l6- depression, the brain n psychedelics Flashcards
1
Q
Evidence that changes to the brain can promote or alleviate depression
depression
A
- a disorder w sad, empty or hopeless mood n loss of pleasure (anhedonia)
- other features: weight change, poor concentration, sleep issues, fatigue n agitation
2
Q
Evidence that changes to the brain can promote or alleviate depression
post stroke depression
robinson et al 1982
A
- 1/3 to 2/3 stroke pts met criteria for depression
- this cant be expl by clinical symps alone
3
Q
Evidence that changes to the brain can promote or alleviate depression
brain region + depression
robinson et al 1984
A
- damage to the anterior frontal lobe, esp on left, was more likely to lead to depression than rught sided damage
4
Q
Evidence that changes to the brain can promote or alleviate depression
frontal tumours + depression
wellisch et al 2002
A
- tumours in the frontal lobe linked to higher rates of depression than tumours in other brain regions
5
Q
Evidence that changes to the brain can promote or alleviate depression
can we really treat the FL as a homogenous entity?
- frontal lobe balance
A
- frontal cortex not 1 thing- needs balance between doroslateral prefrontal cortex (doing complicated tasks)+ ventromedial PFC (being in own head)
6
Q
Evidence that changes to the brain can promote or alleviate depression
depression + lesions
koenig et al 2008
A
- lesions to the DLPFC ^ risk of depression, lesions to the VMPFC reduced it= suggests opposite roles in mood regulation
7
Q
Evidence that changes to the brain can promote or alleviate depression
simple neurocognitive model of depression
A
- Reduced DLPFC activity promotes depression, e.g., Executive functions?
- Increased VMPFC activity promotes depression, e.g., mind wandering/rumination
8
Q
Evidence that changes to the brain can promote or alleviate depression
brain stimulation
Electroconvulsive therapy (ECT)
A
- most famous form
- not focal
- applies strong electrical current under anaesthesia to induce seizures
- effective for servere depression but contreversial due to cog side effects (meechan et al 2021, read et al 2019)
9
Q
Evidence that changes to the brain can promote or alleviate depression
brain stimulation
TMS
A
- non-invasive brain stimulation
- repeated stimulation of the left DLPFC reduced depressive symptoms after 2 weeks (george et al 2000)
10
Q
Evidence that changes to the brain can promote or alleviate depression
brain stimulation
deep brain stimulation
A
- surgical technique that implants electrodes into specific brain regions
- DBS of the VMPFC (subgenual cingulate) helped some treatment-resistant depression patients
11
Q
Evidence that changes to the brain can promote or alleviate depression
brain stimulation
DBS mechanism
A
- before DBS: ↓ DLPFC activity and ↑ VMPFC activity.
- after DBS: this pattern reversed- suggesting VMPFC downregulation may reduce depression
12
Q
Neurochemistry of Depression: Is it all serotonin?
randomised controlled trials
A
- clinical trials where ppts r randomly addigned to active treatment or placebo
- helps remove bias n measure drug effectiveness
- *randomisation helps to remove bias from treatment allocation *
13
Q
blinding in trials
A
- open label- everyone knows
- single blind- ppt doesnt know
- double blind- neither ppts or researcher knows
- placeabos still work better when ppts dont know theyre placebos
14
Q
Neurochemistry of Depression: Is it all serotonin?
serotonin theory of depression
A
- reduicng the raw materials needed to make serotonin can induce depression
- change the way sortonin is recycled at the synpase (SSRIs) is a treatment for depression
- tryptophan=serotonin poathway
Tryptophan → 5-HTP → 5-HT (serotonin).
Depleting tryptophan → less serotonin → increased depression.
15
Q
Neurochemistry of Depression: Is it all serotonin?
tryptophan depletion studies
A
- depleting 5-HT levels increased depressive symptoms n intrusive thoughts, especially under emotional distraction
- 14/21 ppts had a relapse when 5-HT was lowered
16
Q
Neurochemistry of Depression: Is it all serotonin?
SSRIs n their effects
A
- they block the reuptake of serotonin by SERT transporters- more serotinin in snypase= symptom relief
17
Q
Neurochemistry of Depression: Is it all serotonin?
SSRi effectiveness
Cleare et al, 2015 BAP guidelines
A
- strongest for moderate depression
- 50% reduction on clinical scales=response
- meta analysis: 48% response w drug vs 32% w placebo (melander et al 2008)
- number needed to treat= 7
18
Q
SSRis criticism
A
- even if SSris work, that doesnt prove depression is just a ‘chemical imbalance’
19
Q
Depression and Psychedelics.
