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Questions and Answers
According to Jacobs and colleagues' theory, what role does adult hippocampal neurogenesis play in major depression?
According to Jacobs and colleagues' theory, what role does adult hippocampal neurogenesis play in major depression?
- Neurogenesis rates are unrelated to the development or recovery from depression.
- Increased neurogenesis is a primary cause of major depression, while decreased neurogenesis aids in recovery.
- Neurogenesis rates only affect the severity of depressive episodes, not the likelihood of developing the disorder.
- Decreased neurogenesis underlies the development of major depression, while increased neurogenesis facilitates recovery. (correct)
Which of the following factors would be expected to increase the rate of adult hippocampal neurogenesis, according to Jacobs and colleagues?
Which of the following factors would be expected to increase the rate of adult hippocampal neurogenesis, according to Jacobs and colleagues?
- Chronic stress
- Increased glucocorticoids
- Adversity
- Antidepressant drugs (correct)
In the 2018 study, what specific changes were observed in the prefrontal cortex of mice subjected to chronic unpredictable stress?
In the 2018 study, what specific changes were observed in the prefrontal cortex of mice subjected to chronic unpredictable stress?
- No change in dendritic spine density, but a significant decrease in CSF1 messenger RNA levels.
- Increased dendritic spine density on pyramidal neurons and decreased CSF1 messenger RNA levels.
- Decreased dendritic spine density on pyramidal neurons and increased CSF1 messenger RNA levels. (correct)
- Increased density of microglia and decreased CSF1 messenger RNA levels.
What is the role of microglia in the brain, as described in the study?
What is the role of microglia in the brain, as described in the study?
What was the effect of preventing neurons from producing CSF1 in mice exposed to chronic stress?
What was the effect of preventing neurons from producing CSF1 in mice exposed to chronic stress?
What is the connection between reduced connectivity in the prefrontal cortex and depression, as suggested by the research?
What is the connection between reduced connectivity in the prefrontal cortex and depression, as suggested by the research?
What is the significance of finding increased CSF1 messenger RNA levels in the postmortem dorsolateral prefrontal cortex of individuals with depression?
What is the significance of finding increased CSF1 messenger RNA levels in the postmortem dorsolateral prefrontal cortex of individuals with depression?
How does chronic stress impact neural circuits in the brain, and what is the consequence of this alteration?
How does chronic stress impact neural circuits in the brain, and what is the consequence of this alteration?
Based on the information provided, what is the most likely mechanism by which stress-induced signaling impacts mental health?
Based on the information provided, what is the most likely mechanism by which stress-induced signaling impacts mental health?
In the human hippocampal progenitor cell model, what effect does treatment with high doses of cortisol have on neurogenesis?
In the human hippocampal progenitor cell model, what effect does treatment with high doses of cortisol have on neurogenesis?
Why is saliva sampling a common method for cortisol assessment in observational surveys?
Why is saliva sampling a common method for cortisol assessment in observational surveys?
Dexamethasone, a synthetic glucocorticoid and specific GR agonist, reduces the number of MAP2 positive neurons. How does Sertraline modulate this effect?
Dexamethasone, a synthetic glucocorticoid and specific GR agonist, reduces the number of MAP2 positive neurons. How does Sertraline modulate this effect?
Why is dexamethasone used in experiments studying the effects of glucocorticoids on cells?
Why is dexamethasone used in experiments studying the effects of glucocorticoids on cells?
A researcher aims to study the cumulative effect of frequent HPA axis activation on chronic disease development. Which biological sample would be most suitable for measuring cortisol levels?
A researcher aims to study the cumulative effect of frequent HPA axis activation on chronic disease development. Which biological sample would be most suitable for measuring cortisol levels?
What is a key limitation of using single saliva measurements for assessing cortisol levels?
What is a key limitation of using single saliva measurements for assessing cortisol levels?
What is the cortisol awakening response (CAR) and when does it typically occur?
What is the cortisol awakening response (CAR) and when does it typically occur?
A researcher is investigating the effects of chronic stress on HPA axis function. Which assessment method would be most suitable to analyze basal cortisol secretion patterns throughout the day?
A researcher is investigating the effects of chronic stress on HPA axis function. Which assessment method would be most suitable to analyze basal cortisol secretion patterns throughout the day?
In the Netherlands Study of Depression and Anxiety, what was the primary method used to collect saliva samples for cortisol analysis?
In the Netherlands Study of Depression and Anxiety, what was the primary method used to collect saliva samples for cortisol analysis?
In a study comparing cortisol awakening response (CAR) between different groups, which of the following findings would suggest dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis?
In a study comparing cortisol awakening response (CAR) between different groups, which of the following findings would suggest dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis?
A study finds that a new antidepressant drug normalizes the cortisol awakening response (CAR) in depressed patients. What does this suggest about the drug's mechanism of action?
