In a groundbreaking interview published in the October 2025 issue of Genomic Psychiatry, Dr. Bruce M. Cohen, the Robertson-Steele Professor of Psychiatry at Harvard Medical School and Director of the Program for Neuropsychiatric Research at McLean Hospital, offers a transformative vision that could redefine the future of neuropsychiatric disorder research and treatment worldwide. With nearly five decades devoted to unraveling the complex biology of mental illness, Dr. Cohen’s work integrates advanced genomic technologies, cellular modeling, and brain imaging to uncover fundamental disruptions in cellular energy pathways and connectivity that underlie debilitating psychiatric conditions. His research signals a radical departure from neurotransmitter-centric models predominant for over a century, illuminating mitochondrial dysfunction as a critical factor in disorders ranging from schizophrenia to Alzheimer’s disease.
Dr. Cohen’s laboratory has pioneered the application of induced pluripotent stem cell (iPSC) technology to generate patient-specific brain cells in vitro, allowing detailed exploration of molecular and metabolic anomalies otherwise inaccessible in living individuals. “We now have tools giving us leads we lacked forty years ago,” he explains, highlighting how these experimental models reveal consistent abnormalities in mitochondrial energy metabolism that impair neuronal signaling and resilience. These findings suggest that impaired cellular bioenergetics are not secondary effects but fundamental contributors to neuropsychiatric illness pathophysiology. By identifying precise metabolic targets, Dr. Cohen’s approach paves the way for developing innovative therapeutics aimed at restoring cellular energy balance, potentially altering the disease course rather than merely alleviating symptoms.
The implications of these discoveries are profound, marking a paradigm shift in psychiatric science. Traditionally, research emphasis has rested on the neurotransmitter imbalances presumed to cause mental disorders; however, Dr. Cohen’s metabolic perspective reframes psychiatric conditions as systemic disorders rooted in cellular dysfunction. His lab has demonstrated that neurons derived from patients with schizophrenia, bipolar disorder, and Alzheimer’s disease exhibit intrinsic metabolic deficits detectable before clinical symptom onset, underscoring opportunities for early intervention. This places bioenergetic dysfunction at the forefront of potential preventive therapies, a notion that could revolutionize clinical practices worldwide by enabling interventions before irreversible brain damage and functional decline.
Equally transformative is Dr. Cohen’s critique of conventional diagnostic frameworks in psychiatry, which rely heavily on categorical labels like “schizophrenia” and “bipolar disorder.” He advocates for a dimensional approach that replaces rigid categories with symptom-based spectra reflecting biological and clinical heterogeneity. This approach not only reduces stigma but aligns psychiatric nosology with emerging biological data, enhancing diagnostic precision and personalizing treatment strategies. The dimensional model accounts for variability in symptom expression across individuals and cultures, offering a universal language better suited for global application. Such a system would facilitate the formation of more homogeneous research cohorts, accelerating discovery while improving clinical outcomes through targeted therapies attuned to distinct symptom profiles.
Dr. Cohen’s multidisciplinary methodology exemplifies cutting-edge science by integrating genomics, neuroimaging, and cellular models, producing a richly detailed picture of neuropsychiatric disorder mechanisms. Genomic analyses identify risk variants; brain imaging delineates structural and functional abnormalities; and iPSC-derived neuronal cultures enable experimental manipulation and therapeutic screening. This synergy lends unparalleled power to uncover disease-relevant pathways and potential pharmacological targets, setting a new standard for international psychiatric research. As Dr. Cohen explains, “Understanding the biological complexity requires tools from multiple disciplines, combining molecular data with clinical observations to unravel these enigmatic disorders.”
Beyond the laboratory, Dr. Cohen’s tenure as President and Psychiatrist-in-Chief at McLean Hospital illustrates the real-world impact of his vision. From 1997 to 2005, he led significant institutional reforms that reversed financial decline and fostered a culture of innovation and compassionate care. His leadership emphasized empowering frontline clinicians and minimizing bureaucracy, strategies that resulted in expanded clinical programs, increased research funding, and enhanced educational opportunities. Under his stewardship, McLean pioneered community-focused initiatives including Waverley Place, a peer-run support center designed to integrate mental health care with societal reintegration, demonstrating how psychiatric institutions can balance mission-driven service provision with financial sustainability.
Dr. Cohen’s personal journey deeply informs his scientific philosophy. His early fascination with physics and mathematics instilled a rigorous analytic mindset that propelled his psychiatric research. The turning point came during medical training when witnessing a young patient’s remarkable recovery on psychotropic medication solidified his commitment to psychiatry’s transformative potential. Despite personal challenges, including social anxieties, he underscores perseverance and intellectual curiosity as drivers of scientific success. His enduring family support, notably from his prominent internist father and long-standing marriage, provides a grounding that sustains his demanding career. This human dimension enriches the narrative, illustrating how personal and professional experiences intertwine to propel scientific advancement.
Looking ahead, Dr. Cohen expresses guarded optimism about the trajectory of psychiatric research. He highlights the emergence of targetable mechanisms shaping illness risk and underscores the feasibility of preventive interventions, especially as psychotic disorders and dementias typically emerge after adolescence and late adulthood respectively. Advances in cellular reprogramming and high-throughput genomic technologies democratize access to cutting-edge tools, enabling a global scientific community to accelerate discovery. Dr. Cohen calls for broader support of unconventional ideas and early-career investigators, cautioning against funding biases favoring incremental “next step” research within established paradigms. His inclusive vision aligns with open-access models championed by organizations like Genomic Press, ensuring that breakthroughs transcend institutional and geographical barriers.
This richly detailed interview embodies the essence of innovation in psychiatric research — merging molecular biology, clinical insight, and compassionate leadership to unravel one of medicine’s most challenging frontiers. Dr. Bruce M. Cohen’s multidisciplinary approach not only elucidates complex determinants of psychiatric disorders but offers a blueprint for global scientific collaboration and clinical transformation. His insights invite a reimagination of psychiatry’s future — one that embraces biological complexity, fosters diagnostic precision, and prioritizes prevention, ultimately aiming to alleviate the profound human burden of mental illness worldwide.
Subject of Research: People
Article Title: Bruce M. Cohen: An eclectic life and a multidisciplinary approach to the complex determinants and diverse presentations of psychiatric disorders
News Publication Date: 14 October 2025
Web References: http://dx.doi.org/10.61373/gp025k.0104
Image Credits: Bruce M. Cohen
Keywords: neuropsychiatric disorders, mitochondrial dysfunction, induced pluripotent stem cells, energy metabolism, psychiatric diagnostics, dimensional model, genomics, brain imaging, schizophrenia, bipolar disorder, Alzheimer’s disease, psychiatric research innovation
