Lecture 17: Depression and schizophrenia

Question 1

What causes depression?

Answer 1

• Depression is a complex interaction of environmental/biological/genetic factors
• There are strong biological correlates of depression

Question 2

In order to diagnose depression you need:

Answer 2

One Major symptoms: Depressed mood or loss of interest (often overlapping)

Four minor symptoms: Weight/appetite changes, sleep disturbance, psychomotor, fatigue, worthlessness, executive dysfunction, suicidal idealation

Question 3

What is the most common mood disorder?

Answer 3

Depression, defined by the occurrence of at least on single major depressive episode, although its periodic and pts can experience recurrent episodes.

Question 4

What are the monoamine neurotransmitter systems?

Answer 4

Dopamine
Serotonin
Norepinephrine

Question 5

What is dopamine synthesized from?

Answer 5

Tyrosine

Question 6

What breaks down dopamine?

Answer 6

Dopamine transporter or monoamine oxidase

Transport and enzymatic driven

Question 7

What is norepinephrine synthesized from?

Answer 7

Tyrosine-> Dopa -> Dopamine -> Norepinephrine

Question 8

How is norepinephrine cleaned up?

Answer 8

NET transporter
ENzyme: MAO-A (mono amine oxide)

Transporter or enzymatically driven

Question 9

How is serotonin produced?

Answer 9

It is produced from dietary tryptophan and is converted into 5HTP

(5HTP) Converted into 5HT by AAADC

Question 10

How is 5HT eleiminated?

Answer 10

SERT transporter

Degraded by MAO

Question 11

What is monoamine hypothesis of depression?

Answer 11

Depression is caused by a deficiency of monoamine i.e no neurotransmitter

i.e chemical imbalance

But its wrong, good story

Question 12

What are the issues with the monoamine hypothesis?

Answer 12

• Antidepressants take ages to work even though the rise in serotonin levels are almost immediate
• Why dont serotonin reuptake inhibitors enhance the effects of antidepressants
• Reduced dietary tryptophan intake does not cause depression
• Other drugs i.e ketamine can have antidepressant properties
• Genetic manipulation to increase synaptic serotonin is associated with increased depressive symptoms

Question 13

What is the alternative theory to monoamine hypothesis?

Answer 13

The molecular problem may lie in the downstream signaling cascades i.e enter brain-derived neurotrophic factor (BDNF)

Question 14

What is BDNF and what does it do?

Answer 14

• Protein, growth factor

- Supports survival of new neuron’s and growth of new synapses.

Question 15

What is the neurotrophic hypothesis of depression?

Answer 15

It states that depression may be caused by reduced synthesis of proteins involved in neurogenesis and synaptic plasticity.

= Reduced plasticity in hippocampus and cortex, amygdala (involved in stress reactions)

i.e BDNF

Question 16

What happens with low BDNF? What can increase levels?

Answer 16

Cell atrophy / death, less synapses

Monoamines can increase BDNF

If monoamines levels are low then BDNF levels may be low.

Question 17

What can turn off BDNF genes? what can increase their expression?

Answer 17

Environmental stressors

Antidepressant responses with monoamine enhancing drugs increased BDNF expression

Question 18

How can we treat depression?

Answer 18

Psychotherapeutic

Psychopharmacological

Question 19

What is psychosis?

Answer 19

• Psychosis is a set of symptoms that can be associated with many psychiatric disorders
• Defining feature of many disorders
• Delusions / hallucinations but also disorganized speech and behavior

Question 20

What are the different types of psychosis?

Answer 20

Paranoid psychosis

Disorganized / excited psychosis (random behavior)

Depressive psychosis (Psychomotor retardation etc)

Question 21

What is the most common psychotic disorder?

Answer 21

Schizophrenia

1.4x more common in males

Question 22

What are the added symptoms of schizphrenia?

Answer 22

Delusions
Hallucinations (typically auditory)
Agitation
Disorganized speech and behavior

Question 23

What are the subtracted symptoms of scizophrenia?

Answer 23

Blunted affect
Passive
Poor rapport
Lack of spontaneity
Anheonia; lack of pleasure

Question 24

What are the cognitive symptoms of scizophrenia?

Answer 24

Problems focusing, verbal fluency, prioritizing, representing and maintaining goals

Question 25

What is the key neurotransmitter and receptor involved in schizophrenia?

Answer 25

Dopamine and its D2 receptor

Question 26

Write some notes on the D2 receptor and scizophrenia:

Answer 26

• All antipsychotics seem to work by blocking the D2 receptor
• Drugs that enhance dopamine i.e coke and amphetamines can causes paranoid psychosis

This has led to the development of the dopamine hypothesis of schizophrenia

Question 27

What are the key pathways in shizophrenia?

Answer 27

Mesolimbic pathway

Ventral tegmental -> Nucleus accumbens

Pathway is associated with feelings of pleasure, euphoria with drugs abuse, and potentially the positive symptoms of schizophrenia (overactivation)

Mesocortical pathway: Ventral tegmental to dorsolateral prefrontal cortex. Though to be underactive and cause the negative symptoms and cognitive symptoms.

Question 28

How is schizophrenia treated?

Answer 28

-Antipsychotics that target D2

Question 29

What is the different atypical antipsychotics of today?

Answer 29

Adding 5HT2A antagonist / inverse agonist actions

Question 30

How do antipsychotics work?

Answer 30

Block mesolimbic pathway reducing positive symptoms.

Side effects:

• Tardive dyskinesia
• Parkinsons like symptoms
• Increases negative symptoms

B/c blocking the nigral striatal pathway

Side effects accumulate over time.

Question 31

What causes schizophrenia?

Answer 31

• Nature vs nurture debate
• Single genes dont cause mental illness nor do single genes generate specific symptom behavior
• Genes code for proteins not traits

Development and environment are massively important