L3 - Endocrine function and Stress

Question 1

What does neuroendocrine system consist of?

Answer 1

HPA axis and LC-NE/ANS (hypothalamic-pituitary-adrenal axis and locus caeruleus/norepinephrine-autonomic nervous system)

Question 2

What does HPA axis include?

Answer 2

HPA axis includes a group of hormones-secreting glands from the nervous and endocrine systems: the hypothalamus (in the brain), the pituitary gland (just below the brain), and the adrenal glands (above the kidneys).

Question 3

How HPA acts in the presence of stress?

Answer 3

When we experience something stressful, the hypothalamus releases a hormone called corticotropin-releasing hormone (or CRH) and AVP (arginine vasopressin). These hormones trigger the pituitary gland to secrete a hormone called adrenocorticotropic hormone, or ACTH into the bloodstream. ACTH travels down to the adrenal glands where it prompts the release of a hormone called cortisol from the cortex, or outer layer, of the adrenal glands.

Question 4

What is a negative feedback mechanism?

Answer 4

A negative feedback mechanism is a process used by biological systems to maintain stability or balance (also called homeostasis). In this mechanism, a change in a particular condition (like temperature, hormone level, or blood pressure) triggers a response that counteracts or reverses the initial change, bringing the system back to its normal state.

In relation to stress:
Cortisol, after being released in response to stress, feeds back to the brain (hypothalamus and pituitary) to reduce the production of CRH and ACTH, ensuring that cortisol levels do not remain elevated for too long.

Question 4

How does release of cortisol affect the body?

Answer 4

Cortisol helps to mobilize energy like glucose so the body has enough energy to cope with a prolonged stressor. When cortisol levels in the blood get high, this is sensed by receptors in areas of the brain like the hypothalamus and hippocampus, which leads to the shutting off of the stress response through what is known as a negative feedback mechanism.

Known as the “stress hormone,” cortisol increases blood sugar, suppresses the immune system, and helps the body utilize energy efficiently during stress. It follows a circadian rhythm (daily pattern) with levels peaking in the early morning.

Question 5

Why adaptive response is important?

Answer 5

The quantitatively and/or qualitatively appropriate “adaptive response” to stressors is crucial for maintaining homeostasis, whereas acute or chronic hypoactivation or hyperactivation of the stress system may lead to a wide range of, respectively, acute or chronic pathologic conditions, such as allergic reactions, migraine headaches, etc., or diseases, including anxiety, depression, obesity, metabolic syndrome, type 2 diabetes mellitus, and growth, reproductive, sleep, and immune system disorders.

Question 6

What does Autonomic Nervous System (ANS) consist of?

Answer 6

-Sympathetic Nervous System (SNS): Activates the “fight or flight” response, increasing heart rate, breathing, and energy availability by releasing norepinephrine (noradrenaline) and epinephrine (adrenaline).
- Parasympathetic Nervous System (PNS): Works to calm the body down after the threat passes, supporting functions like digestion and rest.

Question 7

How Catecholamines work?

Answer 7

Catecholamines (Adrenaline and Noradrenaline): These hormones help prepare the body for quick action in response to a threat, enhancing heart rate, blood flow, and energy mobilization.

Question 8

How the Stress System Works in Different Situations - Acute stress?

Answer 8

Short-term stress, such as facing an immediate threat, activates the stress system to release adrenaline and cortisol. This results in heightened alertness, increased heart rate, and enhanced physical performance (i.e., the fight-or-flight response).

Question 9

How the Stress System Works in Different Situations - Chronic stress?

Answer 9

Long-term activation of the stress system, as seen in chronic stress, can lead to maladaptive responses. This means the body stays in a state of heightened alert for too long, which can lead to various health issues, including anxiety, depression, obesity, metabolic disorders, and cardiovascular diseases.

Question 10

What is the effect of early life stress?

Answer 10

Early life stressors, such as childhood trauma or prenatal stress, can leave lasting marks on the stress system through epigenetic changes. These are modifications in how genes are expressed without altering the DNA sequence itself. Such changes can affect how the stress system functions later in life, making individuals more vulnerable to stress-related disorders like anxiety, depression, and metabolic syndrome.

Question 11

How does the stress system interact with the brain?

Answer 11

The Stress System and the Brain: The stress system interacts with other brain regions involved in emotional regulation, such as the amygdala (which processes fear and anger) and the hippocampus (which is involved in memory). These regions work together to determine how the body responds to stress and regulate the intensity of the stress response.

