Psychiatric disease in late adolescence and young adulthood. Foetal programming by maternal hypothyroidism?
OBJECTIVE
Lack of maternal thyroid hormones during foetal brain development may lead to structural abnormalities in the brain. We hypothesized that maternal hypothyroidism during the pregnancy could programme the foetus to development of psychiatric disease later in life.


METHODS
Danish nationwide register study.


METHODS
Singletons live-born 1980-1990.


METHODS
Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) with 95% confidence interval for offspring redemption of ≥2 prescriptions of a psychiatric drug from age 15 to 31 years.


RESULTS
Among 542 100 adolescents and young adults included, altogether 3979 (0·7%) were born to mothers with hypothyroidism registered before 1996. In crude analyses, the use of a psychiatric drug was more frequent in late adolescence and young adulthood when the mother had hypothyroidism (P < 0·001); however, several possible confounders had to be taken into account. For example, mothers with hypothyroidism often also had a psychiatric registration (38·5% vs 27·7%, P < 0·001) and the use of psychiatric drugs changed over time. After adjustment for confounders including birth year, maternal age and maternal psychiatric history, maternal hypothyroidism was associated with an increased risk of having redeemed prescriptions of anxiolytics [aHR 1·23 (1·03-1·48)] and antipsychotics [aHR 1·22 (1·03-1·44)] in late adolescence and young adulthood. For antidepressants, aHR was 1·07 (0·98-1·17).


CONCLUSIONS
The association between maternal hypothyroidism and the use of a psychiatric drug in late adolescence and young adulthood was partly confounded by maternal psychiatric history, but foetal programming by maternal hypothyroidism may be part of the mechanisms leading to the use of anxiolytics and antipsychotics.
Department of Endocrinology, Aalborg University Hospital, Aalborg, Denmark.
Stine Linding
SL
Andersen
Jørn
J
Olsen
Chun Sen
CS
Wu
Peter
P
Laurberg
D000293:Adolescent; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D007037:Hypothyroidism / Q000150:complications* / Q000453:epidemiology; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016016:Proportional Hazards Models; D011618:Psychotic Disorders / Q000188:drug therapy / Q000453:epidemiology; D055815:Young Adult
D014151:Anti-Anxiety Agents; D014150:Antipsychotic Agents