PMID- 30249029 OWN - NLM STAT- MEDLINE DCOM- 20190116 LR - 20231004 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 19 IP - 10 DP - 2018 Sep 23 TI - Eradicating Suicide at Its Roots: Preclinical Bases and Clinical Evidence of the Efficacy of Ketamine in the Treatment of Suicidal Behaviors. LID - 10.3390/ijms19102888 [doi] LID - 2888 AB - Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an N-methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics. FAU - De Berardis, Domenico AU - De Berardis D AD - National Health Service, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, "G. Mazzini" Hospital, p.zza Italia 1, 64100 Teramo, Italy. domenico.deberardis@aslteramo.it. AD - Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy. domenico.deberardis@aslteramo.it. FAU - Fornaro, Michele AU - Fornaro M AD - Polyedra Research Group, 64100 Teramo, Italy. dott.fornaro@gmail.com. AD - Department of Neuroscience, Reproductive Science and Odontostomatology, School of Medicine 'Federico II' Naples, 80121 Naples, Italy. dott.fornaro@gmail.com. FAU - Valchera, Alessandro AU - Valchera A AD - Polyedra Research Group, 64100 Teramo, Italy. a.valchera@ospedaliere.it. AD - Villa S. Giuseppe Hospital, Hermanas Hospitalarias, 63100 Ascoli Piceno, Italy. a.valchera@ospedaliere.it. FAU - Cavuto, Marilde AU - Cavuto M AD - Department of Theory, Analysis and Composition, Music Conservatory "L. Canepa", 07100 Sassari, Italy. marilde_cavuto@virgilio.it. FAU - Perna, Giampaolo AU - Perna G AD - Hermanas Hospitalarias, FoRiPsi, Department of Clinical Neurosciences, Villa San Benedetto Menni, Albese con Cassano, 22032 Como, Italy. pernagp@gmail.com. AD - Department of Psychiatry and Neuropsychology, University of Maastricht, 6221 Maastricht, The Netherlands. pernagp@gmail.com. AD - Department of Psychiatry and Behavioral Sciences, Leonard Miller School of Medicine, University of Miami, Coral Gables, FL 33114, USA. pernagp@gmail.com. FAU - Di Nicola, Marco AU - Di Nicola M AD - Institute of Psychiatry and Psychology, Catholic University of Sacred Heart, 00118 Rome, Italy. marcodinicola.md@gmail.com. FAU - Serafini, Gianluca AU - Serafini G AD - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genoa, 16132 Genoa, Italy. gianluca.serafini@uniroma1.it. FAU - Carano, Alessandro AU - Carano A AD - NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "Madonna Del Soccorso", A.S.U.R. 12, 63074 San Benedetto del Tronto, Italy. alessandro.carano@gmail.com. FAU - Pompili, Maurizio AU - Pompili M AUID- ORCID: 0000-0003-1886-4977 AD - Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, 00118 Rome, Italy. maurizio.pompili@uniroma1.it. FAU - Vellante, Federica AU - Vellante F AD - Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy. federica.vellante@gmail.com. FAU - Orsolini, Laura AU - Orsolini L AUID- ORCID: 0000-0002-6882-3770 AD - Polyedra Research Group, 64100 Teramo, Italy. laura.orsolini@hotmail.it. AD - Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, College Lane Campus, University of Hertfordshire, Hatfield SG141LZ, UK. laura.orsolini@hotmail.it. FAU - Fiengo, Annastasia AU - Fiengo A AD - Polyedra Research Group, 64100 Teramo, Italy. annastasia.fiengo@gmail.com. AD - NHS, Department of Mental Health ASUR Marche AV5, Mental Health Unit, 63100 Ascoli Piceno, Italy. annastasia.fiengo@gmail.com. FAU - Ventriglio, Antonio AU - Ventriglio A AD - Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy. a.ventriglio@libero.it. FAU - Yong-Ku, Kim AU - Yong-Ku K AD - Department of Psychiatry, Korea University College of Medicine, Seoul 08826, Korea. yongku@korea.edu. FAU - Martinotti, Giovanni AU - Martinotti G AD - Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy. giovanni.martinotti@gmail.com. FAU - Di Giannantonio, Massimo AU - Di Giannantonio M AD - Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University "G. D'Annunzio", 66100 Chieti, Italy. digiannantonio@unich.it. FAU - Tomasetti, Carmine AU - Tomasetti C AD - Polyedra Research Group, 64100 Teramo, Italy. carmine.tomasetti@aslteramo.it. AD - Department of Neuroscience, Reproductive Science and Odontostomatology, School of Medicine 'Federico II' Naples, 80121 Naples, Italy. carmine.tomasetti@aslteramo.it. LA - eng PT - Journal Article PT - Review DEP - 20180923 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 690G0D6V8H (Ketamine) SB - IM MH - Depressive Disorder/*drug therapy/psychology MH - Humans MH - Ketamine/*therapeutic use MH - Mood Disorders/*drug therapy/psychology MH - *Suicidal Ideation MH - *Suicide Prevention PMC - PMC6213585 OTO - NOTNLM OT - NMDA OT - antidepressants OT - antipsychotics OT - dopamine OT - esketamine OT - glutamate OT - ketamine OT - mood disorders OT - postsynaptic density OT - serotonin OT - suicide COIS- The authors declare no conflict of interest. EDAT- 2018/09/27 06:00 MHDA- 2019/01/17 06:00 PMCR- 2018/10/01 CRDT- 2018/09/26 06:00 PHST- 2018/09/07 00:00 [received] PHST- 2018/09/19 00:00 [accepted] PHST- 2018/09/26 06:00 [entrez] PHST- 2018/09/27 06:00 [pubmed] PHST- 2019/01/17 06:00 [medline] PHST- 2018/10/01 00:00 [pmc-release] AID - ijms19102888 [pii] AID - ijms-19-02888 [pii] AID - 10.3390/ijms19102888 [doi] PST - epublish SO - Int J Mol Sci. 2018 Sep 23;19(10):2888. doi: 10.3390/ijms19102888.