Stress Notes
Stress
Learning Objectives
Understand the concept of 'stress'
Describe endocrine contributions to the stress response
Discuss adaptive and pathological features of the stress response
Discuss what factors can positively and negatively mediate the stress response
What is Stress?
Individuals have competing needs (growth, cellular maintenance, immune function, reproduction, thermogenesis)
Stressors disrupt the homeostasis of these needs
Stress is "anything that throws your body out of homeostatic balance" (Sapolsky, 1994)
Sources of stressors:
environmental (temperature, noise)
physiological (food quality, water deprivation)
psychological (social subordination, novel situations)
What is Stress? (Shortcomings)
Perceptions matter; what is stressful to one individual may be pleasurable to another.
Stress causes arousal that is considered aversive (Kim & Diamond, 2002).
The Stress Response
The stress response consists of physiological and behavioural responses that help to reestablish homeostasis.
Upon perceiving a stressor, the hypothalamus signals neuronally to the adrenal medullae to secrete epinephrine (adrenaline) and norepinephrine (noradrenaline).
Norepinephrine: continuously released into the bloodstream, narrows blood vessels to increase blood pressure.
Epinephrine: only released when stressed; it increases heart rate and blood pressure, blood flow to the muscles and brain, and aids the conversion of glycogen.
The Stress Response (Effects of Epinephrine and Norepinephrine)
Release of epinephrine and norepinephrine has stimulatory effects on the respiratory and cardiovascular systems, increases blood flow to the muscles, and raises blood glucose levels ("fight-or-flight-response") -> readying the body for emergency/survival action.
Benschop et al., 1996
Parachute jump study with time points at -4 hours, +1 hour, and +4 hours relative to the jump.
The Stress Response (HPA Axis)
A few minutes after the release of epinephrine, the hypothalamus releases CRH (Corticotropin-Releasing Hormone), which stimulates ACTH (AdrenoCorticoTropic Hormone) release from the anterior pituitary gland.
ACTH stimulates glucocorticoid secretion from the adrenal cortex.
The HPA Axis
The Hypothalamic-Pituitary-Adrenal (HPA) axis involves the following steps:
The hypothalamus releases CRH (Corticotropin-Releasing Hormone).
CRH stimulates the pituitary gland.
The pituitary gland releases ACTH (Adrenocorticotropic Hormone).
ACTH stimulates the adrenal gland.
The adrenal gland releases glucocorticoids (cortisol) and catecholamines (epinephrine, norepinephrine, aldosterone).
Negative feedback loops regulate the HPA axis at the level of the hypothalamus and pituitary.
Knowledge Check
What is stress?
What is the initial biological response to acute stress?
What is the biological response to long-term stress?
What are Glucocorticoids?
Usually refers to cortisol (corticosterone in rodents, birds, and fish).
Cortisol is involved in the regulation of the sleep-wake cycle with levels peaking in the morning and lowest in the evening.
Cortisol can be found and measured in most physiological samples: blood, urine, faeces, saliva, hair, fingernails, tears, milk, amniotic fluid.
Individual Differences in Cortisol Levels
Perception of the stressor matters, but so do other factors:
Age: cortisol levels generally higher in the elderly (60+) than the younger population (Roelfsema et al., 2017).
Gender: Men show higher cortisol levels in response to challenge than women (Kudielka et al., 2009).
Nicotine: smoking permanently alters the HPA axis and significantly increases salivary cortisol levels (Rohleder & Kirschbaum, 2006).
Caffeine: stimulates ACTH release and increases cortisol levels (Lovallo et al., 2005).
Cortisol and Stress
Cortisol can alter or shut down functions that get in the way of the fight-or-flight response such as digestive or reproductive systems, the immune system, or growth processes.
The 'stress hormone' is best thought of as a mediator of the recovery of a stress response in order to prepare the body for subsequent stressors (Sapolsky et al., 2000).
Adaptive Effects of the Stress Response
Increased availability of energy
Increased oxygen intake
Decreased blood flow to organs not necessary for movement
Inhibition of processes not necessary for immediate survival, e.g. digestion, immune function, reproduction
Decreased pain perception
Enhanced sensory function and memory
Non-specific: exhibited by both predator and prey
General Adaptation Syndrome (GAS)
Stage 1: alarm reaction
Stage 2: resistance
Stage 3: exhaustion/onset of stress pathology
e.g. Selye, 1950: rats in low temperature conditions for
2 days (stress response: immune suppression, atrophy of lymph nodes)
2 weeks (adaptation)
2 months (death)
Resistance to Pathological Effects
The graph illustrates the stages of stress: pre-chronic stress (homeostasis), Stage 1 (alarm), Stage 2 (resistance), and Stage 3 (exhaustion) over time.
