In a revealing Genomic Press Interview published today in Brain Medicine, Sara Poletti, PhD, senior researcher at IRCCS Ospedale San Raffaele Milan, illuminates the profound connections between childhood adversity and lifelong vulnerability to psychiatric disorders through persistent neuroinflammation pathways and alterations in brain structure.
Bridging psychology and neurobiology
Dr. Poletti’s groundbreaking research has transformed understanding of how early life experiences become biologically embedded, creating lasting changes in brain structure and immune function. As the only tenure-track psychologist in psychiatry at her institute, she has pioneered multidisciplinary approaches that combine neuroimaging, genetic analysis, and immunological markers to decode the biological signatures of childhood trauma.
The immune system doesn’t just fight infections-it plays a crucial role in shaping our mental health throughout life. Childhood trauma can fundamentally reprogram these immune responses, creating vulnerability to depression, bipolar disorder, and other psychiatric conditions decades later.”
Sara Poletti, PhD, senior researcher at IRCCS Ospedale San Raffaele Milan
Her work raises critical questions about prevention and intervention: Can we identify biological markers of trauma early enough to prevent psychiatric disorders? How do protective factors buffer against neuroinflammatory responses? What role does timing play in trauma’s biological impact? These questions drive Dr. Poletti’s innovative research program.
From microscope to mind: An unexpected journey
Dr. Poletti’s path to neuroscience began with a childhood microscope and evolved through encounters with Freud’s writings and neuroimaging studies of violent criminals. This eclectic background equipped her with unique perspectives on brain-behavior relationships. Despite warnings that psychedelic and inflammation research was “career suicide” in 2006, she persisted in exploring these then-marginalized areas that have since become central to psychiatric research.
As Project Leader at San Raffaele’s Psychiatry and Clinical Psychobiology Unit, Dr. Poletti coordinates diverse teams of psychologists, physicians, and biologists. Her leadership of a European Research Area Network (ERA-NET) Neuron project on the consequences of infections on mental health exemplifies her ability to foster international collaboration in advancing inflammation’s role in psychiatric disorders.
Transforming challenges into opportunities
One defining moment in Dr. Poletti’s career came when she reluctantly accepted a teaching position in human physiology-a field she knew little about. “It required extensive studying and put me to the test,” she recalls. “However, I learned a great deal from this experience, both scientifically and personally.” This challenge deepened her understanding of body-brain interactions, proving invaluable for her later research on neuroinflammation.
Her resilience in facing academic challenges mirrors the resilience she studies in trauma survivors. Some individuals exposed to severe childhood adversity develop psychiatric disorders while others don’t-understanding these differences could revolutionize preventive psychiatry. What biological factors confer resilience? How can we enhance natural protective mechanisms? Dr. Poletti’s research addresses these fundamental questions.
Clinical implications and future directions
Dr. Poletti’s findings have immediate clinical relevance. By identifying specific inflammatory markers associated with childhood trauma, her work provides potential targets for novel interventions. This precision medicine approach could transform psychiatric treatment from symptom management to addressing underlying biological mechanisms. Following this line of reasoning she published the first paper on the use of an immunomodulatory agent (interleukin 2) to treat mood disorders.
“I aim to further elucidate the role of the immune system and its interaction with the environment in psychiatric disorders,” Dr. Poletti states. Her vision includes developing prevention strategies to reduce mental illness odds, particularly for individuals with trauma histories. This preventive focus represents a paradigm shift from reactive to proactive psychiatric care.
Mountain peaks and scientific summits
The interview reveals how Dr. Poletti’s passion for Italian mountain hiking informs her scientific approach. Standing atop Sasso Nero at 2,847 meters, she finds the clarity and renewal that fuel her research endeavors. This connection to nature reflects her holistic view of mental health, recognizing that human wellbeing extends beyond biological mechanisms to encompass environmental and experiential factors.
Questions about trauma’s transgenerational effects add another dimension to Dr. Poletti’s work. Can childhood trauma alter genetic expression in ways that affect offspring? How do social and cultural factors modulate biological responses to adversity? These considerations expand the scope of trauma research from individual to societal levels.
Advancing global mental health
Dr. Poletti’s research contributes to a growing recognition that mental health is inseparable from physical health, particularly immune function. This integrated perspective challenges traditional boundaries between psychiatry and other medical specialties, promoting more comprehensive approaches to patient care.
The implications extend beyond individual treatment. If childhood trauma creates lasting biological vulnerabilities, what responsibilities do societies have for preventing adverse childhood experiences? How can healthcare systems better integrate trauma screening and early intervention? Dr. Poletti’s work provides scientific grounding for these critical policy discussions.
Dr. Sara Poletti’s Genomic Press interview is part of a larger series called Innovators & Ideas that highlights the people behind today’s most influential scientific breakthroughs. Each interview in the series offers a blend of cutting-edge research and personal reflections, providing readers with a comprehensive view of the scientists shaping the future. By combining a focus on professional achievements with personal insights, this interview style invites a richer narrative that both engages and educates readers. This format provides an ideal starting point for profiles that explore the scientist’s impact on the field, while also touching on broader human themes.
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Journal reference:
Poletti, S., (2025) Sara Poletti: From the cradle to the grave. Brain Medicine. doi.org/10.61373/bm025k.0071.