A study finds that a new antidepressant drug normalizes the cortisol awakening response (CAR) in depressed patients. What does this suggest about the drug's mechanism of action?
Which of the following is a practical advantage of using hair samples over urine samples for measuring cortisol levels?
Which of the following is a practical advantage of using hair samples over urine samples for measuring cortisol levels?
In an experiment using human hippocampal progenitor cells, researchers observe that the addition of a specific compound increases the number of doublecortin-positive neuroblasts, even in the presence of cortisol. What might this suggest about the compound?
In an experiment using human hippocampal progenitor cells, researchers observe that the addition of a specific compound increases the number of doublecortin-positive neuroblasts, even in the presence of cortisol. What might this suggest about the compound?
Before collecting saliva samples for cortisol measurement, participants are typically asked to refrain from certain activities. Which of the following is one of these activities?
Before collecting saliva samples for cortisol measurement, participants are typically asked to refrain from certain activities. Which of the following is one of these activities?
A researcher wants to investigate the relationship between long-term stress and the development of cardiovascular disease. Considering the properties of different biological samples, which would be the most appropriate for assessing long-term cortisol exposure?
A researcher wants to investigate the relationship between long-term stress and the development of cardiovascular disease. Considering the properties of different biological samples, which would be the most appropriate for assessing long-term cortisol exposure?
Based on the studies discussed, what might a higher cortisol awakening response indicate in individuals with a history of depression?
Based on the studies discussed, what might a higher cortisol awakening response indicate in individuals with a history of depression?
In the study of postpartum women, what was a notable difference in cortisol levels between depressed and non-depressed women shortly after awakening?
In the study of postpartum women, what was a notable difference in cortisol levels between depressed and non-depressed women shortly after awakening?
The study of postpartum women draws parallels between the cortisol response of depressed women and which other conditions?
The study of postpartum women draws parallels between the cortisol response of depressed women and which other conditions?
In the Whitehall II study, what factors were independently associated with higher hair cortisol concentrations?
In the Whitehall II study, what factors were independently associated with higher hair cortisol concentrations?
According to the Whitehall II study, how was depressive symptomatology associated with cortisol levels, after adjusting for physical disease and medication?
According to the Whitehall II study, how was depressive symptomatology associated with cortisol levels, after adjusting for physical disease and medication?
What scale was used in the Whitehall II study to assess mental health status and measure symptoms of depression in the general public?
What scale was used in the Whitehall II study to assess mental health status and measure symptoms of depression in the general public?
In the context of stress responses, what characteristics are commonly observed in highly anxious individuals, as indicated by Weger and Sandi's diagram?
In the context of stress responses, what characteristics are commonly observed in highly anxious individuals, as indicated by Weger and Sandi's diagram?
In rodent studies, what physiological change has been observed following exposure to fox odor, and what does this indicate about the nature of stress effects?
In rodent studies, what physiological change has been observed following exposure to fox odor, and what does this indicate about the nature of stress effects?
What cut-off point on the CES-D scale was used in the Whitehall II study to classify individuals as having depression?
What cut-off point on the CES-D scale was used in the Whitehall II study to classify individuals as having depression?
If a researcher aims to study the impact of chronic stress on neurogenesis in rats, which experimental manipulation would serve as an appropriate control group?
If a researcher aims to study the impact of chronic stress on neurogenesis in rats, which experimental manipulation would serve as an appropriate control group?
A study measures circulating corticosterone levels in rats exposed to a stressor. What would be a valid inference if the study finds no significant change in corticosterone levels after the stressor exposure?
A study measures circulating corticosterone levels in rats exposed to a stressor. What would be a valid inference if the study finds no significant change in corticosterone levels after the stressor exposure?
How does adrenalectomy affect neurogenesis in rodents, and what does this reveal about the role of adrenal hormones in the brain?
How does adrenalectomy affect neurogenesis in rodents, and what does this reveal about the role of adrenal hormones in the brain?
In the context of studying stress responses, why is it important to remember that 'what happens in the periphery is not necessarily what is happening in the brain'?
In the context of studying stress responses, why is it important to remember that 'what happens in the periphery is not necessarily what is happening in the brain'?
If a researcher aims to investigate the effects of a novel stress-reducing drug on neurogenesis in rats exposed to fox odor, what would be the most appropriate design for the treatment and control groups?
If a researcher aims to investigate the effects of a novel stress-reducing drug on neurogenesis in rats exposed to fox odor, what would be the most appropriate design for the treatment and control groups?
A researcher finds that a particular stressor significantly elevates circulating corticosterone levels in rats. Based on current knowledge, what downstream effect in the hippocampus would be most likely?
