Lecture 17: Depression and schizophrenia Flashcards

1
Q

What causes depression?

A
  • Depression is a complex interaction of environmental/biological/genetic factors
  • There are strong biological correlates of depression
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2
Q

In order to diagnose depression you need:

A

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

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3
Q

What is the most common mood disorder?

A

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

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4
Q

What are the monoamine neurotransmitter systems?

A

Dopamine
Serotonin
Norepinephrine

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5
Q

What is dopamine synthesized from?

A

Tyrosine

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6
Q

What breaks down dopamine?

A

Dopamine transporter or monoamine oxidase

Transport and enzymatic driven

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7
Q

What is norepinephrine synthesized from?

A

Tyrosine-> Dopa -> Dopamine -> Norepinephrine

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8
Q

How is norepinephrine cleaned up?

A

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

Transporter or enzymatically driven

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9
Q

How is serotonin produced?

A

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

(5HTP) Converted into 5HT by AAADC

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10
Q

How is 5HT eleiminated?

A

SERT transporter

Degraded by MAO

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11
Q

What is monoamine hypothesis of depression?

A

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

i.e chemical imbalance

But its wrong, good story

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12
Q

What are the issues with the monoamine hypothesis?

A
  • 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
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13
Q

What is the alternative theory to monoamine hypothesis?

A

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

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14
Q

What is BDNF and what does it do?

A
  • Protein, growth factor

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

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15
Q

What is the neurotrophic hypothesis of depression?

A

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

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16
Q

What happens with low BDNF? What can increase levels?

A

Cell atrophy / death, less synapses

Monoamines can increase BDNF

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

17
Q

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

A

Environmental stressors

Antidepressant responses with monoamine enhancing drugs increased BDNF expression

18
Q

How can we treat depression?

A

Psychotherapeutic

Psychopharmacological

19
Q

What is psychosis?

A
  • 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
20
Q

What are the different types of psychosis?

A

Paranoid psychosis

Disorganized / excited psychosis (random behavior)

Depressive psychosis (Psychomotor retardation etc)

21
Q

What is the most common psychotic disorder?

A

Schizophrenia

1.4x more common in males

22
Q

What are the added symptoms of schizphrenia?

A

Delusions
Hallucinations (typically auditory)
Agitation
Disorganized speech and behavior

23
Q

What are the subtracted symptoms of scizophrenia?

A
Blunted affect
Passive
Poor rapport
Lack of spontaneity
Anheonia; lack of pleasure
24
Q

What are the cognitive symptoms of scizophrenia?

A

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

25
What is the key neurotransmitter and receptor involved in schizophrenia?
Dopamine and its D2 receptor
26
Write some notes on the D2 receptor and scizophrenia:
- 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
27
What are the key pathways in shizophrenia?
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.
28
How is schizophrenia treated?
-Antipsychotics that target D2
29
What is the different atypical antipsychotics of today?
Adding 5HT2A antagonist / inverse agonist actions
30
How do antipsychotics work?
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.
31
What causes schizophrenia?
- 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