Chapter 4 (Schizophrenia) Flashcards
Theorized brain location correlated with the positive sx of Schizophrenia
Mesolimbic area–specifically the Nucleus Accumbens
Theorized brain location correlated with the negative and affective sx of Schizophrenia
Mesocortical and ventromedial prefrontal cortex
Theorized brain location correlated with the cognitive sx of Schizophrenia
Dorsolateral prefrontal cortex
Theorized brain location correlated with the aggressive/impulsive sx of Schizophrenia
Orbitofrontal cortex and its connections to amygdala
Dopamine is synthesize from which amino acid?
Tyrosine
Enzymes that turn Tyrosine into Dopamine
Tyrosine hydroxylase (rate limiting step ) and then by the enzyme DOPA decarboxylase
How Dopamine synaptic action is terminated
- Reuptake by DAT
- Inside the neuron it is either packaged in a vesicle by Vesicular Monoamine Transporter or it is broken down by MAO-A or MAO-B.
- Outside of the neuron, Dopamine is broken down by COMT
Types of Clinical DA receptors
D1, D2, D3, D4, and D5 are all blocked by various antipsychotics. But only D2 and D5 are understood
How many dopaminergic pathways are there in the brain?
5
Mesolimbic DA Pathway
Projects from Midbrain Ventral Tegmental Area to the Nucleus Accumbens. Control euphoria and delusions/hallucinations, etc.
Mesocortical DA Pathway
Projects from Midbrain Ventral Tegmental Area to the Dorsolateral Prefrontal Cortex. Has a role in the cognitive sx of Schizophrenia. (Hypoactivity may be the problem here)
Nigrostriatal DA Pathway
Projects from Substantia Nigra to the Striatum. Movement and Extrapyramidal Nervous System.
Tuberoinfundibular DA Pathway
Projects from Hypothalamus to the Anterior Pituitary and controls Prolactin Secretion
5th DA Pathway
Projects from all over to the Thalamus. Not well understood.
Glutamate Metabolism
- It is an AA. It is released by Glutamate Neurons in the synapse
- Then it is taken up by Glial Cells and broken down into Glutamine
- Glutamine is released by the Glial Cell and taken up by the Glutamate Neuron and then turned into Glutamate again by the enzyme glutaminase.
Which Glutamate Receptor requires a cotransmitter and what is it?
NMDA requires it and the cotransmitter is Glycine (and sometimes D-Serine).
Glycine Metabolism (as it pertains to Glutamate)
Glycine is not made in Glutamate neurons, but rather mostly produced and secreted by glial cells. There are Glycine Neurons but these do not contribute significantly to Glutamate NMDA transmission because they have strong and fast reuptake pumps.
3 types of ionotropic Glutamate Receptors
AMPA, NMDA, and Kainate. AMPA and Kainate are fast excitatory receptors that let Na in and cause excitatory depolarization. NMDA is different
What 3 things are required for NMDA receptor to activate?
Glutamate binding, Glycine (or D-Serine) binding, Depolarization
NMDA receptor hypofunction hypothesis of schizophrenia
Glutamate activity at NMDA receptors is hypofunctional due to abnormalities in the formation of glutamatergic NMDA synapses during neurodevelopment.
NMDA hypothesis for Schizophrenia is supported by what?
When NMDA antagonists like PCP and Ketamine are given, they induce psychosis. PCP and Ketamine create not only positive sx but also cognitive, affective, and negative sx. Glutamate through downstream effects ends up regulating
Dopamine transmission in the Mesolimbic and Mesocortical Pathways. So this hypothesis can jive with the Dopamine Hypothesis.
NMDA receptors seem to be particularly involved in…
Long-term potentiation. “Strengthening a synapse”. This can cause long-term learning, synaptogenesis, and up regulating the number of AMPA receptors.
Maybe because critical synapses are not strengthened, they get pruned in adolescence and that is why you have onset at that time. Also explains why there is a progressive worsening course for Schizophrenia.
