title: Neuroticism mediates the effect of P2RX7 on outcomes of mood disorders.
abstract: BACKGROUND
  We previously reported an association between P2RX7 variant rs208294, diagnosis, and the longitudinal course of mood disorders. Here, we test whether the personality trait neuroticism mediates the effect of P2RX7 on the course of mood disorders.
  
  
  METHODS
  Patients with DSM-IV mood disorder (256 with major depressive disorder and 168 with bipolar disorder [BD]) were diagnosed with semistructured interviews, genotyped, and followed up for a median of 60 (range 6-83) months. The primary outcome was the prospectively assessed proportion of time spent in any DSM-IV mood episode (time ill). Three types of genetic effect were tested in structural equations models: Model 1: genes directly affect outcome independent of neuroticism, Model 2: neuroticism mediates the effect of genes on outcome, and Model 3: neuroticism and the genetic variant interact in their effect on outcome.
  
  
  RESULTS
  Neuroticism mediated the P2RX7 genetic effect on outcome. The T allele of rs208294 was associated with higher neuroticism, which in turn predicted a higher proportion of time spent in mood episodes (the bootstrap-based test of indirect effect, P = .02). There was no significant interaction between neuroticism and the genotype.
  
  
  CONCLUSIONS
  Neuroticism is likely to lie on the causal pathway between the rs208294 T variant and the adverse long-term course of major depressive and BDs.
authors.affiliation: Department of Mental Health and Substance Use, National Institute for Health and Welfare, Helsinki, Finland. outi.mantere@thl.fi
authors.forename: Outi
authors.initials: O
authors.lastname: Mantere
authors.forename: Pia
authors.initials: P
authors.lastname: Soronen
authors.forename: Rudolf
authors.initials: R
authors.lastname: Uher
authors.forename: Mikko
authors.initials: M
authors.lastname: Ketokivi
authors.forename: Pekka
authors.initials: P
authors.lastname: Jylhä
authors.forename: Tarja
authors.initials: T
authors.lastname: Melartin
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
authors.forename: Erkki
authors.initials: E
authors.lastname: Isometsä
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075384:Neuroticism; D011569:Psychiatric Status Rating Scales; D058486:Receptors, Purinergic P2X7 / Q000235:genetics*; D018709:Statistics, Nonparametric
chemical_list: C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7