Suicide and Genetic Biomarkers: Toward Personalized Tailored-treatment with Lithium and Clozapine

Abstract

Background: Suicide is a major public health problem on a global scale with about 800.000 deaths every year. In particular, it represents one of the main causes of death among adolescents and young adults aged between 15 and 29 years. The World Health Organization (WHO) describes suicide as “an act of deliberate killing,” which is placed at the extreme end of the continuous spectrum of suicidal behaviors (SBs). These include suicidal ideation, attempted suicide, and suicide itself. Objective: The aim of the present review was to better clarify the suicide vulnerability genetic biomarkers and genetic variants correlated with the response to lithium and clozapine and to evaluate some correspondences. Methods: We reviewed the current literature, focusing our attention on genetic molecular studies on neurobiological systems involved in SBs and on pharmacogenetic studies on antisuicidal drugs (lithium and clozapine). Results: The studies we reviewed have shown mixed results. Interestingly, rs1800532 polymorphism of the SLC6A4 gene, encoding for the serotonin transporter, is potentially correlated with both suicide vulnerability and a poor response to lithium and clozapine. Conclusion: Due to the impact of suicide on public health, more studies are needed to open a promising route to prevent suicide in personalized and precise psychiatry.

The impact of quetiapine monotherapy or in combination with lithium on the thyroid function in patients with bipolar depression: A retrospective study

“…Bipolar disorder (BD), a disabling psychiatric disorder characterized by recurrence of manic and depressive episodes, affects approximately 1%-4% of the population worldwide, 1 leading to adverse outcomes including cognitive impairment and suicide, and causing a great burden for the patients and public health institutions. 2,3 Alternations in thyroid function are possibly bidirectionally associated with emotion fluctuation, 4 since patients with mood disorders showed a higher comorbidity rate with hyperthyroidism and hypothyroidism, and thyroid dysfunction could result in mood abnormalities. [5][6][7] Interventions on the hypothalamic-pituitarythyroid axis might reverse depression.…”

“…Bipolar disorder (BD), a disabling psychiatric disorder characterized by recurrence of manic and depressive episodes, affects approximately 1%–4% of the population worldwide, 1 leading to adverse outcomes including cognitive impairment and suicide, and causing a great burden for the patients and public health institutions. 2 , 3 …”

Gut Microbiota – A Potential Contributor in the Pathogenesis of Bipolar Disorder

“…Late adolescence is the average age at which BD develops ( Bauer et al, 2018 ). Epidemiological statistics showed that the prevalence of BD was about 2% ( Merikangas et al, 2011 ), and the risk of mortality rate due to suicide, which partly attributed to the mood states of BD patients, was 20–30 times higher than that of the normal ( Pompili et al, 2013 ; Orsolini et al, 2016 ; Fornaro et al, 2018 ; De Berardis et al, 2021 ). The early diagnosis of BD is difficult, and the final clinical diagnosis is usually made 5–10 years after the recurrence of the initial symptoms ( Fortinguerra et al, 2019 ).…”

A Case of Lithium Encephalopathy with Therapeutic Lithium Levels: The Diagnostic Role of EEG

“…Despite the discovery and introduction of a new generation of mood stabilizers, lithium is still considered a first-line therapy for both the acute phase and maintenance of bipolar disorder (BD) [6,7] and an additional treatment in major depression [8,9]. To his fame and longevity, surely contributed the fact that to this day, it remains the only compound with established antisuicidal properties [10][11][12][13][14] and the only whose prophylactic effect is proven on both new depressive and maniacal episodes [3,15,16].…”