Abstract
Suicide and bipolar disorder (BD) are challenging, complex, and intertwined areas of study in contemporary psychiatry. Indeed, BD is associated with the highest lifetime risk for suicide attempt and completion of all the psychiatric conditions. Given that several clinical risk factors for both suicide and BD have been well noted in the literature, exploring the neurobiological aspects of suicide in BD may provide insights into both preventive measures and future novel treatments. This review synthesizes findings regarding the neurobiological aspects of suicide and, when applicable, their link to BD. Neurochemical findings, genes/epigenetics, and potential molecular targets for current or future treatments are discussed. The role of endophenotypes and related proximal and distal risk factors underlying suicidal behavior are also explored. Lastly, we discuss the manner in which preclinical work on aggression and impulsivity may provide additional insights for the future development of novel treatments.
[1] Abreu L.N., Lafer B., Baca-Garcia E., Oquendo M.A., Suicidal ideation and suicide attempts in bipolar disorder type I: an update for the clinician, Rev. Bras. Psiquiatr., 2009, 31, 271–280 http://dx.doi.org/10.1590/S1516-4446200900500000310.1590/S1516-44462009005000003Search in Google Scholar
[2] Goodwin F.K., Fireman B., Simon G.E., Hunkeler E.M., Lee J., Revicki D., Suicide risk in bipolar disorder during treatment with lithium and divalproex, JAMA, 2003, 290, 1467–1473 http://dx.doi.org/10.1001/jama.290.11.146710.1001/jama.290.11.1467Search in Google Scholar PubMed
[3] Jamison K.R., Suicide and bipolar disorder, J. Clin. Psychiatry, 2000, 61,Suppl. 9, 47–51 Search in Google Scholar
[4] Harris E.C., Barraclough B., Suicide as an outcome for mental disorders. A meta-analysis, Br. J. Psychiatry, 1997, 170, 205–228 http://dx.doi.org/10.1192/bjp.170.3.20510.1192/bjp.170.3.205Search in Google Scholar PubMed
[5] World Health Organization, The World Health Report 2001 — Mental health: new understanding, new hope, World Health Organization, Geneva, 2001 Search in Google Scholar
[6] Undurraga J., Baldessarini R.J., Valenti M., Pacchiarotti I., Vieta E., Suicidal risk factors in bipolar I and II disorder patients, J. Clin. Psychiatry, 2012, 73, 778–782 http://dx.doi.org/10.4088/JCP.11m0704110.4088/JCP.11m07041Search in Google Scholar PubMed
[7] Bellivier F., Yon L., Luquiens A., Azorin J.M., Bertsch J., Gerard S., et al., Suicidal attempts in bipolar disorder: results from an observational study (EMBLEM), Bipolar Disord., 2011, 13, 377–386 http://dx.doi.org/10.1111/j.1399-5618.2011.00926.x10.1111/j.1399-5618.2011.00926.xSearch in Google Scholar PubMed
[8] Mann J.J., Neurobiology of suicidal behaviour, Nat. Rev. Neurosci., 2003, 4, 819–828 http://dx.doi.org/10.1038/nrn122010.1038/nrn1220Search in Google Scholar PubMed
[9] Turecki G., Suicidal behavior: is there a genetic predisposition?, Bipolar Disord., 2001, 3, 335–349 http://dx.doi.org/10.1034/j.1399-5618.2001.30608.x10.1034/j.1399-5618.2001.30608.xSearch in Google Scholar PubMed
[10] van Heeringen K., Stress-diathesis model of suicidal behavior, In: Dwivedi Y. (Ed.), The neurobiological basis of suicide, CRC Press, Boca Raton, FL, USA, 2012, 113–124 http://dx.doi.org/10.1201/b12215-710.1201/b12215-7Search in Google Scholar
[11] Mann J.J., Waternaux C., Haas G.L., Malone K.M., Toward a clinical model of suicidal behavior in psychiatric patients, Am. J. Psychiatry, 1999, 156, 181–189 Search in Google Scholar
[12] Turecki G., Ernst C., Jollant F., Labonte B., Mechawar N., The neurodevelopmental origins of suicidal behavior, Trends Neurosci., 2012, 35, 14–23 http://dx.doi.org/10.1016/j.tins.2011.11.00810.1016/j.tins.2011.11.008Search in Google Scholar PubMed
[13] Gilbert A.M., Garno J.L., Braga R.J., Shaya Y., Goldberg T.E., Malhotra A.K., et al., Clinical and cognitive correlates of suicide attempts in bipolar disorder: is suicide predictable?, J. Clin. Psychiatry, 2011, 72, 1027–1033 http://dx.doi.org/10.4088/JCP.10m0641010.4088/JCP.10m06410Search in Google Scholar PubMed PubMed Central
[14] Bunney W.E.Jr., Fawcett J.A., Possibility of a biochemical test for suicidal potential: an analysis of endocrine findings prior to three suicides, Arch. Gen. Psychiatry, 1965, 13, 232–239 http://dx.doi.org/10.1001/archpsyc.1965.0173003003800610.1001/archpsyc.1965.01730030038006Search in Google Scholar PubMed
[15] Pandey G.N., Dwivedi Y., What can post-mortem studies tell us about the pathoetiology of suicide?, Future Neurol., 2010, 5, 701–720 http://dx.doi.org/10.2217/fnl.10.4910.2217/fnl.10.49Search in Google Scholar PubMed PubMed Central
[16] Stanley M., Stanley B., Traskman-Bendz L., Mann J.J., Meyendorff E., Neurochemical findings in suicide completers and suicide attempters, Suicide Life-Threat., 1986, 16, 286–300 10.1111/j.1943-278X.1986.tb00356.xSearch in Google Scholar PubMed
[17] Stanley M., Stanley B., Biochemical studies in suicide victims: current findings and future implications, Suicide Life-Threat., 1989, 19, 30–42 10.1111/j.1943-278X.1989.tb00364.xSearch in Google Scholar PubMed
[18] Mann J.J., Currier D.M., Stress, genetics and epigenetic effects on the neurobiology of suicidal behavior and depression, Eur. Psychiatry, 2010, 25, 268–271 http://dx.doi.org/10.1016/j.eurpsy.2010.01.00910.1016/j.eurpsy.2010.01.009Search in Google Scholar PubMed PubMed Central
[19] Pandey G.N., Neurobiology of adult and teenage suicide, Asian J. Psychiatr., 2011, 4, 2–13 http://dx.doi.org/10.1016/j.ajp.2011.01.00810.1016/j.ajp.2011.01.008Search in Google Scholar PubMed PubMed Central
[20] Pandey G.N., Dwivedi Y., Peripheral biomarkers for suicide, In: Dwivedi Y. (Ed.), The neurobiological basis of suicide, CRC Press, Boca Raton, FL, USA, 2012, 407–424 http://dx.doi.org/10.1201/b12215-2110.1201/b12215-21Search in Google Scholar
[21] Beautrais A.L., Joyce P.R., Mulder R.T., Fergusson D.M., Deavoll B.J., Nightingale S.K., Prevalence and comorbidity of mental disorders in persons making serious suicide attempts: a case-control study, Am. J. Psychiatry, 1996, 153, 1009–1014 10.1176/ajp.153.8.1009Search in Google Scholar PubMed
[22] Shaffer D., Gould M.S., Fisher P., Trautman P., Moreau D., Kleinman M., et al., Psychiatric diagnosis in child and adolescent suicide, Arch. Gen. Psychiatry, 1996, 53, 339–348 http://dx.doi.org/10.1001/archpsyc.1996.0183004007501210.1001/archpsyc.1996.01830040075012Search in Google Scholar PubMed
[23] McCullumsmith R.E., Meador-Woodruff J.H., Novel approaches to the study of postmortem brain in psychiatric illness: old limitations and new challenges, Biol. Psychiatry, 2011, 69, 127–133 http://dx.doi.org/10.1016/j.biopsych.2010.09.03510.1016/j.biopsych.2010.09.035Search in Google Scholar PubMed
