What the study found
Genetic variation in TPH2, a gene involved in regulating central serotonin (5-HT), appeared to influence how the brain responded to acute tryptophan depletion, a temporary reduction in serotonin signaling. The authors report changes in brain activity and connectivity, with some effects seen regardless of genotype and others specific to one genotype group.
Why the authors say this matters
The authors conclude that TPH2 may be a genetic marker of vulnerability to the neural effects of transient changes in serotonin signaling. They also suggest that serotonin helps regulate the organization of large-scale brain networks involved in emotional reactivity and regulation.
What the researchers tested
The study used a within-subject, randomized, placebo-controlled resting-state fMRI design in 53 healthy men. Participants were grouped by TPH2 genotype (rs4570625; GG vs TT), and the researchers examined spontaneous intrinsic neural activity, functional connectivity, and connectome gradient analyses after acute tryptophan depletion versus placebo.
What worked and what didn't
Acute tryptophan depletion increased spontaneous neural activity in hippocampal CA1 in both genotype groups. It also enhanced communication between this region and the bilateral amygdala and ventromedial prefrontal cortex specifically in GG carriers. In addition, depletion sharpened intrinsic connectome gradient architecture in the salience, frontoparietal, and default mode networks.
What to keep in mind
The abstract only describes healthy male participants, so the findings are limited to that group. It also does not report detailed effect sizes, broader clinical outcomes, or limitations beyond the study scope.
Key points
- TPH2 genotype appeared to change how the brain responded to acute tryptophan depletion.
- Acute tryptophan depletion increased spontaneous activity in hippocampal CA1 in both genotype groups.
- Connectivity between hippocampal CA1, the amygdala, and the ventromedial prefrontal cortex increased specifically in GG carriers.
- Connectome gradient architecture changed in the salience, frontoparietal, and default mode networks.
- The study was done in 53 healthy men using resting-state fMRI.
Disclosure
- Research title:
- Serotonin variation altered brain connectivity in men
- Authors:
- Lan Wang, Congcong Liu, Xianyang Gan, Keith Kendrick, W. G. Will Zhao, Christian Montag, Ting Xu, Benjamin Becker
- Institutions:
- University of Electronic Science and Technology of China, Sichuan Provincial Hospital of Traditional Chinese Medicine, Xinxiang Medical University, University of Macau, Southwest University, Ministry of Education, University of Hong Kong
- Publication date:
- 2026-02-24
- OpenAlex record:
- View
Get the weekly research newsletter
Stay current with peer-reviewed research without reading academic papers — one filtered digest, every Friday.