Secondary Schizophrenia (98 page)

hallucinations,

of corpus callosum

deeply pigmented,

anhedonia, self

with primitive

neglect, disinhibition;

reflexes, bilateral

treatment-resistant

extensor plantars,

disinhibition, and

dementia

20

Angus
et al.

Personality changes,

None

Adrenal

CT: normal; MRI:

Developed

[

alcohol abuse,

insufficiency

symmetrical diffuse

tonic-clonic seizures

xlink:href="c-

self-mutilation, and

increase in T1 and T2

at age 25; by age 26,

12345-

suicide attempts.

signal around

demented, mild

bib100">100]

Diagnosis: bipolar

temporal and

spastic paraparesis,

affective disorder

occipital horns of

gait ataxia, peripheral

lateral ventricles

neuropathy;

functionally totally

dependent; death 10

months after onset of

seizures

33

Sobue
et al.

Mania: irritability,

Fatigability,

ACTH level

MRI: minor

At age 31,

[

aggression, increased

anorexia,

markedly elevated;

periventricular

intellectually normal;

xlink:href="c-

spending,

hyperreflexia,

significant adrenal

T2-weighted signals

age 33, progressive

12345-

restlessness; verbal

bilateral

insufficiency;

cognitive impairment

bib101">101]

outbursts,

extensor

hyperpigmentation

(monozygotic disinhibition

plantars

twins)

32

Sobue
et al.

Anxiety, somatic

None at

ACTH level mildly

MRI: extensive T2

Initially trained as a

[

preoccupation;

presentation

elevated

high intensity signal

dentist; by age 36,

xlink:href="c-

quick-tempered,

in occipital, parietal

IQ
=
65; developed

12345-

grandiose, profligate,

and temporal areas;

spastic ataxic gait,

bib101">101]

belligerent, followed

also involvement of

urinary incontinence,

(monozygotic by depression

hippocampus and

horizontal

twins)

Diagnosis: bipolar

cerebellum

nystagmus,

affective disorder

dysarthria,

hyperreflexia, bilateral

extensor plantars, and

loss of vibration and

proprioception in

both legs

30

Garside
et al.

Extensive history

Wide-based,

ACTH level

CT and MRI revealed

Cognitive decline;

[

predating neurologic

spastic ataxic

markedly elevated;

extensive WMD

mute, wheelchair

xlink:href="c-

symptoms including

gait, right/left

abnormal ACTH

involving left and

bound; death two

12345-

substance abuse,

confusion,

stimulation test

right centrum

years later from sepsis

bib107">107]

psychosis with

apraxia,

semiovale, corona

paranoid delusions,

aphasia,

radiata, and parietal

aggression,

hyperreflexia,

regions; pinpoint

perseveration,

bilateral

signal abnormality in

marked disinhibition,

extensor

basal ganglia and

distractibility

plantars,

pons bilaterally

primitive

reflexes, urinary

incontinence,

peripheral

neuropathy

Chapter 18 – Psychosis associated with leukodystrophies

Table 18.1
(cont.)

Age of

Psychiatric

Neurologic

Adrenal

onset

Reference

findings

findings

involvement

Neuroimaging

Course of illness

32

Gothelf
et al.

Age 32: first

Age 25: EEG –

Addison’s Disease

Age 25 and 30: MRI

Gradual impairment

[

presentation with

diffuse slowing; age 11

normal. Age 32: MRI:

of memory. Died 9

xlink:href="c-

acute onset, markedly gait

asymmetric

months after

12345-

disorganized

disturbance

periventricular WMD

psychiatric

bib109">109]

behavior, “manic

involving pons

presentation:

psychotic” episodes,

complications of

poor social judgment

bulbar palsy

13

Kopala
et al.

Age 13: bizarre,

Normal

None

MRI: extensive WMD

Not included

[

disorganized

of frontal lobes; minor

xlink:href="c-

behavior; eating

involvement of

12345-

chalk, setting fires,

corpus callosum

bib108">108]

aggression, silly,

giddy, auditory

hallucinations

25

Sakakibara

Age 25: emotional

At

Low cortisol

Age 34: MRI T2

Age 38: wheelchair

et al.
[

lability

presentation:

response to ACTH

weighted images

bound. Age 41: died

xlink:href="c-

spastic

stimulation

showed small lesions

of respiratory

12345-

paraparesis;

in internal capsule

infection

bib111">111]

erectile

bilaterally

dysfunction;

peripheral

neuropathy

37

Luda
et al.

