Podcast
Questions and Answers
What is the role of the hypothalamic-pituitary-adrenal axis (HPA axis) in the body?
What is the role of the hypothalamic-pituitary-adrenal axis (HPA axis) in the body?
- It controls neurotransmitter release in the brain.
- It primarily manages endocrine functions in the reproductive system.
- It is involved in stress response and metabolism. (correct)
- It regulates the immune response.
Which neurotransmitter is primarily associated with mood regulation and is often targeted in depression treatment?
Which neurotransmitter is primarily associated with mood regulation and is often targeted in depression treatment?
- Acetylcholine
- Serotonin (correct)
- Dopamine
- Norepinephrine
How do neurotransmitters communicate between neurones?
How do neurotransmitters communicate between neurones?
- By diffusion through the blood circulation.
- Through synapses where they are released from the presynaptic terminal to the postsynaptic terminal. (correct)
- Through direct contact at the cell membrane.
- By binding to receptors on the neurone's axon.
What effect does negative feedback in the HPA axis have on CRH production?
What effect does negative feedback in the HPA axis have on CRH production?
Which factor has been suggested to influence the age of onset of depression based on genetic studies?
Which factor has been suggested to influence the age of onset of depression based on genetic studies?
What is the primary action of Monoamine Oxidase Inhibitors (MAOIs)?
What is the primary action of Monoamine Oxidase Inhibitors (MAOIs)?
How long does it typically take for MAOIs to start showing effects?
How long does it typically take for MAOIs to start showing effects?
What is a consequence of inhibiting the MAO enzyme in the brain?
What is a consequence of inhibiting the MAO enzyme in the brain?
Which patient statement indicates a misunderstanding of MAOIs?
Which patient statement indicates a misunderstanding of MAOIs?
Which neurotransmitters are primarily affected by the action of MAOIs?
Which neurotransmitters are primarily affected by the action of MAOIs?
What is a commonly used example of a Monoamine Oxidase Inhibitor?
What is a commonly used example of a Monoamine Oxidase Inhibitor?
What is the result of enhanced chemical communication due to MAOIs?
What is the result of enhanced chemical communication due to MAOIs?
What effect does the MAOI action have on monoamine degradation in the synapse?
What effect does the MAOI action have on monoamine degradation in the synapse?
What is the primary effect of imipramine on monoamines?
What is the primary effect of imipramine on monoamines?
What may occur to the 5-HT2A postsynaptic receptors in situations where serotonin levels are low?
What may occur to the 5-HT2A postsynaptic receptors in situations where serotonin levels are low?
What is the result of increased monoamine concentrations due to imipramine?
What is the result of increased monoamine concentrations due to imipramine?
What happens to serotonin reuptake when there is minimal serotonin available in the synapses?
What happens to serotonin reuptake when there is minimal serotonin available in the synapses?
Which neurotransmitter's reuptake is inhibited by imipramine?
Which neurotransmitter's reuptake is inhibited by imipramine?
What is a potential consequence of inhibiting the reuptake of monoamines?
What is a potential consequence of inhibiting the reuptake of monoamines?
Which condition may lead to hypersensitivity of postsynaptic receptors?
Which condition may lead to hypersensitivity of postsynaptic receptors?
In depressed patients, what is a likely effect of imipramine on neurotransmitter levels?
In depressed patients, what is a likely effect of imipramine on neurotransmitter levels?
What is the primary function of selective serotonin reuptake inhibitors (SSRIs)?
What is the primary function of selective serotonin reuptake inhibitors (SSRIs)?
Which antidepressant is specifically noted to be more effective on noradrenaline?
Which antidepressant is specifically noted to be more effective on noradrenaline?
Which of the following SSRIs is mentioned as an example?
Which of the following SSRIs is mentioned as an example?
What receptor subtypes are down-regulated by antidepressants according to recent studies?
What receptor subtypes are down-regulated by antidepressants according to recent studies?
What notable side effect is observed with tricyclic antidepressants (TCAs) compared to SSRIs?
