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). This work, performed under the supervision of E. Bleuler, was to our knowledge the first formal genetic study of the then new diagnosis of DP. She investigated 550 DP probands admitted to the Burghölzli hospital with known information about their "heredity burden." For most probands, she had information on parents, siblings, grandparents, and aunts/uncles. Of these patients, only 10% had no psychiatric illness in their families. In the remaining probands, she found rates of the four major categories of psychopathology she investigated: mental illness-56%, nervous disorders-19%, peculiar personalities 12% and alcoholism 13%. Her most novel analyses compared either total familial burden or burden of her four forms of mental disorders on her DP probands divided by subtype and outcome. In neither of these analyses, did she find significant differences.

"Not by a Decree of Fate:" Ellen Richards, Euthenics, and the Environment in the Progressive Era.

In 1904, Ellen Richards introduced "euthenics." By 1912, Lewellys Barker, director of medicine and physician-in-chief at Johns Hopkins Hospital, would tell the New York Times that the "task of eugenics" and the "task of euthenics" was the "Task for the Nation." Alongside the emergence of hereditarian eugenics, where fate was firmly rooted in heredity, this article places euthenics into the same Progressive Era demands for the scientific management over environmental issues like life and labor, health and hygiene, sewage and sanitation. I argue that euthenics not only heralded women as leaders in the quest for what Richards and eugenicists termed "racial improvement," but also aimed to make reforms through environmental and educational changes rather than hereditary interventions. Seeking to recuperate the figure of Ellen Richards in the history of science, I place Richards and her euthenics more into the debate over eugenics rather than over the emergence of home economics. Building on the work of Donald Opitz, Staffan Bergwik, and Brigette Van Tiggelen, this article shows, first, how Richards' career threads the needle between the home and the laboratory as sites of science making, not as separate spheres but as overlapping realms, and helps recover how domestic concerns shaped the focus of the life sciences. Second, this article shows how euthenics shaped eugenics by looking at the writings of American eugenicists Charles Davenport, Paul Popenoe, and David Starr Jordan. Third, the article describes how euthenics took root in new academic departments of domestic science, home economics, and departments child welfare and family life in the 1920 and 1930s, most notably the department of euthenics at the Kansas State Agricultural College from 1926 and the Institute of Euthenics at Vassar College after 1923.

Heredity of Schizophrenia in India: A 1928 debate.

Shaw, a British psychiatrist working in India, observed that the incidence of Schizophrenia was higher among a community of Parsis as compared to other ethnic groups. He published his findings in two British journals. The paper drew responses from two other psychiatrists. The debate is examined in colonial context during which occurred and some implications for contemporary research.

Heredity of pregnancy-related pelvic girdle pain in Sweden.

INTRODUCTION: Pelvic girdle pain during and after pregnancy is a major public health problem with significant daily problems for affected women and their families. There is now accumulating evidence that pregnancy-related pelvic girdle pain originates from the sacroiliac joints and the pubic symphysis as well as their extra-articular ligaments. However, the heritability of the disease remains to be determined. We hypothesized that there is an increased familial risk of pregnancy-related pelvic girdle pain. MATERIAL AND METHODS: A population-based national database linkage registry study of approximately 9.3 million individuals within 4.2 million families in Sweden with a recruitment period from 1997 to 2018. The Swedish Multi-generation register was used to find female pairs of twins, full siblings, half-siblings and first cousins where both in the pairs had a completed pregnancy. The outcome measure was diagnosis of pregnancy-related pelvic girdle pain (International Classification of Diseases-10 O26.7 [1997-2018]) in the first pregnancy. Data was obtained from the Swedish Hospital Discharge Register, the Swedish Outpatient Care Register, the Swedish Medical Birth Register, the Primary Healthcare Register, and Medical Treatment Register. Cox regression analysis was used to calculate adjusted estimated effect of the exposure variable familial history of pregnancy-related pelvic girdle pain on the outcome variable pregnancy-related pelvic girdle pain at first birth. RESULTS: From the registers, 1 010 064 women pregnant with their first child within 795 654 families were collected. In total, 109 147 women were diagnosed with pregnancy-related pelvic girdle pain. The adjusted hazard ratio for a familial risk of pregnancy-related pelvic girdle pain was 2.09 (95% CI 1.85-2.37) among twins (monozygotic and dizygotic), 1.78 (95% CI 1.74-1.82) in full siblings, 1.16 (95% CI 1.06-1.28) in half-siblings from the mother, 1.09 (95% CI 1.024-1.16) in half-siblings from the father and 1.09 (95% CI 1.07-1.12) in first cousins. CONCLUSIONS: This nationwide observational study showed a familial clustering of pregnancy-related pelvic girdle pain. The hazard ratio for the condition was associated with the degree of relatedness, suggesting that heredity factors contribute to the development of pregnancy-related pelvic girdle pain. There is no causal treatment available for pregnancy-related pelvic girdle pain and further studies are now encouraged to clarify the specific genetic factors that contribute to the disease and for future targeted interventions.

