Dear Editor,
we appreciated Borgo and colleagues’ correspondence proposing Gilbert’s syndrome as a potential biological vulnerability state in which non-specific somatic symptoms, including fatigue, autonomic arousal and lowered pain threshold, may be experienced as clinically meaningful and, in some patients, potentially patterned over time. This perspective is valuable because it invites a shift from static diagnostic labels to dynamic models that integrate vulnerability, triggers and symptom trajectories.
A constructive way forward is to test this hypothesis with methods that are already standard in psychiatric epidemiology and clinical psychophysiology. Prospective, preregistered, within-person designs could combine repeated symptom assessments using validated instruments with parallel measures of bilirubin levels, sleep parameters, stress markers and medication exposures. These datasets could then be linked to objective environmental indices, including geomagnetic activity and solar-related parameters, while controlling for seasonality and meteorological covariates. Distributed-lag and mixed-effects approaches would allow separation of short-term fluctuations from background trends and would help quantify any effect size, time window and individual susceptibility.
Importantly, even a null result would be informative, because it would help delimit which symptom patterns are better explained by known triggers in Gilbert’s syndrome, for instance fasting, infection and stress, and which patterns might reflect broader psychobiological processes relevant to somatoform presentations. Conversely, a reproducible association would open a new line of inquiry on sensory and autonomic mechanisms, on top of hepatic metabolism, that could inform both patient counselling and targeted non-pharmacological interventions aimed at arousal reduction.
We therefore welcome this hypothesis-generating correspondence as an invitation to build a shared, testable research agenda that bridges hepatology, psychophysiology and environmental exposure science, in line with the clinical implications raised by Siig and colleagues’ burden estimates.
Sincerely,
Dr. Giovanni Ghirga
Pediatrician
Scientific Committee of Doctors for the Environment
International Society of Doctors for the Environment (ISDE, Italy)
ghirgagiovanni@gmail.com
*Reply to “TO THE EDITOR – LANCET PSYCHIATRY” in Psychomed nn. 1-2-3 Anno XX – 2025 pg.107
