Depression Flashcards
What is responsible for controlling emotions
Limbic System (Subjective feelings)
What is responsible for controlling motivation
Mesocorticolimbic dopamine system (Purposeful and goal-directed behaviour)
Where is the limbic brain and what does it do
Cortical borders circling the brain stem
Receives input from the spinal cord and applies emotional tone to them
What does the limbic brain contain
Amygdala, hippocampus, basal ganglia, and cingulate gyrus
What parts of the brain are active/inactive during depression
Higher activity in Amygdala (Limbic System)
Lower activity in Striatum (Motivation)
Viewed as higher blood flow which means higher neuronal activation
What is the Amine Hypothesis of Depression
Decrease of Monoaminergic neurotransmitters will cause depression
(dopamine, norepinephrine and serotonin)
Evidence for Amine Hypothesis of Depression
Reserpine use depletes neurons of dopamine and norepinephrine transmitters
Ipronazid inhibited Monoamine oxidase, enzyme responsible for the breakdown of monoamines –> Accumulation of monoamines –> Alleviates depression
What are the limits of the Amine Hypothesis of Depression
Drugs that restore monoaminergic levels are only moderately effective in 30-50% of patients
Takes weeks for drugs to see clinical effect, however, they immediately affect synaptic neurotransmitters
MAOIs, SSRIs, and SNRIs, will affect serotonin and noradrenaline levels throughout the body, causes side effects like nausea, indigestion, dizziness, dry mouth, and weight loss
What is the Glutamatergic Hypothesis of Depression
Reduction of glutamatergic signalling in the cortex
Mechanism behind Glutamatergic Hypothesis of Depression
Both excitatory and inhibitory function is inhibited, leading to reduced signal noise –> Becomes harder to recognize required signal
Loss of glutamatergic signalling impacts long-term potentiation and impacts brain’s ability to make long term changes (brain remodeling, synapse formation, BDNF)
MAO
Monoamine Oxidase is an enzyme that breaks down amine neurotransmitters
Inhbition of these enzymes will lead to an increase of monoamines
Ipronazid
Inhibits MAO, blocking amine neurotransmitter breakdown, allowing for an increase in amine neurotransmitters
Must avoid tyramine (found in aged cheese) when using this drug
Tyramine
Sympathomimetic monoamine (acts like noradrenaline)
Also degraded by MAO
When taken with MAO inhibitors a build-up of tyramine occurs and will bind to adrenergic receptors on blood vessels in the heart
Drugs that are selective for SERT
Selective serotonin reuptake inhibitors (SSRI)
Drugs that inhibit both NET and SERT
Serotonin norepinephrine reuptake inhibitors (SNRI)
Fluoxetine
SSRI
Inhibits serotonin transporters causing an increase in the extracellular concentration of neurotransmitters and amplify its effects
Effects of Ketamine
Noncompetitive NMDA receptor antagonist
Dissociative anesthetic will cause hallucinogenic effects
Mechanism behind Ketamine
Blocking of NMDA receptors on GABA interneurons causes a transient burst of glutamate
Glutamate Burst causes synaptic remodelling and resetting of glutamate and GABA systems
Other downstream effects like BDNF release, gene transcription which are long term effects
Benefits and Problems behind Ketamine treatments
Higher effectiveness and effects show after 1 day instead of after weeks (SSRI)
Very narrow therapeutic index
Must use IV in a hospital to administer
What is better Psychedelics or SSRI in treating depression
Psychodelics have a larger effect on improving symptoms of depression
What are the issues of using Psychedelics for depression
Hard to know if positive anti-depressant effect is the result of expectation placebo as during the experiment patients will know immediately if they have received psilocybin
Serious side effects in some studies (suicidal ideation, anxiety, negative trips)
Mechanism behind Psychedelics effect on depression
Synaptic remodeling via intracellular 5HT2a receptors
What determines a 5HT2a agonists ability to causes neural growth
Lipophilicity of the ligand (its ability to cross the membrane)
DMT can cross membrane and drive cortical neuronal remodeling –> Contributes to anti depressant effect of drug
Not related to a ligands ability to induce G protein or beta arrestin signaling
Where are 5HT2a receptors involved in neuronal growth
Inside the cortical neurons, pretty weird for G-protein coupled receptors to be inside a cell
