Search

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. Third, the full manifestation of the disorder requires certain environmental influences that must come into play. In around 30% of cases, the environment can inhibit hereditary factors so that the predisposition does not manifest in schizophrenia. Fourth, the mode of inheritance of schizophrenia remains unknown, although recessivity is more likely than dominance and monomerism is more likely than polymerism. Fifth, current evidence suggests that schizophrenia is likely etiologically homogenous. Sixth, schizophrenia is part of a hereditary circle that includes "normal" variants of the human personality (schizothymia), a pathological version of this dimension (schizoidia), and other schizophrenia-like delusional syndromes. Luxenburger is skeptical of efforts to clarify further Mendelian transmission models in the absence of pathophysiological markers because schizophrenia cannot serve as a typical phenotype for genetic analysis. By contrast, he strongly supports empirical work on hereditary prognosis, which does not depend on assumptions about any particular phenotype-genotype relationship., (© 2024 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

The diagnosis of childhood schizophrenia was widely employed in the U.S. from the 1930s to the late 1970s. In this paper I will provide a history of the diagnosis. Some of the earliest publications on childhood schizophrenia outlined the notion that childhood schizophrenia had different types. I will outline the development of these types, outlining differing symptoms and causes associated with various types. I outline how different types of childhood schizophrenia were demarcated from one another primarily on age of onset and the type of psychosis which was believed to be present. I will outline how various child psychiatrists viewed the types of childhood schizophrenia posited by other child psychiatrists. I will outline the process of abandoning childhood schizophrenia. I use my history to challenge what I believe are misconceptions about childhood schizophrenia. Also, I will use my history to draw lessons for thinking about modern notions of autism. It shows potential problems around formulating psychiatric diagnoses around causes and how compromises might be needed to prevent those problems. Additionally, childhood schizophrenia shows that psychiatrists could formulate subtypes that are not based upon functioning levels and that we can conceive of subtypes as dynamic whereby someone can change which subtype they exhibit over time., (© 2024. The Author(s).)

This paper examines nosological categories relating to borderlines between psychosis and other clinical categories, introduced by Polish psychiatrists in the interwar period. In the United States, the discussion about the borderline between neuroses and psychoses was urged by the 1938 article by psychoanalyst Adolph Stern. In Poland, nosological categories regarding the borderline between neuroses and psychoses were proposed by Adam Wizel, Maurycy Bornsztajn, Jan Nelken, and Władysław Matecki. Wizel coined the term 'underdeveloped schizophrenia', Bornsztajn introduced 'schizothymia reactiva' and 'hypochondriac (somatopsychic) schizophrenia', Nelken described 'mild schizophrenia', first introduced by Moscow psychiatric school of Rosenstein, and Matecki presented the category of neurosis-like (pseudo-neurotic) schizophrenia. Additionally, Julian Dretler, after studying the borderline between schizophrenia and manic-depressive psychosis, coined the term 'mixed psychosis' and expressed conviction that it is an independent nosological entity. Like in the United States, the majority of Polish pioneers of the nosological studies of borderline cases were influenced by psychoanalysis. As a consequence of World War II and the new regime, which forced dialectical materialism and Pavlovism as an official ideology of psychiatry and condemned psychoanalysis, the categories presented in the article became forgotten and have not impacted Polish psychiatric nosology.