[24] Asberg M., Traskman L., Thoren P., 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor?, Arch. Gen. Psychiatry, 1976, 33, 1193–1197 http://dx.doi.org/10.1001/archpsyc.1976.0177010005500510.1001/archpsyc.1976.01770100055005Search in Google Scholar
[25] Agren H., Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid: I. General patterns, Psychiatry Res., 1980, 3, 211–223 http://dx.doi.org/10.1016/0165-1781(80)90038-410.1016/0165-1781(80)90038-4Search in Google Scholar
[26] Agren H., Niklasson F., Suicidal potential in depression: focus on CSF monoamine and purine metabolites, Psychopharmacol. Bull., 1986, 22, 656–660 Search in Google Scholar
[27] Cooper S.J., Kelly C.B., King D.J., 5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia, Lancet, 1992, 340, 940–941 http://dx.doi.org/10.1016/0140-6736(92)92819-210.1016/0140-6736(92)92819-2Search in Google Scholar
[28] Nordstrom P., Samuelsson M., Asberg M., Traskman-Bendz L., Aberg-Wistedt A., Nordin C., et al., CSF 5-HIAA predicts suicide risk after attempted suicide, Suicide Life-Threat., 1994, 24, 1–9 Search in Google Scholar
[29] Mann J.J., Malone K.M., Cerebrospinal fluid amines and higherlethality suicide attempts in depressed inpatients, Biol. Psychiatry, 1997, 41, 162–171 http://dx.doi.org/10.1016/S0006-3223(96)00217-X10.1016/S0006-3223(96)00217-XSearch in Google Scholar
[30] Mann J.J., McBride P.A., Malone K.M., DeMeo M., Keilp J., Blunted serotonergic responsivity in depressed inpatients, Neuropsychopharmacology, 1995, 13, 53–64 http://dx.doi.org/10.1016/0893-133X(95)00016-710.1016/0893-133X(95)00016-7Search in Google Scholar
[31] Stanley M., Mann J.J., Increased serotonin-2 binding sites in frontal cortex of suicide victims, Lancet, 1983, 1, 214–216 http://dx.doi.org/10.1016/S0140-6736(83)92590-410.1016/S0140-6736(83)92590-4Search in Google Scholar
[32] Pandey G.N., Dwivedi Y., Rizavi H.S., Ren X., Pandey S.C., Pesold C., et al., Higher expression of serotonin 5-HT(2A) receptors in the postmortem brains of teenage suicide victims, Am. J. Psychiatry, 2002, 159, 419–429 http://dx.doi.org/10.1176/appi.ajp.159.3.41910.1176/appi.ajp.159.3.419Search in Google Scholar
[33] Arango V., Underwood M.D., Mann J.J., Fewer pigmented locus coeruleus neurons in suicide victims: preliminary results, Biol. Psychiatry, 1996, 39, 112–120 http://dx.doi.org/10.1016/0006-3223(95)00107-710.1016/0006-3223(95)00107-7Search in Google Scholar
[34] Mann J.J., Stanley M., McBride P.A., McEwen B.S., Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims, Arch. Gen. Psychiatry, 1986, 43, 954–959 http://dx.doi.org/10.1001/archpsyc.1986.0180010004800710.1001/archpsyc.1986.01800100048007Search in Google Scholar
[35] Secunda S.K., Cross C.K., Koslow S., Katz M.M., Kocsis J., Maas J.W., et al., Biochemistry and suicidal behavior in depressed patients, Biol. Psychiatry, 1986, 21, 756–767 http://dx.doi.org/10.1016/0006-3223(86)90241-610.1016/0006-3223(86)90241-6Search in Google Scholar
[36] Sher L., Carballo J.J., Grunebaum M.F., Burke A.K., Zalsman G., Huang Y.Y., et al., A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder, Bipolar Disord., 2006, 8, 543–550 http://dx.doi.org/10.1111/j.1399-5618.2006.00319.x10.1111/j.1399-5618.2006.00319.xSearch in Google Scholar
[37] Ohmori T., Arora R.C., Meltzer H.Y., Serotonergic measures in suicide brain: the concentration of 5-HIAA, HVA, and tryptophan in frontal cortex of suicide victims, Biol. Psychiatry, 1992, 32, 57–71 http://dx.doi.org/10.1016/0006-3223(92)90142-M10.1016/0006-3223(92)90142-MSearch in Google Scholar
[38] Soderstrom H., Blennow K., Manhem A., Forsman A., CSF studies in violent offenders. I. 5-HIAA as a negative and HVA as a positive predictor of psychopathy, J. Neural. Transm., 2001, 108, 869–878 http://dx.doi.org/10.1007/s00702017003610.1007/s007020170036Search in Google Scholar PubMed
[39] Heim C., Shugart M., Craighead W.E., Nemeroff C.B., Neurobiological and psychiatric consequences of child abuse and neglect, Dev. Psychobiol., 2010, 52, 671–690 http://dx.doi.org/10.1002/dev.2049410.1002/dev.20494Search in Google Scholar PubMed
[40] Heim C., Newport D.J., Mletzko T., Miller A.H., Nemeroff C.B., The link between childhood trauma and depression: insights from HPA axis studies in humans, Psychoneuroendocrinology, 2008, 33, 693–710 http://dx.doi.org/10.1016/j.psyneuen.2008.03.00810.1016/j.psyneuen.2008.03.008Search in Google Scholar PubMed
[41] Owens M.J., Nemeroff C.B., Physiology and pharmacology of corticotropin-releasing factor, Pharmacol. Rev., 1991, 43, 425–473 Search in Google Scholar
[42] Nemeroff C.B., Owens M.J., Bissette G., Andorn A.C., Stanley M., Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims, Arch. Gen. Psychiatry, 1988, 45, 577–579 http://dx.doi.org/10.1001/archpsyc.1988.0180030007500910.1001/archpsyc.1988.01800300075009Search in Google Scholar PubMed
[43] Merali Z., Kent P., Du L., Hrdina P., Palkovits M., Faludi G., et al., Corticotropin-releasing hormone, arginine vasopressin, gastrinreleasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects, Biol. Psychiatry, 2006, 59, 594–602 http://dx.doi.org/10.1016/j.biopsych.2005.08.00810.1016/j.biopsych.2005.08.008Search in Google Scholar PubMed
[44] Kamali M., Saunders E.F., Prossin A.R., Brucksch C.B., Harrington G.J., Langenecker S.A., et al., Associations between suicide attempts and elevated bedtime salivary cortisol levels in bipolar disorder, J. Affect. Disord., 2012, 136, 350–358 http://dx.doi.org/10.1016/j.jad.2011.11.02710.1016/j.jad.2011.11.027Search in Google Scholar PubMed PubMed Central
[45] Coryell W., Schlesser M.A., Suicide and the dexamethasone suppression test in unipolar depression, Am. J. Psychiatry, 1981, 138, 1120–1121 10.1176/ajp.138.8.1120Search in Google Scholar PubMed
[46] Yerevanian B.I., Feusner J.D., Koek R.J., Mintz J., The dexamethasone suppression test as a predictor of suicidal behavior in unipolar depression, J. Affect. Disord., 2004, 83, 103–108 http://dx.doi.org/10.1016/j.jad.2004.08.00910.1016/j.jad.2004.08.009Search in Google Scholar PubMed
[47] Coryell W., Schlesser M., The dexamethasone suppression test and suicide prediction, Am. J. Psychiatry, 2001, 158, 748–753 http://dx.doi.org/10.1176/appi.ajp.158.5.74810.1176/appi.ajp.158.5.748Search in Google Scholar
[48] Coryell W., Schlesser M., Combined biological tests for suicide prediction, Psychiatry Res., 2007, 150, 187–191 http://dx.doi.org/10.1016/j.psychres.2006.01.02110.1016/j.psychres.2006.01.021Search in Google Scholar
[49] Carroll B.J., Martin F.I., Davies B., Resistance to suppression by dexamethasone of plasma 11-O.H.C.S. levels in severe depressive illness, Br. Med. J., 1968, 3, 285–287 http://dx.doi.org/10.1136/bmj.3.5613.28510.1136/bmj.3.5613.285Search in Google Scholar
