Neurotransmitters and HPA Axis Overview

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Questions and Answers

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?

Acetylcholine

Serotonin (correct)

Dopamine

Norepinephrine

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?

It decreases production and release of CRH. Signup and view all the answers

Which factor has been suggested to influence the age of onset of depression based on genetic studies?

Family history of mood disorders Signup and view all the answers

What is the primary action of Monoamine Oxidase Inhibitors (MAOIs)?

Inhibit the action of MAO enzyme Signup and view all the answers

How long does it typically take for MAOIs to start showing effects?

2-6 weeks Signup and view all the answers

What is a consequence of inhibiting the MAO enzyme in the brain?

Increased cerebral levels of norepinephrine and 5-HT Signup and view all the answers

Which patient statement indicates a misunderstanding of MAOIs?

MAOIs will help me break down more neurotransmitters. Signup and view all the answers

Which neurotransmitters are primarily affected by the action of MAOIs?

Norepinephrine and serotonin Signup and view all the answers

What is a commonly used example of a Monoamine Oxidase Inhibitor?

Iproniazid Signup and view all the answers

What is the result of enhanced chemical communication due to MAOIs?

Improved mood and emotional regulation Signup and view all the answers

What effect does the MAOI action have on monoamine degradation in the synapse?

It reduces the degradation of monoamines. Signup and view all the answers

What is the primary effect of imipramine on monoamines?

It inhibits the reuptake of monoamines. Signup and view all the answers

What may occur to the 5-HT2A postsynaptic receptors in situations where serotonin levels are low?

They may become hypersensitive. Signup and view all the answers

What is the result of increased monoamine concentrations due to imipramine?

Improved chemical transmission. Signup and view all the answers

What happens to serotonin reuptake when there is minimal serotonin available in the synapses?

Reuptake occurs rapidly. Signup and view all the answers

Which neurotransmitter's reuptake is inhibited by imipramine?

All of the above. Signup and view all the answers

What is a potential consequence of inhibiting the reuptake of monoamines?

Increased synaptic cleft concentration of neurotransmitters. Signup and view all the answers

Which condition may lead to hypersensitivity of postsynaptic receptors?

Low levels of serotonin. Signup and view all the answers

In depressed patients, what is a likely effect of imipramine on neurotransmitter levels?

It increases neurotransmitter levels. Signup and view all the answers

What is the primary function of selective serotonin reuptake inhibitors (SSRIs)?

Inhibit serotonin reuptake Signup and view all the answers

Which antidepressant is specifically noted to be more effective on noradrenaline?

Desipramine Signup and view all the answers

Which of the following SSRIs is mentioned as an example?

Fluvoxamine Signup and view all the answers

What receptor subtypes are down-regulated by antidepressants according to recent studies?

5-HT2A and 5-HT2C Signup and view all the answers

What notable side effect is observed with tricyclic antidepressants (TCAs) compared to SSRIs?

Higher dropout rates Signup and view all the answers

Which of the following is considered a noradrenaline reuptake inhibitor (NARI)?

Maprotiline Signup and view all the answers

What effect do animal studies suggest 5-HT2A antagonists may have?

Possess antidepressant effects Signup and view all the answers

What is a limitation observed in the efficacy comparison of SSRIs and SNRIs?

Limited clinically relevant differences Signup and view all the answers

What aspect of SSRIs is significantly beneficial in comparison to TCAs?

Lower dropout rates Signup and view all the answers

Which atypical antidepressant is mentioned as often being used when others do not work?

Trazodone Signup and view all the answers

What is a potential risk associated with non-specific antidepressants that interact with all monoamines?

Increased serotonin syndrome risk Signup and view all the answers

Which compound is indicated to enhance the antidepressant effects of fluoxetine according to studies?

Pindolol Signup and view all the answers

Which type of receptor do chronic MAOIs and TCAs down-regulate?

5-HT2A receptors Signup and view all the answers

What effect does tryptophan have on the body?

Helps in the production of melatonin and serotonin Signup and view all the answers

Which area of the brain shows reduced volume in individuals with recurrent depression?

Hippocampus Signup and view all the answers

How do hypersensitive 5-HT1A auto-receptors in major depressive disorder (MDD) influence serotonin levels?

Inhibit the release of serotonin Signup and view all the answers

What is the primary metabolite of serotonin?

5-Hydroxyindoleacetic acid (5-HIAA) Signup and view all the answers

What structural change is associated with depression in the medial temporal lobe?

Decreased hippocampal volume Signup and view all the answers

What neurotransmitter is primarily involved in mood regulation?

Serotonin Signup and view all the answers

Which of the following could lead to an accelerated antidepressant effect?

Desensitization of 5-HT1A auto-receptors Signup and view all the answers

What role does melatonin play in the human body?

Regulates the sleep-wake cycle Signup and view all the answers

What is a potential consequence of tryptophan depletion regarding mood?

Significant worsening of mood in remitted depressed patients Signup and view all the answers

How does early life stress affect the brain's stress response?

Leads to persistent changes in behavior Signup and view all the answers

What effect does reserpine have on neurotransmitters?

Depletes neuronal stores of norepinephrine and serotonin Signup and view all the answers

Which receptor primarily causes inhibition of 5-HT release when activated?

5-HT1A auto-receptor Signup and view all the answers

What role does BDNF play in the central nervous system?

Regulation of neuronal survival and growth Signup and view all the answers

Which factor is primarily linked to glucocorticoid receptor function in individuals with depression?

Glucocorticoid resistance Signup and view all the answers

Which condition is associated with decreased density of layer III neurons?

Major depressive disorder Signup and view all the answers

What chemical is dangerous when related to aged food consumption?

Tylenine Signup and view all the answers

What effect do NA-active antidepressants have on receptors?

Desensitization of a2 followed by b-receptors Signup and view all the answers

How is MDD thought to result from neurotransmitter dysfunction?

Due to a disruption in various neurotransmitter or metabolic systems Signup and view all the answers

Which process is influenced by neurotrophins during development?

Neuronal differentiation and growth Signup and view all the answers

What is a potential outcome of chronic brain-derived neurotrophic factor: BDNF depletion?

Induction of depressive symptoms Signup and view all the answers

What is the primary relationship between cortisol and inflammation in individuals with depression?

Cortisol inhibits inflammation through BDNF Signup and view all the answers

Which type of receptor does cortisol bind to in the context of depression?

Glucocorticoid receptor Signup and view all the answers

What is a characteristic of major depressive disorder (MDD) regarding neurotransmitter function?

It results from the dysfunction of neurotransmitter systems. Signup and view all the answers

How might antidepressant treatment influence BDNF levels?

By reversing depletion of BDNF Signup and view all the answers

What mechanism has been linked to hyperactivity of the HPA axis in depressed individuals?

Increased inflammation levels Signup and view all the answers

What is assessed through endocrine tests related to HPA activity in the context of depression?

Condition of glucocorticoid resistance Signup and view all the answers

What physiological effect does persistent exposure to stress have on the body regarding neurotransmission?

Decreases levels of neurotrophins Signup and view all the answers

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.

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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.