She is known for destigmatising mental illness, rigorous data driven research methods to study psychiatry, especially depression and bipolar disorder.
[1][3] She had a child during her fourth year of medical school which influenced her to choose a residency in psychiatry instead of internal medicine.
[3] At WUSM, Clayton worked closely with Eli Robins, George Winokur, Samuel Guze, and Ted Reich to develop what became known as the Feighner Criteria, a psychiatric diagnostic criteria based on the medical model, moving psychiatry away from introspection and psychoanalysis.
[2][3] In 1980, four years later, Clayton became the first woman in the United States to chair a department of psychiatry, when she left for the University of Minnesota Medical School.
[1][2] From 2006 to 2014, she was based in New York City, and served the American Foundation for Suicide Prevention as its medical director.