[50] Mann J.J., Currier D., Stanley B., Oquendo M.A., Amsel L.V., Ellis S.P., Can biological tests assist prediction of suicide in mood disorders?, Int. J. Neuropsychopharmacol., 2006, 9, 465–474 http://dx.doi.org/10.1017/S146114570500568710.1017/S1461145705005687Search in Google Scholar
[51] Rush A.J., Giles D.E., Schlesser M.A., Orsulak P.J., Parker C.R.Jr., Weissenburger J.E., et al., The dexamethasone suppression test in patients with mood disorders, J. Clin. Psychiatry, 1996, 57, 470–484 http://dx.doi.org/10.4088/JCP.v57n100610.4088/JCP.v57n1006Search in Google Scholar
[52] Frick M.H., Elo O., Haapa K., Heinonen O.P., Heinsalmi P., Helo P., et al., Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease, N. Engl. J. Med., 1987, 317, 1237–1245 http://dx.doi.org/10.1056/NEJM19871112317200110.1056/NEJM198711123172001Search in Google Scholar
[53] Muldoon M.F., Manuck S.B., Matthews K.A., Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials, BMJ, 1990, 301, 309–314 http://dx.doi.org/10.1136/bmj.301.6747.30910.1136/bmj.301.6747.309Search in Google Scholar
[54] Kunugi H., Takei N., Aoki H., Nanko S., Low serum cholesterol in suicide attempters, Biol. Psychiatry, 1997, 41, 196–200 http://dx.doi.org/10.1016/S0006-3223(95)00672-910.1016/S0006-3223(95)00672-9Search in Google Scholar
[55] Golier J.A., Marzuk P.M., Leon A.C., Weiner C., Tardiff K., Low serum cholesterol level and attempted suicide, Am. J. Psychiatry, 1995, 152, 419–423 10.1176/ajp.152.3.419Search in Google Scholar PubMed
[56] Papassotiropoulos A., Hawellek B., Frahnert C., Rao G.S., Rao M.L., The risk of acute suicidality in psychiatric inpatients increases with low plasma cholesterol, Pharmacopsychiatry, 1999, 32, 1–4 http://dx.doi.org/10.1055/s-2007-97918110.1055/s-2007-979181Search in Google Scholar PubMed
[57] Vuksan-Cusa B., Marcinko D., Nad S., Jakovljevic M., Differences in cholesterol and metabolic syndrome between bipolar disorder men with and without suicide attempts, Prog. Neuropsychopharmacol. Biol. Psychiatry, 2009, 33, 109–112 http://dx.doi.org/10.1016/j.pnpbp.2008.10.01710.1016/j.pnpbp.2008.10.017Search in Google Scholar
[58] Lalovic A., Merkens L., Russell L., Arsenault-Lapierre G., Nowaczyk M.J., Porter F.D., et al., Cholesterol metabolism and suicidality in Smith-Lemli-Opitz syndrome carriers, Am. J. Psychiatry, 2004, 161, 2123–2126 http://dx.doi.org/10.1176/appi.ajp.161.11.212310.1176/appi.ajp.161.11.2123Search in Google Scholar
[59] Ringo D.L., Lindley S.E., Faull K.F., Faustman W.O., Cholesterol and serotonin: seeking a possible link between blood cholesterol and CSF 5-HIAA, Biol. Psychiatry, 1994, 35, 957–959 http://dx.doi.org/10.1016/0006-3223(94)91242-410.1016/0006-3223(94)91242-4Search in Google Scholar
[60] Mauch D.H., Nagler K., Schumacher S., Goritz C., Muller E.C., Otto A., et al., CNS synaptogenesis promoted by glia-derived cholesterol, Science, 2001, 294, 1354–1357 http://dx.doi.org/10.1126/science.294.5545.135410.1126/science.294.5545.1354Search in Google Scholar PubMed
[61] Sher L., Grunebaum M.F., Sullivan G.M., Burke A.K., Cooper T.B., Mann J.J., et al., Testosterone levels in suicide attempters with bipolar disorder, J. Psychiatr. Res, 2012, 46, 1267–1271 http://dx.doi.org/10.1016/j.jpsychires.2012.06.01610.1016/j.jpsychires.2012.06.016Search in Google Scholar PubMed PubMed Central
[62] Perez-Rodriguez M.M., Lopez-Castroman J., Martinez-Vigo M., Diaz-Sastre C., Ceverino A., Nunez-Beltran A., et al., Lack of association between testosterone and suicide attempts, Neuropsychobiology, 2011, 63, 125–130 http://dx.doi.org/10.1159/00031808510.1159/000318085Search in Google Scholar PubMed
[63] Rubinow D.R., Schmidt P.J., Androgens, brain, and behavior, Am. J. Psychiatry, 1996, 153, 974–984 10.1176/ajp.153.8.974Search in Google Scholar PubMed
[64] Sher L., Testosterone and suicidal behavior, Expert Rev. Neurother., 2012, 12, 257–259 http://dx.doi.org/10.1586/ern.12.610.1586/ern.12.6Search in Google Scholar PubMed
[65] Voracek M., Loibl L.M., Genetics of suicide: a systematic review of twin studies, Wien Klin. Wochenschr., 2007, 119, 463–475 http://dx.doi.org/10.1007/s00508-007-0823-210.1007/s00508-007-0823-2Search in Google Scholar PubMed
[66] Mirnics K., Levitt P., Lewis D.A., Critical appraisal of DNA microarrays in psychiatric genomics, Biol. Psychiatry, 2006, 60, 163–176 http://dx.doi.org/10.1016/j.biopsych.2006.02.00310.1016/j.biopsych.2006.02.003Search in Google Scholar PubMed
[67] Anguelova M., Benkelfat C., Turecki G., A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior, Mol. Psychiatry, 2003, 8, 646–653 http://dx.doi.org/10.1038/sj.mp.400133610.1038/sj.mp.4001336Search in Google Scholar PubMed
[68] Bondy B., Buettner A., Zill P., Genetics of suicide, Mol. Psychiatry, 2006, 11, 336–351 http://dx.doi.org/10.1038/sj.mp.400180310.1038/sj.mp.4001803Search in Google Scholar PubMed
[69] Brezo J., Klempan T., Turecki G., The genetics of suicide: a critical review of molecular studies, Psychiatr. Clin. North Am., 2008, 31, 179–203 http://dx.doi.org/10.1016/j.psc.2008.01.00810.1016/j.psc.2008.01.008Search in Google Scholar PubMed
[70] Rujescu D., Giegling I., Mandelli L., Schneider B., Hartmann A.M., Schnabel A., et al., NOS-I and -III gene variants are differentially associated with facets of suicidal behavior and aggression-related traits, Am. J. Med. Genet. B Neuropsychiatr. Genet., 2008, 147B, 42–48 http://dx.doi.org/10.1002/ajmg.b.3056910.1002/ajmg.b.30569Search in Google Scholar PubMed
[71] Perlis R.H., Huang J., Purcell S., Fava M., Rush A.J., Sullivan P.F., et al., Genome-wide association study of suicide attempts in mood disorder patients, Am. J. Psychiatry, 2010, 167, 1499–1507 http://dx.doi.org/10.1176/appi.ajp.2010.1004054110.1176/appi.ajp.2010.10040541Search in Google Scholar PubMed PubMed Central
[72] Currier D., Mann J.J., Stress, genes and the biology of suicidal behavior, Psychiatr. Clin. North Am., 2008, 31, 247–269 http://dx.doi.org/10.1016/j.psc.2008.01.00510.1016/j.psc.2008.01.005Search in Google Scholar PubMed PubMed Central
[73] Dwivedi Y., Rao J.S., Rizavi H.S., Kotowski J., Conley R.R., Roberts R.C., et al., Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects, Arch. Gen. Psychiatry, 2003, 60, 273–282 http://dx.doi.org/10.1001/archpsyc.60.3.27310.1001/archpsyc.60.3.273Search in Google Scholar PubMed
[74] Pandey G.N., Dwivedi Y., Ren X., Rizavi H.S., Roberts R.C., Conley R.R., Cyclic AMP response element-binding protein in post-mortem brain of teenage suicide victims: specific decrease in the prefrontal cortex but not the hippocampus, Int. J. Neuropsychopharmacol., 2007, 10, 621–629 http://dx.doi.org/10.1017/S146114570600723110.1017/S1461145706007231Search in Google Scholar PubMed
[75] Dwivedi Y., Rizavi H.S., Conley R.R., Roberts R.C., Tamminga C.A., Pandey G.N., Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects, Arch. Gen. Psychiatry, 2003, 60, 804–815 http://dx.doi.org/10.1001/archpsyc.60.8.80410.1001/archpsyc.60.8.804Search in Google Scholar PubMed
