?

▪️ Enlarged pituitary gland ▪️ Cortisol hypersecretion ▪️ Dexamethasone non-suppression BUT not as consistent in psychosis - greater heterogeneity?

How does treatment with antipsychotics affect cortisol levels in FEP?

It decreases it to the level of healthy controls throughout the day BUT does not appear to normalise cortisol awakening response (less of a natural increase on awakening)

What is the relationship between cortisol levels and hippocampal volume in FEP?

Moderate negative relationship Increased cortisol = decreased left hippocampal volume

How does cortisol response to Social Stress Test differ in depression and psychosis from healthy controls?

▪️ No difference in cortisol peak response in depression ▪️ Lower peak response in psychosis - blunted?

How does HPA axis activity differ in psychosis to controls?

▪️ Increased cortisol during the day ▪️ Decreased awakening cortisol ▪️ Decreased cortisol response to stress

How does HPA axis activity differ in depression to controls?

▪️ Increased cortisol during the day ▪️ Increased/equal awakening cortisol ▪️ Equal cortisol response to stress

Can cortisol activity predict response to treatment for FEP?

Possibly - non responders had lowest cortisol awakening response

What is the immune system?

▪️ Host defence system ▪️ Protects against disease ▪️ Distinguished pathogens from own healthy tissue

How does psychological stress impact wound healing?

Disrupts immune function thus impairing wound healing Study found mouth wound 3 days before exam healed ~40% slower than during summer holiday

How does the HPA axis affect inflammation and immune response?

▪️ Modulates release of cytokines ▪️ Cytokines alter monoamine metabolism, increased excitotoxicity, and decrease production of trophic factors ▪️ Cortisol = immunosuppressant

What is the relationship between depression and immune activation?

Patients show raised inflammatory markers (proinflammatory cytokines), even before development of depression (e.g., TNF-alpha, IL-6) Glucocorticoid resistance due to high levels so cortisol doesn't suppress as it should

Is there increased inflammation in psychosis?

Yes - elevated levels of pro-inflammatory cytokines (IL1-beta, IL-6, TFG-beta) in both schizophrenia and FEP

How does stress affect inflammation in psychosis?

▪️ Significantly increased levels of TNF-alpha, CRP, and IL-6 in those with childhood trauma ▪️ Significantly increased levels of C reactive protein in those with sexual abuse

What is interleukin-6?

One of the main inflammatory cytokines in the brain, marking inflammation

How does inflammation relate to hippocampal volume in FEP?

Greater inflammation (greater IL-6 expression) = smaller HC volume at onset of psychosis (significant but weak negative correlation)

Can inflammation predict treatment response in FEP?

▪️ Non responders has significantly elevated IL-6 ▪️ Responders still elevated compared to controls but not by a lot (Similar in depression!)

What is the main issues with anti-inflammatory treatments for psychiatric disorders?

▪️ A certain degree of inflammation may be beneficial and neuroprotective ▪️ Should we only target those with increased inflammation?

What did the trial of infliximab (TNF-alpha antagonist) for treatment resistant depression find?

▪️ Placebo better overall ▪️ Those with higher levels of CROP had most benefit ▪️ Thus may only be beneficial to those with inflammation, may be harmful otherwise?

What did the MINDEP clinical trial investigate?

Minocycline in addition to antidepressant for treatment-resistant depression

What is minocycline and why was it chosen for the MINDEP trial?

It is a tetracycline antibiotic that can cross the BBB

What did the MINDEP trial find?

▪️ Overall no difference to placebo ▪️ BUT when divided by baseline CRP, those with higher baseline inflammation showed significant improvement in symptoms (Important to understand threshold for treatment benefit e.g., CRP >3? )