Neuroendocrinology Flashcards
What are the short term consequences of stress?
Effect on brain function ->
adaptation to environment
What are the consequences of long term stress?
Adaptation ->
Psychiatric disorders
How do the nervous system and endocrine system interact?
Neurotransmitters
Hormones
How do the immune system and endocrine system interact?
Cytokines
Hormones
How do the nervous system and immune system interact?
Neurotransmitters
Cytokines
What parts of the CNS are in the endocrine system?
Pineal gland
Hypothalamus
Pituitary gland
What are the pituitary hormones? What are their target organs?
TSH (thyroid)
ACTH (adrenal cortex)
FSH and LH (testes/ovaries)
Growth hormone (entire body)
Prolactin (mammary glands)
Endorphins (brain- pain receptors)
How do the endocrine and nervous system influence each other?
All hormones affect brain activity
Almost all endocrine secretions are controlled by the brain
What are the psychiatric symptoms of Cushing’s syndrome?
Depression
Irritability
Loss of recent memory
How does mineralocorticoid receptor respond to corticosterone and cortisol?
Binds with high affinity to regulate circadian fluctuation of these hormones
How does glucocorticoid receptor respond to corticosterone and cortisol?
Binds with low affinity
Takes a higher level of hormones to initiate response
Regulates response in times of stress, when levels are high
What gets is used when cortisol overproduction is suspected?
Dexamethasone to suporeee cortisol levels
Low dose will differentiate healthy from people producing too much
High dose will differentiate Cushing’s disease
How does the HPA axis regulate stress response?
Stress stimulates hypothalamus to release CRF
CRF stimulates the anterior pituitary to produce ACTH
ACTH stimulates the adrenal glands to produce cortisol
Cortisol stimulates physiological changes (fight or flight) and sends inhibitory signals to hypothalamus and pituitary
What happens when cortisol activates the glucocorticoid receptor?
Receptor released HSP complex and translocated into the nucleus
There the GR regulates gene transcription to initiate physiological changes
How is the HPA axis disrupted in patients with depression?
Glucocorticoid receptors are resistant to
Translocation and downstream effects cannot happen
Negative feedback is disrupted and glucocorticoid levels remain high
How does stress affect neuroplasticity?
Shortens dendrites
Effect is reversible over weeks
Effect seems to be mediated by the HPA axis (cortisol)
What evidence points to elevated disrupted HPA axis in depression and psychosis?
Enlarged pituitary gland
Cortisol hypersecretion
Dexamethasone non suppression
How does high glucocorticoid induce psychosis?
Glucocorticoids increase dopaminergic activity in the mesolimbic pathway
How does cortisol correlate with hippocampal volume in psychosis?
Negative correlation
Higher cortisol = smaller hippocampal volume
How do patients with psychosis differ from patients with depression I. Response to stress?
Patients with psychosis do not mount a stress response to social stress tests, patients with depression do
What biomarker might be useful for predicting non-response to psychosis treatment?
Awakening cortisol response
What biomarkers support the theory of higher inflammation in depression and psychosis?
Higher cytokine levels (TNF, IL6) preceding the onset of depression
How does childhood trauma affect inflammation levels?
Higher levels of inflammatory markers even with disorder group
Has anti inflammatory treatment proved useful in all patients with depression?
No, only in higher levels inflammation
Low level inflammation might be neuro protective
How is the HPA axis involved in inflammation?
CRF activated the locus coeruleus to activate the sympathetic nervous system
This stimulates release of cytokines
Cytokines alter monoamine metabolism, increase excitotoxicity, decrease trophic factor (BDNF) production