[76] Poulter M.O., Du L., Weaver I.C., Palkovits M., Faludi G., Merali Z., et al., GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes, Biol. Psychiatry, 2008, 64, 645–652 http://dx.doi.org/10.1016/j.biopsych.2008.05.02810.1016/j.biopsych.2008.05.028Search in Google Scholar PubMed
[77] Autry A.E., Monteggia L.M., Epigenetics in suicide and depression, Biol. Psychiatry, 2009, 66, 812–813 http://dx.doi.org/10.1016/j.biopsych.2009.08.03310.1016/j.biopsych.2009.08.033Search in Google Scholar PubMed PubMed Central
[78] Gould T.D., Gottesman I.I., Psychiatric endophenotypes and the development of valid animal models, Genes Brain Behav., 2006, 5, 113–119 http://dx.doi.org/10.1111/j.1601-183X.2005.00186.x10.1111/j.1601-183X.2005.00186.xSearch in Google Scholar PubMed
[79] Kovacsics C.E., Gottesman I.I., Gould T.D., Lithium’s antisuicidal efficacy: elucidation of neurobiological targets using endophenotype strategies, Annu. Rev. Pharmacol. Toxicol., 2009, 49, 175–198 http://dx.doi.org/10.1146/annurev.pharmtox.011008.14555710.1146/annurev.pharmtox.011008.145557Search in Google Scholar PubMed
[80] Courtet P., Gottesman I.I., Jollant F., Gould T.D., The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies?, Transl. Psychiatry, 2011, 1, e7 http://dx.doi.org/10.1038/tp.2011.610.1038/tp.2011.6Search in Google Scholar PubMed PubMed Central
[81] Carballo J.J., Akamnonu C.P., Oquendo M.A., Neurobiology of suicidal behavior. An integration of biological and clinical findings, Arch. Suicide Res., 2008, 12, 93–110 http://dx.doi.org/10.1080/1381111070185700410.1080/13811110701857004Search in Google Scholar PubMed PubMed Central
[82] Gottesman I.I., Gould T.D., The endophenotype concept in psychiatry: etymology and strategic intentions, Am. J. Psychiatry, 2003, 160, 636–645 http://dx.doi.org/10.1176/appi.ajp.160.4.63610.1176/appi.ajp.160.4.636Search in Google Scholar PubMed
[83] Lenox R.H., Gould T.D., Manji H.K., Endophenotypes in bipolar disorder, Am. J. Med. Genet., 2002, 114, 391–406 http://dx.doi.org/10.1002/ajmg.1036010.1002/ajmg.10360Search in Google Scholar PubMed
[84] Hasler G., Drevets W.C., Gould T.D., Gottesman I.I., Manji H.K., Toward constructing an endophenotype strategy for bipolar disorders, Biol. Psychiatry, 2006, 60, 93–105 http://dx.doi.org/10.1016/j.biopsych.2005.11.00610.1016/j.biopsych.2005.11.006Search in Google Scholar PubMed
[85] Grunebaum M.F., Ramsay S.R., Galfalvy H.C., Ellis S.P., Burke A.K., Sher L., et al., Correlates of suicide attempt history in bipolar disorder: a stress-diathesis perspective, Bipolar Disord., 2006, 8, 551–557 http://dx.doi.org/10.1111/j.1399-5618.2006.00304.x10.1111/j.1399-5618.2006.00304.xSearch in Google Scholar PubMed
[86] Sheard M.H., Marini J.L., Bridges C.I., Wagner E., The effect of lithium on impulsive aggressive behavior in man, Am. J. Psychiatry, 1976, 133, 1409–1413 10.1176/ajp.133.12.1409Search in Google Scholar PubMed
[87] Muller-Oerlinghausen B., Lewitzka U., Lithium reduces pathological aggression and suicidality: a mini-review, Neuropsychobiology, 2010, 62, 43–49 http://dx.doi.org/10.1159/00031430910.1159/000314309Search in Google Scholar PubMed
[88] Ohmura Y., Tsutsui-Kimura I., Kumamoto H., Minami M., Izumi T., Yamaguchi T., et al., Lithium, but not valproic acid or carbamazepine, suppresses impulsive-like action in rats, Psychopharmacology (Berl.), 2012, 219, 421–432 http://dx.doi.org/10.1007/s00213-011-2496-910.1007/s00213-011-2496-9Search in Google Scholar PubMed
[89] Xu C.M., Wang J., Wu P., Zhu W.L., Li Q.Q., Xue Y.X., et al., Glycogen synthase kinase 3beta in the nucleus accumbens core mediates cocaine-induced behavioral sensitization, J. Neurochem., 2009, 111, 1357–1368 http://dx.doi.org/10.1111/j.1471-4159.2009.06414.x10.1111/j.1471-4159.2009.06414.xSearch in Google Scholar PubMed
[90] Xu C.M., Wang J., Wu P., Xue Y.X., Zhu W.L., Li Q.Q., et al., Glycogen synthase kinase 3beta in the nucleus accumbens core is critical for methamphetamine-induced behavioral sensitization, J. Neurochem., 2011, 118, 126–139 http://dx.doi.org/10.1111/j.1471-4159.2011.07281.x10.1111/j.1471-4159.2011.07281.xSearch in Google Scholar PubMed
[91] Cipriani A., Pretty H., Hawton K., Geddes J.R., Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials, Am. J. Psychiatry, 2005, 162, 1805–1819 http://dx.doi.org/10.1176/appi.ajp.162.10.180510.1176/appi.ajp.162.10.1805Search in Google Scholar PubMed
[92] Baldessarini R.J., Tondo L., Davis P., Pompili M., Goodwin F.K., and Hennen J., Decreased risk of suicides and attempts during longterm lithium treatment: a meta-analytic review, Bipolar Disord, 2006, 8(5 Pt 2), 625–39. http://dx.doi.org/10.1111/j.1399-5618.2006.00344.x10.1111/j.1399-5618.2006.00344.xSearch in Google Scholar PubMed
[93] Tondo L., Baldessarini R.J., Long-term lithium treatment in the prevention of suicidal behavior in bipolar disorder patients, Epidemiol. Psichiatr. Soc., 2009, 18, 179–183 10.1017/S1121189X00000439Search in Google Scholar PubMed
[94] Quiroz J.A., Machado-Vieira R., Zarate C.A.Jr., Manji H.K., Novel insights into lithium’s mechanism of action: neurotrophic and neuroprotective effects, Neuropsychobiology, 2010, 62, 50–60 http://dx.doi.org/10.1159/00031431010.1159/000314310Search in Google Scholar PubMed PubMed Central
[95] O’Donnell K.C., Gould T.D., The behavioral actions of lithium in rodent models: leads to develop novel therapeutics, Neurosci. Biobehav. Rev., 2007, 31, 932–962 http://dx.doi.org/10.1016/j.neubiorev.2007.04.00210.1016/j.neubiorev.2007.04.002Search in Google Scholar PubMed PubMed Central
[96] Oquendo M.A., Galfalvy H.C., Currier D., Grunebaum M.F., Sher L., Sullivan G.M., et al., Treatment of suicide attempters with bipolar disorder: a randomized clinical trial comparing lithium and valproate in the prevention of suicidal behavior, Am. J. Psychiatry, 2011, 168, 1050–1056 http://dx.doi.org/10.1176/appi.ajp.2011.1101016310.1176/appi.ajp.2011.11010163Search in Google Scholar PubMed PubMed Central
[97] Perlis R.H., Hard outcomes: clinical trials to reduce suicide, Am. J. Psychiatry, 2011, 168, 1009–1011 http://dx.doi.org/10.1176/appi.ajp.2011.1108125010.1176/appi.ajp.2011.11081250Search in Google Scholar PubMed
[98] Reid W.H., Mason M., Hogan T., Suicide prevention effects associated with clozapine therapy in schizophrenia and schizoaffective disorder, Psychiatr. Serv., 1998, 49, 1029–1033 10.1176/ps.49.8.1029Search in Google Scholar PubMed
[99] Meltzer H.Y., Alphs L., Green A.I., Altamura A.C., Anand R., Bertoldi A., et al., Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT), Arch. Gen. Psychiatry, 2003, 60, 82–91 http://dx.doi.org/10.1001/archpsyc.60.1.8210.1001/archpsyc.60.1.82Search in Google Scholar PubMed
