Increased
serum levels of substance P in depressed
patients
In
the brain, the neurokinin (NK) peptide,
substance P (SP), is co-localized with serotonin
and noradrenaline, both of which are involved in
the pathophysiology of depression. Animal
studies have shown a decrease in SP content in
certain brain regions after chronic
antidepressant treatment and an increased
serotonergic transmission following blockade of
NK1 receptors. Clinically, the NK1 receptor
antagonist, MK-869, has been shown to have
antidepressant activity. Although a second
study did not replicate this. Measurement of SP
levels in cerebro-spinal fluid of depressed
patients and control subjects are equivocal, and
data on the density of NK1 receptors postmortem
are rare. To further investigate the possible
link between SP and depression, a recent study
measured serum SP levels in depressed patients
before and after antidepressant treatments.
Twenty-three patients diagnosed with major
depression and thirty three healthy control
subjects were enrolled in the study. The SP
serum levels were measured, using an enzyme
immunoassay, in patients at baseline (before
treatment) and after 2 and 4 weeks of
antidepressant therapy (mirtazapine, paroxetine
or nonselective classical antidepressants in
combination with either lithium or
benzodiazepines). SP levels in controls were
determined at baseline and after 4 weeks.
In healthy control subjects, the SP serum levels
were relatively constant over the 4 weeks of the
study. SP levels in drug-free, depressed
patients were significantly higher than in
controls. There was no change in mean SP levels
between baseline and 4-week treatment with
antidepressants. When individual SP levels were
considered, however, 37% of them were decreased
by 15% to 50%, a change which correlated with
the reduction of depression severity.
The fact that serum SP levels are enhanced in
some patients with major depression suggests
that their central neuropeptides may also be
altered and that these subjects might belong to
a subgroup. Although preliminary, these findings
may contribute to better understand the role of
neuropeptides in depression and lead to the
development of new antidepressants. Biol
Psychiatry 53: 538-542, 2003