ORIGINAL ARTICLE

The link between alcohol use disorders and suicidal behavior

 Corelaţia dintre tulburările induse de consumul de alcool şicomportamentul suicidar

First published: 29 septembrie 2023

Editorial Group: MEDICHUB MEDIA

DOI: 10.26416/Psih.74.3.2023.8663

Abstract

Both suicide and excessive ethanol use are major public health problems that society faces. Individuals who develop ethanol abuse or dependence are more likely to develop suicidal ideation throughout their lives, compared to people who are not associated with this addiction. The synchronous presence of a mood disorder can interfere with the relationship between alcohol abuse/dependence and suicide. The risk factors that further contribute to the association of the two entities must be considered as well. For example, maladaptive coping strategies and the way the individual face everyday problems or stressors contribute to a greater exposure to both excessive ethanol consumption and suicidal behavior. These two elements potentiate each other, and the patient can enter into a vicious circle which in many situations can lead to suicide. In order to resort to the act of taking their own lives or expressing suicidal behavior, patients often present disinhibition, decreased judgment and increased impulsivity, which are also the greatest risk factors for ethanol consumers to deviate to a suicidal attempt. The purpose of this review is to better understand the mechanisms underlying suicidal behavior and ethanol dependence, and the link between ethanol consumption and suicidal thoughts. We reviewed articles that reported both alcohol abuse and suicidal behavior, associated or not with mood disorders. We analyzed studies found on Google Scholar and PubMed databases. The searching keywords were “suicide attempt” and “alcohol abuse”. We also looked for evidence that pointed to a link between alcoholism and suicide.
 

Keywords
alcohol use disorders, suicidal behavior, major depression, mood disorders, neurobiology

Rezumat

Atât suicidul, cât şi utilizarea excesivă a etanolului sunt probleme majore de sănătate publică cu care se confruntă societatea. Persoanele care suferă de tulburări ale consumului de alcool sunt mai predispuse să dezvolte idei suicidare de-a lungul vieţii, comparativ cu persoanele care nu prezintă această dependenţă. Prezenţa sincronă a unei tulburări de dispoziţie poate interfera cu relaţia dintre abuzul/dependenţa de alcool şi suicidul. Factorii de risc care contribuie la asocierea celor două entităţi trebuie luaţi în considerare, de asemenea. De exemplu, strategiile de coping şi modul în care individul se confruntă cu problemele de zi cu zi ori factorii de stres contribuie la o expunere mai mare, atât la consumul excesiv de etanol, cât şi la comportamentul suicidar. Aceste două elemente se potenţează reciproc, iar pacientul poate intra într-un cerc vicios care, în multe situaţii, poate conduce la suicid. Pentru a recurge la gestul de a-şi lua propria viaţă sau de a exprima un comportament autolitic, pacienţii prezintă deseori dezinhibiţie, scăderea capacităţii de judecată şi impulsivitate crescută, aceştia fiind totodată cei mai importanţi factori de risc pentru consumatorii de etanol de a prezenta o tentativă de suicid. Scopul acestei lucrări este de a înţelege mai bine mecanismele care stau la baza comportamentului suicidar şi a dependenţei de etanol şi legătura dintre consumul de etanol şi ideaţia autolitică. Am analizat articole care raportau atât abuzul de alcool, cât şi comportamentul suicidar, asociat sau nu cu tulburări de dispoziţie. Am analizat studii din cadrul bazelor de date Google Scholar şi PubMed, folosind următoarele cuvinte de căutare: „tentativă de sinucidere” şi „abuz de alcool”. De asemenea, am căutat dovezi care să conducă la o legătură între tulburarea consumului de alcool şi suicid.

Introduction

According to the World Health Organization (WHO, 2019), approximately 800,000 people die each year by committing suicide(1). Alcohol has always occupied an important place in human history, and the numbers speak for themselves: at least 90% of people occasionally drink alcohol at some point in their lives, and 30% or more of the drinkers will later develop problems related to its consumption(2). Suicide is a public health problem, and alcohol abuse, through disinhibition, impulsivity and impairment of judgment, can be a way to alleviate the suffering.

