MGH Research Scholar Jordan Smoller, MD, ScD, is working to identify the genetic determinants of childhood and adult psychiatric disorders.

Brain Genomics: The Neural and Genetic Architecture of Mental IllnessBrain Genomics: The Neural and Genetic Architecture of Mental Illness

Jordan Smoller, MD, ScD
Jordan Smoller, MD, ScD
Tepper Family MGH Research Scholar 2014-2019
Physician Investigator, Department of Psychiatry
Professor of Psychiatry, Harvard Medical School

Neuropsychiatric disorders, including autism, schizophrenia, and mood and anxiety disorders, are the leading causes of disability worldwide.

Despite this enormous public health burden, treatments for major psychiatric illnesses still rely on a handful of mechanistic insights that date to the 1960s, and no validated tools for risk prediction or prevention exist.

We know two things with certainty: these illnesses are diseases of the brain and genetic vulnerability is the strongest risk factor for their development.

We also know that most of these illnesses arise from developmental perturbations of neural systems that underlie normal brain structure and functional circuitry.

The current diagnostic classification of psychiatric disorders (the DSM) is based on syndromes defined by a consensus of experts, without regard to etiology or pathogenesis.

Using the tools of genomics and clinical neuroscience, recent discoveries by my lab and our colleagues have challenged this “top-down” system in ways that may have fundamental implications for the diagnosis and treatment of mental illness.

The overarching goal of my research plan as an MGH Research Scholar is to dissect the neural, genetic, and behavioral bases of psychiatric disorders from the “bottom-up.”

This research program builds on my extensive experience with clinical and translational studies of psychopathology over the past 15 years, as well as extensive collaborations at Mass General, Harvard, the Broad Institute, and beyond, including national and international consortia.

The key components of the plan are three-fold:

1) Create a uniquely powerful resource for the genetic dissection of brain structure and function related to mental illness

2) Conduct large-scale analyses to identify common and rare genetic variants underlying normal and pathologic variation in brain structure/function and behavior

3) Map the genetic and neural architecture of childhood- and adult-onset psychiatric disorders across development from infancy to adulthood

If successful, this work will facilitate a new understanding of psychiatric disorders by mapping their underlying genetic and neural basis.