Towards a genetics of mental disorders as complex dynamical systems: A symptom-specific and symptom-interactive approach
Abstract
Psychiatric genetics has largely mapped genetic liability onto diagnoses and symptom sum scores. Yet these disorder-level phenotypes are heterogeneous composites: individuals sharing a diagnosis may exhibit markedly different symptoms; the same symptoms recur across multiple disorders; and symptoms influence one another over time. Genetic analyses based on such aggregates may therefore obscure symptom-specific biological signals and overlook the dynamic processes through which genetic liability becomes expressed clinically. We propose a complementary symptom-specific and symptom-interactive framework that conceptualises psychiatric disorders as dynamic systems of mutually influencing symptoms. This framework distinguishes three forms of genetic influence: direct effects of genetic risk on individual symptoms; indirect effects propagated through symptom-to-symptom pathways; and examinations of how genetic risk moderates the strength, persistence, and activation potential of symptom interactions. We show how various genetic and psychometric methods can be integrated to investigate these processes. We identify four priorities for psychiatric genetics research that can be advanced by adopting this framework: improving symptom-level phenotyping; distinguishing disorder-specific and transdiagnostic symptoms; modelling mediated genetic effects across symptoms; and testing whether genetic liability shapes symptom co-activation and their temporal dynamics. Reframing psychopathology as systems of interacting symptoms could sharpen genes-to-phenotype mapping, clarify heterogeneity in illness trajectories, and align psychiatric genetics more closely with novel mechanistic theories of mental disorders and the goals of precision psychiatry.
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BibTeX
@misc{ebrahimi2026towards,
title = {{Towards a genetics of mental disorders as complex dynamical systems: A symptom-specific and symptom-interactive approach}},
author = {Omid V. Ebrahimi and Michel Guillaume Nivard and Ludvig Daae Bjørndal},
howpublished = {PsyArXiv},
year = {2026},
month = sep,
doi = {10.31234/osf.io/ukcfq_v1},
url = {https://osf.io/preprints/psyarxiv/ukcfq_v1/},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Towards a genetics of mental disorders as complex dynamical systems: A symptom-specific and symptom-interactive approach
AU - Omid V. Ebrahimi
AU - Michel Guillaume Nivard
AU - Ludvig Daae Bjørndal
PY - 2026
DA - 2026/09/16
PB - PsyArXiv
DO - 10.31234/osf.io/ukcfq_v1
UR - https://osf.io/preprints/psyarxiv/ukcfq_v1/
AB - Psychiatric genetics has largely mapped genetic liability onto diagnoses and symptom sum scores. Yet these disorder-level phenotypes are heterogeneous composites: individuals sharing a diagnosis may exhibit markedly different symptoms; the same symptoms recur across multiple disorders; and symptoms influence one another over time. Genetic analyses based on such aggregates may therefore obscure symptom-specific biological signals and overlook the dynamic processes through which genetic liability becomes expressed clinically. We propose a complementary symptom-specific and symptom-interactive framework that conceptualises psychiatric disorders as dynamic systems of mutually influencing symptoms. This framework distinguishes three forms of genetic influence: direct effects of genetic risk on individual symptoms; indirect effects propagated through symptom-to-symptom pathways; and examinations of how genetic risk moderates the strength, persistence, and activation potential of symptom interactions. We show how various genetic and psychometric methods can be integrated to investigate these processes. We identify four priorities for psychiatric genetics research that can be advanced by adopting this framework: improving symptom-level phenotyping; distinguishing disorder-specific and transdiagnostic symptoms; modelling mediated genetic effects across symptoms; and testing whether genetic liability shapes symptom co-activation and their temporal dynamics. Reframing psychopathology as systems of interacting symptoms could sharpen genes-to-phenotype mapping, clarify heterogeneity in illness trajectories, and align psychiatric genetics more closely with novel mechanistic theories of mental disorders and the goals of precision psychiatry.
ER -