Biochemistry of Depression

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Questions and Answers

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

Inhibit the degradation of monoamines (correct)

Enhance the degradation of monoamines

Increase the production of monoamines

Block the reabsorption of monoamines

Which neurotransmitters are primarily affected by Monoamine Oxidase Inhibitors?

Acetylcholine and histamine

Dopamine and GABA

Glutamate and glycine

Norepinephrine and serotonin (correct)

What is a potential time frame for noticing effects after starting MAOIs?

1-2 weeks

1-3 days

6-8 hours

2-6 weeks (correct)

What is the role of the MAO enzyme in the nervous system?

To degrade monoamines in the synapse Signup and view all the answers

Which of the following statements about Monoamine Oxidase Inhibitors is true?

They enhance chemical communication in the synapse. Signup and view all the answers

What is the main therapeutic effect expected from using MAOIs?

Improvement in mood disorders Signup and view all the answers

Which of the following statements distinguishes MAOIs from Tricyclic Antidepressants (TCAs)?

MAOIs directly inhibit a degrading enzyme, while TCAs block reuptake of neurotransmitters. Signup and view all the answers

Which of the following could be a result of increased cerebral levels of norepinephrine and serotonin due to MAOI usage?

Increased energy levels Signup and view all the answers

What role do neurotransmitters like dopamine, serotonin, and norepinephrine play in the context of depression?

They are involved in synaptic transmission between neurons. Signup and view all the answers

How does the Hypothalamic-Pituitary-Adrenal (HPA) axis function in response to stress?

It operates through a feedback loop to regulate stress response. Signup and view all the answers

In the context of pharmacology of depression, where does the actual synaptic interaction primarily occur?

Between the axon and the dendrite/post-synaptic terminal. Signup and view all the answers

What do family studies suggest about the genetics of depression?

An earlier age of onset is observed in family members with a history of depression. Signup and view all the answers

What is the result of the HPA axis acting in a negative feedback loop?

Decreased production and release of CRH, regulating stress response. Signup and view all the answers

What effect does imipramine have on monoamine levels in the synapse?

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

How can low serotonin levels affect postsynaptic receptors in depressed patients?

They may become hypersensitive. Signup and view all the answers

What can result from the increased concentration of neurotransmitters due to SSRIs?

More chance for chemical transmission. Signup and view all the answers

What is the consequence of having few receptors available for neurotransmitters?

Higher uptake rates of neurotransmitters. Signup and view all the answers

What characterizes the effect of SSRIs in the context of serotonin?

They inhibit neurotransmitter reuptake. Signup and view all the answers

What happens to neurotransmitter concentrations shortly after administering SSRIs?

They increase within hours. Signup and view all the answers

What is the primary action of imipramine in relation to monoamines?

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

What is likely to happen to postsynaptic receptors when neurotransmitter concentrations are high?

They become desensitized. Signup and view all the answers

What is the role of brain-derived neurotrophic factor (BDNF) in neuronal function?

It supports neuronal survival and plasticity. Signup and view all the answers

Which process is associated with glucocorticoid resistance in major depressive disorder (MDD)?

Enhanced HPA axis activity. Signup and view all the answers

In the context of depression, what does increased inflammation indicate?

It correlates with HPA axis hyperactivity. Signup and view all the answers

How do antidepressants affect neurotrophic factors in depressed individuals?

They may partially reverse protein depletion. Signup and view all the answers

What neurotransmitters are commonly implicated in the dysfunction observed in major depressive disorder?

Norepinephrine and serotonin. Signup and view all the answers

Which receptor does cortisol bind to in the context of stress?

Glucocorticoid receptor (GR). Signup and view all the answers

What is a key characteristic of the monoamines in relation to major depressive disorder (MDD)?

They contribute to neurotransmitter and metabolic dysfunction. Signup and view all the answers

What effect does chronic stress have on neurotrophic factors?

Leads to their depletion. Signup and view all the answers

Which system is inhibited by cortisol, which is relevant to neuroinflammation?