Age 32: hypomanic,

Age 37: lower

Hypoadrenalism

MRI: diffuse WMD of

Age 32–38:

[

character change.

limb spasticity,

centrum semiovale

progressive memory

xlink:href="c-

Age 38:

bilateral

and corpus collosum

disturbance,

12345-

circumstantial; poor

Babinski,

constructional

bib110">110]

insight, perseveration, incontinence,
apraxia. Age 40: died

impulsivity

sensory-motor

of sepsis

neuropathy

Abbreviations: ACTH
=
corticotropin, WM
=
white matter, WMD
=
white matter disease.

Mitochondrial disorders

to the psychiatric manifestations of the disorders. We
Mitchochondria are considered the “power-plants” of
assessed and treated 23 patients who presented with
the cell, and generate the majority of cellular energy
primary psychiatric symptomatology, and who were
through a process known as oxidative phosphoryla-eventually found to have a mitochondrial disorder
tion (OXPHOS)
[123].
Impairment of OXPHOS leads
[128],
suggesting that this is an under-recognized fea-to the formation of reaction oxygen species that cause
ture of mitochondrial disease. We found an additional
lipid peroxidation and oxidative damage to the cell.

38 cases in the literature
[129, 130, 131, 132, 133, 134,

Oligodendrocytes and axons are particularly vulnera-

135, 136, 137, 138]
which, combined with our series
ble to oxidative stress, resulting in significant pathol-of 23 patients, gives a total of 61 cases. Psychosis was
ogy in white matter
[124, 125]
– hence, the designation
a very commonly reported symptom, being present in
of inherited mitochondrial disorders as leukodystro-more than 50% of cases, and patients were often ini-phies
[126].
A recent study found that 90% of patients
tially diagnosed with schizophrenia. In the majority of
with mitochondrial disorders had wide-spread white
cases in which psychosis was reported, positive symp-matter hyperintensities, making this the most frequent
toms were described but there was little mention of
abnormality
[127].

negative symptoms. The majority of cases were associ-Despite the recognition that mitochondrial disor-ated with MELAS, particularly the A3243G mutation.

ders frequently affect the brain and produce white
It is likely that the leukodystrophy associated with
247

matter abnormalities, there has been little attention
mitochondrial disorders plays an important role in
Organic Syndromes of Schizophrenia – Section 3

the development of psychosis and other psychiatric
less severe course often characterized by intellectual
symptoms. This may occur through disruption of
decline, dementia, and spasticity
[142].
Peripheral ner-important pathways that connect different parts of the
vous system involvement is less common in late-onset
brain involved in the control of emotion, thought, and
disease, and patients are often clinically heterogeneous
behavior. In addition, the brain is especially energy-

[143].
Although adult-onset forms have been identi-dependent, and any compromise in ATP produc-fied, there are no reports of psychosis or other psychi-tion may lower the threshold and reduce the safety
atric symptoms in these patients. However, given its
margin for the development of psychiatric illness.

clinical and pathological similarity to more common
Finally, patients with mitochondrial disorders fre-leukodystrophies such as MLD and the involvement
quently experience chronic fatigue and cognitive dys-of CNS white matter in the late-onset form, it is most
function that may ultimately lead to an axis II or per-likely that psychosis can occur but may be unrecog-haps axis I disorder.

nized. Treatment involves bone marrow or umbilical
Currently, there is no curative treatment for mito-cord blood transplantation to restore galactocerebrosi-chondrial disorders. Although clear evidence from
dase levels
[145, 146].

randomized trials is lacking, supportive treatment
with supplements, including creatine and co-enzyme
Q10, is often initiated
[139].

Pelizaeus-Merzbacher Disease

The reader is referred to the Chapter 17 by Velak-Pelizaeus-Merzbacher Disease (PMD) is a rare X-oulis and Walterfang, in which mitochondrial disor-linked recessive dysmyelinating disorder caused by
ders are discussed more fully.

mutations in the proteolipid (PLP) gene
[147].
PLP is
a major constituent of myelin in the CNS, and affected
Krabbe’s Disease

patients demonstrate a classic “tigroid” appearance of
white matter with areas of total loss of myelin inter-Krabbe’s Disease, also known as globoid cell leukodys-spersed with areas of relative preservation. The fre-trophy, is an autosomal recessive disorder caused
quency of PMD is unknown but is estimated to be
by a deficiency in the lysosomal enzyme galacto-at least 1 in 500,000 in the United States. Diagno-sylceramidase. This deficiency impairs degradation of
sis is often suggested by diffuse white-matter abnor-galactolipids, including psychosine and galatosylce-malities on MRI indicating hypomyelination and
ramide, which accumulate in central and peripheral
confirmed by molecular analysis of the PLP gene.