Background: Symptom reduction occurring early in depression treatment is associated with favourable posttreatment outcome, but it is not known how early reduction in specific depression symptoms affect treatment outcome. We aimed to determine the impact of symptom-specific change from pre-treatment to week four during internet-delivered CBT (ICBT) on overall and symptom-specific depression severity at post-treatment. We hypothesized that change in mood and emotional involvement would be most strongly associated with later overall depression severity.

Methods: 1300 participants with Major Depressive Disorder were followed over 12 weeks of ICBT using the selfreport Montgomery-& Aring;sberg Depression Rating Scale gauging nine symptoms. Linear models, informed by causal inference and cross-lagged network analysis methods, were used to estimate associations between early symptom-specific change and post-treatment depression severity, controlling for register-based and self-reported pre-treatment confounders.

Results: Early reduction in all symptoms was associated with lower overall and symptom-specific depression severity post-ICBT. Seven symptoms showed similar associations between early change and overall depression severity post-treatment: mood (standardized beta [(3] = 0.44), feelings of unease ((3 = 0.39), ability to concentrate ((3 = 0.46), initiative ((3 = 0.43), emotional involvement ((3 = 0.42), pessimism ((3 = 0.44), and zest for life ((3 = 0.42). Change in sleep ((3 = 0.27) and appetite ((3 = 0.27) had weaker associations with overall depression severity at post-treatment and were the only symptoms showing the hypothesized difference compared with mood and emotional involvement.

Conclusions: The impact of early symptom-specific reduction on post-treatment depression severity in ICBT for MDD may be similar across most symptoms, but less for the sleep and appetite symptoms, although causal interpretations rests on several assumptions.