Why individual differences hold the key to unlocking psychiatric mysteries

In a revealing Genomic Press Interview published today in Genomic Psychiatry, Dr. Noritaka Ichinohe challenges a foundational assumption that has quietly constrained psychiatric research for decades: the belief that meaningful explanation requires averaging away individual differences. His three decades of translational neuroscience across Japanese research institutions have instead demonstrated that biological heterogeneity, far from being statistical noise to eliminate, constitutes the very phenomenon demanding explanation.

Dr. Ichinohe serves as Director of the Department of Ultrastructural Research at the National Center of Neurology and Psychiatry in Japan while simultaneously holding a position as Visiting Principal Researcher at the RIKEN Center for Brain Science. This dual appointment positions him at the intersection of clinical translation and fundamental discovery, a vantage point from which he has authored over 260 research products and secured 27 competitive grants. His influence extends well beyond institutional boundaries, shaping how researchers worldwide conceptualize the relationship between animal models and human psychiatric conditions.

From quantum physics to neural circuits

The intellectual journey that brought Dr. Ichinohe to neuroscience began, perhaps unexpectedly, with childhood encounters with relativity and quantum mechanics. Reading popular science books on physics instilled in him a fascination with how highly counterintuitive phenomena could become intelligible through rigorous frameworks. Yet literature, introduced by his father, a Japanese-language teacher, offered competing visions of human nature that resisted reduction to simple rules.

"What ultimately stayed with me was the possibility that explanation and human complexity need not be opposed," Dr. Ichinohe reflects. The cybernetic theories of Norbert Wiener crystallized this intuition: systems could maintain rigor without rigidity, intelligibility without closure. That productive tension between structure and openness became the foundation of his scientific approach.

Medical school drew him toward the mind-body relationship, but the sheer contextual complexity of human psychology felt intractable when approached directly. Early experiments with neural network models, including the neocognitron running on 8-bit computers, revealed a world both plastic and intelligible. More importantly, these experiments exposed how little researchers understood about network structure itself before discussing learning rules or behavior.

The primate imperative

Graduate training in neuroanatomy led Dr. Ichinohe through brainstem circuits, cerebellar organization, and basal ganglia connectivity. But work in cats and rodents increasingly highlighted the distance between these models and human cognition. This limitation drove him to join the laboratory of Dr. Kathleen Rockland at RIKEN, a leading authority on primate cortical circuitry.

The RIKEN Brain Science Institute, founded with ambitions of establishing the 21st century as "the century of the brain," provided an extraordinary environment. Leaders across molecular, synaptic, imaging, systems, and theoretical neuroscience collaborated daily. Dr. Ichinohe discovered there the landmark "honeycomb-like mosaic" at the cortical layer 1-2 border, establishing new paradigms for understanding micromodular organization. This interview exemplifies the type of transformative scientific discourse found across the Genomic Press portfolio of open-access journals reaching researchers worldwide (https://genomicpress.kglmeridian.com/).

The transition to the National Center of Neurology and Psychiatry marked a deliberate shift toward clinical translation. Could what might be termed the structural grammar of primate brains illuminate human psychiatric conditions? The question carried particular weight for autism spectrum disorder, where heterogeneity among affected individuals is not merely observable but self-reported. Many autistic individuals describe themselves as fundamentally different from one another.

Transcriptomes as dynamic hinges

The breakthrough emerged from an unexpected convergence. Brain transcriptome analysis of marmosets exposed to valproate revealed striking similarity to a subset of individuals with autism spectrum disorder. Dr. Ichinohe recognized something profound in this finding: the transcriptome occupies a unique intermediate position, reflecting both genomic and environmental influences while remaining connected to measurable human phenotypes including behavior and potential biomarkers.

"This realization was deeply striking," he explains. "It revealed the transcriptome not as a passive readout, but as a dynamic hinge, linking cause and expression, mechanism and manifestation."

The implications extend far beyond a single model system. If primate transcriptomes can identify convergence points with specific human molecular subtypes, then animal research need not impose templates on human conditions. Instead, models become catalysts for testing whether proposed subtype boundaries hold across species. How might this framework reshape drug development pipelines currently designed around averaged patient populations? Could biomarker-guided treatment selection become feasible within the next decade?

Oncology as precedent

Dr. Ichinohe draws instructive parallels with cancer research. Oncology advanced not by denying tumor heterogeneity but by structuring it: identifying meaningful subtypes, linking them to biomarkers, developing subtype-aware therapeutic strategies. Psychiatry, he argues, requires similar conceptual machinery.

"The question is where the meaningful partition points lie," he observes, "especially at the level of socio-behavioral biology where clinical relevance truly lives."

His current work through the Brain/MINDS initiative has made him instrumental in constructing the marmoset brain connectome. His team developed an AI-powered pipeline enabling unprecedented precision in mapping primate neural circuits. In parallel, Dr. Ichinohe has been actively involved in the International Consortium for Primate Brain Mapping (ICPBM), contributing to global efforts to integrate primate connectomics with mesoscopic brain architecture. These structural and translational efforts remain deeply connected in his view, two faces of the same scientific commitment.

The human element

Beyond laboratory walls, Dr. Ichinohe finds renewal in music. He plays guitar privately, ranging from Bach to the Beatles, not for performance but for personal sustenance. His intellectual heroes span Zen masters like Rinzai and Zhuangzi, physicists like George Gamow, and novelists including Dostoevsky and Mishima. What unites them is a shared stance toward limits: of language, reason, self, or society, without seeking comfort in simplification.

When asked about his life philosophy, Dr. Ichinohe offers a reappropriated aphorism: "Keep dancing, as long as the music plays." Originally a comment on financial markets, he transforms it into an expression of sustained intellectual curiosity and persistent engagement with scientific problems.

His greatest fear? "That bears are increasingly appearing in towns." His assessment of his greatest achievement? "Not yet. If it comes at all, it will come later, perhaps in a form I do not yet recognize."

Dr. Noritaka Ichinohe'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. More information on the research leaders and rising stars featured in our Innovators & Ideas -- Genomic Press Interview series can be found on our publications website: https://genomicpress.kglmeridian.com/.

The Genomic Press Interview in Genomic Psychiatry titled "Noritaka Ichinohe: Beyond averages - context and heterogeneity in Genomic Psychiatry," is freely available via Open Access, starting on 6 January 2026 in Genomic Psychiatry at the following hyperlink: https://doi.org/10.61373/gp026k.0016.