{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:54:08Z","timestamp":1791276848863,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>An altered polyamine system has been suggested to play a key role in mood disorders and suicide, a hypothesis corroborated by the evidence that lithium inhibits the polyamine mediated stress response in the rat brain. Recent post-mortem studies have shown that spermidine\/spermine N1-acetyltransferase (SAT1), the key regulator of cellular polyamine content, is under-expressed in brains from suicide victims compared to controls. In our study we tested the effect of in vitro lithium treatment on SAT1 gene and protein expression in B lymphoblastoid cell lines (BLCLs) from bipolar disorder (BD) patients who committed suicide (and for which BLCLs were collected prior to their death), BD patients with high and low risk of suicide and a sample of non-psychiatric controls. Baseline mRNA levels were similar in the four groups of subjects (p &gt; 0.05). Lithium had no effect in suicide completers (p &gt; 0.05) while it significantly increased SAT1 expression in the high risk (p &lt; 0.001) and low risk (p &lt; 0.01) groups as well as in controls (p &lt; 0.001). Protein and mRNA levels were not correlated; lithium significantly reduced protein levels only in the control sample (p &lt; 0.05). Our findings suggest that SAT1 transcription is influenced by lithium and that this effect is altered in BD patients who completed suicide, further supporting a role for polyamines in suicide.<\/jats:p>","DOI":"10.1017\/s1461145713000655","type":"journal-article","created":{"date-parts":[[2013,6,17]],"date-time":"2013-06-17T12:21:52Z","timestamp":1371471712000},"page":"2209-2218","source":"Crossref","is-referenced-by-count":22,"title":["Differential effect of lithium on spermidine\/spermine N1-acetyltransferase expression in suicidal behaviour"],"prefix":"10.1093","volume":"16","author":[{"given":"Alessio","family":"Squassina","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Genetics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Manchia","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy"},{"name":"Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Chillotti","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pharmacology, University Hospital of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Deiana","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Congiu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Paribello","sequence":"additional","affiliation":[{"name":"Department of Public Health, Clinical and Molecular Medicine, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Roncada","sequence":"additional","affiliation":[{"name":"Istituto Sperimentale L. Spallanzani, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Soggiu","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Veterinarie e Sanit\u00e0 Pubblica, Universit\u00e0 degli Studi di Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Piras","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Veterinarie e Sanit\u00e0 Pubblica, Universit\u00e0 degli Studi di Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"IRCCS-Santa Lucia Foundation, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George S.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Department of Pharmacology, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, Nova Scotia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Keddy","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Neurobiology, Department of Pharmacology, Sir Charles Tupper Medical Building, Dalhousie University, Halifax, Nova Scotia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Turecki","sequence":"additional","affiliation":[{"name":"McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy A.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Centre of Excellence in Neuroscience, CHUM Research Center and the Department of Medicine, University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Alda","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Del Zompo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy"},{"name":"Unit of Clinical Pharmacology, University Hospital of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,11,1]]},"reference":[{"key":"2019101113490009100_ref1","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1055\/s-2001-15878","article-title":"Does lithium exert an independent antisuicidal effect?","volume":"34","author":"Ahrens","year":"2001","journal-title":"Pharmacopsychiatry"},{"key":"2019101113490009100_ref2","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1001\/archpsyc.1977.01770220111013","article-title":"The family history method using diagnostic criteria. Reliability and validity","volume":"34","author":"Andreasen","year":"1977","journal-title":"Arch Gen Psychiatry"},{"key":"2019101113490009100_ref3","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1017\/S0033291701003889","article-title":"Suicides and serious suicide attempts: two populations or one?","volume":"31","author":"Beautrais","year":"2001","journal-title":"Psychol Med"},{"key":"2019101113490009100_ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1521\/suli.32.1.1.22184","article-title":"A case control study of suicide and attempted suicide in older adults","volume":"32","author":"Beautrais","year":"2002","journal-title":"Suicide Life Threat Behav"},{"key":"2019101113490009100_ref5","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1176\/ajp.153.8.1009","article-title":"Prevalence and comorbidity of mental disorders in persons making serious suicide attempts: a case-control study","volume":"153","author":"Beautrais","year":"1996","journal-title":"Am J Psychiatry"},{"key":"2019101113490009100_ref6","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/ajmg.c.30041","article-title":"Suicidal behavior prevention: WHO perspectives on research","volume":"133C","author":"Bertolote","year":"2005","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"2019101113490009100_ref7","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1097\/00004714-199810000-00006","article-title":"Suicidal behavior on and off lithium prophylaxis in a group of