PKD1 Nonsense Variant in a Lagotto Romagnolo Family with Polycystic Kidney Disease.

A female Lagotto Romagnolo dog with polycystic kidney disease (PKD) and her progeny, including PKD-affected offspring, were studied. All affected dogs appeared clinically inconspicuous, while sonography revealed the presence of renal cysts. The PKD-affected index female was used for breeding and produced two litters with six affected offspring of both sexes and seven unaffected offspring. The pedigrees suggested an autosomal dominant mode of inheritance of the trait. A trio whole genome sequencing analysis of the index female and her unaffected parents identified a de novo heterozygous nonsense variant in the coding region of the PKD1 gene. This variant, NM_001006650.1:c.7195G>T, is predicted to truncate 44% of the open reading frame of the wild-type PKD1 protein, NP_001006651.1:p.(Glu2399*). The finding of a de novo variant in an excellent functional candidate gene strongly suggests that the PKD1 nonsense variant caused the observed phenotype in the affected dogs. Perfect co-segregation of the mutant allele with the PKD phenotype in two litters supports the hypothesized causality. To the best of our knowledge, this is the second description of a PKD1-related canine form of autosomal dominant PKD that may serve as an animal model for similar hepatorenal fibrocystic disorders in humans.

How do experts in psychiatric genetics view the clinical utility of polygenic risk scores for schizophrenia?

Polygenic risk scores (PRS) are promising for identifying common variant-related inheritance for psychiatric conditions but their integration into clinical practice depends on their clinical utility and psychiatrists' understanding of PRS. Our online survey explored these issues with 276 professionals working in psychiatric genetics (RR: 19%). Overall, participants demonstrated knowledge of how to interpret PRS results. Their performance on knowledge-based questions was positively correlated with participants' self-reported familiarity with PRS (r = 0.21, p = 0.0006) although differences were not statistically significant (Wald Chi-square = 3.29, df = 1, p = 0.07). However, only 48.9% of all participants answered all knowledge questions correctly. Many participants (56.5%), especially researchers (42%), indicated having at least occasional conversations about the role of genetics in psychiatric conditions with patients and/or family members. Most participants (62.7%) indicated that PRS are not yet sufficiently robust for assessment of susceptibility to schizophrenia; most significant obstacles were low predictive power and lack of population diversity in available PRS (selected, respectively, by 53.6% and 29.3% of participants). Nevertheless, 89.8% of participants were optimistic about the use of PRS in the next 10 years, suggesting a belief that current shortcomings could be addressed. Our findings inform about the perceptions of psychiatric professionals regarding PRS and the application of PRS in psychiatry.

Epigenetic control of heredity.

Epigenetics is the field of science that deals with the study of changes in gene function that do not involve changes in DNA sequence and are heritable while epigenetics inheritance is the process of transmission of epigenetic modifications to the next generation. It can be transient, intergenerational, or transgenerational. There are various epigenetic modifications involving mechanisms such as DNA methylation, histone modification, and noncoding RNA expression, all of which are inheritable. In this chapter, we summarize the information on epigenetic inheritance, its mechanism, inheritance studies on various organisms, factors affecting epigenetic modifications and their inheritance, and the role of epigenetic inheritance in the heritability of diseases.