A researcher finds that a particular stressor significantly elevates circulating corticosterone levels in rats. Based on current knowledge, what downstream effect in the hippocampus would be most likely?
Why is the use of animal models, like rodents, considered valuable in studying the biological effects of stress, especially in comparison to human studies?
Why is the use of animal models, like rodents, considered valuable in studying the biological effects of stress, especially in comparison to human studies?
Flashcards
Studying Stress in Animals
Studying Stress in Animals
Animal studies allow researchers to access blood and brain samples to study the biological effects of stress.
Studying Stress in Humans
Studying Stress in Humans
In humans, stress effects can be studied through circulation, blood, urine, saliva, hair, and stem cells.
Periphery vs. Brain
Periphery vs. Brain
What happens in the periphery (e.g., blood) may not always reflect what is happening in the brain.
Corticosterone
Corticosterone
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Adrenal Steroids & Neurogenesis
Adrenal Steroids & Neurogenesis
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Stress & Neurogenesis (Rats)
Stress & Neurogenesis (Rats)
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Adrenalectomy Effect
Adrenalectomy Effect
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Fox Odor Stress
Fox Odor Stress
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Neurogenesis
Neurogenesis
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Jacobs' Neurogenesis Theory
Jacobs' Neurogenesis Theory
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Glucocorticoids (e.g., Cortisol)
Glucocorticoids (e.g., Cortisol)
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Microglia
Microglia
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Chronic Unpredictable Stress (CUS)
Chronic Unpredictable Stress (CUS)
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Colony Stimulating Factor 1 (CSF1)
Colony Stimulating Factor 1 (CSF1)
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Dendritic Spines
Dendritic Spines
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Prefrontal Cortex (PFC)
Prefrontal Cortex (PFC)
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Stress & Mental Health Treatment
Stress & Mental Health Treatment
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Stem Cell Differentiation
Stem Cell Differentiation
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Cortisol's Effect on Neurogenesis
Cortisol's Effect on Neurogenesis
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Dexamethasone Effects
Dexamethasone Effects
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Sertraline's Protective Effect
Sertraline's Protective Effect
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Cortisol Awakening Response (CAR)
Cortisol Awakening Response (CAR)
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HPA Axis Assessment Methods
HPA Axis Assessment Methods
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Cortisol Receptors
Cortisol Receptors
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Saliva Sample Restrictions
Saliva Sample Restrictions
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Limitations of Single Cortisol Measurements
Limitations of Single Cortisol Measurements
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Long-Term Cortisol Level Importance
Long-Term Cortisol Level Importance
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Measuring Long-Term Cortisol
Measuring Long-Term Cortisol
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Hair Sample Collection Advantages
Hair Sample Collection Advantages
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Depression and CAR
Depression and CAR
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Saliva Collection Frequency (CAR)
Saliva Collection Frequency (CAR)
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Cortisol Awakening Response & Depression
Cortisol Awakening Response & Depression
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Postnatal Depression & Cortisol
Postnatal Depression & Cortisol
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Lack of Morning Cortisol Rise
Lack of Morning Cortisol Rise
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Whitehall II Study
Whitehall II Study
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Depression & Hair Cortisol
Depression & Hair Cortisol
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CES-D Scale
CES-D Scale
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Anxiety and Stress Responses
Anxiety and Stress Responses
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Factors Affecting Hair Cortisol
Factors Affecting Hair Cortisol
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Study Notes
- Biological effects of stress can be studied in animals through blood and brain samples.
- Human studies involve circulation, blood tests, urine samples, saliva, hair analysis, and stem cells.
- Peripheral changes may not reflect brain activity, making stem cells useful in human stress studies.
Animal Studies
- In rodents, corticosterone is the main glucocorticoid, equivalent to cortisol in humans.
- Adrenal steroids regulate the proliferation and differentiation of new neurons in the dentate gyrus.
- Increased plasma corticosterone in rats decreases neurogenesis.
- Adrenalectomy (removal of adrenal glands) in rats, which eliminates corticosterone, increases neurogenesis.
- Exposure to fox odor, but not other odors like mint or orange, rapidly decreases proliferating cells in the dentate gyrus.
- The impact of fox odor on cell proliferation relies on stress-induced adrenal hormones.
- Increased circulating corticosterone levels happen when an animal is exposed to fox odor.
- Adrenalectomy prevents the suppression of cell proliferation after exposure to fox odor.
- The decrease in new granule cells due to fox odor is transient, not causing permanent damage.
Neurogenesis and Depression
- Jacobs and colleagues (2000) suggested that neurogenesis rates in the adult hippocampus might influence major depression or recovery.
- Neurogenesis is changeable, with stress and high glucocorticoids decreasing it, and exercise and antidepressants increasing it.
- High cortisol and adversity are depression risks, while exercise and antidepressants aid recovery.