[100] Javitt D.C., Duncan L., Balla A., Sershen H., Inhibition of system A-mediated glycine transport in cortical synaptosomes by therapeutic concentrations of clozapine: implications for mechanisms of action, Mol. Psychiatry, 2005, 10, 275–287 http://dx.doi.org/10.1038/sj.mp.400155210.1038/sj.mp.4001552Search in Google Scholar PubMed
[101] Machado-Vieira R., Lara D.R., Souza D.O., Kapczinski F., Therapeutic efficacy of allopurinol in mania associated with hyperuricemia, J. Clin. Psychopharmacol., 2001, 21, 621–622 http://dx.doi.org/10.1097/00004714-200112000-0001710.1097/00004714-200112000-00017Search in Google Scholar PubMed
[102] Machado-Vieira R., Soares J.C., Lara D.R., Luckenbaugh D.A., Busnello J.V., Marca G., et al., A double-blind, randomized, placebocontrolled 4-week study on the efficacy and safety of the purinergic agents allopurinol and dipyridamole adjunctive to lithium in acute bipolar mania, J. Clin. Psychiatry, 2008, 69, 1237–1245 http://dx.doi.org/10.4088/JCP.v69n080610.4088/JCP.v69n0806Search in Google Scholar PubMed PubMed Central
[103] Fan A., Berg A., Bresee C., Glassman L.H., Rapaport M.H., Allopurinol augmentation in the outpatient treatment of bipolar mania: a pilot study, Bipolar Disord., 2012, 14, 206–210 http://dx.doi.org/10.1111/j.1399-5618.2012.01001.x10.1111/j.1399-5618.2012.01001.xSearch in Google Scholar PubMed
[104] Swann A.C., Impulsivity in mania, Curr. Psychiatry Rep., 2009, 11, 481–487 http://dx.doi.org/10.1007/s11920-009-0073-210.1007/s11920-009-0073-2Search in Google Scholar PubMed
[105] Zarate C.A.Jr., Singh J.B., Carlson P.J., Brutsche N.E., Ameli R., Luckenbaugh D.A., et al., A randomized trial of an N-methyl-Daspartate antagonist in treatment-resistant major depression, Arch. Gen. Psychiatry, 2006, 63, 856–864 http://dx.doi.org/10.1001/archpsyc.63.8.85610.1001/archpsyc.63.8.856Search in Google Scholar PubMed
[106] Diazgranados N., Ibrahim L., Brutsche N.E., Newberg A., Kronstein P., Khalife S., et al., A randomized add-on trial of an N-methyl-Daspartate antagonist in treatment-resistant bipolar depression, Arch. Gen. Psychiatry, 2010, 67, 793–802 http://dx.doi.org/10.1001/archgenpsychiatry.2010.9010.1001/archgenpsychiatry.2010.90Search in Google Scholar PubMed PubMed Central
[107] DiazGranados N., Ibrahim L.A., Brutsche N.E., Ameli R., Henter I.D., Luckenbaugh D.A., et al., Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder, J. Clin. Psychiatry, 2010, 71, 1605–1611 http://dx.doi.org/10.4088/JCP.09m05327blu10.4088/JCP.09m05327bluSearch in Google Scholar
[108] Price R.B., Nock M.K., Charney D.S., Mathew S.J., Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression, Biol. Psychiatry, 2009, 66, 522–526 http://dx.doi.org/10.1016/j.biopsych.2009.04.02910.1016/j.biopsych.2009.04.029Search in Google Scholar
[109] Zarate C.A.Jr., Brutsche N.E., Ibrahim L., Franco-Chaves J., Diazgranados N., Cravchik A., et al., Replication of ketamine’s antidepressant efficacy in bipolar depression: a randomized controlled add-on trial, Biol. Psychiatry, 2012, 71, 939–946 http://dx.doi.org/10.1016/j.biopsych.2011.12.01010.1016/j.biopsych.2011.12.010Search in Google Scholar
[110] Larkin G.L., Beautrais A.L., A preliminary naturalistic study of low-dose ketamine for depression and suicide ideation in the emergency department, Int. J. Neuropsychopharmacol., 2011, 14, 1127–1131 http://dx.doi.org/10.1017/S146114571100062910.1017/S1461145711000629Search in Google Scholar
[111] Kavalali E.T., Monteggia L.M., Synaptic mechanisms underlying rapid antidepressant action of ketamine, Am. J. Psychiatry, 2012, 169, 1150–1156 http://dx.doi.org/10.1176/appi.ajp.2012.1204053110.1176/appi.ajp.2012.12040531Search in Google Scholar
[112] Duman R.S., Aghajanian G.K., Synaptic dysfunction in depression: potential therapeutic targets, Science, 2012, 338, 68–72 http://dx.doi.org/10.1126/science.122293910.1126/science.1222939Search in Google Scholar
[113] Manaker S., Eichen A., Winokur A., Rhodes C.H., Rainbow T.C., Autoradiographic localization of thyrotropin releasing hormone receptors in human brain, Neurology, 1986, 36, 641–646 http://dx.doi.org/10.1212/WNL.36.5.64110.1212/WNL.36.5.641Search in Google Scholar
[114] Callahan A.M., Frye M.A., Marangell L.B., George M.S., Ketter T.A., L’Herrou T., et al., Comparative antidepressant effects of intravenous and intrathecal thyrotropin-releasing hormone: confounding effects of tolerance and implications for therapeutics, Biol. Psychiatry, 1997, 41, 264–272 http://dx.doi.org/10.1016/S0006-3223(97)00372-710.1016/S0006-3223(97)00372-7Search in Google Scholar
[115] Marangell L.B., George M.S., Callahan A.M., Ketter T.A., Pazzaglia P.J., L’Herrou T.A., et al., Effects of intrathecal thyrotropin-releasing hormone (protirelin) in refractory depressed patients, Arch. Gen. Psychiatry, 1997, 54, 214–222 http://dx.doi.org/10.1001/archpsyc.1997.0183015003400710.1001/archpsyc.1997.01830150034007Search in Google Scholar PubMed
[116] Erhardt S., Lim C.K., Linderholm K.R., Janelidze S., Lindqvist D., Samuelsson M., et al., Connecting inflammation with glutamate agonism in suicidality, Neuropsychopharmacology, 2013, 38, 743–752 http://dx.doi.org/10.1038/npp.2012.24810.1038/npp.2012.248Search in Google Scholar PubMed PubMed Central
[117] Lee B.H., Kim Y.K., Potential peripheral biological predictors of suicidal behavior in major depressive disorder, Prog. Neuropsychopharmacol. Biol. Psychiatry, 2011, 35, 842–847 http://dx.doi.org/10.1016/j.pnpbp.2010.08.00110.1016/j.pnpbp.2010.08.001Search in Google Scholar
[118] Nock M.K., Hwang I., Sampson N.A., Kessler R.C., Mental disorders, comorbidity and suicidal behavior: results from the National Comorbidity Survey Replication, Mol. Psychiatry, 2010, 15, 868–876 http://dx.doi.org/10.1038/mp.2009.2910.1038/mp.2009.29Search in Google Scholar
[119] Fountoulakis K.N., Gonda X., Siamouli M., and Rihmer Z., Psychotherapeutic intervention and suicide risk reduction in bipolar disorder: a review of the evidence, J. Affect. Disord., 2009, 113, 21–29 http://dx.doi.org/10.1016/j.jad.2008.06.01410.1016/j.jad.2008.06.014Search in Google Scholar
[120] Meltzer H.Y., Arora R.C., Baber R., Tricou B.J., Serotonin uptake in blood platelets of psychiatric patients, Arch. Gen. Psychiatry, 1981, 38, 1322–1326 http://dx.doi.org/10.1001/archpsyc.1981.0178037002400210.1001/archpsyc.1981.01780370024002Search in Google Scholar
[121] Rausch J.L., Janowsky D.S., Risch S.C., Huey L.Y., A kinetic analysis and replication of decreased platelet serotonin uptake in depressed patients, Psychiatry Res., 1986, 19, 105–112 http://dx.doi.org/10.1016/0165-1781(86)90003-X10.1016/0165-1781(86)90003-XSearch in Google Scholar
[122] Lichtenberg P., Shapira B., Gillon D., Kindler S., Cooper T.B., Newman M.E., et al., Hormone responses to fenfluramine and placebo challenge in endogenous depression, Psychiatry Res., 1992, 43, 137–146 http://dx.doi.org/10.1016/0165-1781(92)90128-P10.1016/0165-1781(92)90128-PSearch in Google Scholar
