Luxenburger's 1939 Essay on "Schizophrenia and its Hereditary Circle".

In 1939, Hans Luxenburger published a detailed overview of the current status of schizophrenia genetics research, reaching six major conclusions. First, schizophrenia is clearly a hereditary disease. Second, however, schizophrenia is not the hereditary trait itself but rather the consequences of a slowly developing biological progress, the nature of which remains entirely unknown.

Bruno Schulz's 1930 article "The Hereditary Relationships of Old-Age Paranoid Psychosis".

In the 1899 6th edition of his influential textbook, Kraepelin proposed a diagnostic category of "Old-Age Paranoid Psychosis." In this 1930 article, Bruno Schulz studied the morbid risk (MR) of several disorders and traits in the parents, siblings, offspring, and nieces/nephews of 51 probands with "Old-Age Paranoid Psychosis." His results permitted an evaluation of the validity of Kraepelin's category of Old-Age Paranoid Psychosis, in particular, whether it was a form of psychosis resulting from "senile changes" or late-onset schizophrenia.

Bruno Schulz's 1936 book "Methodology of medical genetic research particularly with regard to psychiatry".

In 1936, Bruno Schulz published the first detailed, book-length review of the methodology of psychiatric genetic research, based on his experiences at the German Research Institute of Psychiatry. Emphasis is placed on proper selection of relatives and the ascertainment corrections required for Mendelian transmission models. Twin studies are considered as is the impact of reduced fertility on patterns of risk.

Ryssia Wolfsohn's 1907 dissertation on "the heredity of dementia praecox".

In the 19th century, psychiatric genetic studies typically utilized a generic category of "insanity." This began to change after 1899, with the publication of Kraepelin's 6th edition containing, among other disorders, his mature concept of dementia praecox (DP). We here review an article published by Ryssia Wolfsohn in 1907 from her dissertation at the University of Zurich entitled "Die Heredität bei Dementia praecox" (The Heredity of Dementia Praecox).

The examination of Kraepelin's diagnoses of dementia praecox and manic-depressive insanity in pedigrees: Studies of Schuppius in 1912 and Wittermann in 1913.

In the first two decades of the 20th century, a new approach to psychiatric genetics research emerged in Germany from three roots: (i) the wide-spread acceptance of Kraepelin's diagnostic system, (ii) increasing interest in pedigree research, and (iii) excitement about Mendelian models. We review two relevant papers, reporting analyses of, respectively, 62 and 81 pedigrees: S. Schuppius in 1912 and E.

Irma Weinberg's 1928 paper "on the problem of the determination of heredity prognosis: The risk in the cousins of schizophrenics".

Irma Weinberg, a German-Jewish Neuropsychiatrist/Physician, authored the fourth report from the German Research Institute for Psychiatry in Munich examining the risk for dementia praecox (DP) in particular relatives of DP probands, here first-cousins. She examined 977 cousins of 54 DP probands and found a best-estimate risk of 1.4%.

The era of the Dawn of Mendelian research in the field of psychiatry: Rüdin's 1922 review paper "regarding the heredity of mental disturbances".

On September 27, 1922, Ernst Rüdin gave an address to the Annual Conference of the German Society of Genetics entitled "Regarding the Heredity of Mental Disturbances." Published in a 37-page article, Rüdin reviewed the progress in the field of Mendelian psychiatric genetics, then hardly more than a decade old. Topics included (a) the status of Mendelian analyses of dementia praecox and manic-depressive insanity which had expanded to include two and three locus and early polygenic models and sometimes included, respectively, schizoid and cyclothymic personalities; (b) a critique of theories for the explanation of co-occurrence of different psychiatric disorders within families; and (c) a sharp methodologic critique of Davenport and Rosanoff's contemporary work which emphasized Rüdin's commitment to careful, expert phenotyping, a primary focus on well-validated psychiatric disorders and not broad spectra of putatively inter-related conditions, and an emphasis on rigorous statistical modeling as seen in his continued collaboration with Wilhelm Weinberg.

Karl Grassmann's 1896 paper "critical overview of contemporary theories of the heredity of the psychoses".

Four years before the rediscovery of Mendel's work in 1900, Karl Grassmann published a detailed, scholarly review of the heredity of psychosis which we here review. A full translation is in the appendix. We emphasize seven major conclusions from this review.

Hermann Hoffmann's 1921 Monograph: "The Offspring of Endogenous Psychoses: Genealogical-Characterological Examinations".

Five years after the publication of Rüdin's major sibling study, Hermann Hoffmann, working with Rüdin, performed the first systematic study of the risk for dementia praecox (DP) in offspring of DP probands. Field work was limited to 3 months. Hoffmann ascertained families with at least one parent with certain DP, after Kraepelin, with children the youngest of whom were at least 30 years old.

