Chapter 4 (Schizophrenia)

Question 1

Theorized brain location correlated with the positive sx of Schizophrenia

Answer 1

Mesolimbic area–specifically the Nucleus Accumbens

Question 2

Theorized brain location correlated with the negative and affective sx of Schizophrenia

Answer 2

Mesocortical and ventromedial prefrontal cortex

Question 3

Theorized brain location correlated with the cognitive sx of Schizophrenia

Answer 3

Dorsolateral prefrontal cortex

Question 4

Theorized brain location correlated with the aggressive/impulsive sx of Schizophrenia

Answer 4

Orbitofrontal cortex and its connections to amygdala

Question 5

Dopamine is synthesize from which amino acid?

Answer 5

Tyrosine

Question 6

Enzymes that turn Tyrosine into Dopamine

Answer 6

Tyrosine hydroxylase (rate limiting step ) and then by the enzyme DOPA decarboxylase

Question 7

How Dopamine synaptic action is terminated

Answer 7

1. Reuptake by DAT
2. 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.
3. Outside of the neuron, Dopamine is broken down by COMT

Question 8

Types of Clinical DA receptors

Answer 8

D1, D2, D3, D4, and D5 are all blocked by various antipsychotics. But only D2 and D5 are understood

Question 9

How many dopaminergic pathways are there in the brain?

Answer 9

5

Question 10

Mesolimbic DA Pathway

Answer 10

Projects from Midbrain Ventral Tegmental Area to the Nucleus Accumbens. Control euphoria and delusions/hallucinations, etc.

Question 11

Mesocortical DA Pathway

Answer 11

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)

Question 12

Nigrostriatal DA Pathway

Answer 12

Projects from Substantia Nigra to the Striatum. Movement and Extrapyramidal Nervous System.

Question 13

Tuberoinfundibular DA Pathway

Answer 13

Projects from Hypothalamus to the Anterior Pituitary and controls Prolactin Secretion

Question 14

5th DA Pathway

Answer 14

Projects from all over to the Thalamus. Not well understood.

Question 15

Glutamate Metabolism

Answer 15

1. It is an AA. It is released by Glutamate Neurons in the synapse
2. Then it is taken up by Glial Cells and broken down into Glutamine
3. Glutamine is released by the Glial Cell and taken up by the Glutamate Neuron and then turned into Glutamate again by the enzyme glutaminase.

Question 16

Which Glutamate Receptor requires a cotransmitter and what is it?

Answer 16

NMDA requires it and the cotransmitter is Glycine (and sometimes D-Serine).

Question 17

Glycine Metabolism (as it pertains to Glutamate)

Answer 17

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.

Question 18

3 types of ionotropic Glutamate Receptors

Answer 18

AMPA, NMDA, and Kainate. AMPA and Kainate are fast excitatory receptors that let Na in and cause excitatory depolarization. NMDA is different

Question 19

What 3 things are required for NMDA receptor to activate?

Answer 19

Glutamate binding, Glycine (or D-Serine) binding, Depolarization

Question 20

NMDA receptor hypofunction hypothesis of schizophrenia

Answer 20

Glutamate activity at NMDA receptors is hypofunctional due to abnormalities in the formation of glutamatergic NMDA synapses during neurodevelopment.

Question 21

NMDA hypothesis for Schizophrenia is supported by what?

Answer 21

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.

Question 22

NMDA receptors seem to be particularly involved in…

Answer 22

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.