Week 5.3: An introduction to the psychopharmacology of mood disorders Flashcards
How do neurons communicate?
Neurons communicate via neurotransmitters and receptors.
Chemical messengers released by neurons to send signals to other neurons.
Neurotransmitters
Proteins on the surface of neurons that bind to neurotransmitters.
Receptors
The neuron receiving the signal.
Post-synaptic Neuron
When neurotransmitters attach to receptors on the post-synaptic neuron.
Receptor Binding
Open or close in response to neurotransmitter binding.
Ligand-gated Receptors
Activate internal cell processes when bound by neurotransmitters.
G-Protein Linked Receptors
What are the types of receptor binding?
Excitatory: Increases the firing rate of the post-synaptic neuron.
Inhibitory: Decreases the firing rate of the post-synaptic neuron.
Modulatory: Alters the effects of other neurotransmitters or second messenger systems.
Medications that alter brain function by changing neurotransmitter activity.
Mood Disorder Drugs
What are the types of mood disorder drugs?
Agonists: Drugs that mimic neurotransmitters and activate receptors.
Antagonists: Drugs that block receptors and prevent neurotransmitter binding.
What are some examples of mood disorder drugs?
SSRI antidepressants: Increase levels of serotonin in the synapse.
Antipsychotics: Block dopamine D2/3 receptors.
The junction between two neurons where neurotransmitters are released.
Synapse
The primary excitatory neurotransmitter in the brain, crucial for synaptic plasticity and cognitive functions like learning and memory.
Glutamate
The main inhibitory neurotransmitter, which reduces neuronal excitability and helps regulate muscle tone.
GABA (Gamma-Aminobutyric Acid)
What are the monoamine neurotransmitters?
Dopamine: Involved in reward, motivation, and motor control.
Serotonin (5-HT): Regulates mood, appetite, and sleep.
Noradrenaline (Norepinephrine): Influences attention, arousal, and the fight-or-flight response.
Involves neurotransmitters like anandamide, which bind to cannabinoid receptors; THC (from cannabis) also binds to these receptors.
Endocannabinoid System
Shows promising effects on depression by targeting the glutamate system.
Ketamine
A neurotransmitter that increases the likelihood of the post-synaptic neuron firing.
Excitatory Neurotransmitter
A neurotransmitter that decreases the likelihood of the post-synaptic neuron firing.
Inhibitory Neurotransmitter
Intracellular signaling pathways activated by neurotransmitter-receptor interactions.
Second Messenger Systems
Can you walk me through the evolution of pharmacotherapies for mood disorders?
1940s:
Electroconvulsive Therapy (ECT)
Mid-1950s:
Lithium
Mid-1960s:
Monoamine Oxidase Inhibitors (MAOIs)
1980s:
Anticonvulsants
1990s:
Second-Generation Antidepressants
Mid-2000s:
Next-Generation Antipsychotics
1940s
One of the earliest treatments for mood disorders.
Electroconvulsive Therapy (ECT)
Mid-1950s
Became available as a mood stabilizer.
Prevents manic relapse.
May reduce the risk of suicide.
Lithium
Mid-1960s
The first antidepressants.
Monoamine Oxidase Inhibitors (MAOI)
Introduced in the1980s
Such as carbamazepine, lamotrigine, and valproate, used as mood stabilizers.
Anticonvulsants
1990s
Including SSRIs (e.g., fluoxetine) and SNRIs (e.g., venlafaxine).
Second-Generation Antidepressants
Why is it crucial to target the serotonin system in mood disorders?
Lowering Serotonin: Induces depression in people with mood disorders and their relatives.
Increasing Serotonin: Can produce manic symptoms.
Medications: SSRIs and atypical antipsychotics work by altering the serotonin system.
Mid-2000s
Such as quetiapine, olanzapine, and aripiprazole, used for mania and bipolar depression.
Next-Generation Antipsychotics
How does the serotonin system look like in a healthy brain?
Serotonin Neurons: Located in the raphe nucleus.
Projections: Extend to many brain areas, including the subgenual cingulate and the limbic system, which are important for mood regulation.
Increase synaptic serotonin levels by inhibiting the serotonin transporter.
