Increased
tryptophan hydroxylase in the dorsal raphe
nucleus of depressed suicide victims
Serotonin
(5-HT) neurotransmission is reduced in suicide
victims. The levels of the 5-HT metabolite,
5-hydroxyindoleacetic acid (5-HIAA), are
decreased in the cerebrospinal fluid of
depressed suicide attempters. The levels of 5-HT
and 5-HIAA in the brainstem, the cortical 5-HT
transporter and the 5-HT1A autoreceptor binding
capacity in the dorsal raphe nucleus (DRN) are
decreased in suicide victims. However a higher
density and number of DRN neurons was observed
in suicide victims compared to controls.
Tryptophan hydroxylase (TPH) is the
rate-limiting enzyme in the synthesis of 5-HT,
and alterations in TPH could be responsible for
these changes. It was therefore decided to study
serotonin synthesis, by measuring the amount of
TPH, in the DRN and median raphe nucleus (MRN)
of depressed suicides and controls.
Depressed suicide victims (n = 11) were matched
to psychiatrically normal controls (n = 11) for
age, sex, ethnicity, and postmortem interval.
Brainstem including DRN and MRN, was collected
at autopsy, frozen and sectioned (20 µm).
TPH enzyme was labeled using an antibody,
immunoautoradiography performed, slides exposed
to tritium-sensitive film, developed, and
densitometry of audiograms determined.
TPH immunoreactivity (TPH-IR) in the DRN was
13.7% higher in suicides in comparison with
controls, but there was no difference in TPH-IR
between suicides and controls in the MRN. In the
DRN, TPH-IR was 14.6% higher in male suicides
than in male controls, but no difference in
TPH-IR was observed in the MRN between male
suicides and male controls. TPH-IR density was
higher in the rostral and lower in the caudal
DRN in suicides compared to controls.
The higher amount of TPH found in the DRN in
suicide depressed victims compared to controls
is consistent with the increased number and
density of DRN serotonergic neurons in suicide.
A compensatory change in response to serotonin
hypofunction in depressed suicide victims could
be a possible explanation for this amplifying
5-HT activity. Boldrini
M, Underwood MD, Mann JJ, Arango V. More
tryptophan hydroxylase in the brainstem dorsal
raphe nucleus in depressed suicides. Brain Res
2005, 1041: 19-28.