Biology Reference
In-Depth Information
and alleviate depressive symptoms. It may also be beneficial to attempt the opposite
approach: namely, to develop compounds that increase the production of the anti-
inflammatory cytokines.
12.4.1.3 Schizophrenia
Schizophrenia comprises several disease entities, some of which are as yet unde-
fined. However, there is a substantial degree of heterogeneity among them, which
indicates the existence of overlapping etiological factors. The disorder manifests
itself in the form of abnormal mental function and disturbed behavior. These fea-
tures usually appear in the second or third decades of life, as a heterologous group
of clinical symptoms. Positive symptoms include psychotic symptoms such as delu-
sions, hallucinations, and thought disorganization. Negative symptoms include loss
of motivation and flattening of affect. Disturbances in basic cognitive functions such
as attention, executive function, and specific forms of memory are also consistently
noted, and are now thought to be central to the behavioral disturbance and functional
disability that occur in this illness. Additionally, a number of patients have concomi-
tant mood symptoms, including depression and anxiety, which may contribute to the
relatively high (10%) lifetime incidence of suicide in schizophrenics.
Early work on the possible association between schizophrenia and autoimmune dis-
orders
[127-130]
lost favor to the more widely accepted dopamine hypothesis of schizo-
phrenia
[131]
. Subsequently, an attempt was made to integrate the two, working with the
suggestion that the disorder might result from dopamine receptor-stimulating autoanti-
bodies
[132]
. Several inadequacies of the dopamine hypothesis have now become evi-
dent; for example, the facts that the negative symptoms are not ameliorated by classical
(“typical”) neuroleptics and that some groups of patients remain treatment resistant.
Alterations in immune system function have long been known to exist in this dis-
order, and signs of inflammatory disease processes have been observed in treatment-
resistant schizophrenic patients
[133]
. In this group, paranoid or negative symptoms
[134,135]
, disease acuity
[136,137]
, and drug treatment
[138-141]
were found to
influence immunological parameters. Furthermore, infection during pregnancy in
mothers whose offspring subsequently develop schizophrenia has been postulated
to explain the observation that a statistically significant proportion of schizophrenic
patients have birth dates between December and May (seasonality of birth). Exposure
to viral or bacterial infection of the CNS in childhood leads to a fivefold increase in
the risk of developing schizophrenia in later life.
The suggestion that IL-2 plays a role is supported by the observation that 65% of
nonschizophrenic subjects treated with IL-2 exhibited symptoms such as delusions,
severe cognitive impairment, and some degree of affective change
[142]
. However,
in vitro
lymphocytes from schizophrenic subjects show a reduction in mitogen-
stimulated IL-2 production
[143,144]
, which appears to correlate inversely with the
negative symptoms and to be associated with a lower age of disease onset
[145]
.
The decreased production of IL-2
in vitro
could reflect the
increased
production of
IL-2
[146]
. However, it might also be the consequence of a reduced capacity of lym-
phocytes to produce IL-2. The soluble IL-2 receptor (SIL-2r) has also been studied
