Validating genomic biomarkers as risk markers for incidence, non-response and recurrence in depression - CAP Study

• Conditions: F32; F33; Depressive episode; Recurrent depressive disorder

• Registration Number: DRKS00009819
• Lead Sponsor: Max-Planck-Institut für Psychiatrie

Brief Summary

Objective of sub-project SP4 in the OptiMD consortium was the validation of genomic biomarkers in depression from three clinical perspectives: (1) for predicting treatment outcome, (2) for predicting the risk of relapse, and (3) as indicators of disease risk. Based on our own preliminary work as well as on findings of our cooperation partners, the initial data analysis focused on the stress regulation gene FKBP5, which is of particular importance with regard to both, current therapeutic response to antidepressants and long-term outcome of depression. Genetic markers of this gene as well as their epigenetic modifications are suitable as so-called genomic biomarkers to be validated with regard to their diagnostic use in depression. Validation of these biomarkers was carried out from the three perspectives mentioned above, for which four sub-samples were recruited: a patient sample during inpatient depression treatment (MARS Cohort 1, treatment outcome perspective), a catamnestic sample of former study patients (MARS Cohort 2, relapse perspective), as well as a family study with children of depressed and non-depressed mothers (EpiFam Study) and a case-control sample with depressed and healthy children and adolescents (CAP Study, disease risk perspective). Risk markers of the FKBP5 gene were associated with treatment outcome under antidepressant treatment, replicating previous findings. In addition, associations were found with the risk of relapse in remitted depression and with the risk of incident depression in children and adolescents, especially, in interaction with the occurrence of stress and critical life events. Gene expression data also support the particular importance of FKBP5. In interaction with genetic risk markers, increased FKBP5 expression is associated with a negative treatment outcome prognosis. This corresponds with analyses at the protein level where the strongest effect was shown for serum levels of interleukin 1a, which, like FKBP5, has an important function in stress regulation. The specific role of FKBP5 in depressive disorder has also been demonstrated at the epigenetic level. Five independent methylation vectors were identified, which - again in interaction with FKBP5 markers - are associated with antidepressant treatment outcome. Four of these five vectors showed positive associations between maternal and child methylation rates, but only in control families without maternal depression. No associations emerged in families with maternal depression. This provides room for the hypothesis that epigenetically inherited depression risk with respect to FKBP5 may derive from the lack of inherited resilience factors rather than inherited vulnerability factors. It can be concluded that the obtained results confirm and extend previous findings by adding further evidence for the special role of FKBP5 in depression. In addition, the huge amount of data obtained in this project allow many other analytical approaches leading to the expectation of further results on the validation of genomic biomarkers for predicting treatment outcome, risk of relapse, and disease risk in the future.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-01-13
• Study Completion: 2021-01-31
• Results First Posted: 2022-02-22
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

Children and adolescents of both sexes aged 8 to 18 years, balanced in age and sex distribution between cases and controls; study consent of at least one parent or guardian of the study participant as well as oral and / or written consent of the minor study participant.

Exclusion Criteria

Pervasive developmental disorder in study participants (ICD10 F84)

Study & Design

• Study Type: observational
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Case or control group assignment based on a detailed diagnosis using the Diagnostic Interview for Mental Disorders in Children and Adolescents (Kinder-DIPS). Genetic variations and DNA methylation rates in CpG-rich regions of the genes ABCB1, FKBP5, P2RX4 and P2RX7 will be determined as predictors of the case/control status.