Hormones and psychiatric disorders - summary of part of Why zebras don't get ulcers: The acclaimed guide to stress, stress-related diseases, and coping-now revised and updated by Sapolsky

Why zebras don't get ulcers: The acclaimed guide to stress, stress-related diseases, and coping-now revised and updated
By: Sapolsky, R. M. (2004).
New York: Henry Holt.

The hormones of the stress-repsonse

As the master gland, the brain can experience or think of something stressful and activate components of the stress-response hormonally.
Some of the hypothalamus-pituitary-peripheral gland links are activated during stress, some inhibited.

Two hormones vital to the stress-response released by the sympathetic nervous system:

• Epinephrine
• Norepinephrine
  Acts within seconds

Another important class of hormones in the response to stress are called glucocorticoids.
These are steroid hormones secreted by the adrenal gland.
Back the epinephrine activity up over the course of minutes to hours.

Because the adrenal gland is basically witless, glucocorticoid release must ultimately be under the control of the hormones of the brain.
When something stressful happens or you think a stressful thought, the hypothalamus secretes an array of releasing hormones into the hypothalamic-pituitary circulatory system that gets the ball rolling.
The principal such releaser is CRH (coticotropin releasing hormone).
A variety of minor players synergize with CRH
Withing fifteen seconds, CRH triggers the pituitary to release ACTH (corticotrpin) in the bloodstream.
ACTH reaches the adrenal gland and (in a few minutes) triggers glucocorticoid release.

Together, glucocorticoids and the secretions of the sympathetic nervous system (epinephrine and norepinephrine) account for a large percentage of what happens in your body during stress.

In times of stress, your pancreas is stimulated to release a hormone called glucagon.
Glucocorticoids, glucagon, and the systematic nervous system raise circulating levels of the sugar glucose.
These hormones are essential for mobilizing energy during stress.
Other hormones are activated as well.
The pituitary secretes prolactin, which plays a role in suppressing reproduction during stress.
Both the pituitary and the brain secrete endorphins and enkephalins, which help blunt pain perception.
The pituitary secretes vasopressin (antidiuretic hormone), which plays a role in the cardiovascular stress response.

Various hormonal systems are inhibited during stress
The secretion of various reproductive hormones such as estrogen, progesterone, and testosterone are inhibited.
Hormones related to growth are also inhibited.
As are the secretin of insulin.

A few complications

Fight or flight response is a way of conceptualizing the stress-response as preparing the body for that sudden burst of energy demands.
This might be different in females.
In most species, females are typically less aggressive than males, and having dependent young often precludes the option of flight.
Some suggest that the female stress-response is about tend and befriend, taking care of her young and seeking social affiliation.

The hormone oxytocin seems more related to the tend and befriend themes.
The pituitary hormone plays a role in causing the female of various mammalian species to imprint on her child after birth, to stimulate milk production, and to stimulate maternal behaviour.
Oxytocin may be critical for a for a female to form a monogamous pair bond.
Oxytocin is secreted during stress in females.

Sometimes the stress-response in females can be about fight-or-flight rather than affiliation.
And sometimes the stress-response in males can be about affiliation.

Even when considering the classic stress-response built around fight-or-flight, not all of its features work the same way In different species.

Some glucocorticoid actions help mediate the stress-response, others help mediate the recovery form the stress-response, and others prepare you for the next stressor.

There is consistency of the stress-response when it is activated.
This intertwining of the various branches of the stress-response into a package deal starts at the brain, where the same pathway can both stimulate CRH release from het hypothalamus, and activate the sympathetic nervous system.
Epinephrine and glucocorticoids can potentiate each other’s release.
But,
Not all stressors produce exact the same stress-response.
The sympathetic nervous system and glucocorticoids play a role in the response to virtually all stressors.
The speed and magnitudes of the sympathetic and glucocorticoid branches can vary depending on the stressor.
Not all of the other endocrine components of the stress-response are activated for all stressors.
The orchestration and patterning of hormone release tend to vary somewhat from stressor to stressor.
Tissues in various parts of the body may be altered in their sensitivity to a stress hormone in the case of one stressor, but not the other.

Two identical stressors can cause very different stress signatures, depending on the psychological context of the stressors.

The biology of depression

Neurochemistry and depression

Something is awry with the chemistry of brains of depressives.

The proper disposal of neurotransmitters is integral to normal neuronal communication.

