Adolescent prodromal phenotypes of psychiatric disorders: insights from a novel DISC1-perturbed monkey model
- 1Kyoto University
Abstract
Neurodevelopmental deficits frequently lead to mild but significant adolescent social and cognitive changes, representing prodromal manifestations of adult-onset psychiatric disorders in a cross-disease manner. Although experimental medicine utilizes animal models to address the mechanisms, rodent brains lack critical structures for human higher brain functions such as the dorsolateral prefrontal cortex. To fill this translational gap, we generated monkeys with an impaired DISC1 gene locus, targeting the multifunctional protein essential for neurodevelopment and involved in transdiagnostic mental health risks. Here we analyze the F0 animals by minimizing mosaicism. At ages equivalent to human adolescence, these monkeys exhibited blunted responsiveness to social stimuli and increased internal drives, mirroring altered social behaviors in the prodromal stage in humans. Resting-state functional MRI data indicated disrupted global functional connectivity and reorganization of network topology, marked by a shift in the dominance of brain hubs from prefrontal regions to sensory areas. This primate model provides a unique platform for studying psychiatric disorders, such as schizophrenia, across the developmental trajectory.
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BibTeX
@misc{lan2026adolescent,
title = {{Adolescent prodromal phenotypes of psychiatric disorders: insights from a novel DISC1-perturbed monkey model}},
author = {Z. Lan and H. Onoe and T. Tsukiyama and C. Iwatani and C.-Y. Chen and K. Okita and K. Ishizuka and R. Endo and R. Nakai and K. Imamura and K. Hikishima and H. Tsuchiya and M. Nakaya and Y. Fang and A. Kobayashi and Y. Shinto and R. Yamaguchi and M. Matsunaga and K. Oe and K. Omori and Y. Ozeki and T. Tomoda and K. Miura and S.-i. Urayama and N. Oishi and T. Okada and M. Tanaka and H. Inoue and J. Takahashi and A. Sawa and T. Isa},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.11.758339},
url = {https://www.biorxiv.org/content/10.64898/2026.10.11.758339v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Adolescent prodromal phenotypes of psychiatric disorders: insights from a novel DISC1-perturbed monkey model
AU - Z. Lan
AU - H. Onoe
AU - T. Tsukiyama
AU - C. Iwatani
AU - C.-Y. Chen
AU - K. Okita
AU - K. Ishizuka
AU - R. Endo
AU - R. Nakai
AU - K. Imamura
AU - K. Hikishima
AU - H. Tsuchiya
AU - M. Nakaya
AU - Y. Fang
AU - A. Kobayashi
AU - Y. Shinto
AU - R. Yamaguchi
AU - M. Matsunaga
AU - K. Oe
AU - K. Omori
AU - Y. Ozeki
AU - T. Tomoda
AU - K. Miura
AU - S.-i. Urayama
AU - N. Oishi
AU - T. Okada
AU - M. Tanaka
AU - H. Inoue
AU - J. Takahashi
AU - A. Sawa
AU - T. Isa
PY - 2026
DA - 2026/10/11
PB - bioRxiv
DO - 10.64898/2026.10.11.758339
UR - https://www.biorxiv.org/content/10.64898/2026.10.11.758339v1
AB - Neurodevelopmental deficits frequently lead to mild but significant adolescent social and cognitive changes, representing prodromal manifestations of adult-onset psychiatric disorders in a cross-disease manner. Although experimental medicine utilizes animal models to address the mechanisms, rodent brains lack critical structures for human higher brain functions such as the dorsolateral prefrontal cortex. To fill this translational gap, we generated monkeys with an impaired DISC1 gene locus, targeting the multifunctional protein essential for neurodevelopment and involved in transdiagnostic mental health risks. Here we analyze the F0 animals by minimizing mosaicism. At ages equivalent to human adolescence, these monkeys exhibited blunted responsiveness to social stimuli and increased internal drives, mirroring altered social behaviors in the prodromal stage in humans. Resting-state functional MRI data indicated disrupted global functional connectivity and reorganization of network topology, marked by a shift in the dominance of brain hubs from prefrontal regions to sensory areas. This primate model provides a unique platform for studying psychiatric disorders, such as schizophrenia, across the developmental trajectory.
ER -