TY - JOUR

T1 - Serotonin transporter genotype, salivary cortisol, neuroticism and life events

T2 - impact on subsequent psychopathology in healthy twins at high and low risk for affective disorder

AU - Vinberg, Maj

AU - Miskowiak, Kamilla

AU - Kessing, Lars Vedel

N1 - © 2013.

PY - 2014/1/3

Y1 - 2014/1/3

N2 - 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.MATRIAL AND METHODS: 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.

AB - 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.MATRIAL AND METHODS: 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.

KW - Circadian Rhythm

KW - Cohort Studies

KW - Diseases in Twins

KW - Female

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Hydrocortisone

KW - Life Change Events

KW - Male

KW - Mood Disorders

KW - Outcome Assessment (Health Care)

KW - Personality Inventory

KW - Proportional Hazards Models

KW - Psychiatric Status Rating Scales

KW - Risk Factors

KW - Saliva

KW - Serotonin Plasma Membrane Transport Proteins

U2 - 10.1016/j.pnpbp.2013.10.007

DO - 10.1016/j.pnpbp.2013.10.007

M3 - Journal article

C2 - 24140930

VL - 48

SP - 193

EP - 198

JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry

SN - 0278-5846

ER -