Does an early onset cause treatment-resistance in major depressive disorder by affecting educational attainment?

Major depressive disorder (MDD) is a common psychiatric disorder associated with marked individual suffering and a high societal burden.

A third of cases do not respond to initial first-line treatments, but the causes of treatment resistance are largely unknown. One potential cause for treatment resistance is an early age at MDD onset.

Individuals with an early age at onset (typically in adolescence or early adulthood) may fail to fulfil important developmental tasks in sensitive periods, such as achieving their potential in terms of education. In turn, lower educational attainment may decrease the chance that someone will benefit sufficiently from treatment.

This multidisciplinary project will leverage large, multilevel datasets and employ epidemiological and genetic methods to investigate the link between an early age at onset and treatment resistance in MDD.

First, I will test the association between age at MDD onset and treatment resistance while controlling for genetic liability and a history of trauma, and I will use genetic data to probe the putative causality of the relationship (with Mendelian randomization).

Second, I will test whether the relationship can be explained through the effect of an early onset on educational attainment and underachievement, and more broadly assess the relationship between early onset, educational attainment, and treatment resistance.

Taken together, the analyses will enable me to disentangle the complex relationships between age at onset, treatment resistance, and educational attainment, and explore to what extent these relationships could be causal.

As such, this research could identify important targets for monitoring and prevention (in cases with an early onset) and intervention strategies (aiming to improve educational attainment) to increase treatment response in MDD.