What notable side effect is observed with tricyclic antidepressants (TCAs) compared to SSRIs?
Which of the following is considered a noradrenaline reuptake inhibitor (NARI)?
Which of the following is considered a noradrenaline reuptake inhibitor (NARI)?
What effect do animal studies suggest 5-HT2A antagonists may have?
What effect do animal studies suggest 5-HT2A antagonists may have?
What is a limitation observed in the efficacy comparison of SSRIs and SNRIs?
What is a limitation observed in the efficacy comparison of SSRIs and SNRIs?
What aspect of SSRIs is significantly beneficial in comparison to TCAs?
What aspect of SSRIs is significantly beneficial in comparison to TCAs?
Which atypical antidepressant is mentioned as often being used when others do not work?
Which atypical antidepressant is mentioned as often being used when others do not work?
What is a potential risk associated with non-specific antidepressants that interact with all monoamines?
What is a potential risk associated with non-specific antidepressants that interact with all monoamines?
Which compound is indicated to enhance the antidepressant effects of fluoxetine according to studies?
Which compound is indicated to enhance the antidepressant effects of fluoxetine according to studies?
Which type of receptor do chronic MAOIs and TCAs down-regulate?
Which type of receptor do chronic MAOIs and TCAs down-regulate?
What effect does tryptophan have on the body?
What effect does tryptophan have on the body?
Which area of the brain shows reduced volume in individuals with recurrent depression?
Which area of the brain shows reduced volume in individuals with recurrent depression?
How do hypersensitive 5-HT1A auto-receptors in major depressive disorder (MDD) influence serotonin levels?
How do hypersensitive 5-HT1A auto-receptors in major depressive disorder (MDD) influence serotonin levels?
What is the primary metabolite of serotonin?
What is the primary metabolite of serotonin?
What structural change is associated with depression in the medial temporal lobe?
What structural change is associated with depression in the medial temporal lobe?
What neurotransmitter is primarily involved in mood regulation?
What neurotransmitter is primarily involved in mood regulation?
Which of the following could lead to an accelerated antidepressant effect?
Which of the following could lead to an accelerated antidepressant effect?
What role does melatonin play in the human body?
What role does melatonin play in the human body?
What is a potential consequence of tryptophan depletion regarding mood?
What is a potential consequence of tryptophan depletion regarding mood?
How does early life stress affect the brain's stress response?
How does early life stress affect the brain's stress response?
What effect does reserpine have on neurotransmitters?
What effect does reserpine have on neurotransmitters?
Which receptor primarily causes inhibition of 5-HT release when activated?
Which receptor primarily causes inhibition of 5-HT release when activated?
What role does BDNF play in the central nervous system?
What role does BDNF play in the central nervous system?
Which factor is primarily linked to glucocorticoid receptor function in individuals with depression?
Which factor is primarily linked to glucocorticoid receptor function in individuals with depression?
Which condition is associated with decreased density of layer III neurons?
Which condition is associated with decreased density of layer III neurons?
What chemical is dangerous when related to aged food consumption?
What chemical is dangerous when related to aged food consumption?
What effect do NA-active antidepressants have on receptors?
What effect do NA-active antidepressants have on receptors?
How is MDD thought to result from neurotransmitter dysfunction?
How is MDD thought to result from neurotransmitter dysfunction?
Which process is influenced by neurotrophins during development?
Which process is influenced by neurotrophins during development?
What is a potential outcome of chronic brain-derived neurotrophic factor: BDNF depletion?
What is a potential outcome of chronic brain-derived neurotrophic factor: BDNF depletion?
What is the primary relationship between cortisol and inflammation in individuals with depression?
What is the primary relationship between cortisol and inflammation in individuals with depression?
Which type of receptor does cortisol bind to in the context of depression?
Which type of receptor does cortisol bind to in the context of depression?
What is a characteristic of major depressive disorder (MDD) regarding neurotransmitter function?
What is a characteristic of major depressive disorder (MDD) regarding neurotransmitter function?
How might antidepressant treatment influence BDNF levels?
How might antidepressant treatment influence BDNF levels?