Question 12

What is the Circadian System (CLOCK System)?

Answer 12

The stress system is linked to the body’s internal clock, known as the circadian system. Cortisol levels, for example, follow a daily rhythm to prepare the body for the day’s challenges. Chronic stress can disrupt this natural rhythm, leading to long-term health consequences, including chronic diseases.

Question 13

Consequences of hyper- and hypoactivation of the stress system

Answer 13

• Hyperactivation can lead to conditions like anxiety, depression, and metabolic disorders such as obesity and type 2 diabetes.
• Hypoactivation can be associated with conditions like chronic fatigue syndrome and post-traumatic stress disorder (PTSD), where the body’s ability to respond to stress is impaired.

Question 14

What are eustress and distress?

Answer 14

• Eustress: This is a positive form of stress that can enhance performance, learning, and personal growth when challenges are manageable and temporary.
• Distress: Prolonged or excessive stress, leading to harmful physical and psychological effects, such as cardiovascular disease, mental health disorders, and immune dysfunction.

Question 15

How does Catecholamines get released?

Answer 15

Sympathetic Nervous System (SNS): When stress is detected, the sympathetic nervous system activates and sends signals to the adrenal medulla (the inner part of the adrenal gland), which releases adrenaline and noradrenaline into the bloodstream.

Question 16

Effects of adrenaline

Answer 16

• Target Organs: Adrenaline binds to specific receptors called adrenergic receptors located on various organs, such as the heart, lungs, and muscles.
• Effects:
  
  • Increased heart rate: Adrenaline stimulates the heart to beat faster, improving blood flow to muscles and vital organs.
  • Bronchodilation: It relaxes the airways in the lungs, making it easier to breathe.
  • Energy mobilization: Adrenaline promotes the breakdown of glycogen (stored glucose) in the liver and muscles, providing an immediate source of energy.
  • Vasoconstriction: It constricts blood vessels in non-essential areas (like the skin and digestive system), redirecting blood to critical organs like the brain, heart, and muscles.
  • Pupil dilation: It dilates pupils, allowing more light into the eyes for improved vision in a potentially dangerous situation.

Question 17

Effects of noradrenaline

Answer 17

• Target Organs: Like adrenaline, noradrenaline acts on adrenergic receptors, but its effects are more focused on maintaining blood pressure and increasing alertness.
• Effects:
  
  • Vasoconstriction: Noradrenaline strongly constricts blood vessels, especially in the skin and gut, which increases blood pressure and helps maintain blood flow to essential organs.
  • Alertness and Focus: It enhances alertness, attention, and readiness to act, making you more aware of your surroundings.
  • Heart Rate: Although it also increases heart rate, its effect is less pronounced than adrenaline.

Question 18

How catecholamines are terminated?

Answer 18

After catecholamines have triggered their effects, the body works to stop the response. Enzymes like COMT (catechol-O-methyltransferase) and MAO (monoamine oxidase) break down adrenaline and noradrenaline to end their action and return the body to a normal, resting state.

Question 19

Where can we find cortisol? in which body fluids?

Answer 19

Acute: blood an saliva
1-day: urine
Months: hair

Question 20

What are psychological effects observed in patients with diabetes?

Answer 20

Hormonal Issue: In diabetes, the body either doesn’t produce enough insulin (Type 1) or doesn’t effectively use the insulin it produces (Type 2). Insulin is critical for regulating blood sugar levels. Fluctuations in blood glucose directly impact brain function, as the brain relies on glucose as its primary source of energy.

Psychological Effects:

• Depression and Anxiety: Chronic hyperglycemia (high blood sugar) and hypoglycemia (low blood sugar) can both lead to neuroinflammation and oxidative stress, which have been linked to mood disorders like depression and anxiety. Constantly managing blood sugar can cause feelings of overwhelm, anxiety, and a sense of loss of control.
• Cognitive Dysfunction: High blood glucose levels can damage blood vessels in the brain, leading to cognitive decline and memory issues. This is particularly common in patients with long-standing diabetes and poorly controlled blood sugar levels, as glucose dysregulation affects neuronal communication and leads to neurodegeneration.
• Insulin and Brain Function: Insulin receptors are found in the brain, particularly in regions associated with memory and learning (e.g., the hippocampus). Dysregulation of insulin not only impacts glucose metabolism but also neurotransmitter function, leading to memory issues, brain fog, and impaired decision-making.

