title: Investigation of blood mRNA biomarkers for suicidality in an independent sample.
abstract: Changes in the blood expression levels of SAT1, PTEN, MAP3K3 and MARCKS genes have been reported as biomarkers of high versus low suicidality state (Le-Niculescu et al.). Here, we investigate these expression biomarkers in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, of patients with major depressive disorder on a 12-week antidepressant treatment. Blood gene expression levels were available at baseline and week 8 for patients who experienced suicidal ideation during the study (n=20) versus those who did not (n=37). The analysis is well powered to detect the effect sizes reported in the original paper. Within either group, there was no significant change in the expression of these four genes over the course of the study, despite increasing suicidal ideation or initiation of antidepressant treatment. Comparison of the groups showed that the gene expression did not differ between patients with or without treatment-related suicidality. This independent study does not support the validity of the proposed biomarkers.
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Mullins
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Hodgson
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
authors.forename: K E
authors.initials: KE
authors.lastname: Tansey
authors.affiliation: Department of Mental Health and Psychiatry, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Perroud
authors.affiliation: Department of Psychiatry, University of Bonn, Bonn, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Maier
authors.affiliation: Research Department P, Aarhus University Hospital, Risskov, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Mors
authors.affiliation: 1] Department of Psychiatry, University of Bonn, Bonn, Germany [2] Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Laboratory of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Hauser
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb, Zagreb, Croatia.
authors.forename: N
authors.identifier: 0000000253031834
authors.initials: N
authors.lastname: Henigsberg
authors.affiliation: 1] Laboratoire de Psychologie Médicale, Université Libre de Bruxelles, Brussels, Belgium [2] PsyPluriel - Centre Européen de Psychologie Médicale, Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Souery
authors.affiliation: 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK [2] Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.
authors.forename: K
authors.identifier: 0000000211073024
authors.initials: K
authors.lastname: Aitchison
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Farmer
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: McGuffin
authors.affiliation: 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King's College London, London, UK.
authors.forename: G
authors.identifier: 0000000320531792
authors.initials: G
authors.lastname: Breen
authors.affiliation: 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK [2] Department of Psychiatry, Dalhousie University, 5909 Veterans' Memorial Lane, Halifax, NS, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Uher
authors.affiliation: 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK [2] Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, UK.
authors.forename: C M
authors.initials: CM
authors.lastname: Lewis
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D048748:MAP Kinase Kinase Kinase 3 / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D051059:PTEN Phosphohydrolase / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood* / Q000235:genetics*; D059020:Suicidal Ideation; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D000928:Antidepressive Agents; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D048748:MAP Kinase Kinase Kinase 3; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D051059:PTEN Phosphohydrolase; D012333:RNA, Messenger; D000099228:Diamine N-Acetyltransferase; C000619710:MARCKS protein, human; C482625:MAP3K3 protein, human; C494929:PTEN protein, human