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228

Section 3

Organic syndromes of schizophrenia: other neurological disorders

Dennis Velakoulis and Mark Walterfang

Facts box

genes, except for Complex II, which is entirely encoded
r

in the cell nucleus. These complexes participate in a
A primary mitochondrial function is that of

chain of metabolic processes, the overall process being
cellular energy metabolism through the

referred to as oxidative phosphorylation (OXPHOS),
respiratory chain.

which result in the production of ATP. ATP is used
r
Four important concepts in relation to

in the vast majority of cellular metabolic processes as
mitochondrial genetics are those of maternal
an energy source and must be transported out of the
inheritance, heteroplasmy/homoplasmy,

mitochondrion by adenine nucleotide translocator.

mitotic segregation, and the role of

The respiratory chain responds to the energy needs
autosomal genes that code for mitochondrial

of cells, which in some cases may be quite stable,
products.

whereas in others, for example, in the muscle, they
r
More than 100 disease-associated point

may vary dramatically over time. Other functions of
mutations of mitochondrial DNA have been

the mitochondria include cellular homeostasis, fatty
identified.

acid oxidation, the urea cycle, intracellular signaling,
r
Several lines of investigation point to

apoptosis, and the metabolism of amino acids, lipids,
potential mitochondrial involvement in

cholesterol, steroids, and nucleotides
[1, 2].

patients with schizophrenia.

r
The association of mitochondrial disorders
Mitochondrial genetics

with schizophrenia-like psychosis (SLP)

Four important concepts are those of maternal inher-relies on case reports. SLP has been
itance, heteroplasmy/homoplasmy, mitotic segrega-described in some cases. In others, psychosis
tion, and the role of autosomal genes that code for
occurs in the setting of delirium or dementia.

mitochondrial products.

A family history of schizophrenia has been

described in some cases.

Maternal inheritance

r
High rates of psychosis have been described
It is widely but not absolutely accepted that mito-in Wolfram Disease, an autosomal recessive
chondria are inherited through the maternal line. A
disorder with a mutation on chromosome 4.

mother will pass her mitochondria on to all her chil-r
In mitochondrial disorders, psychosis occurs
dren, but only her daughters will pass on their mito-in the setting of a wide range of medical
chondria
[3].
This is considered a consequence of the
comorbidities.

large imbalance between the number of mitochondria
in the female oocoyte (100,000) compared to the few
mitochondria in the male sperm. Furthermore, it is
Mitochondrial functions

now known that male mitochondria are destroyed in
the zygote as if they were a foreign antigen
[1, 4].

A primary mitochondrial function is that of cellular
energy metabolism through the respiratory chain, the
final common pathway for adenosine triphosphate
Heteroplasmy/homoplasmy

(ATP) production. The mitochondrial/respiratory
Mitochondrial DNA is identical (homoplasmic)
chain is a group of five enzyme complexes made up of
within the cells of any one individual at birth. Mito-

229

polypeptides encoded by nuclear and mitochondrial
chondrial DNA is not protected by repair mechanisms
Organic Syndromes of Schizophrenia – Section 3

or histones and mutation rates are ten times greater
3 Mitochondrial respiratory chain disorders will
than for nuclear DNA. Mutations may either be point
most affect tissues with high metabolic needs, for
mutations, which are usually maternally inherited,
example, muscle, central and peripheral nervous
or sporadic partial deletions or duplications
[5].
The
system, heart, endocrine, and eye.

occurrence of a mitochondrial DNA mutation may
4 The clinical expression of mitochondrial disorders
lead to a mixture of normal and mutated mitochon-may vary widely from individual to individual
drial DNA within the one cell (heteroplasmic cell).

with the same mutation depending on the

The proportion of mutated and normal mitochondrial
proportion of mitochondria affected in different
DNA can vary from cell to cell, including maternal
tissues and the interaction of that individual with
oocytes. As a result, children of the same mother may
the environment and the differential metabolic
inherit very different mitochondrial DNA. Further
energy needs of different tissues within the one
adding to the complexity of mitochondrial disorders
individual.

caused by mutations, it is known that a threshold of
mutant DNA is required within a cell before oxidative
Clinical consequences of mitochondrial

dysfunction will occur. This threshold will be determined by cell type, the cells’ oxidative needs, and the
disorders