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

Abstract

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.

Julius Wagner von Jauregg, Otto Diem and research methods for assessing the contributions of hereditary burden to mental illness risk: 1902–1906

“…Wagner then reviews the first serious attempt to obtain a control group for a psychiatric genetic investigation undertaken by Jenny Koller in Switzerland and published in 1895 (Kendler & Klee, 2020; Koller, 1895). Prior to Koller's study, many psychiatric textbooks and mental hospital reports examined, without control groups, the proportion of mental patients with “hereditary burden,” (roughly equivalent to our concept of a “positive family history”) (Legrand Du Saulle, 1873).…”

“…He is both complimentary and critical of her methodology. Since we have reviewed this study previously (Kendler & Klee, 2020), we will not repeat the details except to note that she found a quite high proportion of “hereditary burden” in her controls (59%, n = 370) but an even higher rates in her cases (77%). Wagner reviews the methodological problems with the Koller study.…”

“…The second numbered 370 to match the number of healthy controls she examined selected from admissions in two randomly chosen years (1885–1886). It is the family histories of the latter group of cases that are examined in detail in our prior paper (Kendler & Klee, 2020). For Diem's paper, he compared results from his new series of healthy controls to the 1,850 ill cases previously assembled by Koller.…”

“…After decades of methodological stasis, the rate of change accelerated in the years around 1900. In 1895, Jenny Koller published the first study of rates of hereditary burden in asylum patients in Switzerland compared to healthy controls (Kendler & Klee, 2020; Koller, 1895). Of note, 1900 witnessed the re‐discovery of Mendel's experiments which would, over the next two decades, have a transformative effect on psychiatric genetics.…”

“…Having examined the 1895 paper by Koller previously in this journal (Kendler & Klee, 2020), in this report, we pick up the story by first carefully examining Wagner's 1902 paper. We then review more briefly both Diem's 1905 study and Wagner's 1906 paper.…”