Global alcohol consumption is increasing, with a higher prevalence in developing countries(3,4). Both acute ingestion and addiction increase the risk of an impulsive suicide attempt, even in patients without depression(5). Therefore, there is a close relationship between these two complex phenomena, in which other factors also participate(3). Approximately 80 years ago, the concept of addiction itself was specified by Menninger both as a type of chronic suicide and as a contributing factor in deliberate self-harm(6).

Alcohol consumption can precipitate suicide by providing the impulse or the courage that these people need to complete a plan, a case in which the decision is highly alleviated by alcohol. In other cases, when rational judgment is affected and disinhibition occurs, suicide may seem a reasonable decision to the person concerned(7). At the same time, it has been observed that those who consumed alcohol before their time of death often chose a more lethal method of suicide, such as firearms(8).

The risk of suicide is higher in people with depression, especially when there is noncompliance or resistance to psychotropic drug treatment and, when combined with chronic ethanol consumption, it is even more dangerous. Most attempts took place in the context of a combination between impulsivity caused by alcohol abuse and depression, both occurring simultaneously in 85 out of 100 patients who managed to commit suicide(9).

Risk factors associated with suicide and alcohol use disorders

In the literature, it is often stated that people who have died following a suicide attempt, or who had a history of alcohol consumption, also had a history of multiple suicide attempts and defective family relationships. They have also witnessed a multitude of violent acts and their level of aggression was increased, compared to those who attempt suicide, but who did not have a history of alcohol consumption(10-12). Based on psychological autopsy studies, the results suggest that alcohol use disorder is widespread in people who commit suicide. They also reveal that a potent risk factor for suicidal activity is alcohol use disorder(13).

Risk factors for suicide, in the case of those who are addicted to alcohol, are represented by behavioral disorders, interpersonal conflicts, reduced tolerance to anger, contradictory family circumstances or an older age(10,14-16). When combined and then linked to personality traits or mental illness, these can escalate the way people act in certain circumstances or situations, especially when it comes to suicidal behavior(17). Also, major depressive disorder, bipolar disorder and borderline personality disorder or post-traumatic stress disorder are especially associated with suicidal behavior in people with addictive problems(18-23).

It was found that men had a higher suicide rate compared to women, in a study in which the authors investigated 204 suicide cases, trying to find similarities and differences between women and men. Three ways in which men differed from women were observed. They used more aggressive and lethal approaches, they were three times more likely to be drug users, and they were more concerned with economic issues than women. The authors concluded that differences of the suicide rate seen in men and women need a complex determination, but the most important notice would be that more men compared to women intend to commit suicide(24). Moreover, women are more vulnerable to developing side effects from alcohol consumption than men(2,25,26).

The COVID-19 pandemic has had an overwhelming impact on humanity in the past year, affecting over 100 million people around the world. The prevalence of unhealthy alcohol use and suicide attempts within the population has subsequently increased by adjusting individuals to the changes brought on by this epidemic, such as loneliness, working from home or even loss of employment. Social distancing and quarantine have caused increased feelings of disconnection and have affected the individual by increasing the perception of social pain(27,28). Depression is included among the mental and neurological manifestations of COVID-19 and, also, this new infectious disease exacerbates the preexisting mental conditions. There are high levels of stress and anxiety among the population which is susceptible to depression and risk behaviors(29-31). People who have previously abstained from alcohol are also at an increased risk of recurrence. When this happens, personal failure associated with other changes brought by the pandemic increase the recurrent thoughts of death in vulnerable people. Moreover, under the influence of alcohol, the danger of an impulsive suicidal gesture is high within the population(32).

What are the most common psychiatric disorders associated with alcohol use disorders?

Delusions and delirium, memory and sleep disturbances that arise during intoxication or withdrawal, as well as anxiety, mood and psychotic disorders, dementia and sexual dysfunction are all examples of alcohol-induced disorders(3).

Depression, anxiety and personality disorders are the most common psychological disorders associated with alcohol dependency. Typically, depression is secondary to alcohol dependency(33). The severity of mood disorders varies depending on the amount of alcohol ingested. It also depends on how long this behavior persisted, as well as the time of the last consumption. The individual’s vulnerability is important in the development of psychiatric symptoms in the context of excessive ethanol consumption(34). Alcoholism can complicate or mimic almost any medical symptom encountered in psychiatry, often making it difficult to diagnose the essence of the psychiatric complaints(35). In alcohol use disorders, heavy drinking is frequently associated with a 40% risk of depressive episodes, related with suicidal ideas and attempts, increased anxiety and insomnia(36).

