Secondary Schizophrenia (110 page)

tia. More recent data demonstrates that antipsychotic
A choice of less potent antipsychotics, such as the phe-medication has substantially altered this outlook. Of
nothiazine groups of compounds, lessens the risk of
10 psychotic patients followed for approximately 6

EPS, but anticholinergic difficulties are more promi-years, the median duration of their first psychotic
nent, which may aggravate other difficulties such as
episode was 5 weeks (range 1–72 weeks). Six (60%)
bladder and bowel control and impaired vision. The
of the patients did not experience another psychotic
associated dry mouth may add to dysarthric difficul-episode, three patients had one further relapse, and a
ties. All antipsychotic medication, irrespective of class,
single patient had multiple recurrences. Overall, the
can produce excessive sedation, which may similarly
psychosis remitted in 90% of cases, with a chronic,
affect already impaired coordination and balance.

paranoid psychosis ensuing in a single patient. In gen-Newer atypical antipsychotic drugs offer fewer side
eral, patients did not require long-term oral or depot
effects. Furmaga and colleagues
[20]
have reported
antipsychotic use. If a relapse occurred, short-term
that risperidone was helpful in 10 patients with a het-antipsychotic medication was reintroduced and subse-erogenous mix of medical conditions who became
quently discontinued after improvement in the mental
psychotic and who had not previously responded
state
[6].

to a conventional antipsychotic drug. Olanzapine, a
thiobenzodiazepine, has less EPS than risperidone,
although weight gain and sedation can be problem-

Summary

atic, the latter magnified in a disease where fatigue
Psychosis data have been presented in relation to
is ubiquitous. It also has the advantage of a conve-demyelination, in particular, multiple sclerosis. The
nient once–a-day dose (recommended dose of 10 mg
fact that psychosis occurs more often than by chance
per day) that can be started immediately. Similarly,
challenges prevailing theories of psychosis as a mainly
Seroquel (quetiapine fumarate), a psychotropic agent
cortical phenomenon. Defining the neuroanatomy of
belonging to a chemical class, the dibenzothiazepine
the human cerebral white-matter tracts and assign-derivatives, potentially offers the same benefits, albeit
ing functional relevance to each offers the prospect of
in a slightly less-friendly dosing schedule. Adverse side
novel insights into a complex pathogenesis
[22].

277

Organic Syndromes of Schizophrenia – Section 3

References

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278

Section 3

Organic syndromes of schizophrenia: systemic disorders

Alan S. Brown and Ezra S. Susser

Facts box

exposure to infection is a known cause of many con-r
genital central nervous system (CNS) anomalies, it has
Accumulating evidence supports prenatal

been hypothesized that in utero exposure to infection
infections as potential risk factors for

is a risk factor for schizophrenia.

schizophrenia.

r
Early evidence consisted of proxy measures
Early clues

of in utero infection such as epidemics in

populations.

In the earliest work in this area, investigators assessed
r

proxy measures of in utero infection. Season of birth,
Using documentation of infection based on

which covaries with fluctuations in the incidence of
maternal serologic measures, investigators

many infections, especially influenza and other res-have confirmed previous associations and
piratory pathogens, has been examined in relation
extended the range of infections examined.

r

to risk of schizophrenia. These studies have demon-Prenatal infections associated with
strated a 5% to 15% excess risk of schizophrenia for
schizophrenia in offspring include influenza,
births during January and March
[1].
Urban birth has
toxoplasmosis, rubella, and maternal/genital
also been associated with a greater risk of schizophre-reproductive infections. Elevated prenatal
nia
[2, 3]
. Although there are several potential expla-cytokines have also been related to an
nations for this finding, one compelling interpreta-increased risk of schizophrenia.

r

tion is that increased crowding present in urban areas
Studies have also revealed associations

enhances the likelihood of transmission of pathogenic
between seroprevalence of toxoplasmosis and
microbes. Both season of birth and urbanicity of birth
schizophrenia in adult patients, although the
contribute significantly to the population attributable
direction of cause and effect is inconclusive
risk for development of schizophrenia
[2, 3].

given that most of these studies are

cross-sectional in design.

r

Ecologic studies

Future studies are warranted to replicate

these findings, identify susceptibility genes
Following on these initial clues, a series of inves-that may interact with these infections, and
tigations were conducted on the relationship
identify pathogenic mechanisms by which

between influenza epidemics in large populations and
these agents might increase the risk of

schizophrenia among those who were in utero at the
schizophrenia.

time of the epidemics. The initial studies focused on
the 1957 type A2 influenza epidemic, and additional
studies examined influenza epidemics over periods of

In this chapter, we review accumulating evidence
year but is generally believed to be from 15% to 30%.

that supports prenatal infection in the etiology of
Although several studies yielded positive associations
schizophrenia. There is a considerable amount of
between influenza epidemics and schizophrenia
data from diverse fields of inquiry that schizophrenia
among individuals who would have been in utero
results in part from a disruption in neurodevelopment.

during the second trimester, there have been a number
Given that many, if not most, of the critical neurode-of failures to replicate these results
[4]
. These discrep-

279

velopmental events occur during fetal life, and in utero
ancies may be due in large part to misclassification of
Organic Syndromes of Schizophrenia – Section 3

Table 22.1
Summary table of research findings in prenatal infections and schizophrenia
Citation

Prenatal risk factor

Cohort/sample

Findings
∗

Brown et al., 2000 [26]

Rubella

RBDEP

RR
=
5.2, 95% CI
=
1.9–14.3, p < .001

Brown et al., 2001 [27]

RBDEP

20.4% prevalence of schizophrenia

Brown et al., 2000 [56]

Maternal exposure to respiratory

CHDS/PDS

RR
=
2.1, 95% CI
=
1.1–4.4, p
=
.04

infections, second trimester

Brown et al., 2004 [13]

Maternal influenza exposure, first

CHDS/PDS

OR
=
3.0, 95% CI
=
0.98–10.1, p
=
.05

half pregnancy

Brown et al., 2005 [18]

Elevated maternal toxoplasma IgG

CHDS/PDS

OR
=
2.6, 95% CI
=
1.0–4.8, p
=
.05,
Mortensen et al., 2007 [19]

antibody titre (1:128–1:1024)

OR
=
1.8, 95% CI
=
1.0–3.2, p
=
.05

Elevated neonatal toxoplasma IgG

antibody titre (>75th percentile)