patients with prior suicide attempts","volume":"18","author":"Bocchetta","year":"1998","journal-title":"J Clin Psychopharmacol"},{"key":"2019101113490009100_ref8","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/archpsyc.59.9.801","article-title":"Familial pathways to early-onset suicide attempt: risk for suicidal behavior in offspring of mood-disordered suicide attempters","volume":"59","author":"Brent","year":"2002","journal-title":"Arch Gen Psychiatry"},{"key":"2019101113490009100_ref9","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1097\/01.chi.0000135619.38392.78","article-title":"Familial transmission of mood disorders: convergence and divergence with transmission of suicidal behavior","volume":"43","author":"Brent","year":"2004","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2019101113490009100_ref10","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/j.1399-5618.2007.00516.x","article-title":"Heterogeneity of the risk of suicidal behavior in bipolar-spectrum disorders","volume":"9","author":"Cavazzoni","year":"2007","journal-title":"Bipolar Disord"},{"key":"2019101113490009100_ref11","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1111\/j.1471-4159.1982.tb07904.x","article-title":"Ornithine decarboxylase induction by glucocorticoids in brain and liver of adrenalectomized rats","volume":"38","author":"Cousin","year":"1982","journal-title":"J Neurochem"},{"key":"2019101113490009100_ref12","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.jad.2009.10.020","article-title":"Apples to oranges? A direct comparison between suicide attempters and suicide completers","volume":"124","author":"DeJong","year":"2010","journal-title":"J Affect Disord"},{"key":"2019101113490009100_ref13","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1046\/j.1471-4159.1999.0731121.x","article-title":"G Protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: effects of diagnosis, suicide, and treatment at the time of death","volume":"73","author":"Dowlatshahi","year":"1999","journal-title":"J Neurochem"},{"key":"2019101113490009100_ref14","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1001\/archpsyc.1978.01770310043002","article-title":"A diagnostic interview: the schedule for affective disorders and schizophrenia","volume":"35","author":"Endicott","year":"1978","journal-title":"Arch Gen Psychiatry"},{"key":"2019101113490009100_ref15","first-page":"102","article-title":"Implication of the polyamine system in mental disorders","volume":"33","author":"Fiori","year":"2008","journal-title":"J Psychiatry Neurosci"},{"key":"2019101113490009100_ref16","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1002\/ajmg.b.31040","article-title":"Association of the SAT1 in\/del polymorphism with suicide completion","volume":"153B","author":"Fiori","year":"2010","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"2019101113490009100_ref17","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.biopsych.2009.04.002","article-title":"Identification and characterization of spermidine\/spermine N1-acetyltransferase promoter variants in suicide completers","volume":"66","author":"Fiori","year":"2009","journal-title":"Biol Psychiatry"},{"key":"2019101113490009100_ref18","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1017\/S1461145710001574","article-title":"Global gene expression profiling of the polyamine system in suicide completers","volume":"14","author":"Fiori","year":"2011","journal-title":"Int J Neuropsychopharmacol"},{"key":"2019101113490009100_ref19","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.1440-1819.2006.01504.x","article-title":"Comparison of completed and attempted suicide in Akita, Japan","volume":"60","author":"Fushimi","year":"2006","journal-title":"Psychiatry Clin Neurosci"},{"key":"2019101113490009100_ref20","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/0006-2952(92)90428-L","article-title":"Polyamines in neurotrauma. Ubiquitous molecules in search of a function","volume":"44","author":"Gilad","year":"1992","journal-title":"Biochem Pharmacol"},{"key":"2019101113490009100_ref21","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1046\/j.1471-4159.1996.67051992.x","article-title":"Brain polyamine stress response: recurrence after repetitive stressor and inhibition by lithium","volume":"67","author":"Gilad","year":"1996","journal-title":"J Neurochem"},{"key":"2019101113490009100_ref22","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1023\/A:1025036532672","article-title":"Overview of the brain polyamine-stress-response: regulation, development, and modulation by lithium and role in cell survival","volume":"23","author":"Gilad","year":"2003","journal-title":"Cell Mol Neurobiol"},{"key":"2019101113490009100_ref23","doi-asserted-by":"crossref","first-page":"L149","DOI":"10.1016\/0024-3205(92)90289-2","article-title":"Chronic lithium treatment prevents the dexamethasone-induced increase of brain polyamine metabolizing enzymes","volume":"50","author":"Gilad","year":"1992","journal-title":"Life Sci"},{"key":"2019101113490009100_ref24","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/0006-8993(94)91016-2","article-title":"Lithium exerts a time-dependent and tissue-selective attenuation of the dexamethasone-induced polyamine response in rat brain and liver","volume":"636","author":"Gilad","year":"1994","journal-title":"Brain Res"},{"key":"2019101113490009100_ref25","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1002\/ajmg.b.30901","article-title":"Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior","volume":"150B","author":"Guipponi","year":"2009","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"2019101113490009100_ref26","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1111\/j.1399-5618.2005.00182.x","article-title":"Clinical correlates of current level of functioning in primary care-treated bipolar patients","volume":"7","author":"Hajek","year":"2005","journal-title":"Bipolar Disord"},{"key":"2019101113490009100_ref27","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.jneumeth.2007.11.017","article-title":"Increased lactate levels and reduced pH in postmortem brains of schizophrenics: medication