Population studies have found that people with anxiety disorder are two to five times more likely to have problems regarding alcohol or opioid usage, compared to those without anxiety disorder(37). Severe anxiety disorders increase the risk of suicide attempts in people with mood disorders(38).

People with alcohol-induced disorders consume high amounts of alcoholic beverages, and high blood alcohol levels are associated with impaired judgment and increased disinhibition. Moreover, in addition to depressive moods and suicidal ideation, impulsive behaviors with self-harm attempts can be a real danger to patients(39). Psychopathological studies have shown that alcohol consumption and depression coexist. People with mood disorders may resort to ethanol consumption to be able to fight negative feelings. Initially, symptoms can be minimized by ethanol consumption, but in the long run, alcohol use can be addictive, and this exacerbates depressive symptoms(40). Studies have shown that depression and anxiety may be the only clinical symptoms of severe somatic pathology(41-43). Therefore, when encountering an alcoholic patient who presents with both depression and suicidal ideation, an organic cause should be considered, in addition to a toxic one. Patients who associate somatic pathology with feelings of guilt can develop severe psychotic depression, with an aggravating prognosis of the disease(44).

The neurobiology of suicide attempts and alcohol use disorders

Suicide is a major cause of death in the world, being one of the main three causes of death in people aged between 15 and 34 years old(45). Almost every case is a complication of a psychiatric condition, 90% of the people who resorted to this gesture had a serious mental illness, the most reported being mood disorders (about 60% of cases), of which depressive disorder was the most common(15). Other conditions include schizophrenia, alcoholism, substance abuse, personality disorders, epilepsy, obsessive-compulsive disorder and body dysmorphic disorder(46-57). About 22% of suicide deaths are attributed to ethanol consumption(1).

There is evidence that suicidal behavior can result from the activity of three neurobiological systems: hyperactivity of the noradrenergic system, changes in the normal function of the serotonergic system, and increased activity of the hypothalamic-pituitary-adrenal axis(58,59).

When speaking about suicide, major depressive disorder and alcohol use disorder, serotonin neurotransmitter deficits are identified(60). In the brain of the suicidal decedents and the cerebrospinal fluid of non-fatal suicide attempts(61,62), suffering from a major depressive disorder and alcohol disorder, impaired serotonin neurotransmission was observed(60,63,64). The reduced activity of this hormone is also associated with increased aggression and impulsivity, traits that are more likely to lead to suicidal behavior(65,66). It should also be noted that, in the suicide attempts with severe depression, schizophrenia and personality disorders, the low cerebrospinal fluid concentration of 5-hydroxyindoleacetic acid has been documented, similar to individuals who do not attempt suicide but have the same psychiatric diagnosis(46).

In response to the reduced serotoninergic transmission, alcoholic suicides can fail to up-regulate ventral prefrontal 5-HT1A receptors, raising the risk of suicidal actions. Only suicide attempts suffering from alcoholism have been found to have low binding capacity in the serotonin transporter, indicating a link to suicide. In alcoholic patients, lesser 5-HT1D terminal auto-receptor binding supports impaired serotonergic innervation related to alcoholism(3).

In literature, it is stated that the genetic abnormalities in the dopaminergic system are related to pathological aggression(67). Self-directed pathological aggression can also be considered suicidal behavior. Furthermore, dopamine deficiencies have been shown to be associated with impulsiveness, mental dysregulation and alcohol use disorders(68). In patients diagnosed with depression with a history of violent or non-violent suicide attempts, lower levels of the homovanillic acid were detected in the cerebrospinal fluid, compared to the control groups(69). High aggression, impulsivity and suicidal tendencies are also associated with alcoholism(70,71).

It is, therefore, rational to conclude that the genetically determined dopaminergic dysfunction can play an important role in the suicidal behavioral pathophysiology of alcoholism(72-74). In patients diagnosed with psychotic depression who have committed suicide, there is a decrease in the level of dopamine described in the literature. In the field of biomarkers, new advances have been made, including a new scientific research direction with implications for dopamine treatment using voltammetric techniques on electrodes of different types, with the scope of the rapid determination of the biological fluids and active type components in various pharmaceutical formulation (benserazide and L-DOPA)(75,76).