Ex.
Citalopram: 20-40 mg/day.
Sertraline: 50-200 mg/day.
Fluoxetine (Prozac): 20-60 mg/day.
Selective Serotonin Reuptake Inhibitors (SSRIs)
Increase both serotonin and noradrenaline levels by inhibiting their respective transporters.
Ex.
Venlafaxine (Effexor): 75-375 mg/day.
Duloxetine (Cymbalta): 60 mg/day
Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)
Mechanism: Blocks 5-HT3 and 5-HT7 receptors, stimulates 5-HT1A receptor.
Dosage: 10-20 mg/day.
Benefits: May improve cognitive impairment through 5-HT7 blockade.
Vortioxetine (Brintillex)
A procedure where electric currents are passed through the brain to treat severe depression.
Electroconvulsive Therapy (ECT)
A class of antidepressants that inhibit the enzyme monoamine oxidase, which breaks down neurotransmitters like serotonin and dopamine.
Monoamine Oxidase Inhibitors (MAOIs)
What is dopamine’s role?
Increased Dopamine: Can produce effects similar to mania.
Reduced Dopamine: Improves manic symptoms but can worsen depression.
Reward and Impulsivity: Mediated by dopamine, often abnormal in mood disorders.
A dopamine pathway involved in cognition and mood regulation.
Mesocortical Pathway
A dopamine pathway involved in reward and psychosis.
Mesolimbic Pathway
Drugs that block dopamine receptors to reduce dopamine activity.
Dopamine Antagonists
A dopamine pathway involved in movement control.
Nigrostriatal Pathway
A dopamine pathway that regulates prolactin secretion.
Tuberoinfundibular Pathway
Is a hormone produced by the pituitary gland, which is located just below the brain. It plays several important roles in the body, including:
Lactation
Breast Tissue Development
Regulation of Prolactin Levels
High levels can cause issues like:
Erectile Dysfunction
Irregular Periods
Infertility
Prolactin
Mania has been conceptualised as being caused by increases in dopamine in this system.
Nigro Limbic System
Used to treat manic symptoms and as mood stabilizers.
Some are used for depressive episodes in bipolar disorder.
Antipsychotics
What are examples of antipsychotics?
Quetiapine:
Uses: Prevents manic episodes and depressive recurrence.
Receptors Blocked: Dopamine D2 and 5-HT2A receptors.
Olanzapine:
Uses: Treatment of mania and bipolar depression.
Receptors Blocked: Dopamine D2, 5-HT2A, histamine H1, and alpha-1 receptors.
Aripiprazole:
Uses: Prevents manic relapse.
Mechanism: Dopamine stabilizer, blocks 5-HT2 receptors, and has partial effects on 5-HT1A receptors.
Are crucial because they mediate the effects of serotonin, a key neurotransmitter involved in regulating mood, anxiety, sleep, appetite, and other physiological processes.
5-HT Receptors (serotonin receptors)
What are examples of medications targeting GABA-A Receptors?
Benzodiazepines:
Examples: Diazepam (Valium), Clonazepam (Klonopin).
Uses: Short-term treatment of anxiety disorders.
Z-Type Hypnotics:
Examples: Zopiclone, Zolpidem (Ambien).
Uses: Short-term treatment of sleep impairment (insomnia).
Sodium Valproate:
Uses: Mood stabilizer for conditions like bipolar disorder.
Medications that target the GABA-A receptor, such as benzodiazepines and Z-type hypnotics which have a calming effect on the brain and body
Downers
What can second messenger systems do?
They can enhance the release of neurotransmitters.
They can also influence other cellular processes, such as gene expression and enzyme activity.
They help coordinate various cellular processes.
They ensure the cell responds appropriately to external signals (neurotransmitters).
The concentration of a drug in the blood plasma, which is the liquid component of blood.
Plasma Levels
A type of receptor that activates second messenger systems when bound by a neurotransmitter.
G-Protein Coupled Receptor
Why are plasma levels important?
Therapeutic Range: For a drug to be effective, its plasma levels need to be within a specific range.
Monitoring: Doctors monitor plasma levels to ensure the drug is working effectively and to avoid toxicity.