confounds","volume":"169","author":"Halim","year":"2008","journal-title":"J Neurosci Methods"},{"key":"2019101113490009100_ref28","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.biocel.2009.07.009","article-title":"Modulation of cellular function by polyamines","volume":"42","author":"Igarashi","year":"2010","journal-title":"Int J Biochem Cell Biol"},{"key":"2019101113490009100_ref29","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1002\/ajmg.b.30920","article-title":"Profiling brain expression of the spermidine\/spermine N1-acetyltransferase 1 (SAT1) gene in suicide","volume":"150B","author":"Klempan","year":"2009","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"2019101113490009100_ref30","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1111\/j.1749-6632.1986.tb27882.x","article-title":"Suicidal people. One population or two?","volume":"487","author":"Linehan","year":"1986","journal-title":"Ann N Y Acad Sci"},{"key":"2019101113490009100_ref31","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1016\/j.biopsych.2006.06.019","article-title":"Critical factors in gene expression in postmortem human brain: focus on studies in schizophrenia","volume":"60","author":"Lipska","year":"2006","journal-title":"Biol Psychiatry"},{"key":"2019101113490009100_ref32","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/S0893-133X(00)00228-1","article-title":"The neurobiology and genetics of suicide and attempted suicide: a focus on the serotonergic system","volume":"24","author":"Mann","year":"2001","journal-title":"Neuropsychopharmacology"},{"key":"2019101113490009100_ref33","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1176\/appi.ajp.162.9.1672","article-title":"Family history of suicidal behavior and mood disorders in probands with mood disorders","volume":"162","author":"Mann","year":"2005","journal-title":"Am J Psychiatry"},{"key":"2019101113490009100_ref34","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1007\/BF00279094","article-title":"A routine method for the establishment of permanent growing lymphoblastoid cell lines","volume":"73","author":"Neitzel","year":"1986","journal-title":"Hum Genet"},{"key":"2019101113490009100_ref35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF03160353","article-title":"Polyamines in cerebral ischemia","volume":"9","author":"Paschen","year":"1988","journal-title":"Neurochem Pathol"},{"key":"2019101113490009100_ref36","doi-asserted-by":"publisher","first-page":"E995","DOI":"10.1152\/ajpendo.90217.2008","article-title":"Spermidine\/spermine-N(1)-acetyltransferase: a key metabolic regulator","volume":"294","author":"Pegg","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2019101113490009100_ref37","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/YCO.0b013e3280106868","article-title":"Suicide risk in mood disorders","volume":"20","author":"Rihmer","year":"2007","journal-title":"Curr Opin Psychiatry"},{"key":"2019101113490009100_ref38","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1034\/j.1399-5618.4.s1.3.x","article-title":"Bipolar disorders and suicidal behavior","volume":"4","author":"Rihmer","year":"2002","journal-title":"Bipolar Disord"},{"key":"2019101113490009100_ref39","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/S0165-0327(00)00275-5","article-title":"Suicidal behavior in twins: a replication","volume":"66","author":"Roy","year":"2001","journal-title":"J Affect Disord"},{"key":"2019101113490009100_ref40","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1001\/archpsyc.1991.01810250031003","article-title":"Suicide in twins","volume":"48","author":"Roy","year":"1991","journal-title":"Arch Gen Psychiatry"},{"key":"2019101113490009100_ref41","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1001\/archpsyc.63.1.35","article-title":"Implication of SSAT by gene expression and genetic variation in suicide and major depression","volume":"63","author":"Sequeira","year":"2006","journal-title":"Arch Gen Psychiatry"},{"key":"2019101113490009100_ref42","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/sj.mp.4001969","article-title":"Patterns of gene expression in the limbic system of suicides with and without major depression","volume":"12","author":"Sequeira","year":"2007","journal-title":"Mol Psychiatry"},{"key":"2019101113490009100_ref43","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.4088\/JCP.v65n0802","article-title":"Bipolar patients with suicidal behavior: toward the identification of a clinical subgroup","volume":"65","author":"Slama","year":"2004","journal-title":"J Clin Psychiatry"},{"key":"2019101113490009100_ref44","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1001\/archpsyc.1978.01770300115013","article-title":"Research diagnostic criteria: rationale and reliability","volume":"35","author":"Spitzer","year":"1978","journal-title":"Arch Gen Psychiatry"},{"key":"2019101113490009100_ref45","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00508-007-0823-2","article-title":"Genetics of suicide: a systematic review of twin studies","volume":"119","author":"Voracek","year":"2007","journal-title":"Wien Klin Wochenschr"},{"key":"2019101113490009100_ref46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1042\/BJ20031327","article-title":"A perspective of polyamine metabolism","volume":"376","author":"Wallace","year":"2003","journal-title":"Biochem J"}],"container-title":["International Journal of Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ijnp\/article-pdf\/16\/10\/2209\/30135775\/16-10-2209.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ijnp\/article-pdf\/16\/10\/2209\/30135775\/16-10-2209.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T13:54:54Z","timestamp":1715522094000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ijnp\/article\/16\/10\/2209\/652930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,1]]},"references-count":46,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,11,1]]}},"URL":"https:\/\/doi.org\/10.1017\/s1461145713000655","relation":{},"ISSN":["1469-5111","1461-1457"],"issn-type":[{"value":"1469-5111","type":"electronic"},{"value":"1461-1457","type":"print"}],"subject":[],"published-other":{"date-parts":[[2013,11]]},"published":{"date-parts":[[2013,11,1]]}}}