2026 ECNP Congress

PS03-3022

Family-history variables are associated with remission in the OLIVE trial

Onur Serçe — C. Eulenburg, G. Daniel, B. Myhsok, L. Arvaston, E. Papanastasiou, H. Eriksson · HMNC Brainhealth, Clinical Development, Munich, Germany

2026 ECNP Congress

Introduction

Family history of depressive illness is a clinically accessible proxy for inherited and shared-environment vulnerability to major depressive disorder (MDD). Prior studies have linked familial loading to earlier onset, recurrence and greater severity of depression, but its value as a predictor of short-term treatment outcome remains uncertain. In STAR*D, family history of depression was associated with greater clinical complexity, but not with clear differences in overall response or remission rates [1]. This lack of predictive value may partly arise from simplistic family-history measures, as more granular familial-loading measures may capture vulnerability more accurately than simple dichotomous family-history indicators [2].

Aims

Analyzing clinical data from a large phase 2 randomized clinical trial (RCT) in MDD (BH-200-03, OLIVE; EudraCT 2022-002757-26), we evaluated whether MDD history in patients’ relatives influenced response or remission rates; whether first-degree or parental MDD history improved the signal beyond a coarse binary label; and whether associations differed by treatment arm.

Methods

The post-hoc analysis included 293 OLIVE participants with baseline and week-8, primary endpoint data from the 17-item Hamilton Depression Rating Scale (HAMD-17). The coarse family-history MDD variable and granular variables (e.g. first-degree, parent, sibling, etc.) were derived from the same associated-person medical history and supplemental text records. Outcomes were remission (week-8 HAMD-17 total score <8), response, (>= 50% HAMD-17 total score reduction from baseline), week-8 HAMD-17 total score, and percentage of HAMD-17 total score reduction. Logistic and linear regression models were adjusted for age, sex, baseline HAMD-17 total score and treatment arm. Treatment-predictive effects were assessed using family-history-by-treatment-arm interaction terms.

Results

Using the coarse family-history label, 53/293 participants (18.1%) were classified as positive. Remission occurred in 23/53 participants with a family history of MDD versus 45/240 without (43.4% vs 18.8%; Fisher OR 3.32, p=2.7×10⁻⁴). After adjustment for age, sex, baseline HAMD-17 total score, and treatment arm, the association remained (OR 2.66, 95% CI 1.37–5.18, p=3.9×10⁻³).

Granular variables resulted in stronger associations. First-degree MDD history (46 participants) was associated with remission (47.8% vs 18.6%; adjusted OR 3.36, 95% CI 1.68–6.74, p=6.4×10⁻⁴) and parental MDD history (33 participants) showed the strongest effect (54.5% vs 19.2%; adjusted OR 4.06, 95% CI 1.82–9.05, p=6.1×10⁻⁴). Response associations were weaker: first-degree OR 1.93, p=5.3×10⁻²; parental OR 1.99, p=8.5×10⁻²; coarse label OR 1.85, p=5.8×10⁻². Treatment-arm interactions did not support a predictive effect for remission (p-values: coarse 6.60×10⁻¹, first-degree 9.24×10⁻¹, parental 7.84×10⁻¹, maternal 6.70×10⁻¹) or response (coarse 5.62×10⁻¹, first-degree 9.54×10⁻¹, parental 6.50×10⁻¹, maternal 3.77×10⁻¹).

Continuous outcomes were directionally consistent, especially for parental history. Subgroup analyses across sex, age tertiles, and baseline HAMD-17 tertiles showed no subgroup-specific effects, albeit heterogeneity was observed for parental remission by age tertile.

Conclusion

A family-history of MDD, particularly first-degree and parental MDD history, was associated with higher likelihood of remission, but not clearly with response. Lack of treatment-arm interaction supports a prognostic, rather than treatment-predictive, interpretation. These findings warrant further evaluation of structured family-history variables as prognostic covariates in MDD trials.

References

  1. Husain, M.M., Rush, A.J., Wisniewski, S.R., et al., 2009. Family history of depression and therapeutic outcome: findings from STAR*D. J. Clin. Psychiatry 70 (2), 185-195.
  2. van Sprang, E.D., Maciejewski, D.F., Milaneschi, Y., et al., 2022. Familial risk for depressive and anxiety disorders: associations with genetic, clinical, and psychosocial vulnerabilities. Psychol. Med. 52 (4), 696-706.