Clozapine was first manufactured in China in 1976. Clozapine is currently used not only for treatment-refractory schizophrenia (TRS), but also continues to be used in the treatment of patients with non-TRS and other mental disorders; moreover, low-dose clozapine is also used in sedative-hypnotic therapy and in combination with other drugs. There is need for studies in China using various titrations and assessing their risk for myocarditis and aspiration pneumonia. The Chinese clozapine package insert will also greatly benefit from these changes., Competing Interests: Declaration of competing interest In the last 3 years, the authors report no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Arthur Schopenhauer (1788-1860) was one of the most important thinkers of the 19th century. Although his writings have exerted great influence in many different disciplines, his epistemological concepts and analysis of the body and self-experience were rarely considered in the context of psychiatric research of schizophrenia spectrum disorders (SSD) and depression (MDD)., Methods: The method applied for the study of anomalous self and body-experience first consists in the close reading and analysis of Schopenhauer's most influential writings, namely his opus magnus "The World as Will and Representation" and his dissertation "On the Fourfold Root of the Principle of Sufficient Reason". Second, psychopathological and phenomenological aspects of the anomalous body and self, as well as altered space and time experience, are discussed by means of Schopenhauer's philosophy and four patient cases., Results: Schopenhauer's insights contribute to contemporary psychiatry by (1) unifying materialistic (neurobiological) and idealistic (subjective) conceptions of psychiatric disorders and improving the awareness of methods in psychiatric research; (2) emphasizing the integral significance of the body as a gateway to the surrounding world and basal self-experience; (3) delineating subjective space and time-experience as crucial dimensions of the conditio humana in SSD and MDD; and (4) demonstrating the feasibility of transferring his theories directly to clinical case vignettes stemming from the daily clinical routine., Conclusion: Close reading of Schopenhauer's texts might help bridge the gap between different scientific methods in psychiatry and overcome the translational crisis of contemporary psychiatry by unifying neurobiological and subjective approaches to SSD and MDD., Competing Interests: Declaration of competing interest The authors have declared that there are no conflicts of interest in relation to the subject of this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study examines the temporal and geographical evolution of polygenic scores (PGSs) across cognitive measures (Educational Attainment [EA], Intelligence Quotient [IQ]), Socioeconomic Status (SES), and psychiatric conditions (Autism Spectrum Disorder [ASD], schizophrenia [SCZ]) in various populations. Our findings indicate positive directional selection for EA, IQ, and SES traits over the past 12,000 years. Schizophrenia and autism, while similar, showed different temporal patterns, aligning with theories suggesting they are psychological opposites. We observed a decline in PGS for neuroticism and depression, likely due to their genetic correlations and pleiotropic effects on intelligence. Significant PGS shifts from the Upper Paleolithic to the Neolithic periods suggest lifestyle and cognitive demand changes, particularly during the Neolithic Revolution. The study supports a mild hypothesis of Gregory Clark's model, showing a noticeable rise in genetic propensities for intelligence, academic achievement and professional status across Europe from the Middle Ages to the present. While latitude strongly influenced height, its impact on schizophrenia and autism was smaller and varied. Contrary to the cold winters theory, the study found no significant correlation between latitude and intelligence.

The article reconstructs attempts to create scientifically coherent, internationally agreed-upon diagnostics for mild forms of schizophrenia throughout the 20th century. A particular focus here lies on what became known as bland-or sluggish-schizophrenia, a particular term coined in the USSR, which became known for its frequent use in internationally contested diagnoses of human rights activists. The argument follows the diagnosis of sluggish schizophrenia from its inception in a highly productive and equally international psychiatric community of the early 20th century pioneered by prominent Soviet scholar Andrey Snezhnevsky and through its epistemic detachment and content-related transformation in the highly isolated Soviet psychiatric community since the interwar period. This transformation is analyzed with help of the case study on the International Classification of Diseases (ICD). Released by the World Health Organization, the ICD-and in particular its ninth revision-played a crucial role in the attempt to legitimize sluggish schizophrenia. The comparative study of four presumably identical ICD-passages from three languages helps reconstructing how internationally accorded terms would become adapted to the Soviet societal and political realities. The ultimate aim of the attempted adaptation, the article claims, was to provide the elsewhere contested diagnostic term "sluggish" schizophrenia with additional legitimacy per authority of the WHO and, thus, much needed credibility for domestic, and often political, use., (© 2023. The Author(s).)

While the evolution of our modern concepts of mania and melancholia over the 19th century is relatively well-understood, no such clear narrative exists for the nonaffective psychotic syndromes that culminated in Kraepelin's concept of dementia praecox in 1899. These narratives were relatively distinct in Germany and France. An important milestone in the French literature is the 1852 essay by the alienist and polymath Charles Lasègue which contained the first detailed modern description of a persecutory delusional syndrome. Lasègue was a careful clinical observer who emphasized a symptomatic approach to psychiatric nosology and was less concerned with course and outcome. He details the evolution of persecutory delusions from increasing referential observations of real events, to the resulting anxious confusion and then the emergence of explanatory delusional beliefs. Once formed, these beliefs, he notes, are relatively impervious to correction. Lasègue was unusual for his time in emphasizing a "first-person perspective" on psychotic experiences, and quotes from his patients in his case history, of which he presents 15. Of these, 12 had auditory hallucinations and 4 passivity phenomena. While conceptualized differently than mid-19th century pre-Kraepelinian German writing on delusional syndromes, and unique on its focus on persecutory delusions, Lasègue's important essay shared a common view on the key features of a broad nonaffective delusional-hallucinatory syndrome. It was this syndrome that Kraepelin, over multiple drafts in the first 6 editions of his textbook from 1883 to 1899, was to divide into his mature concepts of paranoia and the paranoid subtype of dementia praecox., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In the mid-twentieth century in the Soviet Union, latent schizophrenia became an important concept and a matter of research and also of punitive psychiatry. This article investigates precursor concepts in early Russian psychiatry of the nineteenth century, and examines whether - as claimed in recent literature - Russian and Soviet research on latent schizophrenia was mainly influenced by the work of Eugen Bleuler.