[123] Mann J.J., McBride P.A., Brown R.P., Linnoila M., Leon A.C., DeMeo M., et al., Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients, Arch. Gen. Psychiatry, 1992, 49, 442–446 http://dx.doi.org/10.1001/archpsyc.1992.0182006002200310.1001/archpsyc.1992.01820060022003Search in Google Scholar
[124] Mann J.J., Malone K.M., Sweeney J.A., Brown R.P., Linnoila M., Stanley B., et al., Attempted suicide characteristics and cerebrospinal fluid amine metabolites in depressed inpatients, Neuropsychopharmacology, 1996, 15(6), 576–586 http://dx.doi.org/10.1016/S0893-133X(96)00102-910.1016/S0893-133X(96)00102-9Search in Google Scholar
[125] Arora R.C., Meltzer H.Y., Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects, Am. J. Psychiatry, 1989, 146, 730–736 10.1176/ajp.146.6.730Search in Google Scholar
[126] Arango V., Underwood M.D., Gubbi A.V., Mann J.J., Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims, Brain Res., 1995, 688, 121–133 http://dx.doi.org/10.1016/0006-8993(95)00523-S10.1016/0006-8993(95)00523-SSearch in Google Scholar
[127] Hrdina P.D., Demeter E., Vu T.B., Sotonyi P., Palkovits M., 5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala, Brain Res., 1993, 614, 37–44 http://dx.doi.org/10.1016/0006-8993(93)91015-K10.1016/0006-8993(93)91015-KSearch in Google Scholar
[128] Underwood M.D., Khaibulina A.A., Ellis S.P., Moran A., Rice P.M., Mann J.J., et al., Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims, Biol. Psychiatry, 1999, 46, 473–483 http://dx.doi.org/10.1016/S0006-3223(99)00043-810.1016/S0006-3223(99)00043-8Search in Google Scholar
[129] Boldrini M., Underwood M.D., Mann J.J., Arango V., More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides, Brain Res., 2005, 1041, 19–28 http://dx.doi.org/10.1016/j.brainres.2005.01.08310.1016/j.brainres.2005.01.083Search in Google Scholar
[130] Brown G.L., Goodwin F.K., Ballenger J.C., Goyer P.F., Major L.F., Aggression in humans correlates with cerebrospinal fluid amine metabolites, Psychiatry Res., 1979, 1, 131–139 http://dx.doi.org/10.1016/0165-1781(79)90053-210.1016/0165-1781(79)90053-2Search in Google Scholar
[131] Galfalvy H., Currier D., Oquendo M.A., Sullivan G., Huang Y.Y., John Mann J., Lower CSF MHPG predicts short-term risk for suicide attempt, Int. J. Neuropsychopharmacol., 2009, 12, 1327–1335 http://dx.doi.org/10.1017/S146114570999022810.1017/S1461145709990228Search in Google Scholar PubMed PubMed Central
[132] Meana J.J., Garcia-Sevilla J.A., Increased alpha 2-adrenoceptor density in the frontal cortex of depressed suicide victims, J. Neural. Transm., 1987, 70, 377–381 http://dx.doi.org/10.1007/BF0125361210.1007/BF01253612Search in Google Scholar PubMed
[133] Callado L.F., Meana J.J., Grijalba B., Pazos A., Sastre M., Garcia-Sevilla J.A., Selective increase of alpha2A-adrenoceptor agonist binding sites in brains of depressed suicide victims, J. Neurochem., 1998, 70, 1114–1123 http://dx.doi.org/10.1046/j.1471-4159.1998.70031114.x10.1046/j.1471-4159.1998.70031114.xSearch in Google Scholar PubMed
[134] Escriba P.V., Ozaita A., Garcia-Sevilla J.A., Increased mRNA expression of alpha2A-adrenoceptors, serotonin receptors and mu-opioid receptors in the brains of suicide victims, Neuropsychopharmacology, 2004, 29, 1512–1521 http://dx.doi.org/10.1038/sj.npp.130045910.1038/sj.npp.1300459Search in Google Scholar PubMed
[135] Arango V., Ernsberger P., Marzuk P.M., Chen J.S., Tierney H., Stanley M., et al., Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims, Arch. Gen. Psychiatry, 1990, 47, 1038–1047 http://dx.doi.org/10.1001/archpsyc.1990.0181023005400910.1001/archpsyc.1990.01810230054009Search in Google Scholar PubMed
[136] Roy A., Agren H., Pickar D., Linnoila M., Doran A.R., Cutler N.R., et al., Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression, Am. J. Psychiatry, 1986, 143, 1539–1545 10.1176/ajp.143.12.1539Search in Google Scholar PubMed
[137] Roy A., Karoum F., Pollack S., Marked reduction in indexes of dopamine metabolism among patients with depression who attempt suicide, Arch. Gen. Psychiatry, 1992, 49, 447–450 http://dx.doi.org/10.1001/archpsyc.1992.0182006002700410.1001/archpsyc.1992.01820060027004Search in Google Scholar
[138] Noga J.T., Hyde T.M., Herman M.M., Spurney C.F., Bigelow L.B., Weinberger D.R., et al., Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains, Synapse, 1997, 27, 168–176 http://dx.doi.org/10.1002/(SICI)1098-2396(199711)27:3<168::AID-SYN2>3.0.CO;2-B10.1002/(SICI)1098-2396(199711)27:3<168::AID-SYN2>3.0.CO;2-BSearch in Google Scholar
[139] Kim S., Choi K.H., Baykiz A.F., Gershenfeld H.K., Suicide candidate genes associated with bipolar disorder and schizophrenia: an exploratory gene expression profiling analysis of post-mortem prefrontal cortex, BMC Genomics, 2007, 8, 413 http://dx.doi.org/10.1186/1471-2164-8-41310.1186/1471-2164-8-413Search in Google Scholar
[140] Steiner J., Bielau H., Brisch R., Danos P., Ullrich O., Mawrin C., et al., Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide, J. Psychiatr. Res., 2008, 42, 151–157 http://dx.doi.org/10.1016/j.jpsychires.2006.10.01310.1016/j.jpsychires.2006.10.013Search in Google Scholar
[141] Sequeira A., Mamdani F., Ernst C., Vawter M.P., Bunney W.E., Lebel V., et al., Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression, PLoS One, 2009, 4, e6585 10.1371/journal.pone.0006585Search in Google Scholar
[142] Fiori L.M. Turecki G., Broadening our horizons: gene expression profiling to help better understand the neurobiology of suicide and depression, Neurobiol. Dis., 2012, 45, 14–22 http://dx.doi.org/10.1016/j.nbd.2010.11.00410.1016/j.nbd.2010.11.004Search in Google Scholar
[143] Nowak G., Ordway G.A., and Paul I.A., Alterations in the N-methyl-Daspartate (NMDA) receptor complex in the frontal cortex of suicide victims, Brain Res., 1995, 675, 157–164 http://dx.doi.org/10.1016/0006-8993(95)00057-W10.1016/0006-8993(95)00057-WSearch in Google Scholar
[144] Bielau H., Steiner J., Mawrin C., Trubner K., Brisch R., Meyer-Lotz G., et al., Dysregulation of GABAergic neurotransmission in mood disorders: a postmortem study, Ann. NY Acad. Sci., 2007, 1096, 157–169 http://dx.doi.org/10.1196/annals.1397.08110.1196/annals.1397.081Search in Google Scholar
[145] Gos T., Gunther K., Bielau H., Dobrowolny H., Mawrin C., Trubner K., et al., Suicide and depression in the quantitative analysis of glutamic acid decarboxylase-immunoreactive neuropil, J. Affect. Disord., 2009, 113, 45–55 http://dx.doi.org/10.1016/j.jad.2008.04.02110.1016/j.jad.2008.04.021Search in Google Scholar