Question 21

What are psychological effects observed in patients with Hypothyroidism (Low Thyroid Hormones)?

Answer 21

Hormonal Issue: Hypothyroidism is characterized by low levels of thyroid hormones (T3 and T4), which are crucial for regulating metabolism, energy levels, and brain function. The thyroid hormones directly affect neurotransmitters like serotonin, dopamine, and norepinephrine, which are critical for mood regulation.

Psychological Effects:

• Depression: Low thyroid hormones reduce the activity of serotonin in the brain, a neurotransmitter associated with happiness and well-being. This leads to persistent low mood, lack of interest in activities, and a sense of hopelessness. In fact, hypothyroidism is commonly associated with clinical depression, and treating thyroid dysfunction can sometimes alleviate depressive symptoms.
• Anxiety: Although hypothyroidism is more strongly linked to depression, anxiety can also occur. Low thyroid hormone levels may reduce dopamine and norepinephrine levels, leading to emotional instability and increased stress sensitivity.
• Cognitive Impairment: Thyroid hormones play a critical role in brain development and function. Deficiency leads to slowed mental processing, memory lapses, and difficulty concentrating, often referred to as brain fog. This occurs because reduced thyroid hormones impair synaptic transmission, affecting how neurons communicate.

Question 22

What are psychological effects observed in patients with Cushing’s Disease (Excess Cortisol)?

Answer 22

Hormonal Issue: Cushing’s disease is caused by excessive levels of cortisol, a glucocorticoid hormone produced by the adrenal glands. Cortisol is often called the “stress hormone” because it is released in response to stress. However, chronic overproduction, as seen in Cushing’s, leads to widespread effects on the brain and body.

Psychological Effects:

• Depression and Anxiety: High levels of cortisol disrupt the normal balance of serotonin and dopamine in the brain, which are critical for mood regulation. This can lead to severe depression, irritability, and emotional instability. Cortisol also triggers the amygdala, the brain’s fear center, leading to increased anxiety and stress responses.
• Cognitive Decline: Chronic high cortisol can damage brain structures like the hippocampus, which is responsible for memory formation and emotional regulation. This can lead to memory problems, reduced cognitive function, and difficulty with attention. Over time, high cortisol levels may even contribute to neurodegenerative diseases like Alzheimer’s.
• Sleep Disorders: Excess cortisol disrupts the normal sleep-wake cycle, often leading to insomnia or fragmented sleep. Poor sleep exacerbates mood disorders like anxiety and depression, further aggravating the psychological impact.
• Psychosis: In extreme cases, the chronic elevation of cortisol can lead to psychotic symptoms, such as hallucinations and paranoia, although this is less common.

Question 23

How cortisol affects the brain?

Answer 23

High levels of cortisol impair the hippocampus, which plays a role in memory and emotional regulation, and the prefrontal cortex, responsible for decision-making and social behavior. Cortisol also overstimulates the amygdala, the brain’s emotional center, heightening fear and anxiety responses.

Question 24

How Thyroid Hormones affect the brain?

Answer 24

Thyroid hormones influence levels of neurotransmitters like serotonin, dopamine, and norepinephrine, which regulate mood, motivation, and pleasure. Low levels of thyroid hormones lead to disruptions in these neurotransmitter systems, explaining the strong connection between hypothyroidism and depression.

Question 25

How Insulin affects the brain?

Answer 25

Insulin is essential for synaptic plasticity, the brain’s ability to adapt and form new connections, which is crucial for learning and memory. In diabetes, insulin resistance or deficiency impairs brain function, leading to cognitive issues.

Question 26

What is passive diffusion?

Answer 26

Passive diffusion refers to the movement of molecules (like cortisol) across a membrane (e.g., the lipid bilayer of cells) without requiring energy. Molecules move from an area of high concentration to low concentration.

Question 27

Which factors affect diffusion?

Answer 27

- Concentration Gradient: A greater difference between the concentration inside and outside the cell speeds up diffusion. The larger this difference, the more rapidly molecules will move. - Solvent Density: If the surrounding solvent (like the extracellular fluid) is dense (e.g., dehydration makes it thicker), diffusion is slower.

Question 28

Important cofounders and covariates which affect reaction to stress?

Answer 28

Hormone medication, food & beverage intake, sex and age (cortisol increases with age and is higher in men)

Question 29

HPA Axis Hyperreactivity and what is its effect on human's psycho?

