Teenage suicide is a major public health concern. Although there is
some understanding of the psychosocial factors associated with teenage suicide,
little is known about the neurobiologic factors of teenage suicide. Protein
kinase C (PKC) is a critical phosphorylating enzyme in the phosphoinositide
signaling pathway (which is involved in many physiologic functions in the
brain and has been implicated in the pathogenesis of mood disorders) and is
also a target for the therapeutic action of mood-stabilizing drugs.
To examine whether the pathogenesis of teenage suicide is associated
with changes in PKC.
Postmortem brain study.
Seventeen teenage suicide victims and 17 nonpsychiatric control subjects.
Main Outcome Measures
Catalytic activity of PKC and protein and messenger RNA levels of various
PKC isozymes, such as PKC α, β, and γ, were determined in
the prefrontal cortex and hippocampus of both groups.
Protein kinase C activity was statistically significantly decreased
in membrane and cytosol fractions of the prefrontal cortex and hippocampus
of teenage suicide victims compared with control subjects. Statistically significant
decreases in protein levels of PKC α, βI, βII, and γ
isozymes were also observed in both of these fractions. These decreases were
associated with decreases in levels of their respective messenger RNAs.
Because many physiologic functions are mediated through phosphorylation
by PKC and because PKC is a target for the therapeutic action of psychoactive
drugs, our findings indicate that the pathogenesis of teenage suicide may
be associated with abnormalities in PKC and that PKC may be a target for therapeutic
intervention in patients with suicidal behavior.