[146] Gross-Isseroff R., Dillon K.A., Israeli M., Biegon A., Regionally selective increases in mu opioid receptor density in the brains of suicide victims, Brain Res., 1990, 530, 312–316 http://dx.doi.org/10.1016/0006-8993(90)91301-V10.1016/0006-8993(90)91301-VSearch in Google Scholar
[147] Zavitsanou K., Katsifis A., Mattner F., Huang X.F., Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder, Neuropsychopharmacology, 2004, 29, 619–625 http://dx.doi.org/10.1038/sj.npp.130050910.1038/sj.npp.1300509Search in Google Scholar
[148] Cowburn R.F., Marcusson J.O., Eriksson A., Wiehager B., O’Neill C., Adenylyl cyclase activity and G-protein subunit levels in postmortem frontal cortex of suicide victims, Brain Res., 1994, 633, 297–304 http://dx.doi.org/10.1016/0006-8993(94)91552-010.1016/0006-8993(94)91552-0Search in Google Scholar
[149] Pacheco M.A., Stockmeier C., Meltzer H.Y., Overholser J.C., Dilley G.E., Jope R.S., Alterations in phosphoinositide signaling and G-protein levels in depressed suicide brain, Brain Res., 1996, 723, 37–45 http://dx.doi.org/10.1016/0006-8993(96)00207-710.1016/0006-8993(96)00207-7Search in Google Scholar
[150] Dwivedi Y., Rizavi H.S., Conley R.R., Roberts R.C., Tamminga C.A., Pandey G.N., mRNA and protein expression of selective alpha subunits of G proteins are abnormal in prefrontal cortex of suicide victims, Neuropsychopharmacology, 2002, 27, 499–517 10.1016/S0893-133X(02)00335-4Search in Google Scholar
[151] Pandey G.N., Dwivedi Y., Pandey S.C., Teas S.S., Conley R.R., Roberts R.C., et al., Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects, Am. J. Psychiatry, 1999, 156, 1895–1901 Search in Google Scholar
[152] Pandey G.N., Dwivedi Y., Pandey S.C., Conley R.R., Roberts R.C., Tamminga C.A., Protein kinase C in the postmortem brain of teenage suicide victims, Neurosci. Lett., 1997, 228, 111–114 http://dx.doi.org/10.1016/S0304-3940(97)00378-910.1016/S0304-3940(97)00378-9Search in Google Scholar
[153] Pandey G.N., Dwivedi Y., Rizavi H.S., Ren X., Conley R.R., Decreased catalytic activity and expression of protein kinase C isozymes in teenage suicide victims: a postmortem brain study, Arch. Gen. Psychiatry, 2004, 61, 685–693 http://dx.doi.org/10.1001/archpsyc.61.7.68510.1001/archpsyc.61.7.685Search in Google Scholar
[154] Coull M.A., Lowther S., Katona C.L., Horton R.W., Altered brain protein kinase C in depression: a post-mortem study, Eur. Neuropsychopharmacol., 2000, 10, 283–288 http://dx.doi.org/10.1016/S0924-977X(00)00084-510.1016/S0924-977X(00)00084-5Search in Google Scholar
[155] Pandey G.N., Dwivedi Y., Ren X., Rizavi H.S., Mondal A.C., Shukla P.K., et al., Brain region specific alterations in the protein and mRNA levels of protein kinase A subunits in the post-mortem brain of teenage suicide victims, Neuropsychopharmacology, 2005, 30, 1548–1556 http://dx.doi.org/10.1038/sj.npp.130076510.1038/sj.npp.1300765Search in Google Scholar PubMed
[156] Dwivedi Y., Conley R.R., Roberts R.C., Tamminga C.A., Pandey G.N., [(3)H]cAMP binding sites and protein kinase a activity in the prefrontal cortex of suicide victims, Am. J. Psychiatry, 2002, 159, 66–73 http://dx.doi.org/10.1176/appi.ajp.159.1.6610.1176/appi.ajp.159.1.66Search in Google Scholar PubMed
[157] Ernst C., Deleva V., Deng X., Sequeira A., Pomarenski A., Klempan T., et al., Alternative splicing, methylation state, and expression profile of tropomyosin-related kinase B in the frontal cortex of suicide completers, Arch. Gen. Psychiatry, 2009, 66, 22–32 http://dx.doi.org/10.1001/archpsyc.66.1.2210.1001/archpsyc.66.1.22Search in Google Scholar PubMed
[158] Lopez J.F., Palkovits M., Arato M., Mansour A., Akil H., Watson S.J., Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims, Neuroendocrinology, 1992, 56, 491–501 http://dx.doi.org/10.1159/00012626610.1159/000126266Search in Google Scholar
[159] Szigethy E., Conwell Y., Forbes N.T., Cox C., Caine E.D., Adrenal weight and morphology in victims of completed suicide, Biol. Psychiatry, 1994, 36, 374–380 http://dx.doi.org/10.1016/0006-3223(94)91212-210.1016/0006-3223(94)91212-2Search in Google Scholar
[160] Hiroi N., Wong M.L., Licinio J., Park C., Young M., Gold P.W., et al., Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls, Mol. Psychiatry, 2001, 6, 540–546 http://dx.doi.org/10.1038/sj.mp.400090810.1038/sj.mp.4000908Search in Google Scholar
[161] Austin M.C., Janosky J.E., and Murphy H.A., Increased corticotropinreleasing hormone immunoreactivity in monoamine-containing pontine nuclei of depressed suicide men, Mol. Psychiatry, 2003, 8, 324–332 http://dx.doi.org/10.1038/sj.mp.400125010.1038/sj.mp.4001250Search in Google Scholar
[162] Roy A., Hypothalamic-pituitary-adrenal axis function and suicidal behavior in depression, Biol. Psychiatry, 1992, 32, 812–816 http://dx.doi.org/10.1016/0006-3223(92)90084-D10.1016/0006-3223(92)90084-DSearch in Google Scholar
[163] Jokinen J., Nordstrom P., HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients, J. Affect. Disord., 2009, 116, 117–120 http://dx.doi.org/10.1016/j.jad.2008.10.01510.1016/j.jad.2008.10.015Search in Google Scholar PubMed
[164] McGowan P.O., Sasaki A., D’Alessio A.C., Dymov S., Labonte B., Szyf M., et al., Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse, Nat. Neurosci., 2009, 12, 342–348 http://dx.doi.org/10.1038/nn.227010.1038/nn.2270Search in Google Scholar PubMed PubMed Central
[165] Sinclair D., Fullerton J.M., Webster M.J., Shannon Weickert C., Glucocorticoid receptor 1B and 1C mRNA transcript alterations in schizophrenia and bipolar disorder, and their possible regulation by GR gene variants, PLoS One, 2012, 7, e31720 http://dx.doi.org/10.1371/journal.pone.003172010.1371/journal.pone.0031720Search in Google Scholar PubMed PubMed Central
[166] Sequeira A., Gwadry F.G., Ffrench-Mullen J.M., Canetti L., Gingras Y., Casero R.A., Jr., et al., Implication of SSAT by gene expression and genetic variation in suicide and major depression, Arch. Gen. Psychiatry, 2006, 63, 35–48 http://dx.doi.org/10.1001/archpsyc.63.1.3510.1001/archpsyc.63.1.35Search in Google Scholar PubMed
[167] Fiori L.M., Gross J.A., Turecki G., Effects of histone modifications on increased expression of polyamine biosynthetic genes in suicide, Int. J. Neuropsychopharmacol., 2012, 15, 1161–1166 http://dx.doi.org/10.1017/S146114571100152010.1017/S1461145711001520Search in Google Scholar PubMed
[168] Lindqvist D., Janelidze S., Hagell P., Erhardt S., Samuelsson M., Minthon L., et al., Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity, Biol. Psychiatry, 2009, 66, 287–292 http://dx.doi.org/10.1016/j.biopsych.2009.01.03010.1016/j.biopsych.2009.01.030Search in Google Scholar PubMed
[169] Tonelli L.H., Stiller J., Rujescu D., Giegling I., Schneider B., Maurer K., et al., Elevated cytokine expression in the orbitofrontal cortex of victims of suicide, Acta Psychiatr. Scand., 2008, 117, 198–206 http://dx.doi.org/10.1111/j.1600-0447.2007.01128.x10.1111/j.1600-0447.2007.01128.xSearch in Google Scholar PubMed PubMed Central