Answer 29

- What it Means: The hypothalamic-pituitary-adrenal (HPA) axis is overly active, leading to excess cortisol secretion. - Linked to: - Depression: About 50% of newly diagnosed depressions show elevated cortisol levels, indicating hyperactivity of the HPA axis. This kind of depression may involve severe emotional dysregulation, stress, and mood swings. - Bipolar Disorder: In cases with suicidal ideation, the HPA axis is often hyperreactive, reflecting a high level of physiological stress. - Chronic Stress and Anxiety: People with chronic stress, anxiety, or Type D personality (characterized by distress and negative emotions) also exhibit hyperactivity of the HPA axis, resulting in persistent high cortisol levels, which worsens stress responses.

Question 30

What is HPA Axis Hyporeactivity and what is its effect on human's psycho?

Answer 30

- What it Means: The HPA axis is underactive, leading to low cortisol secretion or a blunted stress response. - Linked to: - Early Life Stress or Adverse Events: Experiences of stress or trauma early in life may lead to an underactive HPA axis later, affecting emotional and physical health. - Somatic Symptom Disorders: Conditions like Fibromyalgia (FMS), Chronic Fatigue Syndrome (CFS), and Irritable Bowel Syndrome (IBS) are associated with HPA hyporeactivity, where the body does not manage stress well, often leading to physical symptoms. - Addiction: People with addiction might have a hyporeactive HPA axis, making it difficult for them to regulate stress, which could be partly genetic. - Depression (Blunted): Lower depression scores are seen in some people with HPA hyporeactivity, meaning their depression might be characterized by low energy and apathy rather than heightened stress or anxiety. - Behavioral Disorders: Conditions like Antisocial Personality Disorder, Conduct Disorder, and ADHD are also linked to a hypoactive HPA axis, possibly resulting in impulsive or risk-taking behaviors.

Question 31

What are the mechanisms of Hyporeactivity?

Answer 31

- Reduced biosynthesis: There's a decrease in the production of cortisol. - Hypersecretion with subsequent downregulation of target receptors: Initially, more cortisol is secreted due to stress, but over time, the receptors for cortisol become less sensitive. - Enhanced negative feedback sensitivity: The feedback loop that regulates cortisol becomes overly sensitive, causing the body to reduce cortisol production too much. - Decreased availability of free cortisol: Less cortisol is available in its active form to carry out normal functions. - Cortisol resistance of target tissue: Tissues in the body become resistant to cortisol, meaning it becomes less effective even if present.

Question 32

What is the developmental Model of Hyporeactivity?

Answer 32

1. Period of prolonged stress: This could be due to various factors like work stress, social stress, or infections. During this period, there is hypercortisolism (excess cortisol production) as a response. 2. Onset of hypocortisolemic symptoms: Eventually, after prolonged stress, symptoms of hypocortisolism (low cortisol levels) appear. These include: - Fatigue - Pain - Sensitivity to stress

Question 33

Which factors might affect stress response variability?

Answer 33

Weekday vs weekend day, perseverance in task completion, low socio-economic status, ethnic minority status

Question 34

Allostatic load

Answer 34

Allostatic load refers to the cumulative burden of chronic stress and life events. It involves the interaction of different physiological systems at varying degrees of activity. When the body is frequently exposed to stressors, it can lead to a cumulative wear and tear known as allostatic load. High allostatic load can result from chronic stress and is associated with various health issues, such as cardiovascular disease, obesity, and mental health disordersological Systems**: Allostasis engages various biological systems, including the HPA axis (hypothalamic-pituitary-adrenal axis), the autonomic nervous system, and the immune system. These systems work together to regulate responses to stress .

Question 34

What is Allostasis?

Answer 34

Allostasis is a concept that refers to the process by which the body achieves stability through change. It describes how the body maintains homeostasis (a stable internal environment) by adapting to varying environmental demands and stressors over time. Allostasis is the efficient regulation required to prepare the body to satisfy its needs before they arise by budgeting those needed resources such as oxygen, insulin etc., as opposed to homeostasis, in which the goal is a steady state.

Question 35

SAM axis

Answer 35

The SAM axis, or Sympathetic-Adrenal-Medullary axis, is a critical part of the body's response to stress. It involves the sympathetic nervous system and the adrenal medulla, which are activated during stressful situations to prepare the body for a "fight-or-flight" response.