Psychedelics.
A
- drugs like psilocybin (magic mushrooms) or lsd that cause altered perception n cognition
- often activate serotonin 5-HT2A receptors
20
Q
Depression and Psychedelics.
Psychedelics- set and setting
A
- set= ur mental state before taking the drug
- setting= the enviroment where u take the drug
both massively influence psychedelic experince
21
Q
Psychedelics what is n isnt one?
A
- clasical vs non callsical (NUTT): ‘non-classical’, ecstasy, ket
- LSD
- magic mushrooms
22
Q
Depression and Psychedelics.
5-ht2a receptor antagoniosts
A
- Psychedelics mimic serotonin by binding to 5ht2a receptors- changes in perception n brain activity
23
Q
Depression and Psychedelics.
measuring psychedelics in the brain
PET imaging
A
- inject radioactive molecules that bind to specific receptors (eg 5HT2A)- scan to see how much is occupied
24
Q
Depression and Psychedelics.
measuring psychedelics in the brain
Psilocybin PET study-
madsen et al 2019
A
- explored diff subjects w diff doses
- higher 5-HT2A receptor occupancy=stronger psychedelic experience
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# Depression and Psychedelics.
Psychedelics VS traditional antidepressants
SSRIs vs psilocybin
- SSRis- increase serotonin levels across the brain
- psilocbyin- activates 5-HT2A receptors in specific areas
- they work on diff parts of the serotonin system
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# Depression and Psychedelics.
tretament- resistant depression
- ppl who havent responded to multiple treatments
- psilocybin showed large symptom reductions in this group
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# Depression and Psychedelics.
Psychedelics vs Traditional Antidepressants
head to head trials
(psilocybin Vs citalopram)
- 2 doses of psilocybin (25mg) vs daily citalopram (10-20mg)
- psilocybin showed greater reductions in depression
- also improved wellbeing more (WEMWBS scores)
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# Depression and Psychedelics.
what does psilocybin do to the brain?
psilocybin n fmri (carhart harris et al 2016)
- decreased overall brain activity (BOLD signal)
- increased connectivity between brain areas like subgenual cingulate + posterior cingulate
- strength of this connectivity linked to positive response
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# light physical properties
photon
- indiviudal packet of electromagnetic energy that makes up light
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# light:phsyical properties
wavelength
- property of a photon that determines its colour
- the human eye is sensitive to wl between 400-700 nanometers
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# light:phsyical properties
nanometer (nm)
- unit of measurement equal to 1 billion of a meter (0.000000001)
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# light:phsyical properties
light transmission
- photons travel in a straight line unless theyre scattered, reflected, refracted or absorbed
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# light:phsyical properties
image formation
- light reflected from an object n reaching the eye forms an image on the retina
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# light:phsyical properties
visual angle
- a measure of an objects size on the retina
- eg 1cmat 57 cm= 1degree
- thumbnail (2cm) at arms lengyj=~2 degrees
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# the eye
retinal focus
- light must be focused onto the retina for a clear image
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# the eye
pupil dilation
- the pupil widens to allow more light into the eye
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# the eye
peripheral vision
- lower resolution compared to centrasl vision
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# accomadation
accomadation
- the process where the eye changes its refractive power to focus on near objects
- speed: ~0.25 seconds
- range at birth: ~15 dioptres
- dioptre: reciprocal of focal length in metres
- 15D-- focus 1/15 = 0.067m= 6.7cm
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# accomadation
presbyopia
- age related decline in ability to accomadate
- decrease of ~1 dioptre every 5 years until age 30
- by age 40-50: accomadation range falls below 2.5D (ie, cannot focus closer than 0.4m)
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# refractive errors
refractive error
- occurs when light isnt focused properly on the retina
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# refractive errors
astigmatism
- blur caused by irregular curvature of the cornea
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# the retina
retina
- photosensiitive layer at the back of the eye that detects light
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# the retina
5 cell types in the retina
- vertical pathway: photreceptors (rods+cones), bipolar cells, ganglion cells
- horizontal pathway: horizontal cells, amacrine cells
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# photoreceptors
photoreceptors
- ~100mn total
- rods: ~90-120mn, sensitive to dim light
- cones: ~4-5mn, sensitive to bright light
- duplex retina: combination of rods n cones
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# photoreceptors
cone types
- s(short): blue-sensitive
- m(medium): green-sensitive
- L(long): red-sensitive
- L:M:S ratio= 12:6:1
- no s-cones in the fovea
- high indivual variability
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# photoreceptors
luminous efficacy
