Secondary Schizophrenia (137 page)

activity in salient brain regions. Copper might have
determine risk factors and disease correlates,
effects on primary firing of monoamine nuclei, such as
including neurological signs and hepatic status, in
ventral tegmental mesolimbic projections, or on corti-those developing psychosis
cal and other feedback acting on monoamine systems.

4. Determination of the correlates of specific
Copper might also affect neurotransmitter receptor
psychotic symptoms and functional decline

efficacy or may turn on or off genes amplifying post-5. Systematic evaluation and reporting of MRI
synaptic receptor effects through G protein coupling
structural imaging correlates in WD patients

or postreceptor effector signaling. Copper could also
presenting with WD psychotic features, specifying
affect enzymes involved in neurotransmitter degrada-precisely the psychotic feature under
tion. Copper may have effects on ligand and voltage
investigation, with close attention to:

gated ion channels, thus influencing neuronal mem-

brane potentials and modulating neuronal firing. Sin-a) The specific pattern of regional involvement in
gle cell studies and functional imaging may eluci-striatal and pontine copper deposition
date these or other mechanisms. Similarly, the phe-b) Involvement of specific corticostriatopallido-nomenon of antipsychotic-refractory psychotic fea-thalamocortical circuits
tures may represent copper deposition in target ventral
c) The pattern of midbrain copper deposition
striatum, or cuprous transection of corticostriatopallid) The pattern of cerebral cortical, subcortical,
343

dothalamocortical circuits, preventing antipsychotics
temporo-limbic, brainstem, and cerebellar
Organic Syndromes of Schizophrenia – Section 3

copper deposition, with special attention to
7. Studies of variables of treatment outcome would
structures that have been implicated in

be informative, including:

functional and structural imaging studies
[68,

a) Controlled studies of antipsychotic treatment
69],
including:
in WD psychosis

(1) Middle prefrontal gyrus (especially

b) The role of clozapine (and other

Brodmann areas 6 and 8), inferior

antipsychotics) in treating psychosis in

prefrontal gyrus (especially area 44), and
WD in terms of safety in regard to seizures,
dorso-medial thalamus, implicated in

bone marrow suppression, and cognition vs.

schizophrenia

safety in the context of extrapyramidal

(2) Broca’s area, implicated in hallucinating
disorders

patients with schizophrenia

c) Risk factors for NMS and other EPS

(3) Anterior thalamic nuclei, implicated in
developing with antipsychotic use in WD

psychosis

d) Copper deposition correlates of:

(4) Hippocampus, and medio-temporal and

(1) Anticopper therapy-induced psychosis

frontal cortices, implicated in negative

(2) Anticopper therapy-responsive psychosis
symptoms

(3) Antipsychotic-refractory psychosis

6. Similar investigations with functional magnetic
(4) Novel psychotropic-responsive psychosis
resonance (fMR), single photon emission

(5) Antimuscarinic-refractory and dopamine
computed tomography (SPECT), and PET, with
agonist-refractory EPS in WD

close attention to particular structures and
(6) ECT safety and efficacy

systems implicated in schizophrenia and

WD represents a prototypic neuropsychiatric disorder.

psychosis
[68, 69, 70],
including:
The prevalence and correlates of psychosis still remain
a) Glucose metabolism and cerebral blood flow
to be defined despite more than a century of expe-correlates of WD psychosis
rience with this disease. Understanding psychosis in
b) Presynaptic release and receptor binding
WD not only promises to improve our treatment of
studies of dopamine, glutamate, GABA,

patients with this disease, but also carries the potential
norepinephrine, and serotonin in WD

to expand our understanding of psychosis in general,
psychosis

and schizophrenia in particular.

344

Chapter 27 – Wilson’s Disease

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