Question 36

Androgens

Answer 36

Androgens are a group of hormones that play a role in the development of male traits and reproductive activity. The most well-known androgen is testosterone, but there are others like dehydroepiandrosterone (DHEA) and androstenedione.

Question 37

When is a stress response adaptive? When maladaptive?

Answer 37

Adaptive Stress Response A stress response is considered adaptive when it helps an individual cope with immediate challenges or threats, enhancing their chances of survival and well-being. Here are some situations where the stress response is beneficial: Immediate Danger: In life-threatening situations, such as encountering a predator or a physical threat, the fight-or-flight response prepares the body to either confront the threat or escape from it. This response increases heart rate, sharpens focus, and mobilizes energy reservese Enhancement**: Moderate levels of stress can improve performance in tasks requiring focus and attention. For instance, stress can enhance motivation during exams or competitions, allowing individuals to perform better under pressure . **Learning - Stressful experiences can lead to increased resilience and better coping strategies in the future. Successfully navigating stress can foster personal growth and adaptability . Maladaptive Stress Responsess response becomes maladaptive when it leads to negative consequences, especially if it is prolonged or excessive. Here are examples of maladaptive stress responses: Chronic Stress: Prolonged activation of the stress response can result in health issues such as cardiovascular disease, anxiety disorders, and depression. Chronic stress can lead to dysregulation of the HPA axis, contributing to a range of psychological and physical problems . Avoidance Behavior: Instead of confroividuals may develop avoidance behaviors, such as substance abuse or social withdrawal, which can worsen the situation and lead to isolation and further distress . Impaired Functioning: Excessive stress can impair cogni as memory and decision-making, reducing overall quality of life and productivity .

Question 38

Corticosteroid

Answer 38

Corticosteroids are a class of steroid hormones produced in the adrenal cortex, which are vital for various physiological functions in the body. They are broadly categorized into two main types: glucocorticoids and mineralocorticoids. Key Features of Corticosteroids: Types: Glucocorticoids (e.g., cortisol) are primarily involved in glucose metabolism, immune response regulation, and inflammation control. They help the body respond to stress and are critical in maintaining homeostasis. Mineralocorticoids (e.g., aldosterone) are mainly responsible for regulating sodium and potassium balance, influencing blood pressure and fluid balance. Functions: Metabolism: Glucocorticoids increase glucose availability by promoting gluconeogenesis in the liver and inhibiting glucose uptake in other tissues. Immune Response: They suppress inflammation and immune responses, which is why corticosteroids are often used in treating autoimmune diseases and allergies. Stress Response: Corticosteroids are crucial in the body’s response to stress, helping to mobilize energy and maintain blood pressure.

Question 39

Describe the circadian rhythm of cortisol

Answer 39

The circadian rhythm of cortisol refers to the daily pattern of cortisol secretion in the body, regulated by the body's internal clock, or circadian rhythm. Cortisol, often referred to as the "stress hormone," is produced by the adrenal glands and plays a crucial role in metabolism, immune response, and the regulation of various bodily functions. Key Features of the Circadian Rhythm of Cortisol: Daily Cycle: Cortisol levels typically follow a predictable daily rhythm, peaking in the early morning (around 6–8 AM) and gradually declining throughout the day. Levels reach their lowest point late in the evening or during the night (around midnight to 4 AM)l pattern aligns with sleep-wake cycles, helping to regulate various physiological processes and maintain energy levels throughout the day. Triggers for Release: The secretion of cortisol is primarily influenced by the hypothalamic-pituitary-adrenal (HPA) axis. The hypothalamus releases corticotropin-releasing hormone (CRH), stimulating the pituitary gland to produce adrenocorticotropic hormone (ACTH), which in turn prompts the adrenal glands to secrete cortisol . External t exposure, sleep patterns, and stress levels can also impact cortisol release and its circadian rhythm.

Question 40

Which brain neurotransmitters are involved into stress response?

