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Background: Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders., Methods: Within the German research network for mental disorders, 895 participants ( n  = 476 female, n  = 602 anxiety disorder, n  = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP)., Results: The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: β = -0.35; NVS: β = 0.39; CS: β = -0.12; SP: β = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association., Limitations: The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for., Conclusion: Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways., Competing Interests: FP is a member of the European Scientific Advisory Board of Brainsway Inc., Jerusalem, Israel, and the International Scientific Advisory Board of Sooma, Helsinki, Finland. He has received speaker’s honoraria from Mag&More GmbH, the neuroCare Group, Munich, Germany, and Brainsway Inc. His lab has received support with equipment from neuroConn GmbH, Ilmenau, Germany, Mag&More GmbH and Brainsway Inc. TB served in an advisory or consultancy role for eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Förstner, Böttger, Moldavski, Bajbouj, Pfennig, Manook, Ising, Pittig, Heinig, Heinz, Mathiak, Schulze, Schneider, Kamp-Becker, Meyer-Lindenberg, Padberg, Banaschewski, Bauer, Rupprecht, Wittchen, Rapp and Tschorn.)