What mechanism has been linked to hyperactivity of the HPA axis in depressed individuals?
What mechanism has been linked to hyperactivity of the HPA axis in depressed individuals?
What is assessed through endocrine tests related to HPA activity in the context of depression?
What is assessed through endocrine tests related to HPA activity in the context of depression?
What physiological effect does persistent exposure to stress have on the body regarding neurotransmission?
What physiological effect does persistent exposure to stress have on the body regarding neurotransmission?
Flashcards
MAOI (Monoamine Oxidase Inhibitor)
MAOI (Monoamine Oxidase Inhibitor)
A class of antidepressants that work by inhibiting the activity of monoamine oxidase (MAO), an enzyme responsible for breaking down neurotransmitters like serotonin and norepinephrine in the brain.
Monoamine Oxidase (MAO)
Monoamine Oxidase (MAO)
An enzyme found in the brain that breaks down monoamines, such as serotonin and norepinephrine, into inactive metabolites.
TCA (Tricyclic Antidepressants)
TCA (Tricyclic Antidepressants)
A class of antidepressants that work by blocking the reuptake of serotonin and norepinephrine in the synapse, leading to increased concentrations of these neurotransmitters in the brain.
Reuptake
Reuptake
Signup and view all the flashcards
Serotonin
Serotonin
Signup and view all the flashcards
Norepinephrine
Norepinephrine
Signup and view all the flashcards
Synapse
Synapse
Signup and view all the flashcards
Slowly Acting Drug
Slowly Acting Drug
Signup and view all the flashcards
Imipramine
Imipramine
Signup and view all the flashcards
What are SSRIs?
What are SSRIs?
Signup and view all the flashcards
What are 5-HT2A receptors?
What are 5-HT2A receptors?
Signup and view all the flashcards
How do low serotonin levels affect 5-HT2A receptors?
How do low serotonin levels affect 5-HT2A receptors?
Signup and view all the flashcards
How does Imipramine affect 5-HT2A receptors?
How does Imipramine affect 5-HT2A receptors?
Signup and view all the flashcards
How does Imipramine increase the chances of chemical transmission?
How does Imipramine increase the chances of chemical transmission?
Signup and view all the flashcards
How do low serotonin levels affect chemical transmission?
How do low serotonin levels affect chemical transmission?
Signup and view all the flashcards
How quickly do Imipramine's effects take place?
How quickly do Imipramine's effects take place?
Signup and view all the flashcards
Hypothalamic-Pituitary-Adrenal (HPA) axis
Hypothalamic-Pituitary-Adrenal (HPA) axis
Signup and view all the flashcards
Norepinephrine (Noradrenaline)
Norepinephrine (Noradrenaline)
Signup and view all the flashcards
Dopamine
Dopamine
Signup and view all the flashcards
Serotonin Reuptake
Serotonin Reuptake
Signup and view all the flashcards
Selective Serotonin Reuptake Inhibitors (SSRIs)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Signup and view all the flashcards
SNRI
SNRI
Signup and view all the flashcards
Monoamine Oxidase Inhibitor (MAOI)
Monoamine Oxidase Inhibitor (MAOI)
Signup and view all the flashcards
Norepinephrine Reuptake Inhibitors (NARIs)
Norepinephrine Reuptake Inhibitors (NARIs)
Signup and view all the flashcards
Atypical Antidepressants
Atypical Antidepressants
Signup and view all the flashcards
MAOI-Associated Food Interactions
MAOI-Associated Food Interactions
Signup and view all the flashcards
Serotonin Syndrome
Serotonin Syndrome
Signup and view all the flashcards
Desensitization
Desensitization
Signup and view all the flashcards
5-HT2A Receptor
5-HT2A Receptor
Signup and view all the flashcards
5-HT2C Receptor
5-HT2C Receptor
Signup and view all the flashcards
Down-regulation of 5-HT2A Receptors
Down-regulation of 5-HT2A Receptors
Signup and view all the flashcards
5-HT2A Antagonists
5-HT2A Antagonists
Signup and view all the flashcards
