Lecture 6 the brain Depression the brain and psychedelics

Question 1

Core needs for a diagnosis of depression

Answer 1

Mood change and/or anhedonia

Question 2

Other key symptoms of depression

Answer 2

weight changes
poor concentration
fatigue
agitation
hyper/insomnia

Question 3

Evidence that physiological damage to the brain can cause depression, Robinson et al, 1982

Answer 3

103 patients who had suffered a stroke
1/3-2/3 after found to meet the criteria for depression, not explained by clinical symptoms
Those with left hemisphere damage had more depression than right hemisphere
Closer lesion is to frontal lobe increase likelihood of depression

Question 4

Incidence of depression in people who have brain tumours in their frontal lobes (Wellisch et al, 2002)

Answer 4

Patients with tumours in the frontal lobe were much more likely to have depression compared to those with tumours elsewhere

Question 5

which lesion of the brain increases likelihood of depression

Answer 5

The dorsolateral prefrontal cortex

Question 6

Which lesion of the brain reduces likelihood of depression

Answer 6

ventromedial prefrontal cortex

Question 7

Effect of reduces activity of DLPFC

Answer 7

promotes depression

Question 8

Effects of increased activity of VMPFC

Answer 8

promotes depression

Question 9

Brain stimulation techniques: Electroconvulsive therapy

Answer 9

• Involves applying current to the brain of sufficient intensity of induce seizures (anesthetized state)
• Not focal and quite controversial
• ECT argued to be effective in treating severe depression, some disputals
• Can produce cognitive defects

Question 10

Brain stimulation techniques: Transcranial magnetic stimulation, George et al., 2000

Answer 10

Experimental group: 2 weeks of TMS stimulation to the left Dorsolateral Prefrontal Cortex, switching between high and low intensities
Control group had 2 weeks of ‘Sham’ no electrical stimulation involved

Question 11

Brain stimulation techniques: Transcranial magnetic stimulation, George et al., 2000 findings

Answer 11

After two weeks of TMS stimulation to the left dorsolateral prefrontal cortex depressive symptoms were reduced
higher up of stimulation the less depressed

Question 12

Ventromedial prefrontal cortex:Deep brain stimulation

Answer 12

Surgically implanting electrodes into the brain to change activity in a specific region

Question 13

Ventromedial prefrontal cortex:Deep brain stimulation, Mayberg et al, 2005

Answer 13

Electrodes were implanted into the ventromedial prefrontal cortex: can be effective for some but may only work in the short term

Question 14

What does deep brain stimulation do to the brain?

Answer 14

At baseline patients with severe depression show hypoactivation in dorsolateral prefrontal cortex and hyperactive ventrolateral prefrontal cortex. DBS reverses this pattern after 6 months of stimulation is underactive compared to controls - reduced activity in ventromedial prefrontal cortex, reducing depression

Question 15

Why it is needed in depression to turn of the VMPFC

Answer 15

enables concentration and people to turn of their wandering brain from all their thoughts

Question 16

How to test the effects of drugs on behaviour

Answer 16

compare the effects of a placebo substance and an active substance through a questionnaire and a cognitive test

Question 17

Clinical evidence: Randomised controlled trial (RCT)

Answer 17

• Active treatment
• Comparator
  Randomly allocate to a condition
  Assess the outcome
  Important method as removed bias from treatment allocation

Question 18

RCTs in mental health

Answer 18

Active insulin injection, placebo substance found no evidence for difference on psychotic symptoms between the two groups after 6 months

Question 19

Khan and Brown (2015) RCTs in mental health

Answer 19

Placebo = 40% symptom reduction
waiting list = 10% symptom reduction
Antidepressants = 50% symptom reduction
Both psychotherapy and antidepressants together 60-70% symptom reduction

Question 20

Lines of evidence for serotonin theory of depression

Answer 20

• Reducing the raw materials needed to make serotonin can induce depression
• Change the way serotonin is recycled at the synapse is a treatment for depression

Question 21

What serotonin is made from

Answer 21

Tryptophan absorbed through our diets e.g., salmon, beef, milk

Question 22

What are the effects of changing tryptophan levels in healthy participants (men) Young et al., 1985:

Answer 22

• Gave people a Tryptophan-Free Drink(Depletes 5-Ht - less serotonin levels)
• Balanced Amino Acid Drink (~normal 5-HT) - maintain regular serotonin levels
• Tryptophan-containing drink (Boosts 5-HT) - increases serotonin levels

Question 23

What are the effects of changing tryptophan levels in healthy participants (men) Young et al., 1985:Findings

Answer 23

depleting 5-HT levels increased depression

Question 24

What are the effects of changing tryptophan levels in healthy participants (men) Young et al., 1985:Findings, relating to emotional material

Answer 24

They did this with earphones on
Three levels of distractions:
- Low (stats)
- High (Bombings)
- Dysphoric (feelings of hopelessness)The group who has their Tryptophan levels depleted, lower serotonin, had more interference from emotional material.