Immune system. Signup and view all the answers

What is a potential outcome of antidepressant treatment in relation to BDNF levels?

Increase in BDNF levels over time. Signup and view all the answers

What characterizes HPA axis hyperactivity in patients with depression?

Increased levels of glucocorticoids. Signup and view all the answers

Which is a major component contributing to depressive symptoms in remitted patients?

Decreased neurotrophic factor signaling. Signup and view all the answers

What physiological function do neurotrophins primarily serve?

Regulate neuronal survival and differentiation. Signup and view all the answers

What condition might result from deficits in norepinephrine and serotonin neurotransmission?

Development of major depressive disorder. Signup and view all the answers

Which type of antidepressant primarily works by inhibiting the reuptake of serotonin?

Selective serotonin reuptake inhibitors (SSRIs) Signup and view all the answers

What receptor subtypes are down-regulated by antidepressants according to the information?

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

Which antidepressant is more effective on norepinephrine?

Desipramine Signup and view all the answers

Which antidepressant class had a higher dropout rate in comparison to SSRIs?

Tricyclic antidepressants (TCAs) Signup and view all the answers

What is a potential effect of administering pindolol?

It accelerates the action of SSRIs. Signup and view all the answers

Which of the following is considered an atypical antidepressant?

Mianserin Signup and view all the answers

What is a significant possible side effect of non-specific antidepressants?

Serotonin syndrome Signup and view all the answers

Which antidepressant is specifically known for its action on the 5-HT1A receptor?

Paroxetine Signup and view all the answers

How do SSRIs generally compare to SNRIs in terms of clinical relevance?

They show no difference in efficacy. Signup and view all the answers

Which type of antidepressant is specifically cited to be useful for treatment-resistant patients?

Atypical antidepressants Signup and view all the answers

Which receptor interactions are thought to contribute to additional side effects of TCAs?

Alpha receptors and muscarinic receptors Signup and view all the answers

What is the major function of serotonin-noradrenaline reuptake inhibitors?

They inhibit reuptake of serotonin and noradrenaline. Signup and view all the answers

What characteristic is associated with tricyclic antidepressants (TCAs) when compared to SSRIs?

Higher drop-out rates Signup and view all the answers

What chemical does aged food contain?

Tylenine Signup and view all the answers

Which receptor does trazodone primarily act as an antagonist for?

5-HT2A Signup and view all the answers

What effect does tryptophan have in the body?

Helps create melatonin and serotonin Signup and view all the answers

What is associated with reduced cortical thickness in depression?

Cortical atrophy Signup and view all the answers

Which of the following describes a characteristic of mice with higher 5-HT1A auto-receptor levels?

Blunted response to acute stress Signup and view all the answers

What happens when the presynaptic 5-HT1A auto-receptor is activated?

Inhibits serotonin release Signup and view all the answers

What is a common neurological characteristic observed in people with recurrent depression?

Hippocampus volume reductions Signup and view all the answers

Which neurotransmitter metabolite is associated with noradrenaline?

3-Methoxy-4-hydroxyphenylglycol (MHPG) Signup and view all the answers

What role does melatonin play in the body?

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

What is the primary consequence of increased connectivity in the amygdala during stress?

Increased levels of corticotrophin releasing hormone (CRH) Signup and view all the answers

Which early life stress outcome is noted in animal studies related to depression?

Persistent behavioral changes Signup and view all the answers

What mechanism does reserpine utilize to affect neurotransmitter levels?

Depletes neuronal stores of monoamine neurotransmitters Signup and view all the answers

What is indicated when there is a hypersensitivity of 5-HT1A auto-receptors in depression?

Low serotonin release Signup and view all the answers

What is a potential effect of tryptophan depletion in individuals taking SSRIs?

