Kenneth Kendler

This paper explores the interpretation and use of polygenic risk scores (PRSs). We argue that PRSs generally do not directly embody causal information. Nonetheless, they can assist us in tracking other causal relationships concerning genetic effects. Although their purely predictive/correlational use is important, it is this tracking feature that contributes to their potential usefulness in other applications, such as genetic dissection, and their use as controls, which allow us, indirectly, to "see" more clearly the role of environmental variables.

Prosper Lucas (1808–1885) is a unique figure in the history of psychiatric genetics. A physician-alienist, he authored one of the most important books on human genetics in the mid-19th century cited frequently by Darwin: the 1,500 page treatise—Philosophical and Physiological Treatise on Natural Heredity (1847–1850). This book contained a novel theory of the nature of inheritance and a detailed review of the heredity of a range of human traits and disorders, including various forms of insanity. Lucas postulated four forms of heredity (direct, crossed, indirect, and atavistic), supported the importance of hereditary factors in insanity, accepted the inheritance of acquired characteristics, considered it important to examine both ancestors and collateral relatives, and recognized that heredity could influence both primary insanity and insanity secondary to other medical conditions. He reviewed the then available literature on most major forms of insanity including separate sections on hallucinations and suicidal monomania. The literature consisted of case reports of unusual families with high concentrations of illness. Lucas advocated for the homogeneity of transmission of forms of illness in families but recognized that—just as the form of illness could evolve within individuals over time—it could change forms when transmitted between relatives.

In psychiatry, many scientists desire to move from a classification system based on symptoms toward a system based on biological causes. The idea is that psychiatric diseases should be redefined such that each disease would be associated with specific biological causes. This desire is intelligible because causal disease models often facilitate understanding and identification of new ways to intervene in disease processes. In its attempt to move from syndromal to specific etiological definitions, psychiatry follows the trend of general medicine.Current psychiatric...

Levels of Analysis in Psychopathology draws research from psychiatry, philosophy, and psychology to explore the variety of explanatory approaches for understanding the nature of psychiatric disorders both in practice and research. The fields of psychiatry and clinical psychology incorporates many useful explanatory approaches and this book integrates this range of perspectives and makes suggestions about how to advance etiologic theories, classification, and treatment. The editors have brought together leading thinkers who have been widely published and are well-respected in their area of expertise, including several developers of the Diagnostic and Statistical Manual of Mental Disorders and authors of the US National Institute of Mental Health's Research Domain Criteria Project. Each main chapter has a commentary provided by one of the other authors and an introduction written by one of the editors to create an accessible, interdisciplinary dialog.

This multidisciplinary collection explores three key concepts underpinning psychiatry -- explanation, phenomenology, and nosology -- and their continuing relevance in an age of neuroimaging and genetic analysis. An introduction by Kenneth S. Kendler lays out the philosophical grounding of psychiatric practice. The first section addresses the concept of explanation, from the difficulties in describing complex behavior to the categorization of psychological and biological causality. In the second section, contributors discuss experience, including the complex and vexing issue of how self-agency and free will affect mental health. The third and final section examines the organizational difficulties in psychiatric nosology and the instability of the existing diagnostic system. Each chapter has both an introduction by the editors and a concluding comment by another of the book's contributors. Contributors: John Campbell, Ph.D.; Thomas Fuchs, M.D., Ph.D.; Shaun Gallagher, Ph.D.; Kenneth S. Kendler, M.D.; Sandra D. Mitchell, Ph.D.; Dominic P. Murphy, Ph.D.; Josef Parnas, M.D., Dr.Med.Sci.; Louis A. Sass, Ph.D.; Kenneth F. Schaffner, M.D., Ph.D.; James F. Woodward, Ph.D.; Peter Zachar, Ph.D

This essay selectively reviews, from an historical and philosophical perspective, the dopamine (DA) hypothesis of schizophrenia (DHS; Table 1 lists the abbreviations used in this essay). Our goal is not to adjudicate the validity of the theory—although we arrive at a generally skeptical conclusion—but to focus on the process whereby the DHS has evolved over time and been evaluated. Since its inception, the DHS has been the most prominent etiologic theory in psychiatry and is still referred to widely in current textbooks (e.g., Buchanan and Carpenter, Jr. 2005, 1336; Cohen 2003, 225; Gazzaniga 2004, 1257;Kandel et al. 2000, 1200). Understanding its origins and evolution should help to clarify the nature of modern ..

We are gratified at the largely positive comments on our essay on the dopamine hypothesis of schizophrenia (DHS) by these two distinguished commentators from the fields of biological psychiatry (Dr. Tamminga) and the philosophy of psychiatry (Dr. Murphy). There is little that they have said with which we disagree. Rather, we want to expand briefly on their commentaries.We found Dr. Tamminga's reactions to be particularly fascinating because she has been an "insider" to the story of the DHS as it has unfolded. She provides substantial insight into the "extra-scientific" reasons for the persistence of the DHS despite its poor empirical record.She validates our impression that the DHS was in its first years of ..