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%. She conducted within-study analyses, showing a much higher risk for DP in the siblings than cousins of DP probands. She studied DP-related personalities showing a familial link between these conditions and risk for DP. She demonstrated that the risk for DP in cousins was impacted substantially by the distribution, in ancestors, of psychosis and personality abnormalities. After completing work on this article, Weinberg worked in private practice in Frankfurt, emigrating to the Netherlands in 1934, where she worked at a Jewish psychiatric hospital. In 1943, German occupiers evacuated the hospital, transporting the patients and staff, either directly to Auschwitz or, like Weinberg, to the Westerbork transit camp. On September 4, 1944, Dr. Weinberg was transported to Theresienstadt and soon thereafter to Auschwitz, where she was murdered at the age of 53. Her history raises painful questions about the relationship between genetic studies of psychiatric illness in prewar Germany and the Holocaust.

Biologist Nikolai K. Koltzoff: the forgotten genius.

Nikolai K. Koltzoff (Koltsov) (1872-1940) is one of the key figures in Russian biology. He essentially initiated Russian physicochemical biology and established a large scientific school in the area. Among his disciples, there are the geneticists B.L. Astaurov, S.S. Chetverikov, N.P. Dubinin, V.P. Efroimson, I.A. Rapoport, V.V. Sakharov, and N.V. Timofeeff-Ressovsky; histologist G.I. Roskin, experimental surgeon A.G. Lapchinsky, developmental biologist M.M. Zavadovsky, physiologist L.V. Krushinsky, microbiologist S.M. Gershenson, biochemist V.A. Engelhardt, hydrobiologist G.G. Vinberg, cytologist M.A. Peshkov, and many other famous Soviet biologists. He made several fundamental discoveries; the first of them was the discovery of the cytoskeleton (1903). He was the first to formulate the idea of a crystal-like mechanism for copying inherited information (1927) and the principles of epigenetics (as well as the term itself, in 1934; it seems astonishing, but as early as 1915, he hypothesized that the gene methylation might be a mechanism of genetic variability). He started the work which later led his disciples V.V. Sakharov and I.A. Rapoport to the discovery of chemical mutagenesis. His research on sex regulation in silkworms was later successfully continued by B.L. Astaurov. Koltzoff encouraged S.S. Chetverikov, the entomologist, to study the genetics of natural Drosophila populations, which went on to form the basis of the Modern Synthesis reconciling Darwinian evolutionary theory and the Mendelian laws of heredity. Unfortunately, the name of N.K. Koltzoff has almost sunk into oblivion. This is largely due to the fact that mentioning his name was prohibited in the USSR over a long period of time, since he was a staunch opponent of Lysenko. In this paper dedicated to the 150th anniversary of Koltzoff, we briefly describe the milestones of the life and scientific research of this outstanding biologist and his scientific school.

Associations between heredity, height, BMI, diabetes mellitus type 1 or 2 and gene variants in the insulin receptor (INSR) gene in patients with schizophrenia.

