Abstract # 1845 Age- and depression-related changes in FKBP4 and FKBP5 expression across adolescence

Abstract

FK506-binding protein 5 (FKBP5) has repeatedly been shown to be a critical determinant of depression. For example, FKBP5 polymorphisms emerged as moderators of depression risk and protein levels have been linked to disease severity. However, little is known about FKBP5 in the context of depression pathogenesis. To address this gap, we repeatedly assessed 42 female adolescents (14-19yrs) at high risk for depression over the course of 2.5 years. Every 6 months, participants underwent a diagnostic interview and venipuncture to measure FKBP5 and FKBP4 mRNA levels. To assess the role of age, four equally-sized age groups were formed (14–15, 16–17, 18, 19 yrs). Over the study period, 21 adolescents showed at least one episode of depression (DEP), while 21 stayed symptom-free (SF). FKBP5 expression increased across age groups independent of health status, such that 14–15yrs old DEP and SF adolescents showed the lowest and 19yrs old DEP and SF adolescents showed the highest FKPB5 expression across time (age: F = 3.22, p = .035). While a similar pattern emerged for FKBP4 in SF adolescents, DEP adolescents exhibited overall lower as well as less age-variable FKBP4 mRNA levels (FBKP4-by-age-by-health status: F = 2.28, p = .023). In summary, while changes in FKBP4 and FKBP5 expression across adolescence showed a similar up-regulatory pattern in healthy participants, depression was associated with a potential de-synchronization of the two co-chaperons suggesting reduced glucocorticoid receptor signaling.