Conclusions

The most common mood disorders in patients with chronic ethanol use are depressive disorders and bipolar disorders. It is important to detect as early as possible both the mood changes and the pathologic alcohol consumption, to correctly conduct the management of the patient, to reduce the suicide risk and to prevent suicide attempts. Screening for alcoholism associated with depression is important not only for the improvement of quality of life, but also for the early detection of these diseases, which can reduce the costs of health services and economic damages. A significant percentage of people who intend or commit suicide have an increased consumption of alcoholic beverages.

All patients with alcoholism should, however, be assessed for the possibility of suicide. Awareness of the risk and susceptibility of alcoholism culminating with suicidal actions still outweighs our perception of protective factors and resilience. Future studies need to be carried out to determine which interventions can decrease the suicidal activity in the alcoholic patients. Additionally, several questions remain unanswered about the relationship between drug use disorders and suicide, indicating the need for future study.

Through comprehensive reporting, which in turn will provide useful guidelines for the clinical practice, our knowledge about alcohol use and other drugs in suicide deaths could be improved. Researchers and physicians have continued to establish alternative therapies that simultaneously target these conditions, with early signs of effectiveness, but there is still much to improve when it comes to alcohol consumption and addiction.
 

Conflict of interest: none declared  
Financial support: none declared
This work is permanently accessible online free of charge and published under the CC-BY. 

Bibliografie

  1. World Health Organization. Suicide. 2019.

  2. Sher L. Neurobiological and Clinical Aspects. Alcohol and suicide: neurobiological and clinical aspects. Sci World J. 2006;6:700–706.

  3. Pompili M, Serafini G, Innamorati M, Dominici G, Ferracuti S, Kotzalidis GD, et al. Suicidal behavior and alcohol abuse. Int J Environ Res Public Health. 2010;7(4):1392–431.

  4. Tian G, Liu F. Is the demand for alcoholic beverages in developing countries sensitive to price? Evidence from China. Int J Environ Res Public Health. 2011;8(6):2124–31.

  5. Lejoyeux M, Huet F, Claudon M, Fichelle A, Casalino E, Lequen V. Characteristics of suicide attempts preceded by alcohol consumption. Arch Suicide Res. 2008;12(1):30–8.

  6. Menninger KA. Man against Himself. Psychohist Rev. 1985;13:9–14.

  7. Kresnow M, Powell KE, Webb KB, Mercy JA, Potter LB, Simon TA, et al. Assigning time-linked exposure status to controls in unmatched case-control studies: alcohol use and nearly lethal suicide attempts. Stat Med. 2001;20(9-10):1479–85.

  8. Sher L. Alcohol consumption and suicide. QJM. 2006;99(1):57–61.

  9. Barraclough B, Bunch J, Nelson B, Sainsbury P. A hundred cases of suicide: clinical aspects. Br J Psychiatry. 1974;125(0):355–73.

  10. Kõlves K, Draper BM, Snowdon J, De Leo D. Alcohol-use disorders and suicide: results from a psychological autopsy study in Australia. Alcohol. 2017;64:29–35.

  11. Popa-Velea O, Lala AI, Sturzu LM, Bobirnac G, Spinu DA. The usefulness of the Draw-a-Person (DAP) test in diagnosing domestic violence. Rev Med Leg. 2016;24(3):231–5.

  12.  Popa-Velea O, Lala AI, Sturzu LM, Bobirnac G, Spinu DA. The usefulness of the Draw-a-Person (DAP) test in diagnosing domestic violence on children. Rev Med Leg. 2017;25(2):217–220. 

  13. Sher L. Risk and protective factors for suicide in patients with alcoholism. Sci World J. 2006;6:1405–11.

  14. Lamis DA, Malone PS, Langhinrichsen-Rohling J, Ellis TE. Body investment, depression, and alcohol use as risk factors for suicide proneness in college students. Crisis. 2010;31(3):118–27.

