Depression

Question 1

What is responsible for controlling emotions

Answer 1

Limbic System (Subjective feelings)

Question 2

What is responsible for controlling motivation

Answer 2

Mesocorticolimbic dopamine system (Purposeful and goal-directed behaviour)

Question 3

Where is the limbic brain and what does it do

Answer 3

Cortical borders circling the brain stem

Receives input from the spinal cord and applies emotional tone to them

Question 4

What does the limbic brain contain

Answer 4

Amygdala, hippocampus, basal ganglia, and cingulate gyrus

Question 5

What parts of the brain are active/inactive during depression

Answer 5

Higher activity in Amygdala (Limbic System)
Lower activity in Striatum (Motivation)

Viewed as higher blood flow which means higher neuronal activation

Question 6

What is the Amine Hypothesis of Depression

Answer 6

Decrease of Monoaminergic neurotransmitters will cause depression
(dopamine, norepinephrine and serotonin)

Question 7

Evidence for Amine Hypothesis of Depression

Answer 7

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

Question 8

What are the limits of the Amine Hypothesis of Depression

Answer 8

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

Question 9

What is the Glutamatergic Hypothesis of Depression

Answer 9

Reduction of glutamatergic signalling in the cortex

Question 10

Mechanism behind Glutamatergic Hypothesis of Depression

Answer 10

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)

Question 11

MAO

Answer 11

Monoamine Oxidase is an enzyme that breaks down amine neurotransmitters

Inhbition of these enzymes will lead to an increase of monoamines

Question 12

Ipronazid

Answer 12

Inhibits MAO, blocking amine neurotransmitter breakdown, allowing for an increase in amine neurotransmitters

Must avoid tyramine (found in aged cheese) when using this drug

Question 13

Tyramine

Answer 13

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

Question 14

Drugs that are selective for SERT

Answer 14

Selective serotonin reuptake inhibitors (SSRI)

Question 15

Drugs that inhibit both NET and SERT

Answer 15

Serotonin norepinephrine reuptake inhibitors (SNRI)

Question 16

Fluoxetine

Answer 16

SSRI

Inhibits serotonin transporters causing an increase in the extracellular concentration of neurotransmitters and amplify its effects

Question 17

Effects of Ketamine

Answer 17

Noncompetitive NMDA receptor antagonist

Dissociative anesthetic will cause hallucinogenic effects

Question 18

Mechanism behind Ketamine

Answer 18

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

Question 19

Benefits and Problems behind Ketamine treatments

Answer 19

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

Question 20

What is better Psychedelics or SSRI in treating depression

Answer 20

Psychodelics have a larger effect on improving symptoms of depression

Question 21

What are the issues of using Psychedelics for depression

Answer 21

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)

Question 22

Mechanism behind Psychedelics effect on depression

Answer 22

Synaptic remodeling via intracellular 5HT2a receptors

Question 23

What determines a 5HT2a agonists ability to causes neural growth

Answer 23

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

Question 24

Where are 5HT2a receptors involved in neuronal growth

Answer 24

Inside the cortical neurons, pretty weird for G-protein coupled receptors to be inside a cell