Biology Reference
In-Depth Information
in schizophrenia. Concentrations were found to be increased and associated with
early age of onset and negative symptoms of the disease. Similarly, levels of IFN-
in blood from schizophrenics are dependent on the type of psychopathology present.
Patients having mainly positive symptoms (delusions, hallucinations, bizarre behav-
ior, and thought disorder) show evidence of increased levels of IFN-, whereas those
with negative symptoms (asocial behavior, withdrawal, flattened affect, impaired
attention, and apathy) exhibit a decrease in IFN- production
[147-149]
.
Elevated plasma concentrations of IL-6, which parallel the duration of the disease,
have also been noted
[150-152]
. More recently, Garver et al.
[153]
assessed differ-
ences in IL-6 concentrations in the CSF of two distinct subgroups of schizophrenic
patients (delayed responders and poor responders) during neuroleptic-free periods in
which their psychotic symptoms were present. These were subsequently compared
with the data from a group of normal subjects. Interleukin-6 concentrations in the
CSF were found to be significantly higher in the delayed responders compared with
the poor responders and the controls, thus indicating that immune activation is pres-
ent in patients suffering from a distinct subtype of schizophrenia. Furthermore, high
SIL-6r levels in the serum and CSF are correlated with paranoid-hallucinatory symp-
toms
[141]
. These studies indicate that abnormalities of the IL-6 system tend to be
associated with an unfavorable course of the disease, with respect to duration, treat-
ment resistance, or more marked paranoid-hallucinatory symptomatology. IL-6 is a
product of macrophage-monocyte activation and also of activation of the Th2 system
[154]
. Supporting the suggestion that this system is activated in schizophrenia are
observations that levels of other cytokines produced by these cells, such as IL-10
and IL-4, are also altered. For example, an increase in IL-10 concentrations related
to negative symptoms has been reported
[155,156]
. Additionally, an increase in CSF
IL-4 levels has been reported in juvenile schizophrenics
[157]
. Increased levels of
immunoglobulin E (IgE), a sign of an increased Th2 response, were found in schizo-
phrenic patients compared with controls
[158]
. Thus, it has been postulated that in
schizophrenia there is a reduction in activity of the Th1 (cellular immune) system
and an activation of the reciprocally linked Th2 (humoral immune) system
[159]
.
This shift is particularly evident in patients having predominantly negative symptoms
and/or a poor therapeutic outcome
[160]
. However, other investigators
[149]
have
concluded that the deficient production of Th1 cytokines in schizophrenia is not due
to either a change in the number of immunocompetent cells or to counter-regulation
of the Th2 cytokine IL-10. Studies concerning levels and/or production of IL-1 and
TNF- in patients with this disorder have so far been inconclusive.
In vivo
, the pro-inflammatory cytokines can significantly inhibit cortical neu-
ron dendritic development in a manner consistent with the neuropathology noted in
schizophrenia
[161]
. Furthermore, a study
[162]
examining the effect of peripheral
cytokine challenge on neurobehavioral development demonstrated that IL-1, IL-2,
IL-6, and IFN- all affect physical development. This is accompanied by behavioral
changes related to fear/anxiety levels and in sensorimotor gating at different stages
of development, suggesting that challenge with pro-inflammatory cytokines during
early postnatal development could give rise to future psychobehavioral and/or cogni-
tive impairments with various latencies.