Pindolol
Pindolol
Signup and view all the flashcards
5-HT1A Autoreceptor Desensitization
5-HT1A Autoreceptor Desensitization
Signup and view all the flashcards
Serotonin (5-HT)
Serotonin (5-HT)
Signup and view all the flashcards
5-HT1A Autoreceptor (Presynaptic)
5-HT1A Autoreceptor (Presynaptic)
Signup and view all the flashcards
Hypersensitive 5-HT1A Autoreceptors in Depression
Hypersensitive 5-HT1A Autoreceptors in Depression
Signup and view all the flashcards
Cortical Atrophy in Depression
Cortical Atrophy in Depression
Signup and view all the flashcards
Mianserin
Mianserin
Signup and view all the flashcards
Trazodone
Trazodone
Signup and view all the flashcards
Reserpine
Reserpine
Signup and view all the flashcards
Tryptophan Conversion
Tryptophan Conversion
Signup and view all the flashcards
Tryptophan Depletion
Tryptophan Depletion
Signup and view all the flashcards
5-HIAA (5-Hydroxyindoleacetic Acid)
5-HIAA (5-Hydroxyindoleacetic Acid)
Signup and view all the flashcards
MHPG (3-Methoxy-4-hydroxyphenylglycol)
MHPG (3-Methoxy-4-hydroxyphenylglycol)
Signup and view all the flashcards
Limbic System
Limbic System
Signup and view all the flashcards
Hippocampus
Hippocampus
Signup and view all the flashcards
Brain-Derived Neurotrophic Factor (BDNF)
Brain-Derived Neurotrophic Factor (BDNF)
Signup and view all the flashcards
Neurotrophins
Neurotrophins
Signup and view all the flashcards
Receptor Sensitization
Receptor Sensitization
Signup and view all the flashcards
Glucocorticoid Resistance
Glucocorticoid Resistance
Signup and view all the flashcards
HPA Axis
HPA Axis
Signup and view all the flashcards
Glucocorticoid Receptor (GR)
Glucocorticoid Receptor (GR)
Signup and view all the flashcards
HPA Axis Hyperactivity
HPA Axis Hyperactivity
Signup and view all the flashcards
Monoamine Theory of Depression
Monoamine Theory of Depression
Signup and view all the flashcards
Monoamines
Monoamines
Signup and view all the flashcards
Neurotransmitter Reuptake
Neurotransmitter Reuptake
Signup and view all the flashcards
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Signup and view all the flashcards
Stress Vulnerability
Stress Vulnerability
Signup and view all the flashcards
Neural Activation
Neural Activation
Signup and view all the flashcards
Neural Plasticity
Neural Plasticity
Signup and view all the flashcards
Study Notes
Biochemistry and Pharmacology of Depression
- Depression is a syndrome diagnosed by a sufficient number of symptoms, including lowered mood, loss of interest, and reduced energy.
- Major Depressive Disorder (MDD) is diagnosed based on the DSM-5 criteria: five or more symptoms during a two-week period, including depressed mood or loss of interest, causing significant distress or impairment, not related to substances, medical disorders, or bereavement.
- Depression is a global health concern, leading cause of disability, and a significant contributor to the global burden of disease. It can lead to suicide and has effective psychological and pharmacological treatments.
- Genetics play a role in depression, with a heritability of approximately 35-37% with a higher rate seen in first-degree relatives.
- The monoamine theory suggests that MDD results from dysfunction in neurotransmitter systems, specifically dopamine, serotonin, and norepinephrine/noradrenaline.
- Low levels of these monoamines cause depressive symptoms.
- Reserpine, a blood pressure drug, depletes neuronal stores of noradrenaline and serotonin, inducing depressive symptoms.
- Biomarkers like 5-HIAA (serotonin metabolite) and MHPG (noradrenaline metabolite) are reduced in depressed patients compared to controls.
- Tryptophan depletion worsens mood in remitted depressed patients.
Early Antidepressants
- Early antidepressants had non-specific actions, resulting in many side effects, interactions, and the need for further development.
