Lecture 19 - Depression

Question 1

Which NT is important for CNS

Answer 1

-Serotonin (5-HT)

Question 2

How is serotonin (5-HT) synthesized?

Answer 2

-Tryptophan [from high protein foods; BBB transporter] –> tryptophan hydroxylase turns tryptophan into 5-HTP –> AADC turns 5-HTP into 5-HT

Question 3

What are 2 other compounds are synthesized from 5-HT?

Answer 3

-melatonin (pineal gland)
-5-HIAA [5-HT turned into 5-HIAA by MAO]

Question 4

MDMA

Answer 4

-lasts 3 hours
-taken up by SERT reverses VMAT to take 5-HT out of the vesicles …
-floods […] with serotonin

Question 5

What are the 2 subsections of raphé nucleus?

Answer 5

-dorsal raphé: fine axons, small varicosities
-ventral raphé: beaded axons, large varicosities
*studies show that there is a 26% reduction in 5-HT in the dorsal raphé of MDMA users

Question 6

What are the serotonin receptors?

Answer 6

-GPCRS: 5-HT1 family [A, B, D, F]; 5-HT2 family [A, B, C]; 5-HT4; 5-HT6; 5-HT7
-LGICs: 5-HT3

Question 7

5% of the population experiences depression. What are the treatments and their effectiveness?

Answer 7

-all treatments are equally effective for MDD
-antidepressants are effective for 60-70% of MDD population [same for CBT]
-30-40% have treatment-resistant depression

Question 8

How do antidepressants work?

Answer 8

-all current antidepressants act by enhancing 5-HT, NE, or both

Question 9

What were the first antidepressants developed?

Answer 9

-TCA (tricyclic antidepressants)
-act as non-selective reuptake inhibitor of monoamines
-problem with TCA: very narrow TI [LD50 2-6] –> a lot of OD

Answer 10

-MAOI (monoamine oxidase inhibitors)
-inhibit enzyme MAO which ADD
-important for the breakdown of tyramine or there is high blood pressure

Question 11

What are SSRI’s?

Answer 11

-selective serotonin reuptake inhibitors
-very wide TI
-currently, the most widely used antidepressants

Question 12

What are alternatives to SSRI’s?

Answer 12

-NSRI’s (Norepinephrine selective reuptake inhibitors) –> prevent EPI and NET from being reuptaken
-SNRI’s (Serotonin and Norepinephrine Reuptake Inhibitors)
-Wellbutrin (DAT and NET)

Question 13

What are side effects of antidepressants?

Answer 13

-nausea
-no libido
-absent orgasm
-erectile dysfunction
-weight gain or loss
-sleep disruption

Question 14

How long does it take for antidepressants to work?

Answer 14

-2-6 weeks for them to work

Question 15

What is the Monoamine theory of depression?

Answer 15

-depression is caused by a deficit of serotonin, norepinephrine, or both [also DA]

Question 16

SERT blocked…

Question 17

What is the Glutamate theory of depression?

Answer 17

-people with depression have increased Glu in their blood
-increased Glu in the brain is toxic
-SSRI’s reverse this increase
-ketamine blocks Glu transmission by blocking NMDA channel
-ketamine acts rapidly and helps with TRD [but effectiveness decreases over time; after first treatment]

Question 18

What is the Neuroinflammatory (Cytokine) theory of depression?

Question 19

What are pro-inflammatory cytokines?

Answer 19

-small proteins secreted to cause inflammation and recruit immune cells [part of signalling pathways of PNS]
-includes proteins such as interleukin and tumor necrosis factor

Answer 20

-they are higher in the brain tissue of i