Lecture 17: Depression and schizophrenia Flashcards
What causes depression?
- Depression is a complex interaction of environmental/biological/genetic factors
- There are strong biological correlates of depression
In order to diagnose depression you need:
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
What is the most common mood disorder?
Depression, defined by the occurrence of at least on single major depressive episode, although its periodic and pts can experience recurrent episodes.
What are the monoamine neurotransmitter systems?
Dopamine
Serotonin
Norepinephrine
What is dopamine synthesized from?
Tyrosine
What breaks down dopamine?
Dopamine transporter or monoamine oxidase
Transport and enzymatic driven
What is norepinephrine synthesized from?
Tyrosine-> Dopa -> Dopamine -> Norepinephrine
How is norepinephrine cleaned up?
NET transporter
ENzyme: MAO-A (mono amine oxide)
Transporter or enzymatically driven
How is serotonin produced?
It is produced from dietary tryptophan and is converted into 5HTP
(5HTP) Converted into 5HT by AAADC
How is 5HT eleiminated?
SERT transporter
Degraded by MAO
What is monoamine hypothesis of depression?
Depression is caused by a deficiency of monoamine i.e no neurotransmitter
i.e chemical imbalance
But its wrong, good story
What are the issues with the monoamine hypothesis?
- 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
What is the alternative theory to monoamine hypothesis?
The molecular problem may lie in the downstream signaling cascades i.e enter brain-derived neurotrophic factor (BDNF)
What is BDNF and what does it do?
- Protein, growth factor
- Supports survival of new neuron’s and growth of new synapses.
What is the neurotrophic hypothesis of depression?
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
What happens with low BDNF? What can increase levels?
Cell atrophy / death, less synapses
Monoamines can increase BDNF
If monoamines levels are low then BDNF levels may be low.
What can turn off BDNF genes? what can increase their expression?
Environmental stressors
Antidepressant responses with monoamine enhancing drugs increased BDNF expression
How can we treat depression?
Psychotherapeutic
Psychopharmacological
What is psychosis?
- 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
What are the different types of psychosis?
Paranoid psychosis
Disorganized / excited psychosis (random behavior)
Depressive psychosis (Psychomotor retardation etc)
What is the most common psychotic disorder?
Schizophrenia
1.4x more common in males
What are the added symptoms of schizphrenia?
Delusions
Hallucinations (typically auditory)
Agitation
Disorganized speech and behavior
What are the subtracted symptoms of scizophrenia?
Blunted affect Passive Poor rapport Lack of spontaneity Anheonia; lack of pleasure
What are the cognitive symptoms of scizophrenia?
Problems focusing, verbal fluency, prioritizing, representing and maintaining goals
What is the key neurotransmitter and receptor involved in schizophrenia?
Dopamine and its D2 receptor
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
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.
How is schizophrenia treated?
-Antipsychotics that target D2
What is the different atypical antipsychotics of today?
Adding 5HT2A antagonist / inverse agonist actions
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.
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