Pre-Kraepelinian observations converged in Kahlbaum's and Hecker's description of Hebephrenia. For Kraepelin, Hebephrenia was an 'idiopathic incurable dementia whose onset is in adolescence'. It became the core of 'Dementia Praecox', and then Bleulerian 'Schizophrenia'. In recent decades, the resurgence of the 'late neurodevelopment' hypothesis of schizophrenia has brought into focus Hecker's clinical reports of adolescents who, as a result of a putative loss of psychic energy, showed a rapidly progressive cognitive impairment leading to functional and behavioural disorganization. This paper summarizes the nineteenth-century conceptualization of Hebephrenia as a developmental illness.

In 1921, at the age of 65, 6 years after completing the final edition of his textbook, 22 years after first proposing the concept of dementia praecox (DP), and 1 year before retiring from clinical work, Emil Kraepelin completed the last edition of his "Introduction to Clinical Psychiatry," which contained a mini-textbook for students, 10 pages of which were devoted to DP. This work also included a series of new detailed case histories, 3 of which examined DP. This neglected text represents a distillation of what Kraepelin judged, near the end of his long career, to be the essential features of DP. The relevant text and case histories are translated into English for the first time. Kraepelin did not define DP solely by its chronic course and poor prognosis, acknowledging that remissions and even full recovery might be possible. His clinical description emphasized the frequency of bizarre delusions and passivity symptoms. He recognized the heterogeneity of the clinical presentations, outlining 6 subtypes of DP, including dementia simplex, depressive and stuporous dementia, and an agitated and circular DP. Kraepelin's original concept of DP was not impervious to change and expanded somewhat, especially with the inclusion of Diem's concept of simple DP. He also reviews several contributions of Bleuler, including his concept "latent schizophrenia." He writes poignantly of the psychological consequences of DP. His 3 DP cases, for advanced students, included simple DP, "periodic catatonic," and "speech confusion.", (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Although contemporary approaches to schizophrenia pinpoint 'disturbances of the self' as a central aetiological factor, historical insight into the link between accounts of schizophrenia and theories of subjectivity and self-consciousness is poor. This paper aims to overcome this gap by providing the outlines of a largely forgotten but crucial part of the intellectual history of schizophrenia. In particular, the impact of the German tradition of apperceptionism on nineteenth-century accounts of schizophrenia is unearthed. This tradition emerged from German Idealism, and culminated in Emil Kraepelin's account of dementia praecox. In addition to filling an important gap in the historiography of psychiatry, this analysis contributes to ongoing efforts to correct some common misunderstandings regarding Kraepelin's theoretical position.

The third part of the triptych of my 50-year activity in psychiatry is about psychopharmacology. This way of treatment changed the picture of contemporary psychiatry. The introduction of neuroleptic (antipsychotic) drugs and tricyclic antidepressants in the 1950s resulted in a therapeutic revolution and contributed to the ‛medicalization' of psychiatry and its therapeutic similarity to other non-surgical specialties. Adiscovery of prophylactic lithium activity in the1960s initiated the mood-stabilizing drugs.During the last half-century, the most dynamic was the 1990s when most antipsychotic and antidepressant drugs of the so-called new generation were introduced. The twenty-first century marks a debut of next antidepressant and antipsychotic drugs, some of the latter having long-acting injectable preparations. An interesting event was a demonstration of the antidepressant activity of ketamine. My research domain in psychopharmacology was lithium treatment of affective illnesses. Lithium makes the topic of many papers I authored, more than 150 of them are in the PubMed database. Many clinical and research aspects related to lithium administration have been reported as first in Polish literature and some are pioneering in the world. Recently, I wrote the book Lithium - the amazing drug in psychiatry which has also its English version. I have carried much research on antidepressant drugs, pharmacotherapy of treatment-resistant depression, and mood-stabilizing drugs for which I proposed a modern classification. I participated in European projects EUFEST and OPTIMISE on the optimization of using antipsychotic drugs in schizophrenia. I also performed much research on the antidepressant effect of ketamine and electroconvulsive therapy.

In this paper, I evaluate Sabina Spielrein's life and ideas from a contemporary understanding. I do this by considering the context and situation in which she lived: a journey from being a hospitalized psychiatric patient to becoming a psychoanalyst herself. From her crucial life experiences she learned that the main psychic conflicts stem from the struggle between life and death, and not from opposing ego drives and sexual desires. Spielrein's considerable creative potentials were nurtured, as well as blocked by her inner conflicts, but also by the enormous historical conflicts of her time.

