Rats exposed to both prenatal immune activation and adolescent THC showed brain changes detectable by imaging and gene expression, even before behavioral problems appeared.
Schizophrenia researchers, developmental neuroscientists, adolescent mental health advocates
Combined prenatal infection + adolescent THC leaves hidden molecular brain marks
What the researchers found
While adolescent THC did not trigger visible behavioral disruptions, PET brain scans revealed alterations dependent on the combination of prenatal immune activation and THC. Gene expression analysis showed maternal immune activation affected dopamine, glutamate, and serotonin genes, with the two-hit combination shifting expression from downregulation to upregulation. Blood biomarkers of inflammatory pathway changes were identified.
Why it matters
This is the first study to show that the combination of prenatal immune challenge and adolescent THC leaves detectable molecular and neuroimaging marks even before behavioral symptoms emerge, suggesting a hidden vulnerability window.
The numbers in context
Both male and female rats tested. Increasing THC doses during adolescence. PET scans at multiple time points. RNA sequencing of orbitofrontal cortex and peripheral blood mononuclear cells. Gene expression shifts identified in dopaminergic, glutamatergic, and serotonergic pathways.
How the study worked
Two-hit animal model combining maternal immune activation with adolescent THC exposure in male and female rats, followed by behavioral testing, longitudinal PET neuroimaging, RNA sequencing of orbitofrontal cortex and blood cells.
What this study cannot tell us
Animal model of immune activation may not fully replicate human prenatal infection. THC doses may not reflect human use patterns. Behavioral effects may emerge later than the observation window. Blood biomarkers need human validation.
How to read the evidence
Sophisticated multi-method animal study, but translational gap to human psychiatric risk remains significant.
When this study was published
2025 study with novel two-hit model combining imaging and transcriptomics.
The bigger picture
The "two-hit" hypothesis of schizophrenia suggests that prenatal insults create vulnerability that later environmental factors, like adolescent cannabis use, can trigger. This study shows the combination leaves biological traces even without overt symptoms.
Questions still open
- Could blood biomarkers identify at-risk individuals before psychosis develops? Would avoiding cannabis in adolescence prevent the molecular changes? Do the brain alterations eventually lead to behavioral symptoms?
Common questions
Can prenatal infection make adolescent cannabis use more dangerous?
Could a blood test predict who is at risk?
Read the original research
A Hidden Mark of a Troubled Past: Neuroimaging and Transcriptomic Analyses Reveal Interactive Effects of Maternal Immune Activation and Adolescent THC Exposure Suggestive of Increased Neuropsychiatric Risk.
Biological psychiatry global open science, 5(3), 100452
Citation
Moreno-Fernández, Mario; Luján, Víctor; Baliyan, Shishir; Poza, Celia; Capellán, Roberto; de Las Heras-Martínez, Natalia; Morcillo, Miguel Ángel; Oteo, Marta; Ambrosio, Emilio; Ucha, Marcos; Higuera-Matas, Alejandro. (2025). A Hidden Mark of a Troubled Past: Neuroimaging and Transcriptomic Analyses Reveal Interactive Effects of Maternal Immune Activation and Adolescent THC Exposure Suggestive of Increased Neuropsychiatric Risk.. Biological psychiatry global open science, 5(3), 100452. https://doi.org/10.1016/j.bpsgos.2025.100452
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