Bruno Schulz's 1933 Monograph: On the Hereditary Etiology of Schizophrenia.

In his 1933 article, Bruno Schulz reported a follow-up and reanalysis of the schizophrenic probands and their relatives first studied by Rüdin 20 years earlier that sought to clarify whether schizophrenia was a valid "unit-character" for Mendelian genetic analysis. He proposed a range of subgroupings of probands, particularly traditional subtyping, presence or absence of identifiable causal influences, and outcome. He then compared those subgroupings in several ways, most commonly by the risk for schizophrenia in their siblings and by the level of resemblance among proband-sibling affected pairs.

Rüdin's 1916 Monograph: On the Inheritance and Primary Origin of Dementia Praecox.

In 1916, Ernst Rüdin published the first modern family study in the history of psychiatric genetics, the major goal of which was to test whether the pattern of risk in the siblings of dementia praecox (DP) probands followed Mendelian expectations. He utilized systematic ascertainment of probands and multisourced diagnostic assessments of probands and relatives, applying the narrow Kraepelinian concept of DP. In a novel step, he collaborated closely with a statistical geneticist-Wilhelm Weinberg-and applied his sibling, proband, and age correction methods.

The Beginnings of Scientific Psychiatric Twin Research: Luxenburger's 1928 "Preliminary Report on the Psychiatric Examination of a Series of Twins".

While reports of twin pairs concordant for insanity began to appear in the 19th century, the first modern psychiatric twin study that fulfilled Galton's 1875 promise of the value of the twin method was published by the German Psychiatrist and Geneticist Hans Luxenburger in 1928. Luxenburger introduced four major methodological advances: the use of representative sampling, proband-wise concordance, rigorous zygosity diagnoses, and age correction. He used a narrow Kraepelinian diagnostic approach diagnosis and ascertained twins hospitalized, on a specific day, in all large Bavarian asylums.

Bruno Schulz and his 1926 Article: "Regarding the Problem of Determining Hereditary Prognosis. The Affliction Prospects for Nephews and Nieces of Schizophrenics".

Authored by one of Rüdin's most productive colleagues, Bruno Schulz, the main goal of this article was to estimate risk for dementia praecox (DP) in nieces/nephews (n/n) of DP probands to address practical questions for genetic counseling. Schulz selected 76 primary probands from records of the genealogical department of the German Research Institute of Psychiatry who both had DP and had siblings-secondary probands-with children aged 20 years or greater. Those children had a morbid risk for DP of 1.

'Regarding the scientific viewpoint in psychiatry', lecture by Carl Wernicke (1880).

In 1880 Carl Wernicke gave this plenary lecture at an annual meeting of German physicians and natural scientists. He used principles from his 1874 aphasia monograph to build a neural model of mental illness. He proposed that the brain keeps a record of experiences in distinct areas of the sensory and motor cortices in the form of memory images, which allows for recognition of objects and the planning of motor acts.

The place of Franz Kallmann's 1938 "the genetics of schizophrenia" in the history of psychiatric genetics.

This essay provides the historical context and key findings of one of the largest fieldwork-based family studies ever done in the history of psychiatric genetics conducted in Berlin by Franz Kallmann from 1929 to 1933. It included over 1,000 schizophrenic probands and 12,500 of their relatives including siblings, offspring, nieces/nephews and grandchildren. The work was analyzed in close collaboration with Rüdin, Schulz, and Luxenburger in Munich.

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

After decades of methodological stasis in 19th century psychiatric genetics, when uncontrolled studies reported high rates of hereditary burden in hospitalized patients, Koller completed the first controlled study in 1895. We pick up this narrative 7 years later when the well-known Julius Wagner v. Jauregg published a biting critique of the then current psychiatric genetics' literature.

Philipp Jolly and his 1913 "the heredity of psychosis": Homogeneity versus heterogeneity of familial transmission and an early look at Mendelian models for manic-depressive illness and dementia praecox.

Philipp Jolly's 1913 extensive monograph "The Heredity of Psychoses" provides, in both his detailed literature review and new pedigree study, an extensive assessment of a key issue in the psychiatric genetics of his day: the degree to which the familial transmission of psychiatric disorders was specific (or homogeneous) versus nonspecific (or heterogeneous). Contrary to a number of earlier observations, Jolly concludes that heterogeneous transmission is rare. Multiple psychiatric disorders can occur in one family because members of a family may have elevated predispositions to more than one disorder rather than one predisposition which increases risk for a wide range of conditions.

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.