  15. Lasota D, Al-Wathinani A, Krajewski P, Mirowska-Guzel D, Goniewicz K, Hertelendy AJ, et al. Alcohol and the Risk of Railway Suicide. Int J Environ Res Public Health. 2020;17(19):7003. 

  16. Cole AB, Leavens EL, Brett EI, Lopez SV, Pipestem KR, Tucker RP, et al. Alcohol use and the interpersonal theory of suicide in American Indian young adults. J Ethn Subst Abuse. 2020;19(4):537–52.

  17. Yuodelis-Flores C, Ries RK. Addiction and suicide: A review. Am J Addict. 2015;24(2):98–104.

  18. Schultebraucks K, Duesenberg M, Di Simplicio M, Holmes EA, Roepke S. Suicidal Imagery in Borderline Personality Disorder and Major Depressive Disorder. J Pers Disord. 2020;34(4):546–64.

  19. Ducasse D, Lopez-Castroman J, Dassa D, Brand-Arpon V, Dupuy-Maurin K, Lacourt L, et al. Exploring the boundaries between borderline personality disorder and suicidal behavior disorder. Eur Arch Psychiatry Clin Neurosci. 2020;270(8):959–67.

  20. Cameron AY, Erisman S, Palm Reed K. The relationship among shame, nonsuicidal self-injury and suicidal behaviors in borderline personality disorder. Psychol Rep. 2020;123(3):648–59. 

  21. Kuehn KS, King KM, Linehan MM, Harned MS. Modeling the suicidal behavior cycle: understanding repeated suicide attempts among individuals with borderline personality disorder and a history of attempting suicide. J Consult Clin Psychol. 2020;88(6):570–81.

  22. Brown LA, Chen S, Narine K, Contractor AA, Oslin D. DSM-5 PTSD symptom clusters and suicidal ideation in veterans. Psychiatry Res. 2020;288:112942.

  23. Bertrand L, Bourguignon C, Beaulieu S, Storch KF, Linnaranta O. Suicidal Ideation and Insomnia in Bipolar Disorders: Idéation suicidaire et insomnie dans les troubles bipolaires. Can J Psychiatry. 2020;65(11):802–10.

  24. Rich CL, Ricketts JE, Fowler RC, Young D. Some differences between men and women who commit suicide. Am J Psychiatry. 1988;145(6):718–22.

  25. Wilsnack SC, Wilsnack RW. International gender and alcohol research: recent findings and future directions. Alcohol Res Health. 2002;26(4):245–50.

  26. Kovacs EJ, Messingham KA. Influence of alcohol and gender on immune response. Alcohol Res Health. 2002;26(4):257–63. 

  27. Conejero I, Berrouiguet S, Ducasse D, et al. Épidémie de COVID-19 et prise en charge des conduites suicidaires: challenge et perspectives [Suicidal behavior in light of COVID-19 outbreak: Clinical challenges and treatment perspectives]. Encephale. 2020;46(3S):S66-S72. 

  28. Ramalho R. Alcohol consumption and alcohol-related problems during the COVID-19 pandemic: a narrative review. Australas Psychiatry. 2020;28(5):524–6.

  29. Adhanom Ghebreyesus T. Addressing mental health needs: an integral part of COVID-19 response. World Psychiatry. 2020;19(2):129–30.

  30. Thomas SP. Coronavirus Challenges for Psychiatric-Mental Health Nursing in 2021. Issues Ment Health Nurs. 2021;42(1):1–2.

  31. Unützer J, Kimmel RJ, Snowden M. Psychiatry in the age of COVID-19. World Psychiatry. 2020;19(2):130–1.

  32. Kim JU, Majid A, Judge R, Crook P, Nathwani R, Selvapatt N, et al. Effect of COVID-19 lockdown on alcohol consumption in patients with pre-existing alcohol use disorder. Lancet Gastroenterol Hepatol. 2020;5(10):886–7.

  33. Lejoyeux M, Marinescu M. [Alcohol dependence and abuse and psychiatric disorders]. Rev Prat. 2006;56(10):1081–5.

  34.  Masten AS, Faden VB, Zucker RA, Spear LP. Underage Drinking: A Developmental Framework. Pediatrics. 2008;121:S235–51. 

