title: Serotonin transporter genotype, salivary cortisol, neuroticism and life events: impact on subsequent psychopathology in healthy twins at high and low risk for affective disorder.
abstract: OBJECTIVE
  To investigate if cortisol alone or in interaction with other risk factors (familial risk, the serotonin transporter genotype, neuroticism and life events (LEs)) predicts onset of psychiatric disorder in healthy individuals at heritable risk.
  In a high-risk study, 234 healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorder (high and low risk twins) were baseline assessed. Participants were followed up for seven years and then reassessed with a personal interview revealing whether they had developed psychiatric illness.
  
  
  RESULTS
  36 participants (15.4%) developed psychiatric disorder. Using Cox proportional hazards ratio (HR) estimates neither morning nor evening salivary cortisol at baseline did predict illness onset. In multivariate Cox models, the two-way interaction between morning cortisol and LEs lifetime before baseline was significantly associated with onset. Further, the HR of onset was higher concerning individuals carrying the short allele of the 5-HTTPLR and having experienced more LEs lifetime. Familial risk for affective disorder predicted illness and the risk of onset was further increased in individuals at familial risk carrying the short allele of the 5-HTTPLR.
  
  
  CONCLUSIONS
  Cortisol levels alone do not increase the risk of onset of psychiatric illness but the interaction of a lower cortisol level and the experience of more LEs do. The 5-HTTLPR genotype seems to interact and contribute to increased stress vulnerability in combination with other stress indicators of illness thereby adding to the risk of subsequent psychopathology.
authors.affiliation: Psychiatric Centre Copenhagen, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: maj.vinberg@regionh.dk.
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.forename: Kamilla
authors.initials: K
authors.lastname: Miskowiak
authors.forename: Lars Vedel
authors.initials: LV
authors.lastname: Kessing
mesh_terms: D002940:Circadian Rhythm / Q000502:physiology*; D015331:Cohort Studies; D004200:Diseases in Twins; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008016:Life Change Events; D008297:Male; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D017063:Outcome Assessment, Health Care; D010555:Personality Inventory; D016016:Proportional Hazards Models; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D012463:Saliva / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone
keywords: 5-HTTPLR; Affective disorders; BDI; Beck depression Inventory; CI; Confidence Interval; Cortisol; DZ; Dizygotic; EPO; Eysenck Personality Questionnaire; HPA; HR; HTTLPR; Hazard Ratio; Hypothalamus–pituitary–adrenal; ICD-10; ICD-8; International Classification of Diseases “10th” revision; International Classification of Diseases “8th” revision; LEs; Life events; MDQ; MZ; Mood Disorder Questionnaire; Risk factors; SCAN; SD; Schedules for Clinical Assessment in Neuropsychiatry; Standard Deviation; monozygotic; serotonin-transporter-linked polymorphic region