The turn to controls and the refinement of the concept of hereditary burden: The 1895 study of Jenny Koller.

Throughout the 19th century, many alienists reported the proportion of their patients who were "hereditarily burdened," meaning they had a positive family history for mental illness. The rates of such burden differed widely because different authors used divergent definition of illness and investigated different groups of relatives. Most importantly, no authors compared rates of burden with those seen in a nonpatient control group. The first such study in the history of psychiatric genetics was published in 1895, the doctoral dissertation of a Swiss physician Jenny Koller working under Auguste Forel. She obtained histories of a range of mental/neurologic disorders in the parents, aunts/uncles, grandparents and siblings of 370 hospitalized psychiatric patients and 370 controls. Rates of any hereditary burden were only modestly higher in cases (78%) than controls (59%). However, when examining individual syndromes, only major mental illness and eccentricities, but not apoplexy, nervous disorders or dementia, were more common in proband than control families. Furthermore, the rates of mental illness and eccentricities were substantially elevated in the first-degree relatives of cases versus controls but not in the second-degree relatives. Koller's study represented a major methodological advance in psychiatric genetics, helping to define which disorders coaggregated with major mental illness.