  35. Shivani R, Goldsmith RJ, Anthenelli RM. Alcoholism and Psychiatric Disorders: diagnostic Challenges. Alcohol Res Health. 2002;26:90–8.

  36. Schuckit MA. Alcohol-use disorders. Lancet. 2009;373(9662):492–501.

  37. Smith JP, Randall CL. Anxiety and alcohol use disorders: comorbidity and treatment considerations. Alcohol Res. 2012;34(4):414–31.

  38. Sareen J, Cox BJ, Afifi TO, de Graaf R, Asmundson GJ, ten Have M, et al. Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch Gen Psychiatry. 2005;62(11):1249–57. 

  39. Sung YK, La Flair LN, Mojtabai R, Lee LC, Spivak S, Crum RM. The Association of Alcohol Use Disorders with Suicidal Ideation and Suicide Attempts in a Population-Based Sample with Mood Symptoms. Arch Suicide Res. 2016;20(2):219–32. 

  40. Quello SB, Brady KT, Sonne SC. Mood disorders and substance use disorder: a complex comorbidity. Sci Pract Perspect. 2005;3(1):13–21. 

  41. Papacocea T, Roşca T, Bădărău A, Papacocea R, Ciornei C, Ion AD. [Cystic meningioma]. Chirurgia (Bucur). 2009;104(1):99–103. 

  42. Ciobanu AM, Roşca T, Vlădescu CT, Tihoan C, Popa MC, Boer MC, et al. Frontal epidural empyema (Pott’s puffy tumor) associated with Mycoplasma and depression. Rom J Morphol Embryol. 2014;55(3 Suppl):1203–7. 

  43. Ciobanu AM, Lisievici MG, Coman TC, Ciubotaru GV, Drăghia A, Drăghia F, et al. Giant wing sphenoid meningioma with principal manifestation depression. Rom J Morphol Embryol. 2009;50(4):713–7. 

  44. Ciobanu AM, Popa C, Marcu M, Ciobanu CF. Psychotic depression due to giant condyloma Buschke-Löwenstein tumors. Rom J Morphol Embryol. 2014;55(1):189–95.

  45. Kutcher SP, Szumilas M. Youth suicide prevention. CMAJ. 2008;178(3):282–5.

  46. De Sousa A, Shah B, Shrivastava A. Suicide and schizophrenia: an interplay of factors. Curr Psychiatry Rep. 2020;22(12):65.

  47. Grigoriou M, Upthegrove R. Blunted affect and suicide in schizophrenia: A systematic review. Psychiatry Res. 2020;293:113355.

  48. Ran MS, Xiao Y, Fazel S, Lee Y, Luo W, Hu SH, et al. Mortality and suicide in schizophrenia: 21-year follow-up in rural China. BJ Psych Open. 2020;6(6):e121.

  49. Bartels SJ, Drake RE, McHugo GJ. Alcohol abuse, depression, and suicidal behavior in schizophrenia. Am J Psychiatry. 1992;149(3):394–5. 

  50. Wang W, Zhou Y, Wang J, Xu H, Wei S, Wang D, et al. Prevalence, clinical correlates of suicide attempt and its relationship with empathy in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2020;99:109863.

  51. Amiri S, Behnezhad S. Alcohol use and risk of suicide: a systematic review and meta-analysis. J Addict Dis. 2020;38(2):200–13.

  52. Edwards AC, Ohlsson H, Sundquist J, Sundquist K, Kendler KS. Alcohol Use Disorder and Risk of Suicide in a Swedish Population-Based Cohort. Am J Psychiatry. 2020;177(7):627–34. 

  53. Orpana H, Giesbrecht N, Hajee A, Kaplan MS. Alcohol and other drugs in suicide in Canada: opportunities to support prevention through enhanced monitoring. Inj Prev. 2021;27(2):194-200.

  54. Perez J, Beale E, Overholser J, Athey A, Stockmeier C. Depression and alcohol use disorders as precursors to death by suicide. Death Stud. 2022;46(3):619-627.

  55. Eskander N, Limbana T, Khan F. Psychiatric Comorbidities and the Risk of Suicide in Obsessive-Compulsive and Body Dysmorphic Disorder. Cureus. 2020;12(8):e9805.