- Monoamine oxidase inhibitors (MAOIs) increase cerebral levels of noradrenaline and serotonin by inhibiting the breakdown of monoamines.
- Tricyclic antidepressants (TCAs) inhibit the reuptake of monoamines, increasing their presence in the synapse, but with potential side effects due to additional receptor blocking actions.
Drug Development
- Selective serotonin reuptake inhibitors (SSRIs), noradrenaline reuptake inhibitors (NARIs), and serotonin-noradrenaline reuptake inhibitors (SNRIs) are newer, more specific antidepressants.
- Atypical antidepressants are used if other treatments are ineffective.
SSRIs
- SSRIs inhibit serotonin reuptake, increasing serotonin levels.
- Examples include fluoxetine, citalopram, fluvoxamine, paroxetine, and sertraline.
Efficacy Comparisons
- Studies show similar efficacy between TCAs and SSRIs, but SSRIs have lower drop-out rates due to better tolerance and fewer side effects.
- A slight advantage exists for SNRIs compared to SSRIs, but the difference may not be clinically relevant.
Therapeutic Delay and Serotonin
- Antidepressants can take 2-6 weeks to show effects, although neurotransmitter levels can change within hours.
- 5-HT1A autoreceptors, located on the presynaptic neuron, inhibit serotonin release. MDD patients may have hypersensitive autoreceptors, leading to low serotonin release.
- Desensitization of 5-HT1A autoreceptors can enhance antidepressant effects.
- Administration of pindolol, a 5-HT1A antagonist, can accelerate the action of SSRIs.
5-HT2A Postsynaptic Receptors
- In depression, low serotonin levels lead to hypersensitive postsynaptic receptors.
- Antidepressants down-regulate 5-HT2A and 5-HT2C receptors.
- 5-HT2A antagonists have shown antidepressant effects in animal studies, enhancing the effects of SSRIs.
Noradrenaline and Depression
- Similar mechanisms explain the role of noradrenaline in depression, focusing on presynaptic alpha2 and postsynaptic beta receptors.
- Desensitization of these receptors is involved in the therapeutic effect of noradrenaline-active antidepressants.
Depression and Brain Structure
- Depression can be associated with brain structural changes like enlarged ventricles, reduced cortical thickness, reduced density of layer III neurons in the dorsolateral prefrontal cortex, and decreased hippocampus volume.
- Increased amygdala activation and connectivity are also observed in depression.
Stress and MDD
- Early-life stress can increase corticotrophin-releasing hormone (CRH) levels.
- Chronic stress overactivates the hypothalamic-pituitary-adrenal (HPA) axis, leading to glucocorticoid resistance, hypercortisolaemia, and potential hippocampal damage.
- Glucocorticoid receptors regulate the HPA axis's response to stress, but dysfunction can occur in MDD.
HPA axis function and MDD
- MDD is associated with hypercortisolaemia (high cortisol levels).
- Chronic stress activates the HPA axis, causing desensitization of glucocorticoid receptors and reduced HPA axis feedback inhibition, leading to high cortisol.
- Dexamethasone suppression tests can be used to assess HPA axis function in MDD patients.
Functional Brain Circuits and MDD
- Functional connectivity changes are associated with inflammation, glucocorticoid signalling, and stress in depression.
- The affective-salience and fronto-parietal cognitive control circuits are particularly impacted.
New Directions: Ketamine
- Ketamine, a rapid-acting glutamatergic antidepressant, shows potential, but potential adverse effects, recommended doses, and long-term efficacy need to be better understood.
Gene-Environment Interaction
- Studies have shown complex interactions between genes, such as the 5-HTT gene (serotonin transporter), and environmental factors in the development of MDD, but results have been inconsistent.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
This quiz explores the functions of the hypothalamic-pituitary-adrenal (HPA) axis and its role in mood regulation. It also delves into the mechanisms of neurotransmitter communication and the effects of Monoamine Oxidase Inhibitors (MAOIs) in depression treatment. Test your knowledge on these critical topics in neuropsychology.
