Cross-species mapping of acute psychedelic-responsive genes links HTR2A cortical expression, cell-type enrichment, and human cortical expression modules.
- 1Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
- 2Department of Neurology, University of California, San Francisco, CA, USA.
- 3Department of Neurology, University of California, San Francisco, CA, USA. [email protected].
Abstract
Psychedelic drugs exert rapid and profound effects on human consciousness [1-7] and are increasingly being investigated for their therapeutic potential [8-14]. Yet the transcriptional programs through which they may reshape brain function and structure remain incompletely understood, in part because the available evidence is heterogeneous and largely preclinical [15, 16]. In a structured scoping review of transcriptomic studies in animal models and neural cell cultures, we identified genes reported in the source literature to change within 3 h of classical psychedelic administration and intersected them with the Allen Human Brain Atlas to define an acute expression set. This retained set showed cortex-centered enrichment, a marker-based deep-layer projection-neuron component, and ontology enrichment for neuron projection and related synaptic terms. A smaller subset overlapped with human accelerated region-associated genes and showed greater-than-random spatial alignment with a human cortical-expansion map. The retained cortical-expression maps showed serotonergic spatial alignment in the human cortex, most prominently with HTR2A expression. Clustering identified three cortical spatial-expression modules, including an association/limbic-weighted module enriched for plasticity and synaptic-organization terms. Together, these findings provide a human cortical framework linking acute psychedelic-responsive transcription to cortical cell-type enrichment, HTR2A spatial expression, cortical spatial-expression modules, and cortical-expansion, while leaving receptor-specific, causal, translational, and cell-type-resolved mechanisms for future work.
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BibTeX
@article{mcconnell2026crossspecies,
title = {{Cross-species mapping of acute psychedelic-responsive genes links HTR2A cortical expression, cell-type enrichment, and human cortical expression modules.}},
author = {Patrick A McConnell and Jackson Raffety and Andrew Li and Eric Steinberg and Syed Rahim and Christian Valtierra and Adam Gazzaley and Robin L Carhart-Harris and Lorenzo Pasquini},
journal = {Translational psychiatry},
year = {2026},
month = aug,
doi = {10.1038/s41398-026-04349-z},
url = {https://europepmc.org/article/MED/42957634},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cross-species mapping of acute psychedelic-responsive genes links HTR2A cortical expression, cell-type enrichment, and human cortical expression modules.
AU - Patrick A McConnell
AU - Jackson Raffety
AU - Andrew Li
AU - Eric Steinberg
AU - Syed Rahim
AU - Christian Valtierra
AU - Adam Gazzaley
AU - Robin L Carhart-Harris
AU - Lorenzo Pasquini
PY - 2026
DA - 2026/08/01
JO - Translational psychiatry
DO - 10.1038/s41398-026-04349-z
UR - https://europepmc.org/article/MED/42957634
AB - Psychedelic drugs exert rapid and profound effects on human consciousness [1-7] and are increasingly being investigated for their therapeutic potential [8-14]. Yet the transcriptional programs through which they may reshape brain function and structure remain incompletely understood, in part because the available evidence is heterogeneous and largely preclinical [15, 16]. In a structured scoping review of transcriptomic studies in animal models and neural cell cultures, we identified genes reported in the source literature to change within 3 h of classical psychedelic administration and intersected them with the Allen Human Brain Atlas to define an acute expression set. This retained set showed cortex-centered enrichment, a marker-based deep-layer projection-neuron component, and ontology enrichment for neuron projection and related synaptic terms. A smaller subset overlapped with human accelerated region-associated genes and showed greater-than-random spatial alignment with a human cortical-expansion map. The retained cortical-expression maps showed serotonergic spatial alignment in the human cortex, most prominently with HTR2A expression. Clustering identified three cortical spatial-expression modules, including an association/limbic-weighted module enriched for plasticity and synaptic-organization terms. Together, these findings provide a human cortical framework linking acute psychedelic-responsive transcription to cortical cell-type enrichment, HTR2A spatial expression, cortical spatial-expression modules, and cortical-expansion, while leaving receptor-specific, causal, translational, and cell-type-resolved mechanisms for future work.
SN - 2158-3188
ER -