Biology Reference
In-Depth Information
stress, whether it is acute or chronic, and whether the individual is perceived to have
any degree of control over it. The effects are also dependent on the tissue and partic-
ular cytokine under investigation. Acute psychological or physical stress produces an
increase in CD8 T lymphocytes and NK cells and a decrease in B lymphocytes, and
increases the stimulated production of TNF- and IL-6
[70,71]
. Individuals exposed
to chronic stress have fewer circulating B cells, T cells, and granulocytes, as well as
a reduced capacity for mitogen-induced lymphocyte proliferation and decreased NK
cell activity compared with controls
[72-74]
. However, there are some inconsisten-
cies. For example, patients with panic disorder or social phobia have increased NK
cell numbers, and the former group also has increased numbers of B lymphocytes
and human leukocyte antigen-D-related (HLA antigen-DR)-presenting cells. Subjects
who show clear signs of anxiety during an academic exam have significantly higher
IFN-, IL-1ra, and soluble interleukin-6 receptor (SIL-6r) levels in the serum com-
pared with those with low anxiety scores
[75]
. However, results from another study
demonstrated decreased IFN- production accompanied by increased IL-10 expres-
sion during exam stress
[76]
. Interestingly, treatment of neonatal male rats with
endotoxin, on postnatal days 3 and 5, can alter anxiety behavior in adulthood com-
pared with vehicle-treated controls. These observations underlie the importance of
early life exposure to immunological challenges in the development of emotional
behavior, and further suggest that neonatal infection may be an important predictor
of susceptibility to anxiety-related disorders in adulthood
[77]
.
12.4.1.1 Depression
One of the most consistent abnormalities in patients with major depression is dys-
regulation of the HPA axis
[78,79]
. Basal plasma cortisol or adrenocorticotropic hor-
mone (ACTH) concentrations tend to be normal or slightly increased. However, there
is a significant increase in 24-hour urinary cortisol excretion
[80]
and in CSF CRH
concentrations
[81]
. Elevated CSF CRH and plasma cortisol concentrations have
been reported in drug-free patients with major depression, compared with healthy
subjects or those with other psychiatric disorders, whereas these values were within
the normal range for depressed subjects treated with the antidepressant fluoxetine.
Postmortem studies have shown elevated CRH concentrations and CRH mRNA in
the hypothalamic paraventricular nucleus (PVN) of depressed patients. Impaired glu-
cocorticoid negative feedback control of the HPA axis exists in a significant propor-
tion of depressed subjects, as evidenced by nonsuppression of cortisol secretion after
dexamethasone administration
[82]
. A reduction in the number of glucocorticoid
receptors (GRs) in the CNS has also been noted in depressed patients.
Pro-inflammatory cytokines such as IL-1 and IL-6 are potent stimulators of CRH
synthesis and thus are activators of the HPA system. As CRH hypersecretion is
often present in major depression, it may be hypothesized that HPA dysfunction in
these patients may be a consequence of an increase in the release of these cytokines.
Conversely, in accordance with the bidirectional nature of CNS-immune system
interactions, the chronically increased CRH drive can itself influence the production
and action of central cytokines
[83]
.