[170] Ellison L.F., Morrison H.I., Low serum cholesterol concentration and risk of suicide, Epidemiology, 2001, 12, 168–172 http://dx.doi.org/10.1097/00001648-200103000-0000710.1097/00001648-200103000-00007Search in Google Scholar PubMed
[171] Evans S.J., Prossin A.R., Harrington G.J., Kamali M., Ellingrod V.L., Burant C.F., et al., Fats and factors: lipid profiles associate with personality factors and suicidal history in bipolar subjects, PLoS One, 2012, 7, e29297 10.1371/journal.pone.0029297Search in Google Scholar PubMed PubMed Central
[172] Ernst C., Chen E.S., Turecki G., Histone methylation and decreased expression of TrkB.T1 in orbital frontal cortex of suicide completers, Mol. Psychiatry, 2009, 14, 830–832 http://dx.doi.org/10.1038/mp.2009.3510.1038/mp.2009.35Search in Google Scholar PubMed
[173] Keller S., Sarchiapone M., Zarrilli F., Videtic A., Ferraro A., Carli V., et al., Increased BDNF promoter methylation in the Wernicke area of suicide subjects, Arch. Gen. Psychiatry, 2010, 67, 258–267 http://dx.doi.org/10.1001/archgenpsychiatry.2010.910.1001/archgenpsychiatry.2010.9Search in Google Scholar PubMed
[174] Jollant F., Bellivier F., Leboyer M., Astruc B., Torres S., Verdier R., et al., Impaired decision making in suicide attempters, Am. J. Psychiatry, 2005, 162, 304–310 http://dx.doi.org/10.1176/appi.ajp.162.2.30410.1176/appi.ajp.162.2.304Search in Google Scholar PubMed
[175] Cha C.B., Najmi S., Park J.M., Finn C.T., Nock M.K., Attentional bias toward suicide-related stimuli predicts suicidal behavior, J. Abnorm. Psychol., 2010, 119, 616–622 http://dx.doi.org/10.1037/a001971010.1037/a0019710Search in Google Scholar PubMed PubMed Central
[176] Keilp J.G., Sackeim H.A., Brodsky B.S., Oquendo M.A., Malone K.M., Mann J.J., Neuropsychological dysfunction in depressed suicide attempters, Am. J. Psychiatry, 2001, 158, 735–741 http://dx.doi.org/10.1176/appi.ajp.158.5.73510.1176/appi.ajp.158.5.735Search in Google Scholar PubMed
[177] Jollant F., Lawrence N.L., Olie E., Guillaume S., Courtet P., The suicidal mind and brain: a review of neuropsychological and neuroimaging studies, World J. Biol. Psychiatry, 2011, 12, 319–339 http://dx.doi.org/10.3109/15622975.2011.55620010.3109/15622975.2011.556200Search in Google Scholar PubMed
[178] Keilp J.G., Gorlyn M., Russell M., Oquendo M.A., Burke A.K., Harkavy-Friedman J., et al., Neuropsychological function and suicidal behavior: attention control, memory and executive dysfunction in suicide attempt, Psychol. Med., 2012, 10, 1–13 10.1017/S0033291712001419Search in Google Scholar PubMed PubMed Central
[179] Grunebaum M.F., Ellis S.P., Duan N., Burke A.K., Oquendo M.A., John Mann J., Pilot randomized clinical trial of an SSRI vs bupropion: effects on suicidal behavior, ideation, and mood in major depression, Neuropsychopharmacology, 2012, 37, 697–706 http://dx.doi.org/10.1038/npp.2011.24710.1038/npp.2011.247Search in Google Scholar PubMed PubMed Central
[180] Khan A., Khan S.R., Hobus J., Faucett J., Mehra V., Giller E.L., et al., Differential pattern of response in mood symptoms and suicide risk measures in severely ill depressed patients assigned to citalopram with placebo or citalopram combined with lithium: role of lithium levels, J. Psychiatr. Res., 2011, 45, 1489–1496 http://dx.doi.org/10.1016/j.jpsychires.2011.06.01610.1016/j.jpsychires.2011.06.016Search in Google Scholar PubMed
[181] Rucci P., Frank E., Scocco P., Calugi S., Miniati M., Fagiolini A., et al., Treatment-emergent suicidal ideation during 4 months of acute management of unipolar major depression with SSRI pharmacotherapy or interpersonal psychotherapy in a randomized clinical trial, Depress. Anxiety, 2011, 28, 303–309 http://dx.doi.org/10.1002/da.2075810.1002/da.20758Search in Google Scholar PubMed PubMed Central
[182] Lauterbach E., Felber W., Muller-Oerlinghausen B., Ahrens B., Bronisch T., Meyer T., et al., Adjunctive lithium treatment in the prevention of suicidal behaviour in depressive disorders: a randomised, placebo-controlled, 1-year trial, Acta Psychiatr. Scand., 2008, 118, 469–479 http://dx.doi.org/10.1111/j.1600-0447.2008.01266.x10.1111/j.1600-0447.2008.01266.xSearch in Google Scholar PubMed
[183] Reeves H., Batra S., May R.S., Zhang R., Dahl D.C., Li X., Efficacy of risperidone augmentation to antidepressants in the management of suicidality in major depressive disorder: a randomized, doubleblind, placebo-controlled pilot study, J. Clin. Psychiatry, 2008, 69, 1228–1336 http://dx.doi.org/10.4088/JCP.v69n080510.4088/JCP.v69n0805Search in Google Scholar PubMed
[184] Lauterbach E., Ahrens B., Felber W., Oerlinghausen B.M., Kilb B., Bischof G., et al., Suicide prevention by lithium SUPLI—challenges of a multi-center prospective study, Arch. Suicide Res., 2005, 9, 27–34 http://dx.doi.org/10.1080/1381111059051288610.1080/13811110590512886Search in Google Scholar PubMed
[185] Verkes R.J., Van der Mast R.C., Hengeveld M.W., Tuyl J.P., Zwinderman A.H., Van Kempen G.M., Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major depression, Am. J. Psychiatry, 1998, 155, 543–547 10.1176/ajp.155.4.543Search in Google Scholar PubMed
[186] McCarthy M.J., Leckband S.G., Kelsoe J.R., Pharmacogenetics of lithium response in bipolar disorder, Pharmacogenomics, 2010, 11, 1439–1465 http://dx.doi.org/10.2217/pgs.10.12710.2217/pgs.10.127Search in Google Scholar PubMed
[187] Bonnin C.M., Martinez-Aran A., Sanchez-Moreno J., Torrent C., Franco C., Pacchiarotti I., et al., [Bipolar disorder, cognitive functioning and hypothalamic-pituitary-thyroid axis], Actas Esp. Psiquiatr., 2010, 38, 223–228 Search in Google Scholar
[188] Furey M.L., Drevets W.C., Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebocontrolled clinical trial, Arch. Gen. Psychiatry, 2006, 63, 1121–1129 http://dx.doi.org/10.1001/archpsyc.63.10.112110.1001/archpsyc.63.10.1121Search in Google Scholar PubMed PubMed Central
[189] Drevets W.C., Furey M.L., Replication of scopolamine’s antidepressant efficacy in major depressive disorder: a randomized, placebocontrolled clinical trial, Biol. Psychiatry, 2010, 67, 432–438 http://dx.doi.org/10.1016/j.biopsych.2009.11.02110.1016/j.biopsych.2009.11.021Search in Google Scholar PubMed PubMed Central
[190] Machado-Vieira R., Purinergic system in the treatment of bipolar disorder: uric acid levels as a screening test in mania, J. Clin. Psychopharmacol., 2012, 32, 735–736 http://dx.doi.org/10.1097/JCP.0b013e318268391d10.1097/JCP.0b013e318268391dSearch in Google Scholar PubMed
[191] Sperlagh B., Csolle C., Ando R.D., Goloncser F., Kittel A., Baranyi M., The role of purinergic signaling in depressive disorders, Neuropsychopharmacol. Hung., 2012, 14, 231–238 Search in Google Scholar
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