Significant worsening of mood Signup and view all the answers

Study Notes

Biochemistry and Pharmacology of Depression

Monoamine Theory: Depression results from dysfunction of various neurotransmitter or metabolic systems. Low levels of one or more monoamines (dopamine, serotonin, norepinephrine) are implicated.
Neurotransmitters: These chemicals transmit signals between neurons. Monoamines are a class of neurotransmitters characterized by a specific chemical structure.
Synapse: The gap between neurons where neurotransmitters are released. Low levels of neurotransmitters in the synapse can lead to symptoms of depression.
Serotonin (5-HT): A monoamine neurotransmitter crucial for regulating mood, appetite, sleep, and pain. Low 5-HT levels are linked to depression.
Serotonin Reuptake Inhibitors (SSRIs): These drugs work by inhibiting the reuptake of serotonin, increasing its levels in the synapse. Fluoxetine (Prozac), citalopram are examples.
Tricyclic Antidepressants (TCAs): Inhibit the reuptake of both norepinephrine (NA) and serotonin (5-HT), but with different extents of action. Imipramine is an example.
Noradrenaline (NA): A biogenic amine, essential in regulating alertness, focus or arousal. Low NA levels are also associated with depression.
Monoamine Oxidase Inhibitors (MAOIs): Decrease the breakdown of monoamines (NA and 5-HT) leading to higher levels in the synapse. Iproniazid is an example.
5-HT2A receptors: Postsynaptic receptors. High sensitivity can be induced if serotonin is low in depressed patients, possibly leading to hypersensitivity of the corresponding receptors, therefore potentially desensitization could be beneficial.
5-HT1A auto-receptors: Located on presynaptic neurons. Activation inhibits the release of 5-HT. Hypersensitivity of these receptors in MDD may lead to low 5-HT release.
Glutamate and NMDA receptors: Glutamate is an amino acid neurotransmitter crucial for learning and memory. Dysfunction of NMDA receptors is associated with depression. Ketamine, a glutamate agonist, is a rapidly acting antidepressant.

Depression and Brain Structure

Hippocampus: A brain structure crucial for memory and emotion regulation. Changes in hippocampal volume and function are often seen in individuals with depression. Reduced hippocampal volume related to the effects of cortisol excess.
Prefrontal Cortex (PFC): Essential for higher-level cognitive functions. Changes in PFC activity and connectivity are also implicated in depression. Impaired connectivity in the fronto-parietal circuit linked to inappropriate cognitive appraisals of negative events potentially associated with depression.

Stress and Depression

Hypothalamic-Pituitary-Adrenal (HPA) Axis: A complex system regulating the body's stress response, involving hypothalamus, pituitary, and adrenal gland to produce cortisol. Chronic stress results in HPA axis hyperactivity and potential glucocorticoid resistance (reduced sensitivity to cortisol). Cortisol excess is linked to hippocampal atrophy.
Cortisol: A hormone released during stress. Chronic hypercortisolaemia (high cortisol levels) is implicated in depression.
Glucocorticoid Receptors (GRs): Proteins that bind cortisol and regulate its effects. Reduced GR function or desensitization is associated with depression. Antidepressant treatment can potentially upregulate GR function in some individuals.
Brain-Derived Neurotrophic Factor (BDNF): A protein that promotes neuronal survival and growth. Decreased function of this neurotrophic factor linked to depression.

Depression Diagnosis and Treatment

Major Depressive Disorder (MDD): A mood disorder characterized by a combination of symptoms including depressed mood, loss of interest, reduced energy, and cognitive impairments, etc.
DSM-5: Diagnostic and Statistical Manual of Mental Disorders.
Disability-adjusted life years (DALYs): A measure of the burden of disease; significant factor in evaluating disease.
Biological Markers: 5-HIAA, MHPG, etc. (monoamines' metabolites) are related to depression.

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Description

Explore the biochemistry and pharmacology underlying depression, focusing on the monoamine theory and the role of neurotransmitters. This quiz covers essential concepts such as serotonin, its receptors, and the mechanisms of various antidepressant medications. Test your knowledge on how these elements contribute to depressive symptoms and treatments.