Academic journal article Current Psychiatry

Cholesterol, Mood, and Vascular Health: Untangling the Relationship: Does Low Cholesterol Predispose to Depression and Suicide, or Vice Versa?

Academic journal article Current Psychiatry

Cholesterol, Mood, and Vascular Health: Untangling the Relationship: Does Low Cholesterol Predispose to Depression and Suicide, or Vice Versa?

Article excerpt

A growing body of literature examining the putative links among cholesterol, mood disorders, and suicide has produced inconsistent findings and unclear clinical implications that may leave psychiatrists unsure of how to interpret the data. Understanding cholesterol's role in mood disorders may be relevant to the 2 primary causes of excess deaths in patients with mood disorders: suicide and vascular disease. (1)


Plausible links

In the early 1990s several studies suggested a link between low cholesterol (<160 mg/dL) and unnatural deaths, including suicide. (2-4) Follow-up studies confirmed associations between low cholesterol and suicide attempts, especially violent ones. (5) These associations are compelling given the neurobiologic effects of cholesterol, such as a net reduction of serotonergic function (Box 1, page 18). Low cholesterol may predispose an individual to aggression, impulsivity, and violence (Table 1, page 19). (6) Many studies have found that patients with mood disorders have lower cholesterol levels; (7) however, other research suggests they are at increased risk of hyperlipidemia, typically hypertriglyceridemia rather than hypercholesterolemia. (8)

Table 1

Psychiatric features associated with low cholesterol *


Anxiety, depressed mood, emotional lability, euphoria, impulsivity, irritability, suicidal ideation, aggression


Anorexia nervosa, bipolar disorder, borderline personality disorder, major depressive disorder, seasonal affective disorder


Suicide and suicide attempts, violence

* Small studies have suggested possible relationships with dissociative and panic disorders

Box 1

Neurobiologic implications of low cholesterol

The neurobiologic effects of low cholesterol--particularly those related to serotonergic hypofunction--are thought to be mediate impulsive, aggressive, and violent behaviors that may predispose an individual to suicide. (a), (b) The CNS contains one-fourth of the body's free cholesterol, (c) which is synthesized primarily in situ.

Cholesterol improves membrane stability, reduces permeability, and may influence serotonergic function. Cholesterol depletion may impair function of 5-HT1A and 5-HT7 receptors (d), (e) and serotonin transporter activity. (f) Reduced cholesterol after treatment with simvastatin--an HMG-CoA reductase inhibitor that readily crosses the blood-brain barrier--resulted in acute (1-month) increases in serotonin transporter activity followed by subacute (>2 months) decreases. (9) Lower cholesterol levels may further decrease expression of serotonin receptors and cause a net reduction in serotonergic activity.

In addition, cholesterol is necessary for synapse formation and myelin production. Cholesterol depletion may have more diffuse effects on neurotransmission, such as gamma-aminobutyric acid receptors, (h) N-methyl-D-aspartate receptors, (i) opioid signaling, (j) and excitatory amino acids transport. (k)

Impulsivity associated with low serotonergic function and low total cholesterol has been suggested as a potential pathway for suicide. (l) Low cholesterol is associated with self-report measures of impulsivity; (m) however, increased impulsivity associated with lipid-lowering therapy may be temporary, (n) which is similar to the time-limited changes in serotonin transporter activity. (9) Human and animal data have suggested that low cholesterol may be linked to violent behaviors, including suicide. (o)

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Depression. Several studies have shown an association between low cholesterol and depressive symptoms, although this finding has not been replicated in Asian subjects. (9), (10) Patients with manic or mixed syndromes have been found to have lower serum cholesterol, (11) and individuals with major depression and bipolar disorder have lower cholesterol levels in the brain compared with healthy controls. …

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