Suicidal ideation pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vindhya BellamKonda, M.B.B.S [2]

Overview

It is thought that suicidal ideation is caused by decreased expression of serotonin transporter gene, studies have shown that there is decreased expression of 5 HTT(SLC6A4 gene) in prefrontal and cortical region. MAO and MAOB have also been implicated.

Pathophysiology

Decreased cerebrospinal fluid (CSF) serotonin levels and serotonin receptor dysfunction are strong risk factors for suicide attempt and completion. Dysfunction in central serotonin systems is associated with a lowered threshold for self-directed and externally directed aggressive behavior. In 1976, As berg et al reported a bi-modal distribution of serotonin metabolites (5-HIAA) in the CSF of depressed patients.In this study, significantly more of the depressed patients in the "low" CSF 5-HIAA group had attempted suicide compared to the "high" CSF group. A five-year follow-up study of depressed patients concluded that patients who attempted suicide before the index admission and who reattempted suicide during the follow-up had significantly lower CSF levels of 5-HIAA.To date, more than 20 studies have reported low concentrations of CSF 5-HIAA in suicide attempters with a broad range of diagnoses, making this one of the strongest findings in biological psychiatry. The absolute reduction in the concentration of CSF 5-HIAA appears to correlate well with lethality, increased planning, and medical damage of the suicide attempt.The pharmacotherapy of suicidal patients often aims at increasing serotonin availability in the brain stem.

Genetics

Associated Conditions

The following conditions are associated with increased risk of suicidal ideation:

References

  1. Kaminsky Z, Wilcox HC, Eaton WW, Van Eck K, Kilaru V, Jovanovic T, Klengel T, Bradley B, Binder EB, Ressler KJ, Smith AK (2015). "Epigenetic and genetic variation at SKA2 predict suicidal behavior and post-traumatic stress disorder". Transl Psychiatry. 5: e627. doi:10.1038/tp.2015.105. PMC 4564560. PMID 26305478.

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