OBJECTIVES: Schizophrenia is a psychotic disorder with high heritability. There are also indications that an autoimmune-mediated process in the brain underlies development of schizophrenia, and that the insulin receptor A may constitute a main antigen target. Therefore, as the insulin receptor gene hitherto has been little studied in schizophrenia, this study was undertaken to investigate this gene in schizophrenia susceptibility. MATERIALS AND METHODS: To identify gene variants of possible interest, the whole insulin receptor gene was first DNA-sequenced in all or subgroups of patients with schizophrenia and controls, using the Sanger method and the SOLiD technology. Then, association analyses of total 50 identified gene variants were carried out in the whole study population, consisting of 94 patients and 60 controls. RESULTS: No significant differences in genotype- and allele frequencies for the 50 gene variants were found between all patients and controls. However, in subgroup analyses, rs2229431 and rs747721248 tended to associate with heredity for schizophrenia, rs2229431 associated with height, rs41505247 with body mass index, rs59765738 and rs57476618 with diabetes mellitus (DM) type 1 and/ or heredity for DM type 1, and rs2962, rs2352954, rs2352955 and rs2252673 with DM type 2 and/ or heredity for DM type 2 in patients. CONCLUSIONS: In this study, we show associations between heredity, height, body mass index, DM type 1, or DM type 2 and gene variants in the insulin receptor gene in patients with schizophrenia. Taken together, these findings clearly point to that the insulin receptor gene is involved in schizophrenia susceptibility.

Heredity as a problem. On Claude Bernard's failed attempts at resolution.

Heredity has been dismissed as an insignificant object in Claude Bernard's physiology, and the topic is usually ignored by historians. Yet, thirty years ago, Jean Gayon demonstrated that Bernard did elaborate on the subject. The present paper aims at reassessing the issue of heredity in Claude Bernard's project of a "general physiology". My first claim is that Bernard's interest in heredity was linked to his ambitious goal of redefining general physiology in relation to morphology. In 1867, not only was morphology included within experimental physiology, but it also theoretically grounded physiological investigations. By 1878, morphology and physiology were considered as completely independent sciences, and only the latter was perceived as suitable to experimentation. My second claim is that this reversal reflected the existence of two opposite attitudes towards heredity. In the late 1860s, Bernard was convinced that heredity would soon be accessible to experimental manipulation and that new species would be produced in the laboratory exactly like organic chemistry succeeded to do for raw bodies. Ten years later, he ascertained that this was impossible. My third claim is that Bernard was epistemologically ill-equipped to address the issue of heredity. Bernard was strongly committed to a general reasoning scheme that acknowledged only three categories: determining conditions, constant laws and phenomena. This scheme was a key factor in his successes as a physiologist who was able to capture new mechanisms in living bodies. Nonetheless, it also prevented him from understanding how time and history could be endowed with a causal action that cannot be reduced to timeless parameters.

Species Transformation and Social Reform: The Role of the Will in Jean-Baptiste Lamarck's Transformist Theory.

Jean-Baptiste Lamarck is well known as a pre-Darwinian proponent of evolution. But much of what has been written on Lamarck, on his 'Lamarckian' belief in the inheritance of acquired characters, and on his conception of the role of the will in biological development mischaracterizes his views. Indeed, surprisingly little in-depth analysis has been published regarding his views on human physiology and development. Further, although since Robert M. Young's signal 1969 essay on Malthus and the evolutionists, Darwin scholars have sought to place Darwin's work in its social and political context, this has yet to be done adequately for Lamarck. Here I address this gap. I argue that the will was of particular importance to Lamarck's social commentary and his hopes for the transformation of the French people and nation. Further, I argue that if we are to really grasp Lamarck's ideas and intentions we need to contextualize his works in relation to prevailing debates in France about the physiology of mind and morals and the future of the nation.

Epigenetic inheritance in adaptive evolution.

Since the Modern Synthesis, our ideas of evolution have mostly centered on the information encoded in the DNA molecule and their mechanisms of heredity. Increasing evidence, however, suggests that epigenetic mechanisms have the potential to perpetuate gene activity states in the context of the same DNA sequence. Here, we discuss recent compelling evidence showing that epigenetic signals triggered by environmental stress can persist over very long timeframes, contributing to phenotypic changes in relevant traits upon which selection could act. We argue that epigenetic inheritance plays an important role in fast phenotypic adaptation to fluctuating environments, ensuring the survival of the organisms of a population under environmental stress in the short term while maintaining a "bet-hedging" strategy of reverting to the original state if the environment returns to standard conditions. These examples call for a reevaluation of the role of nongenetic information in adaptive evolution, raising questions about its broader relevance in nature.

