Cholesterol and apolipoprotein E in suicidal behavior

Introduction: Low cholesterol has repeatedly been associated with an increased risk of suicidal and violent behavior. The increase in risk is believed to be associated with alterations in serotonergic signaling, which is associated with low cholesterol. Apolipoprotein E is an important factor in cholesterol metabolism, especially in the CNS, where it is involved in uptake, redistribution, and excretion of cholesterol. There are only a few studies dealing with apolipoprotein E in relation to suicide and suicidal behavior.

Aim: The overall aim of this thesis was to study a possible relationship between cholesterol, apolipoprotein E, and serotonin with respect to suicidal and violent behavior in patients with a recent suicide attempt.

Methods: This thesis is based on two clinical studies on patients having made a recent suicide attempt, all recruited at the Karolinska University Hospital. The suicide attempters (N = 181) were diagnosed and evaluated using a number of clinical rating scales measuring suicide intent, interpersonal violence, and depression severity. Samples of blood and cerebrospinal fluid were acquired for the analysis of biomarkers, primarily the serotonergic metabolite 5-HIAA, total serum cholesterol, and ApoE in both plasma and CSF.

Results: Total serum cholesterol was associated with the serotonergic metabolite CSF 5-HIAA. Low serum total cholesterol was found to be associated with the effect of exposure to violence as a child with respect to the risk of violent behavior as an adult. Plasma apolipoprotein E was found to be associated with the number of previous suicide attempts and repeater status, while CSF apolipoprotein E was associated with seriousness of the suicide attempt as measured by reversibility of the method of the current suicide attempt.

Conclusions: Our findings further indicate associations between cholesterol, factors involved in cholesterol metabolism, the serotonergic system, and suicidal and violent behavior. Total serum cholesterol appears to correlate with CSF 5-HIAA in suicide attempters, low total serum cholesterol may be a factor in the “Cycle of Violence” and ApoE may be related to the seriousness of the suicidal behavior.

List of scientific papers

I. Asellus P, Nordström P, Jokinen J. Cholesterol and CSF 5-HIAA in attempted suicide. Journal of Affective Disorders. 2010;125(1-3):388-92.
https://doi.org/10.1016/j.jad.2010.02.111

II. Asellus P, Nordström P, Nordström AL, Jokinen J. Cholesterol and the “Cycle of Violence” in attempted suicide. Psychiatry Research. 2014;215(3):646-50.
https://doi.org/10.1016/j.psychres.2014.01.009

III. Asellus P, Nordström P, Nordström AL, Jokinen J. Plasma apolipoprotein E and severity of suicidal behavior. Journal of Affective Disorders. 2016;190:137-42.
https://doi.org/10.1016/j.jad.2015.09.024

IV. Asellus P, Nordström P, Nordström AL, Jokinen J. CSF apolipoprotein E in attempted suicide. [Manuscript]