1. Identify the emerging neurobiological hypothesis of schizophrenia.
o The hypothesis: (focus on the most detail with the Dopamine Theory)
❖ The only pharmacological treatment that we have are dopamine (D2 receptors)
and serotonin (5HT2A)
❖ Dopamine Theory
▪ Hyperactive dopamine at D2 receptors in the mesolimbic pathway
In the mesolimbic pathway is responsible for the positive symptoms;
the hypoactivity is responsible for the negative
▪ Mesolimbic pathway it’s overactive dopamine receptors or overactive
dopamine on the dopamine receptors in mesolimbic pathways but it is
also hypoactive dopamine at the D2 receptors in the mesocortical
pathway
▪ Most detailed knowledge about this theory because that has been our
foundational understanding of schizophrenia up until the very recent past
so the other two, we don’t have as much detail about. But the other two
just give us a much fuller understanding as far as why the Dopamine
Theory happened in the first place.
❖ Glutamate Theory
▪ Hypoactive dopamine at N-Methyl-D-Asperate (NMDA) receptor
▪ NMDA receptors are hypofunctioning and because of that, it leads to
hyperactive dopamine in the mesolimbic pathway and hypoactive
dopamine in the mesocortical pathway.
▪ The NMDA receptor is on the GABA interneurons
▪ Emerging one
❖ Serotonin Theory
▪ Hyperactive dopamine at the 5HT2A receptors in the mesocortical
pathway
5HT2A receptors are overly active
In the mesocortical pathway is responsible for the negative
symptoms
1
, ▪ 5HT2A receptors are hyperfunctioning, which leads to over functioning or
overactive dopamine on those receptors in them as a mesolimbic
pathway and hypoactive dopamine receptors in that mesocortical
pathway
o Positive symptoms
❖ Delusions, Hallucinations o Negative symptoms
❖ Apathy, Anhedonia, Cognitive Blunting,
Neuroleptic dysphoria
2
,2. Identify the different dopamine pathways and what role each pathway plays in
relation to schizophrenia/psychosis and treatment.
o Dopamine Pathways – 2 pathways are related to pathophysiology
(nigrostriatal & tuberoinfundibular) and 2 pathways are responsible for signs &
symptoms of schizophrenia (mesolimbic & mesocortical)
❖ Mesolimbic
❖ Mesocortical
❖ Nigrostriatal
❖ Tuberoinfundibular o 2 are responsible for the symptoms, the signs &
symptoms of schizophrenia (positive/negative signs)
❖ Mesolimbic & Mesocortical
▪ How are the positive/negative manifesting in the mesolimbic area and
mesocortical area? What dopamine is doing, and what’s the difference?
Mesolimbic Pathway
➢ Hyperactive
➢ Looney pathway, where too much dopamine is happening
➢ The way the medications will work is by blocking the
dopamine, can’t get so excessive
➢ You can think of L as lunacy/looney because that is where
the positive symptoms are. The positive symptoms are if
you saw that individual in the street, you would think they
are positively insane because they might be hearing voices,
talking to themselves, or responding to internal stimuli.
➢ Negative symptoms are harder to catch because the
person is more withdrawn, not social, they tend to not have
a lot of emotional expressions
❖ Mesocortical Pathway
▪ Hypoactive
▪ What is dopamine doing in that pathway as far as negative symptoms?
Too little
Blocking dopamine will make a bad situation worse like anhedonia
o These drugs we have currently, do a really good job in reducing the positive symptoms
but because these drugs do not have selectivity for just the one pathway that is
involved in the positive symptoms, they tend to make the bad situation being too little
dopamine on that cortical pathway even worse. Thus far there is not a specific agent
that treats the negative symptoms. The newer meds have a tendency not to make the
problem worse but do not fix the problem either.
o The other 2, what is involved in collateral damage of the treatment that we administer
for schizophrenia
❖ Nigrostriatal Pathway
❖ Tuberoinfundibular Pathway
3
, ❖ What happens to the nigrostriatal pathway and the tuberoinfundibular pathway
when we are treating schizophrenia? Under normal circumstances individuals
with schizophrenia there is nothing wrong with schizophrenia. When we throw
our treatments at them, is when we cause problems. What kinds of problems
happen we have when we block dopamine in those pathways?
▪ Nigrostriatal
Has to do with extrapyramidal systems like motor function,
Parkinsonian type activity like rigidity and tremors
Too little dopamine causes movement disorders like
Parkinson’s disease, akathisia, and dystonia
Too much dopamine causes hyperkinetic movement disorders like
chorea, dyskinesias, and tics
Chronic blockade of D2 receptors can lead to tardive dyskinesia
▪ Tuberoinfundibular
When dopamine is blocked, prolactin levels rise
Increased prolactin level (hyperprolactinemia)
➢ Gynecomastia – breast enlargement of breast
development
➢ Amenorrhea – loss of menstrual periods ➢
Galactorrhea – breast secretions
o Tip to help remember:
❖ Nigrostriatal – think “stride” because this area impacts movement. When we
don’t move, we get stiff and sluggish. Decreased dopamine in this area causes
Parkinsonism.
❖ Mesolimbic – think four limbs like a plus sign. Too much dopamine in this area
causes positive symptoms.
❖ Mesocortical – think about the core of who you are (emotions). Decreased
dopamine in this area causes depression (and negative symptoms)
❖ Tuberoinfundibular – think about infants depending on lactation.
Blocked dopamine causes too much prolactin.
4
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