Chapter 36
Molecular Pathogenesis for Schizophrenia and Major Depression
Norbert Mueller and Markus J. Schwarz
Questions
1.
The NMDA hypothesis of schizophrenia refers to the following neurotransmitter disturbance:
a. mesolimbic hyperactivity of dopamine
b. tuberoinfundibular inhibition of prolactin release by dopamine
c. hypofunction of the glutamatergic cortico-striatal pathway
d. mesolimbic hyperactivity of glutamate
e. all of the above
2.
a.
b.
c.
d.
e.
3.
The proposed neurotransmitter imbalance in major depression is best characterized by:
a. increased serotonin, increased glutamate, reduced norepinephrine
b. increased serotonin, increased norepinephrine, reduced glutamat
c. increased glutamate, decreased serotonin, decreased norepinephrine
d. none of the above
4.
a.
b.
c.
d.
e.
5.
The so far only known endogenous NMDA receptor antagonist is:
glutamate
glycine
ketamine
kynurenic acid
quinolinic acid
The best replicated immune findings in schizophrenia are:
increased in vitro production of IL-2 and decreased serum levels of IL-6
decreased in vitro production of IL-2 and IFN-γ and decreased serum levels of IL-6
decreased in vitro production of IL-2 and IFN-γ and increased serum levels of IL-6
increased serum levels of IL-2 and IFN-γ and decreased in vitro production of IL-6
none of the above
The following immune response can be frequently detected in depressed patients:
an allergy-like Th2 predominance with increased levels of IgE in nearly all depressed patients
a decreased Th1 activation in melancholic patients and an increased Th1 activation in non-melancholic
depressed patients
c. an increased activation of the adaptive immune system in melancholic patients and an increased
activation of the specific immune system in non-melancholic patients
d. an increased Th1 activation in melancholic patients and a decreased Th1 activation in non-melancholic
depressed patients
a.
b.
6.
The most common psychiatric side effect of IFN-α administration is:
a. paranoid ideation
b. optical and – less frequent – acoustic hallucinations
c. manic episodes
d. depression
e. tics
7.
IFN-α administration induces the degradation of the amino acid:
a. choline
b. cysteine
c. serine
d. tryptophan
e. tyrosine
8.
The typical immunological effect of antidepressant drugs is:
a. induction of a more specific immune response
b. inhibition of B cell proliferation and antibody production
c. downregulation of Th1 cytokine production
d. downregulation of Th2 cytokine production
e. upregulation of Th1 cytokine production
36.
9.
Molecular Pathogenesis for Schizophrenia and Major Depression
Norbert Mueller and Markus J. Schwarz
2
The following enzymes of the kynurenine pathway are induced by pro-inflammatory cytokines such
as IFN-γ and TNF-α:
a. tryptophan 2,3 dioxygenase, indoleamine 2,3-dioxygenase, kynurenine monoxygenase
b. indoleamine 2,3-dioxygenase, kynurenine hydroxylase (monoxygenase), kynurenine aminotransferase
c. indoleamine 2,3-dioxygenase, kynurenine hydroxylase (monoxygenase)
d. tryptophan 2,3 dioxygenase, kynurenine hydroxylase (monoxygenase)
e. only indoleamine 2,3-dioxygenase
10. The limiting step in serotonin synthesis is in all probability:
a. tryptophan availability
b. serotonin availability in a negative feed back
c. tryptophan hydroxylase activity
d. a and c
e. b and c
11. Glucocorticoids:
a. induce central nervous production of pro-inflammatory mediators
b. inhibit central nervous production of pro-inflammatory mediators
c. induce glutamate signal at the NMDA receptor
d. inhibit glutamate signal at the NMDA receptor
e. a and c
f. b and d
g. b and c
12.
a.
b.
c.
d.
e.
Astrocytes are:
immunologically ‘silent’ glial cells
responsible for a Th1-like immune response within the CNS
part of the nerve sheath within the brain
responsible for a Th2-like immune response within the CNS
not involved in neurotransmitter re-uptake and metabolism
a.
b.
c.
d.
e.
f.
Proinflammatory cytokines:
stimulate the HPA axis
have no effect on the HPA axis
induce dendritic atrophy
none of the above
a and c
b and c
a.
b.
c.
d.
e.
Inhibition of cyclooxygenase isoforms has the following effects:
COX-1 inhibition increases the levels of kynurenic acid
COX-2 inhibition decreases the levels of kynurenic acid
COX-2 inhibition induces a Th1 shift under non-inflammatory conditions
all of the above
b and c
13.
14.
15. Administration of the COX-2 inhibitor celecoxib was shown to:
a. induce exacerbation of psychotic symptoms in schizophrenia
b. improve psychotic and especially cognitive in schizophrenia
c. be more efficient in chronic schizophrenia than in the early stages
d. enhance antidepressant therapy when added to a conventional antidepressant drug
e. a and c
f. b and d
36.
Molecular Pathogenesis for Schizophrenia and Major Depression
Norbert Mueller and Markus J. Schwarz
Answers
1.
c
2.
d
3.
c
4.
c
5.
b
6.
d
7.
d
8.
c
9.
c
10.
a
11.
e
12.
d
13.
e
14.
d
15.
f
3