Question 25

Reasons why lowering serotonin levels can induce depression

Answer 25

you have less defences against negative information Serotonin is a shield from negative information

Question 26

Tryptophan depletion can induce depressive relapse: Delgado et al, 1990

Answer 26

14/21 patients experienced depressive relapse after taking the tryptophan depleting mixture.

Question 27

Change the way serotonin is recycled at the synapses is a treatment for depression:

Answer 27

- Neuronal communication is chemical, so stopping presynaptic activity is not going to stop communication. You need to stop post-synaptic chemical interactions. - Serotonin reuptake transporter (SERT) sucking up all the serotonin - Selective Serotonin Reuptake inhibitors (SSRI) stop this, therefore increase the amount of serotonin the the synapse

Question 28

Effectiveness of SSRIs

Answer 28

- Strongest evidence for treating moderate depression - Responding often defined as a 50% reduction in score of clinical rating tool - Meta analysis of 56 trials (7374 (Melander et al, 2008) found a 16% different in response rates (Drugs = 48% responder; Placebo = 32%; Number needed to Treat (NNT) = 7)

Question 29

Criticisms of the 'chemical' imbalance theory of depression

Answer 29

Argues it's overly simplistic Reductionists Reduces depression down to just chemical imbalances

Question 30

Modern day use of psychedelics

Answer 30

Hofman discovery of LSD in 1940's Francis Crick discovered DNA supposedly whilst under LSD Steve Jobs, used LSD to boost creativity

Question 31

What are psychedelics

Answer 31

soul revealing compounds cause a radical shift in how you understand yourself and allegedly the universe

Question 32

Classical psychedelics

Answer 32

LSD, Magic Mushrooms

Question 33

Non-classical psychedelics

Answer 33

ecstasy, ketamine

Question 34

Effect of the setting of having a psychedelic drug

Answer 34

where you consume a psychoactive substance can modulate it's effects e.g., having caffeine in a coffee shop vs a library

Question 35

Effecting of the set when consuming a psychedelic drug

Answer 35

your mental state prior to consuming this substance can also modulate the effect of drugs, e.g., having a coffee while being relaxed vs whilst being stressed

Question 36

How do we find out what psychedelics do at the molecular levels in the brain?

Answer 36

Psychedelics, such as psilocybin (Magic Mushrooms), are Serotonin (aka 5-HT) 5-HT2A agonists Psychedelics mimic the effects of serotonin, somewhat selectively at 5-HT2A receptors

Question 37

Agonist definition

Answer 37

a substance that binds to a receptor resulting in activation

Question 38

How do we find out what psychedelics do at the molecular levels in the brain? Measuring

Answer 38

Cannot use FMRIs - to measure serotonin levels in human brains - But we can pair a specific biomolecule with a radioactive isotope

Question 39

PET scans to measure effect of drugs on the brain

Answer 39

Participants are injected with a radioactive compound that binds to a specific biological component (e.g., D1 receptors)they function as serotonin 5-HT1A agonists Level of occupancy of receptors is related to the “psychedelic” experience The psychedelic experience people have is related to the 5-HT2A receptor binding

Question 40

Can psilocybin help with treatment resistant depression? Carhart-Harris et al ., 2016

Answer 40

Psilocybin led to significant reductions in depressive symptomology, lasts for 3 months

Question 41

Can we show that psilocybin is better than antidepressants? Carhart-Harris et al., 2016

Answer 41

Appropriate placebos given in each arm Anti depressant = - citalopram (10-20mg) daily for 6 weeks - Psilocybin magic mushroom) two doses of 25 mg 3 weeks apart

Question 42

Can we show that psilocybin is better than antidepressants? Carhart-Harris et al., 2016, results

Answer 42

Psilocybin reduced depressive symptom more than escitalopram (antidepressant)

Question 43

What effects does psilocybin have on the brain?

Answer 43

Leads to decreases in activation (BOLD signal) in the brain of healthy volunteers, in the ventromedial prefrontal cortex. Decreasing activity here is associated with treatment response. Psilocybin increased the connectivity (’talk’) between the subgenual cingulate and posterior cingulate cortex

Question 44

Functional segregation

Answer 44

One brain region supports one psychological function

Question 45

Functional integration: Psilocybin

Answer 45

Lots of brain regions work together to support one psychological function - Psilocybin promotes interactions between different brain regions (less modularity)

Question 46

Psilocybin reduced brain modularity - more talk between regions: Daws et al., 2022

Answer 46

The more psilocybin increased ‘talk’ between different brain areas the greater the symptomatic improvement Whereas, Citalopram (SSRI) did not consistently change communication between different brain regions No relation between brain modularity changes and symptom reduction