  56. Mesraoua B, Deleu D, Hassan AH, Gayane M, Lubna A, Ali MA, et al. Dramatic outcomes in epilepsy: depression, suicide, injuries, and mortality. Curr Med Res Opin. 2020;36(9):1473–80. 

  57. Falcone T, Dagar A, Castilla-Puentes RC, Anand A, Brethenoux C, Valleta LG, et al. Digital conversations about suicide among teenagers and adults with epilepsy: A big-data, machine learning analysis. Epilepsia. 2020;61(5):951–8.

  58. Mann JJ. The neurobiology of suicide. Nat Med. 1998;4(1):25–30.

  59. Papacocea MT, Bădărău IA, Rădoi M, Papacocea IR. The predictive role of biochemical plasma factors in patients with severe traumatic brain injuries. Rev Chim. 2019;70(5):1754–7.

  60. van Heeringen K. The neurobiology of suicide and suicidality. Can J Psychiatry. 2003;48(5):292–300.

  61. Underwood MD, Kassir SA, Bakalian MJ, Galfalvy H, Dwork AJ, Mann JJ, et al. Serotonin receptors and suicide, major depression, alcohol use disorder and reported early life adversity. Transl Psychiatry. 2018;8(1):279. 

  62. van Heeringen K, Mann JJ. The neurobiology of suicide. Lancet Psychiatry. 2014;1(1):63–72.

  63. Savitz JB, Drevets WC. Neuroreceptor imaging in depression. Neurobiol Dis. 2013;52:49–65.

  64. LeMarquand D, Pihl RO, Benkelfat C. Serotonin and alcohol intake, abuse, and dependence: clinical evidence. Biol Psychiatry. 1994;36(5):326–37.

  65. Underwood MD, Mann JJ, Arango V. Serotonergic and noradrenergic neurobiology of alcoholic suicide. Alcohol Clin Exp Res. 2004;28(5 Suppl):57S–69S.

  66. Placidi GP, Oquendo MA, Malone KM, Huang YY, Ellis SP, Mann JJ. Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels. Biol Psychiatry. 2001;50(10):783–91.

  67. Seo D, Patrick CJ, Kennealy PJ. Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders. Aggress Violent Behav. 2008;13(5):383–95.

  68. Chen TJ, Blum K, Mathews D, Fisher L, Schnautz N, Braverman ER, et al. Are dopaminergic genes involved in a predisposition to pathological aggression? Hypothesizing the importance of “super normal controls” in psychiatricgenetic research of complex behavioral disorders. Med Hypotheses. 2005;65(4):703–7.

  69. Tupala E, Tiihonen J. Dopamine and alcoholism: neurobiological basis of ethanol abuse. Prog Neuropsychopharmacol Biol Psychiatry. 2004;28(8):1221–47.

  70. Sher L. Alcoholism and suicidal behavior: a clinical overview. Acta Psychiatr Scand. 2006;113(1):13–22.

  71. Vrînceanu D, Bănică B, Papacocea R, Papacocea T. Self-inflicted laryngeal penetrating wounds with suicidal intention: two clinical cases. Rev Med Leg. 2018;26:16–20.

  72. LeMarquand D, Pihl RO, Benkelfat C. Serotonin and alcohol intake, abuse, and dependence: findings of animal studies. Biol Psychiatry. 1994;36(6):395–421.

  73. Badawy AA. Alcohol, aggression and serotonin: metabolic aspects. Alcohol Alcohol. 1998;33(1):66–72.

  74. Pietraszek MH, Urano T, Sumioshi K, Serizawa K, Takahashi S, Takada Y, et al. Alcohol-induced depression: involvement of serotonin. Alcohol Alcohol. 1991;26(2):155–9.

  75. Rabinca AA, Buleandra M, Tache F, Mihailciuc C, Ciobanu AM, Ştefănescu DC, et al. Voltammetric Method for Simultaneous Determination of L-Dopa and Benserazide. Curr Anal Chem. 2017;13(3):218–24.

  76. Pătraşcu DG, David V, Bălan I, Ciobanu A, David IG, Lazar P, et al. Selective DPV method of dopamine determination in biological samples containing ascorbic acid. Anal Lett. 2010;43(7-8):1100–10.