ADHD genetics pioneer maps molecular pathways to behaviour

ADHD, 29 May 25/ in Featured Articles, Neurology

In a Genomic Psychiatry interview, Professor Barbara Franke reveals how her revolutionary interdisciplinary approach is transforming ADHD research. Her innovative methodology combines cutting-edge genomics, experimental models, and international collaboration to decode biological pathways from genetic variations to behavioural changes, offering unprecedented insights for personalised neurodevelopmental treatments.

Professor Barbara Franke has emerged as one of the world’s most influential voices in biological psychiatry, pioneering revolutionary approaches to understanding attention deficit hyperactivity disorder (ADHD) and other neurodevelopmental conditions. With over 500 peer-reviewed publications and recognition among the top 1% most cited scientists globally, her work is fundamentally reshaping how researchers approach the complex relationship between genes and behaviour.

Revolutionary interdisciplinary methodology

Franke’s research philosophy represents a paradigm shift in psychiatric genetics. Rather than focusing solely on gene identification, her team at Radboud University Medical Center employs a comprehensive suite of experimental approaches that bridges multiple scientific disciplines. This includes advanced bioinformatics, brain imaging genetics, and experimental models ranging from fruit flies to human induced pluripotent stem cells.

“I am absolutely amazed at how much we can already learn about the biological pathways and brain-cellular substrates underlying psychiatric conditions using data science methods,” Franke notes, whilst emphasising the critical importance of experimental validation alongside computational approaches.

The molecular psychiatrist’s journey began with an unexpected pivot during her doctoral studies. Originally planning to study great apes in Africa, a pivotal laboratory session isolating DNA from HeLa cells sparked her passion for molecular genetics. This serendipitous moment ultimately led her to psychiatric genetics, where she found her calling in addressing the controversial and often misunderstood nature of ADHD.

International collaboration driving discovery

Recognising early that advancing psychiatric genetics required unprecedented international cooperation, Franke became a founding member of the Psychiatric Genomics Consortium (PGC). Her leadership extends to multiple international research consortia, including the International Multicentre persistent ADHD Collaboration (IMpACT) and the ECNP Network ADHD across the lifespan.

This collaborative approach has proven transformative for the field. The international scale of genetic studies has enabled researchers to achieve the large sample sizes necessary for identifying subtle genetic effects that contribute to complex psychiatric conditions.

From genes to behavioural phenotypes

Franke’s most significant contribution lies in her systematic approach to understanding how genetic variations translate into altered behaviour and disease symptoms. Her research extends far beyond traditional gene identification to illuminate the biological mechanisms underlying neurodevelopmental conditions.

The team’s innovative use of complementary experimental systems allows them to validate computational predictions with real-world biological evidence. This multi-layered approach has revealed critical insights into the cellular and molecular substrates that mediate the transition from genetic risk to clinical presentation.

Pioneering epigenetics research

Currently heading the Medical Neuroscience department at Radboud University Medical Center, Franke has recently expanded into epigenetics research, investigating how environmental factors interact with genetic predispositions. This represents a natural evolution of her work, exploring the relationship between heritable and environmental influences on psychiatric conditions.

“Time is finally ripe for such research in complex, multifactorial conditions like ADHD, now that we have tools and methods available to measure different types of epigenetic modifications and transcriptomes at single-cell resolution,” she explains.

Towards personalised psychiatric medicine

Franke’s ultimate ambition extends beyond basic scientific discovery to practical clinical applications. Her research aims to contribute to improved diagnosis, treatment, and management of psychiatric conditions, with particular focus on ADHD. The identification of biological pathways could potentially lead to more personalised treatment approaches based on individual genetic profiles.

“We still need a new nosology in psychiatry, and I want to contribute to that by identifying genes and pathways,” she states, acknowledging the long journey ahead whilst emphasising the field’s current focus on risk and vulnerability, where resilience and protection mechanisms remain largely unexplored.

Mentoring the next generation

Beyond her scientific contributions, Franke has established herself as an influential mentor, particularly for women in science. Her “jump first, think later” philosophy encourages young researchers to seize opportunities in competitive research environments, reflecting her own career transformation from an initially introverted early-career scientist to a confident international research leader.

Her balanced approach to work and life, guided by the German proverb “Die Suppe wird nicht so heiß gegessen, wie sie gekocht wird” (“The soup is not eaten as hot as it is cooked”), exemplifies her pragmatic approach to navigating complex scientific challenges.

The research represents a critical foundation for future advances in psychiatric genetics, with implications extending far beyond ADHD to other neurodevelopmental and psychiatric conditions. As biological insights continue to accumulate, the translation of these discoveries into tangible improvements in patient care remains the ultimate goal.

The interview was published in Genomic Psychiatry on 27 May 2025.

Reference

Franke, B. (2025). Barbara Franke: Understanding the biological pathways from genes to altered behaviour in neurodevelopmental conditions like ADHD – paving the way for improved understanding and care in psychiatry. Genomic Psychiatry. https://doi.org/10.61373/gp025k.0053