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The MGH Superstruct Project Creating a World Class Resource for Psychiatric Neuroscience

One of the great discoveries of modern science is that thought, feeling and behavior consist of physiological activity in the brain. Through the neuroimaging revolution of the 1990s, images of activity in the thinking brain are a familiar sight. A second revolution, occurring over the last decade, is genomics, the study of DNA and RNA sequences of the human genome.

The synergy of advanced brain imaging and genomics holds great promise to help unlock the neurobiological underpinnings of mental illness. “Brain imaging through structural and functional MRIs is like a magnifying glass for understanding the complex effects of interacting genes,” says Randy Buckner, PhD, director of Psychiatric Neuroimaging Research at Massachusetts General Hospital.

Multiple Genes, Small Effects

Unlike illnesses such as Huntington’s disease and sickle cell anemia that involve a single gene, many different genes in different combinations are thought to be responsible for causing psychiatric illnesses. To understand how genes work interactively to influence brain circuitry in both mental health and disease requires large populations to study.

The Department of Psychiatry has initiated a project of unprecedented scale to construct a Brain Genomics Library. The goal is to collect and store images from brain scans, DNA samples and neuropsychological assessments for 5,000 healthy adults. The library will serve as a reference for understanding the brain and its normal variation and for comparison with similar data collected from groups of individuals with particular psychiatric disorders. In addition to Buckner, project leaders are Joshua Roffman, MD, MMSc, director of Brain Genomics Research, and Jordan W. Smoller, MD, ScD, director of Psychiatric Genetics and associate vice chair of the department.

Economy and Efficiency

The project is named “Superstruct” because it builds over or upon other structures, in this case Boston’s rich academic medical research community. Every year, many thousands of brain scans are performed at Mass General and affiliated institutions. The MGH team saw the vast promise of designing a common brain imaging protocol that could easily be applied in different locations to yield uniform data. Lasting less than 15 minutes, it is brief enough to simply add on to existing studies. Since a full-length brain scan typically takes 60 minutes and costs many hundreds of dollars, the Superstruct protocol is incredibly efficient and economical.

Participants also provide DNA through a saliva sample and take an on-line battery of tests that measure thinking, behavior and emotions. Researchers can then match genomic and neurocognitive data with information gathered from the brain images.

Progress Toward Goal of 5,000The Superstruct project was started just two and a half years ago. To date 22 research teams from Mass General, Harvard University, Massachusetts Institute of Technology and McLean Hospital are collaborating. “The Superstruct project is akin to the Human Genome Project. It is helping us understand the fundamental architecture of the brain, in mental health and illness.” says Roffman. The Brain Genomics Library now contains data from 2,700 participants – making it already one of the largest repositories of brain imaging, neurocognitive and genetics information in the world.

When the 5,000-subject milestone is reached, the library will be large enough to enable scientists to determine how particular genes affect brain structure and function. For example an investigator who has identified a candidate gene or genes can “look up” the effects of these genes on the brain. “We will thus begin to address fundamental questions such as where in the brain gene effects occur; what the degree of effect is; and how gene effects relate to age, cognitive performance or family history of illness,” says Smoller.

The MGH Brain Genomics Library will ultimately be available to scientists everywhere as a repository for a broad range of research in mental illness.