Answer 40

Several brain neurotransmitters are involved in the stress response and the functioning of the HPA axis. Here’s an overview of the key neurotransmitters and their roles: 1. Corticotropin-Releasing Hormone (CRH): Function: Released from the hypothalamus, CRH stimulates the pituitary gland to secrete ACTH, initiating the stress response. Role in Stress: CRH is crucial in the early stages of the stress response, influencing the release of other hormones and modulating behaviors related to anxiety and stress. Sources: Research indicates that CRH can influence various aspects of stress reactivity, including anxiety-like behavior​ KARGER ​ TEACHMEPHYSIOLOGY . 2. Norepinephrine (Noradrenaline): Function: Released from the locus coeruleus in the brainstem, norepinephrine is critical for the fight-or-flight response. Role in Stress: It increases alertness, arousal, and attention during stressful situations. Elevated norepinephrine levels can also enhance memory formation for stressful events. Sources: Studies show that norepinephrine plays a significant role in the body's acute stress response, affecting heart rate and blood pressure​ KARGER ​(L3 Basic Concepts and H…). 3. Dopamine: Function: Dopamine is involved in reward processing, motivation, and mood regulation. Role in Stress: Stress can alter dopamine pathways, potentially leading to changes in mood and motivation. Dysregulation of dopamine systems is linked to mood disorders and stress-related conditions. Sources: Research highlights the relationship between stress, dopamine levels, and behaviors such as motivation and reward-seeking​ KARGER ​ TEACHMEPHYSIOLOGY . 4. Serotonin: Function: Often referred to as the "feel-good" neurotransmitter, serotonin regulates mood, emotion, and anxiety. Role in Stress: Stress can decrease serotonin levels, contributing to anxiety and depression. The relationship between serotonin and the stress response is complex, as serotonin can also influence the functioning of the HPA axis. Sources: Numerous studies indicate that serotonin's role in mood regulation is critical, particularly during stressful times​ KARGER ​(L3 Basic Concepts and H…). 5. Gamma-Aminobutyric Acid (GABA): Function: GABA is the primary inhibitory neurotransmitter in the brain. Role in Stress: GABA reduces neuronal excitability and promotes relaxation, counteracting the effects of excitatory neurotransmitters like norepinephrine and glutamate. During stress, increased GABA activity can help mitigate anxiety. Sources: Research suggests that GABA plays a protective role against stress-induced anxiety and is often targeted in anxiety treatments

Question 41

Can you link what you know about the dopaminergic reward system in extraverts to stress / HPA axis sensitivity

Answer 41

Dopaminergic Reward System and Extraversion Dopamine and Reward Sensitivity: The dopaminergic system, particularly the mesolimbic pathway, plays a crucial role in the processing of rewards and motivation. This system involves the release of dopamine in response to rewarding stimuli, reinforcing behaviors that lead to pleasure. Research indicates that extraverts tend to have higher dopamine activity, making them more sensitive to rewards and social interactions. They often seek out rewarding experiences, such as social engagements and activities that provide positive feedback​ KARGER ​ TEACHMEPHYSIOLOGY . Extraversion and Stress Response: Extraverts generally exhibit a more resilient stress response, often utilizing social support to mitigate stress effects. Their higher baseline levels of dopamine can buffer the effects of stress, leading to a more adaptive response when faced with challenges​ KARGER ​(L3 Basic Concepts and H…). Studies have shown that extraversion is associated with lower levels of perceived stress and better coping mechanisms during stressful situations. This may be partly due to the enhanced functioning of the dopaminergic system​ KARGER . HPA Axis Sensitivity HPA Axis and Stress: The HPA axis regulates the body’s response to stress through the release of cortisol and other hormones. Sensitivity in this axis can influence how one experiences and reacts to stress. Individuals with heightened HPA axis sensitivity may have exaggerated stress responses, leading to higher cortisol levels during stress, which can be detrimental over time​ KARGER ​(L3 Basic Concepts and H…). Interplay Between Dopamine and HPA Axis: The interaction between dopamine and the HPA axis is crucial in stress responses. Elevated cortisol levels, often seen in individuals with a more sensitive HPA axis, can negatively impact dopamine signaling​ KARGER . Research suggests that chronic stress can lead to dysregulation of the dopaminergic system, which may further complicate the stress response and emotional regulation in individuals, especially in those with high HPA axis sensitivity​ TEACHMEPHYSIOLOGY ​(L3 Basic Concepts and H…). Conclusion In summary, the dopaminergic reward system is linked to extraversion through its role in reward sensitivity and motivation. Extraverts, with their more robust dopaminergic activity, are typically more resilient to stress and exhibit less HPA axis sensitivity compared to introverts. Conversely, those with heightened HPA axis sensitivity may experience more pronounced stress responses, negatively impacting their dopaminergic functioning and overall well-being.