- Chronic stress alters brain neural circuits, raising the risk of depression and anxiety.
- Researchers discovered a novel cellular pathway contributing to the pathophysiology of stress-induced disorders (January 2018).
- Microglia, the brain's immune cells, help remodel neural circuits and are responsible for fending off infections.
- Intermittent exposure to stressful conditions provoke anxiety and depression-like behaviours in mice.
- Neurons in the prefrontal cortex show increased messenger RNA levels of colony stimulating factor one or CSF1 under stress conditions.
- Changes occur in microglia, corresponding with reduced dendritic spine density on pyramidal neurons.
- Limited connectivity in the prefrontal cortex links to major depression in clinical studies.
- Increased CSF1 messenger RNA levels were observed In the postmortem dorsolateral prefrontal cortex of individuals with depression.
- Preventing neurons from producing CSF1 through viral knockdown stops mice from developing anxiety or depression symptoms when exposed to chronic stress.
- Stress-induced signaling between neurons and microglia is a potential target for treating anxiety and depression in patients.
Human Stem Cell Studies
- Human stem cells can be used to study mental health.
- Human hippocampal progenitor cells, genetically modified to proliferate indefinitely, differentiate into neurons, astrocytes, and oligodendrocytes when growth factors and a chemical are removed.
- High cortisol doses reduce neurogenesis
- High cortisol doses reduce doublecortin-positive neuroblasts
- High cortisol doses reduce MAP2-positive neurons
Antidepressants
- Dexamethasone, a synthetic glucocorticoid and GR agonist, reduces MAP2-positive neurons and doublecortin-positive neuroblasts (27% and 25%, respectively)
- Sertraline, a selective serotonin reuptake inhibitor, plus dexamethasone abolishes the reduction of MAP2 and Dcx-positive cells.
Cortisol Measurements
- Cortisol production follows a circadian rhythm.
- Cortisol concentrations increase before awakening, peaking within 30-45 minutes after awakening, known as the cortisol awakening response (CAR).
- Cortisol levels decrease during the day.
- The HPA axis can be assessed through diurnal basal secretion, cortisol response to stress tasks or pharmacological challenges, and CAR.
- CAR associates with lifestyle factors and psychological traits.
Saliva Sampling
- Saliva samples are a common, minimally intrusive method for observational surveys.
- Participants must avoid eating, smoking, drinking, or brushing teeth 15 minutes before collection.
- Multiple saliva samples collected via swabs are centrifuged.
- Single cortisol measurements reflect short-term levels due to pulsatile cortisol secretion.
- Long-term cortisol levels are relevant to chronic diseases because frequent HPA axis activation has cumulative effects.
- Urine samples are impractical for measuring cortisol levels over time.
- Hair samples are a good alternative as they are non-invasive and can be taken by non-healthcare workers at any time.
Depression and Cortisol Studies
- A Netherlands Society of Depression and Anxiety study compared control subjects, remitted major depression subjects, and current major depression diagnosis subjects.
- Saliva samples were collected at home at awakening, and 30, 45, and 60 minutes later.
- Remitted and current depressed groups showed a higher cortisol awakening response compared to control subjects.
- Higher cortisol awakening response may indicate increased biological vulnerability for depression.
Postnatal Depression
- A study of women with postpartum depression and non-perinatal controls collected saliva at awakening, 30 minutes post awakening, 3 hours post awakening and 12 hours post awakening.
- Non-depressed postnatal women show a similar cortisol secretion pattern to non-perinatal controls over the day.
- Depressed women had significantly higher cortisol levels at awakening and no increase at 30 minutes later.
- The lack of morning rise in depressed women links to post-traumatic stress disorder and chronic fatigue syndrome, reflecting response in women to cortisol withdrawal after delivery.
Whitehall II Study
- A study involving 3,500 London-based civil service participants measured hair cortisol concentrations.
- Prevalent diabetes, use of systemic corticosteroids, and cardiovascular medication independently associated with higher cortisol levels.
- Depressive symptoms, assessed using the CES-D scale, are associated with higher cortisol levels after adjusting for physical disease and medication
Anxiety, Stress and Depression
- Highly anxious individuals show behavioral alterations and more reactive physiological stress responses.
- Molecular variations in neurobiological systems (neurotransmitters, HPA axis) define the high anxiety trait phenotype.
- High anxiety traits plus suboptimal environmental conditions create vulnerability for psychopathology.
- Stressful life events associate with major depressive episodes.
- Reactions to stress determine its impact.
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Description
Explore adult hippocampal neurogenesis role in major depression and factors increasing its rate. Study the impact of chronic unpredictable stress on the prefrontal cortex and the effects of CSF1 production prevention on mice under chronic stress. Discover the link between reduced prefrontal cortex connectivity and depression.