Prolonged Pathological Effects
Pathological effects involve cardiovascular, metabolic, reproductive, digestive, immune, anabolic, behavioural, and psychological processes (Chrousos, 2000).
Peptic ulcers from inhibited digestion and immune system suppression (Helicobacter pylori).
Prolonged glucocorticoid secretion, including breakdown of glycogen and lipids to elevate blood glucose concentrations, leads to myopathy (muscle loss).
Inhibits growth and repair process (nails, hair, wound healing; Kiecolt-Glaser et al., 1995).
Elevated corticosterone reduces neurogenesis in the hippocampus (Gould et al., 1990).
Adaptive and Pathological Effects
Acute stress response vs. Pathological state associated with chronic stress:
Shift from energy storage to energy use vs. Fatigue; myopathy; steroid diabetes
Increased cardiovascular tone vs. Hypertension
Inhibited digestion vs. Peptic ulcers
Inhibited growth vs. Psychosocial dwarfism
Inhibited reproduction vs. Impotence; anovulation; loss of libido
Altered immune function and inflammatory response vs. Impaired disease resistance; cancer
Enhanced cognition vs. Accelerated neural degeneration during aging
Enhanced analgesia
Knowledge Check
What is the function of cortisol?
Is cortisol adaptive/maladaptive in the short term?
Is cortisol adaptive/maladaptive in the long term?
When does short-term stress become long-term stress?
Stress Responsiveness
Cessation of glucocorticoid secretion is under negative feedback regulation.
Glucocorticoids can have both activational and organizational effects on brain and behaviour.
The effects of early stressors can be enduring and irreversible throughout life.
Prenatal Stress in Rats
Offspring of stressed pregnant rats show increased activation of the HPA axis.
Elevated blood corticosterone concentrations as adults (Henry et al., 1994).
More likely to be anxious and to self-administer drugs (cocaine, amphetamines; Deminiere et al., 1992).
Prenatal Stress in Humans
Reduced birth weight, developmental delays, attentional deficits, hyperanxiety, impaired social behaviours, impaired coping strategies (Weinstock, 1997).
e.g. van Os & Selten, 1998: 1940 invasion of Netherlands -> increased incidence of schizophrenia.
Low birth weight in turn is associated with adult cardiovascular and metabolic disorders such as hypertension and insulin resistance (Nyirenda & Seckl, 1998).
Neonatal Stress in Rats
Early stressful experience affect reactions to stress in later life (stress immunization effect).
e.g. brief separation of rat pups from mother is mildly stressful.
Upon return, mother will lick pups more.
As adults, these rats pups are better able to cope with stressors than non-separated pups (Liu et al., 1997).
Moderate or severe stressors as pups lead to elevated stress responses (=less coping) throughout life (Rots et al., 1996).
Early Adversity in Humans
e.g. Romanian orphanages: conditions of malnutrition, sensory deprivation, poor hygiene, disease, low levels of social interaction.
Likelihood of long-term behavioral problems and endocrine dysregulation increase with length of institutional experience.
Gunnar et al., 2001
Cortisol concentrations as a function of time spent in orphanage. Hormone concentrations at 6-12 years.
Vanderwert et al., 2010
Time spent in orphanage linked to decreases in EEG alpha power (associated with perception and attention). Placing into foster care aids recovery, but only in children < 24 months old.
CAUG – care as usual group (orphanage)
> 24mo FCG – placed into foster care at 24+ months old
<24mo FCG - placed into foster care when younger than 24 months old
NIG – never institutionalised group
Knowledge Check
What effects can glucocorticoids have on brain and behaviour?
What effect do high levels of prenatal or neonatal stress have on adult rats?
What effect do high levels of prenatal or neonatal stress have on adult humans?
What effect do mild levels of neonatal stress have on adult rats?
Stress and Coping
Bi-directional relation: Stress affects behaviour, but behaviour can also affect the stress response.
Often a stressor can be psychological rather than physical (e.g. public speaking).
Individual differences in perceived stress.
Stress response is affected by:
Control
Predictability
Outlets for dealing with frustration
Habituation
Control
Weiss, 1968: rats who could control the rate of electric shock showed lower glucocorticoid secretions than yoked control rats.
Predictability
Warning signals prior to shock reduce glucocorticoid concentrations (Sapolsky, 1992).
Length of gastric ulcerations in rats. After Weiss, 1972.
Outlets for Frustration
When rats are shocked, they show lower glucocorticoid concentrations if they can chew on a piece of wood (Sapolsky, 1992).
"Leg swinging" in children reduces heart rate (Soussignan & Koch, 1985).
Habituation
=learning that a stimulus originally perceived as a stressor is not a stressor
e.g. lots of public speaking! After Ursin et al., 1978