- the eyes sensitivity to light varies by wavelength
- rods peak at shorter wavelengths than cones
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# photoreceptors
photoreceptor density
- highest cone density in the fovea
- highest rod density in the periphery
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# fundus
fundus
- interior surface of the eye, includes:
- retina
- vascular tree
- macula
- fovea
- optic disc
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# bipolar cells
midget bipolar cells
- location:fovea
- input:cones
- convergence: low (1:1)
- function: high resolution (fine detail)
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# bipolar cells
diffuse bipolar cells
- location: periphery
- input: rods+cones
- convergence: high (many:1)
- function: high sensitivity (good in dim light )
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# bipolar cells
ON bipolar cells
- depolarise (activate) when light becomes more positive
- membrane potential becomes more positive
52
# bipolar cells
OFF bipolar cells
- hyperpolarise (decrease activity) when light increases
- membrane potential becomes more negative
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# bipolar cells
signal type
- graded potentials (not spikes)
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# convergence
low convergence
- eg: cone- 1 bipolar- 1 ganglion
- result: high activity (sharp vision), low sensitvity (less good in dim light)
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# convergence
high convergence
- eg: many rods- 1 bipolar - 1 ganglion
- result: low acuity, high sensitivity (better in low light)
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# ganglion cells
P cells (parvocellular pathway)
- 70% of ganglion cells
- input: midget bipolar cells
- receptive fields: small
- function: colour n detail
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# ganglion cells
M cells (magnocellular pathway)
- 10% of ganglion cells
- input: diffuse bipolar cells
- receptive fields: large
- function: motion n broad contrast
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# ganglion cells
koniocellular cells
- 20%
- input: s-cones
- role: color processing
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# ganglion cells
ganglion cells output
- spikes only
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# light transduction
photoreceptors
- convert light into neural signals via a multistep process
1. photon capture: chromophore (retinal) in outer segment absorbs light
2. photoactivation: energy transfered- chromophore changes shape
- 11-cis-retinal---all trans retinal--detachs from opsin
3. hyperpolarization: membrane becomes more negative (Na+ channels close)
4. calcium channels close: less glutamate released
5. signal strength: less glutamate=more photons detected
6. graded potentials sent to bipolar cells--ganglion cells--brain
61
# ganglion cells
opsin+chromophore= photopigment (eg rhodopsin in rods)
- opsin= protein
- chromophore= light-catching molecule
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# receptive field
receptive field
- defintion: the specific area of visual space where light can affect the activity of a given neuron
- each photoreceptor, bipolar n ganglion cell has its own receptive field
- first measured in cat retina (Kuffler,1953) later in primates
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# centre-surrond receptive fields
on- center, off-surrond
- increases firing when light is on the center
- decreases firing when light is on the surround
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# centre-surrond receptive fields
OFF-center, On-surrond
- decreases firing when light is on the center
- increases firing when light is on the surrond
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# centre-surrond receptive fields
centre-surrond receptive fields
- acts like a contrast detector, responding best to edges n differences in brightness
- helps filter out uniform illumination (eg broad sunlight)
66
# effect of spot size on ON-center cells
effect of spot size on ON-center cells
- maximum responses occurs when light matches the size of the center
- too large: light spills onto the surrond-- reduced response
- too small: doesnt stimulate enough center-- weaker response
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# lateral inhibition
lateral inhibition
- inhibition of a neuron by activity in neighboring cells
- enables centre-surrond receptive field structure
- enhances detection of contrast n edges in the scene
- horizontal cells meditate lateral inhibition at the level of the retina
- works by reducing response when light falls on both center n surrond
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# edge detection
edge detection
- ganglion cells respond strongly to edges (brightness changes), not to unfirm light
- useful for identifying object boundaries in a scene
- doesnt respond much to average light level
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mach bands
- visual illusions where bands of light/dark r seen at the borders of gradients
- casued by later inhibition in the reitna
- enhances edge contrast even when no real edge exists
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hermann grid illusion
- grey spots appear at intersections (not along the streets)
- caused by larger receptive fields in the peripheryh
- more light falls on surrond=less firing
- no spots in fovea: receptive fields r smaller, stay within light region= no inhibition
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