Question 42

Explain how different receptors for cortisol play a different role in the day rhythm and responsivity of the HPA axis

Answer 42

Cortisol exerts its effects through two main types of receptors: glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs). These receptors play distinct roles in the regulation of the HPA axis and are involved in the body's circadian rhythm and responsiveness to stress. 1. Glucocorticoid Receptors (GRs) Location and Function: GRs are widely distributed in various tissues, including the brain, liver, and immune cells. When cortisol binds to GRs, it influences gene expression, leading to various physiological responses, including metabolism, immune regulation, and stress response​ KARGER ​ TEACHMEPHYSIOLOGY . Role in Circadian Rhythm: GRs are crucial for the daily rhythm of cortisol release. Cortisol levels peak in the early morning and gradually decline throughout the day, aligning with the body's circadian clock. GRs help modulate the sensitivity of the HPA axis to cortisol, affecting how the body responds to stress at different times of the day​ KARGER . The expression and sensitivity of GRs can vary throughout the day, which may influence how effectively cortisol can exert its effects during peak periods of secretion​ TEACHMEPHYSIOLOGY ​(L3 Basic Concepts and H…). Responsivity: During acute stress, GRs facilitate a robust response by enhancing the effects of cortisol. However, chronic elevation of cortisol can lead to GR desensitization, reducing the effectiveness of cortisol signaling and contributing to stress-related disorders​ KARGER . 2. Mineralocorticoid Receptors (MRs) Location and Function: MRs are primarily found in the kidneys, heart, and certain brain regions. They are mainly involved in regulating sodium and potassium balance and blood pressure but also influence stress response​ KARGER ​(L3 Basic Concepts and H…). Role in Circadian Rhythm: MRs have a high affinity for cortisol, particularly at lower levels, which helps in regulating the HPA axis's sensitivity to cortisol throughout the day. They contribute to the maintenance of homeostasis and modulate the body’s response to daily stressors​ KARGER ​ TEACHMEPHYSIOLOGY . MRs help maintain circadian rhythms in the HPA axis by influencing the set points for cortisol release, thus ensuring that the body adapts to diurnal changes in stress and metabolism​ KARGER ​(L3 Basic Concepts and H…). Responsivity: MRs play a protective role against the harmful effects of chronic stress by promoting resilience and adaptation. Activation of MRs can enhance the body's ability to cope with stress, particularly during the initial phases of the stress response​(L3 Basic Concepts and H…). Summary of Cortisol Receptor Roles GRs are crucial for mediating the effects of cortisol during stress and influencing the HPA axis's responsiveness. They help shape the daily rhythm of cortisol levels and can become desensitized with chronic exposure. MRs, on the other hand, help regulate baseline cortisol effects and maintain homeostasis. They are key in adapting the body's response to daily stressors and preserving the circadian rhythm of cortisol secretion.

Question 43

Give an example of how an early life stressor may lead to adult depression through biological alterations . Use biological knowledge from the paper. Whichhormones are involved? Which receptors? Genes? Environment?

Answer 43

In the context of early life stress (ELS) leading to adult depression, several biological mechanisms involving hormones, receptors, and genes are described in the research literature, such as the one you've shared. Based on general biological understanding and possible references from the document, here's how ELS might contribute to depression: Hormones: Early life stress can activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased secretion of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), which in turn stimulates the release of cortisol, a key stress hormone. Chronic overexposure to cortisol during critical developmental windows can dysregulate this system and make it more reactive or unregulated in adulthood, contributing to the development of depression. Receptors: Prolonged elevation of cortisol can downregulate or desensitize glucocorticoid receptors (GR) in the brain, especially in regions like the hippocampus and prefrontal cortex, which are involved in regulating mood and stress responses. This impaired feedback loop on the HPA axis can lead to sustained high cortisol levels, promoting depressive symptoms. Genes: The FKBP5 gene is a key player in the regulation of the HPA axis and its stress response. Variations or epigenetic changes in FKBP5 (such as DNA methylation) can alter its expression, making individuals more susceptible to stress and, consequently, depression. ELS can induce epigenetic modifications on genes like NR3C1, which encodes the glucocorticoid receptor, thereby altering the brain's ability to manage stress and increasing the risk for depression. Environment: The environment, particularly exposure to chronic or traumatic stress in early childhood, interacts with these biological systems. Such environmental factors can lead to long-term alterations in brain structure and function, including changes in neuroplasticity, inflammatory pathways, and neurotransmitter systems (e.g., serotonin and dopamine), all of which can predispose an individual to depression later in life.