In a landmark interview published in Brain Medicine, Professor Siegfried Kasper, MD, Professor Emeritus at the Medical University of Vienna, unpacks decades of pioneering work that have fundamentally altered psychiatric medicine worldwide. His career, marked by relentless pursuit of biological underpinnings of mental health disorders, charts a trajectory from clinical observations to transformative scientific breakthroughs. Kasper’s insights shed light on how the integration of clinical phenomena into basic science — a process he terms “back-translation” — has revolutionized the diagnosis and treatment of complex psychiatric conditions, particularly treatment-resistant depression.
Kasper’s early academic formation was deeply influenced by his exposure to brain anatomy, which sparked his curiosity about neural substrates of psychiatric disorders. This foundation was significantly strengthened during his studies at the Central Institute of Mental Health in Mannheim, Germany. It was here that Kasper linked Michel Jouvet’s seminal animal research on lesions to the raphe nuclei—a critical serotonergic brainstem cluster—with the prominent sleep disturbances evident in depressed patients. This connection challenged the then-prevailing norepinephrine theory of depression and pivoted research focus towards serotonin’s central role, sparking a paradigm shift in understanding mood regulation at a neurochemical level.
The significance of Kasper’s insight cannot be overstated. By identifying the serotonergic system as a crucial modulator in depression, Kasper laid groundwork that would lead to the development and clinical adoption of selective serotonin reuptake inhibitors (SSRIs). These compounds became a cornerstone of antidepressant therapy due to their ability to enhance synaptic serotonin availability, thus alleviating depressive symptoms. Kasper’s clinical acumen and laboratory investigations bridged the translational gap, moving from theoretical neuroscience to tangible patient outcomes, a hallmark of his scientific philosophy.
Extending beyond pharmacology, Kasper’s research pursued circadian biology and its relationship to mood disorders. During his tenure at the National Institute of Mental Health in the United States, he spearheaded the first epidemiological studies correlating latitude and seasonal affective disorder (SAD), revealing intriguing geographic variations in mood symptomatology. These findings illuminated how environmental factors interplay with neurobiological mechanisms, a complex interface that requires multi-disciplinary research approaches to fully elucidate.
Kasper’s methodological innovation is epitomized by his advocacy for “back-translation”—the iterative process by which clinical observations inform basic science hypotheses, which in turn guide improved clinical interventions. Rather than unidirectional bench-to-bedside science, this bidirectional dialogue optimizes research relevance and accelerates discovery. His work exemplifies this approach, particularly visible in his early recognition of the mood-enhancing effects of transcranial magnetic stimulation (TMS), initially discovered serendipitously through epileptology collaborators. After personally verifying TMS’s safety and efficacy, Kasper championed its adoption for treatment-resistant depression, pioneering non-invasive neuromodulation therapies now deployed worldwide.
Kasper’s contributions extend into psychopharmacology beyond depression. He extensively researched atypical antipsychotics, scrutinizing their unique receptor profiles which confer efficacy not only against schizophrenia’s positive symptoms but also depressive and negative symptoms traditionally resistant to treatment. These agents exhibit improved side effect profiles compared to earlier generations, facilitating better patient adherence and quality of life. Kasper’s work in this domain has helped reconfigure schizophrenia treatment paradigms, influencing prescribing practices globally.
At the organizational level, Kasper has been a formidable force in shaping psychiatric research agendas and clinical standards through leadership of key international bodies. As the founding president of the Austrian Society of Neuropsychopharmacology and Biological Psychiatry and former leader of the World Federation of Societies of Biological Psychiatry and International College of Neuropsychopharmacology, Kasper helped unify disparate research efforts. His stewardship fostered global collaboration, standardized research methodologies, and accelerated the translation of neuroscience discoveries into clinical guidelines.
A testament to his impact is evident in his leadership of the European Group for the Study of Resistant Depression, which synthesized data from over 3000 patients across Europe. Their consensus criteria for treatment-resistant depression have gained regulatory endorsement, including adoption by the European Medicines Agency, and informed the development of intranasal esketamine — a novel, rapid-acting antidepressant therapy addressing an unmet clinical need. This collaborative effort has recalibrated clinical thinking about treatment resistance and expanded therapeutic options for patients worldwide.
Kasper’s career honors encompass Austria’s most prestigious decorations, reflecting national and international recognition of his scientific excellence. Awards such as the Grand Decoration of Honor in Silver, the Austrian Cross of Honor for Science and Art First Class, and the 2025 CINP Pioneer Award underscore his transformative role in psychiatric science. These accolades celebrate not only research achievements but also his dedication to mentoring emerging scientists, thereby ensuring sustained advancement in the field through successive generations.
Beyond empirical rigor, the interview reveals Kasper’s humanistic philosophy toward research and patient care. He emphasizes attentive listening to patients combined with a vigilant engagement with scientific literature, embodying Louis Pasteur’s dictum that “chance favors only the prepared mind.” This approach reflects a scientific temperament that is both curious and disciplined, recognizing that breakthrough discoveries often arise at the intersection of careful observation and robust experimentation.
Kasper also shares personal facets that illuminate the broader context of his scientific creativity. His affinity for nature, time spent at his informal research retreat in Puglia, Italy, and companionship with his Lakeland terrier provide a grounded, holistic perspective on the scientific endeavor. These elements highlight how diverse life experiences and environmental inspiration can fuel innovative thinking in medical research, humanizing the portrait of a celebrated scientist.
This comprehensive Genomic Press interview is part of the Innovators & Ideas series, which spotlights leading figures advancing fundamental biomedical knowledge and its clinical translation. Kasper’s narrative offers a compelling blend of personal reflection and technical insight, illustrating the profound impact that a single visionary scientist can have on an entire discipline. By weaving rigorous research with human storytelling, the interview resonates widely, offering both scientific inspiration and a meaningful connection to the individuals driving progress.
For readers and researchers keen to explore the full interview, it is freely accessible via Open Access in the September 2, 2025 issue of Brain Medicine. This journal serves as a critical platform for cross-disciplinary research spanning basic neuroscience to clinical neurology and psychiatry, committed to understanding and treating brain disorders with innovation and scientific excellence.
Subject of Research: People
Article Title: Siegfried Kasper: The importance of back-translation of clinical findings to basic science
News Publication Date: 2-Sep-2025
Web References: http://dx.doi.org/10.61373/bm025k.0104
Image Credits: Credit: Siegfried Kasper, MD
Keywords: Siegfried Kasper, biological psychiatry, treatment-resistant depression, selective serotonin reuptake inhibitors, atypical antipsychotics, transcranial magnetic stimulation, circadian rhythms, seasonal affective disorder, back-translation, psychiatric research, neuroscience, intranasal esketamine
