title: The serotonin transporter genotype modulates the relationship between early stress and adult suicidality in bipolar disorder.
abstract: OBJECTIVE
  Bipolar disorder (BD) is associated with a higher risk of suicide and with worse early life stress. A serotonin (5-hydroxytryptamine; 5-HT) transporter-linked polymorphic region (5-HTTLPR) has been shown to influence the relationship between stress and the risk of attempting suicide in the general population, but has not been investigated in BD.
  
  
  METHODS
  We studied 136 inpatients (93 females, 43 males) with a major depressive episode in the course of BD. Early and recent stressful life events were scored on the Social Readjustment Rating Scale (SRRS). Regional gray matter (GM) volumes were analyzed, acquiring T1-weighted images on a 3.0 Tesla scanner.
  
  
  RESULTS
  Homozygote l/l patients attempted suicide in a higher proportion than *s carriers. A separate-slopes logistic regression showed a significant effect of 5-HTTLPR on the relationship between stress, depression, and suicide among *s carriers, but not among l/l homozygotes, early stress associated with worse probability of attempting suicide and with earlier age at onset of BD. Exposure to early stress correlated with GM volumes in the right prefrontal cortex (Brodmann area 46) - again, in *s carriers only.
  
  
  CONCLUSIONS
  5-HTTLPR modulated the relationship between early life stress and the core features of bipolar illness. 5-HTTLPR*s carriers showed a higher sensitivity to the effects of stress; when exposed to low levels of early stress, they were protected against suicide in respect to l/l, but higher levels of stress progressively increased their risk of suicide and reduced the age at onset of illness.
authors.affiliation: Department of Clinical Neurosciences, Scientific Institute Ospedale San Raffaele and University Vita-Salute, Milano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Benedetti
authors.forename: Roberta
authors.initials: R
authors.lastname: Riccaboni
authors.forename: Sara
authors.initials: S
authors.lastname: Poletti
authors.forename: Daniele
authors.initials: D
authors.lastname: Radaelli
authors.forename: Clara
authors.initials: C
authors.lastname: Locatelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Lorenzi
authors.forename: Adele
authors.initials: A
authors.lastname: Pirovano
authors.forename: Enrico
authors.initials: E
authors.lastname: Smeraldi
authors.forename: Cristina
authors.initials: C
authors.lastname: Colombo
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology / Q000523:psychology*; D001921:Brain / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008016:Life Change Events; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000150:complications* / Q000523:psychology; D013405:Suicide / Q000523:psychology*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins
keywords: serotonin; stress; suicide