Depression involves abnormal levels of the neurotransmitters norepinephrine, serotonin and dopamine.
Most of the drugs that lessen depression increase the amount of signalling by these neurotransmitters.

Two theories

• It’s not too little neurotransmitter, it’s actually too much
  There is actually too much norepinephrine, serotonin, and/or dopamine in parts of the brains of depressives.
  The cell doesn’t listen as carefully, it decreases the number of receptors for that neurotransmitter, in order to decrease its sensitivity to that messenger.
  When you prescribe antidepressants that increase signalling of these neurotransmitters
  • At first, it should make depressive symptoms worse
  • Over the course of a few weeks, the dendrites down-regulate the receptors a whole lot
    If this occurs and more than compensates for the increased neurotransmitter signal, the depressive problem of excessive neurotransmitter signalling goes away
• There is really too little norepinephrine, serotonin, and/or dopamine
  Not only do dendrites contain receptors for neurotransmitters, on the axon terminals of the ‘sending’ neuron have them as well.
  Some neurotransmitters float back to the autoreceptors and serve as some feedback signal.
  • The antidepressant drugs cause increased signalling.
  • Because of the increased signalling, over the course of weeks there will be down-regulation of norepinephrine, serotonin, and dopamine receptors.
  • The autorceptors on the first neuron will down-regulate to a greater extent than the receptors on the second neuron.
  • If that happens, the second neuron may not be listening as well, but the first one will be releasing sufficient extra neurotransmitter to more than overcome that

There are a lot of links between these neurotransmitters and function.
Serotonin is thought to have something to do with incessant ideation in depression.
A shortage of norepinephrine may explain the psychomotor retardation.
Dopamine has something to do with pleasure.
Subsance P plays a role in pain perception.

Psychiatric disorders and abnormal stress-responses

A number of psychiatric disorders involve personalities, roles, and temperaments that are associated with distinctive stress-responses.
There is a discrepancy between the sorts of stressors they are exposed to and the coping responses they come up with.
Learned helplessness is an underpinning of depression.

Anxiety disorders
Anxiety is rooted in a cognitive distortion.
People prone toward anxiety overestimate risks and the likelihood of a bad outcome.

Unlike depressives, the anxiety-prone person is still attempting to mobilize coping responses.
The discrepancy is the distorted belief that stressors are everywhere and perpetual, and that the only hope for safety is constant mobilization of coping responses.

Anxiety disorders are associated with chronically overactive stress-responses, and with increased risk of may disease.
Glucocorticoid excess is not the usual response.
It‘s too much sympathetic activation, an overabundance of circulationg catecholamines (epinephrine and norepinephrine).
They defend you against stressors by handing out guns from the gun locker within seconds.
Glococritcoids work longer.
Catecholamines mediate the response to a current stressor while glucocorticoids mediate preparation for the next stressor.

When it comes to psychiatric disorders, it seems that increases in the catecholamines have something to do with still trying to cope and the effort that involves.
Overabundance of glucocorticoids seems more of a signal of having given up on attempting to cope.

The biology of anxiety

There are some things that mammals get anxious about that are innate.
Most things that make us anxious are learned.
Organisms are predisposed to learn some of those associations more readily than others.

Implicit learning is where a certain automatic response in your body has been conditioned.
Like Pavlov.
While mild transient stress enhances declarative learning, prolonged or severe stress disrupts it.
In the case of pre-conscious, implicit, automatic learning, any type of stress enhances it.
This is outside the realm of the hippocampus.

Anxiety and fear conditioning are the province of the amygdala.
The amygdala gests sensory information before that information reaches the cortex and causes conscious awareness of the sensation.
The amygdala gest information from the autonomic nervous system, what is the significance of this?

The outputs from the amygdala make perfect sense, mostly projections to the hypothalamus and related outposts, which initiate the cascade of glucocorticoid release and activate the sympathetic nervous system.
The amygdala communicates by using CRH as a neurotransmitter.

In people with anxiety disorders, the amygdala seems to by hyperactive.

Why does the amygdala work differently in people who are anxious?
Major stressors and glucocorticoids disrupt hippocampal function, the synapses aren’t able to do that long-term potentiation business, and the dendritic processes in the neuron shrink.
Stress and glucocorticoids do the opposite in the amygdala.
Synapses become more excitable and neurons grown more of the cables that connect the cells to each other.