Prenatal diagnosis of recurrent hypoplastic left heart syndrome associated with MYH6 variants: a case report.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a rare but genetically complex and clinically and anatomically severe form of congenital heart disease (CHD). CASE PRESENTATION: Here, we report on the use of rapid prenatal whole-exome sequencing for the prenatal diagnosis of a severe case of neonatal recurrent HLHS caused by heterozygous compound variants in the MYH6 gene inherited from the (healthy) parents. MYH6 is known to be highly polymorphic; a large number of rare and common variants have variable effects on protein levels. We postulated that two hypomorphic variants led to severe CHD when associated in trans; this was consistent with the autosomal recessive pattern of inheritance. In the literature, dominant transmission of MYH6-related CHD is more frequent and is probably linked to synergistic heterozygosity or the specific combination of a single, pathogenic variant with common MYH6 variants. CONCLUSIONS: The present report illustrates the major contribution of whole-exome sequencing (WES) in the characterization of an unusually recurrent fetal disorder and considered the role of WES in the prenatal diagnosis of disorders that do not usually have a genetic etiology.

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.

Epigenetic Regulation During Plant Development and the Capacity for Epigenetic Memory.

The establishment, maintenance, and removal of epigenetic modifications provide an additional layer of regulation, beyond genetically encoded factors, by which plants can control developmental processes and adapt to the environment. Epigenetic inheritance, while historically referring to information not encoded in the DNA sequence that is inherited between generations, can also refer to epigenetic modifications that are maintained within an individual but are reset between generations. Both types of epigenetic inheritance occur in plants, and the functions and mechanisms distinguishing the two are of great interest to the field. Here, we discuss examples of epigenetic dynamics and maintenance during selected stages of growth and development and their functional consequences. Epigenetic states are also dynamic in response to stress, with consequences for transposable element regulation. How epigenetic resetting between generations occurs during normal development and in response to stress is an emerging area of research.

Transgenerational Epigenetic Inheritance of Traumatic Experience in Mammals.

In recent years, we have seen an increasing amount of evidence pointing to the existence of a non-genetic heredity of the effects of events such as separation from parents, threat to life, or other traumatising experiences such as famine. This heredity is often mediated by epigenetic regulations of gene expression and may be transferred even across several generations. In this review, we focus on studies which involve transgenerational epigenetic inheritance (TEI), with a short detour to intergenerational studies focused on the inheritance of trauma or stressful experiences. The reviewed studies show a plethora of universal changes which stress exposure initiates on multiple levels of organisation ranging from hormonal production and the hypothalamic-pituitary-adrenal (HPA) axis modulation all the way to cognition, behaviour, or propensity to certain psychiatric or metabolic disorders. This review will also provide an overview of relevant methodology and difficulties linked to implementation of epigenetic studies. A better understanding of these processes may help us elucidate the evolutionary pathways which are at work in the course of emergence of the diseases and disorders associated with exposure to trauma, either direct or in a previous generation.

New historical and philosophical perspectives on quantitative genetics.

The aim of this virtual special issue is to bring together philosophical and historical perspectives to address long-standing issues in the interpretation, utility, and impacts of quantitative genetics methods and findings. Methodological approaches and the underlying scientific understanding of genetics and heredity have transformed since the field's inception. These advances have brought with them new philosophical issues regarding the interpretation and understanding of quantitative genetic results. The contributions in this issue demonstrate that there is still work to be done integrating old and new methodological and conceptual frameworks. In some cases, new results are interpreted using assumptions based on old concepts and methodologies that need to be explicitly recognised and updated. In other cases, new philosophical tools can be employed to synthesise historical quantitative genetics work with modern methodologies and findings. This introductory article surveys three general themes that have dominated philosophical discussion of quantitative genetics throughout history: (1) how methodologies have changed and transformed our knowledge and interpretations; (2) whether or not quantitative genetics can offer explanations relating to causation and prediction; and (3) the importance of defining the phenotypes under study. We situate the contributions in this virtual special issue within a historical framework addressing these three themes.