title: Differential effect of lithium on spermidine/spermine N1-acetyltransferase expression in suicidal behaviour.
abstract: 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 > 0.05). Lithium had no effect in suicide completers (p > 0.05) while it significantly increased SAT1 expression in the high risk (p < 0.001) and low risk (p < 0.01) groups as well as in controls (p < 0.001). Protein and mRNA levels were not correlated; lithium significantly reduced protein levels only in the control sample (p < 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.
authors.affiliation: Laboratory of Molecular Genetics, Section of Neuroscience and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.forename: Mirko
authors.initials: M
authors.lastname: Manchia
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Valeria
authors.initials: V
authors.lastname: Deiana
authors.forename: Donatella
authors.initials: D
authors.lastname: Congiu
authors.forename: Francesco
authors.initials: F
authors.lastname: Paribello
authors.forename: Paola
authors.initials: P
authors.lastname: Roncada
authors.forename: Alessio
authors.initials: A
authors.lastname: Soggiu
authors.forename: Cristian
authors.initials: C
authors.lastname: Piras
authors.forename: Andrea
authors.initials: A
authors.lastname: Urbani
authors.forename: George S
authors.initials: GS
authors.lastname: Robertson
authors.forename: Paul
authors.initials: P
authors.lastname: Keddy
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.forename: Guy A
authors.initials: GA
authors.lastname: Rouleau
authors.forename: Martin
authors.initials: M
authors.lastname: Alda
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D018692:Antimanic Agents / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D001714:Bipolar Disorder / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000523:psychology*; D002170:Canada; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007558:Italy; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D059020:Suicidal Ideation; D013405:Suicide; D013406:Suicide, Attempted; D055815:Young Adult; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D018692:Antimanic Agents; D018021:Lithium Chloride; D012333:RNA, Messenger; D000099228:Diamine N-Acetyltransferase