During the first half of the twentieth century, German psychiatry came to consider ' Ich-Störungen ', best translated as self-disorders, to be important features of schizophrenia. The present text is a translation of a chapter by the German psychiatrist Hans Gruhle, which is extraordinarily clear and emblematic for this research line. Published in 1929, it was part of a book co-written with Josef Berze, The Psychology of Schizophrenia (concerning its subjectivity). Gruhle claims that the essential core of schizophrenia is of an affective nature, a 'mood' manifesting itself as self-disorder, an unstable, incomplete pre-reflective self-awareness. His impact on contemporary psychiatry was probably limited due to his confrontational style, but this text has great significance for the modern revival of phenomenological research in schizophrenia.

In 1917, Eugen Bleuler published an article (Mendelismus bei Psychosen, speziell bei der Schizophrenie [Mendelism in the Psychoses, especially Schizophrenia]) in response to the recently published first systematic family study of dementia praecox (DP) by Ernst Rüdin, then working under Kraepelin in Munich. Although briefly commented upon by David Rosenthal in 1978, this article has never been thoroughly reviewed or translated. Of the many themes addressed, four are especially noteworthy. First, Bleuler argues that understanding the transmission patterns of schizophrenia in families requires definitive knowledge about the boundaries of the phenotype which he argues are unknown. Rüdin's choice-Kraepelin's concept of DP-is, he asserts, too narrow. Clarifying the genetics of schizophrenia is inextricably bound up with the problem of defining the phenotype. Second, Bleuler argues for the importance of "erbschizose" (literally "inherited schizoidia") wondering whether his "4 As" or other "brain-anatomical, chemical, [or] neurological characteristics" might underlie the genetic transmission of schizophrenia. Third, Bleuler was deeply interested in the nature of the onset of schizophrenia, suggesting that environmental adversity could provoke "latent illness to become manifest." It was important, he argued, to identify such risk factors and incorporate them into genetic models. Fourth, although not optimistic that current knowledge would permit a resolution of the transmission model for schizophrenia, he finds single-locus models implausible and at several points wonders whether polygenic models might better apply. A complete translation of the article is provided., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

While the roots of mania and melancholia can be traced to the 18th century and earlier, we have no such long historical narrative for dementia praecox (DP). I, here, provide part of that history, beginning with Kraepelin's chapter on Verrücktheit for his 1883 first edition textbook, which, over the ensuing 5 editions, evolved into Kraepelin's mature concepts of paranoia and paranoid DP. That chapter had 5 references published from 1865 to 1879 when delusional-hallucinatory syndromes in Germany were largely understood as secondary syndromes arising from prior episodes of melancholia and mania in the course of a unitary psychosis. Each paper challenged that view supporting a primary Verrücktheit as a disorder that should exist alongside mania and melancholia. The later authors utilized faculty psychology, noting that primary Verrücktheit resulted from a fundamental disorder of thought or cognition. In particular, they argued that, while delusions in mania and melancholia were secondary, arising from primary mood changes, in Verrücktheit, delusions were primary with observed changes in mood resulting from, and not causing, the delusions. In addition to faculty psychology, these nosologic changes were based on the common-sense concept of understandability that permitted clinicians to distinguish individuals in which delusions emerged from mood changes and mood changes from delusions. The rise of primary Verrücktheit in German psychiatry in the 1860-1870s created a nosologic space for primary psychotic illness. From 1883 to 1899, Kraepelin moved into this space filling it with his mature diagnoses of paranoia and paranoid DP, our modern-day paranoid schizophrenia., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Through a close reading of texts, this essay traces the development of catatonia from its origination in Kahlbaum's 1874 monograph to Kraepelin's catatonic subtype of his new category of Dementia Praecox (DP) in 1899. In addition to Kraepelin's second to sixth textbook editions, I examine the six articles referenced by Kraepelin: Kahlbaum 1874, Brosius 1877, Neisser 1887, Behr 1891, Schüle 1897, and Aschaffenburg 1897 (Behr and Aschaffenburg worked under Kraepelin). While Brosius and Neisser confirmed Kahlbaum's descriptions, Behr, Schüle, and Aschaffenburg concluded that his catatonic syndrome was nonspecific and only more narrowly defined forms, especially those with deteriorating course, might be diagnostically valid. Catatonia is first described by Kraepelin as a subform of Verrücktheit (chronic nonaffective delusional insanity) in his second to fourth editions. In his third edition, he adds a catatonic form of Wahnsinn (acute delusional-affective insanity). His fourth and fifth editions contain, respectively, catatonic forms of his two proto-DP concepts: Psychischen Entartungsprocesse and Die Verblödungsprocesse. Kahlbaum's catatonia required a sequential phasic course. Positive psychotic symptoms were rarely noted, and outcome was frequently good. While agreeing on the importance of key catatonic signs (stupor, muteness, posturing, verbigeration, and excitement), Kraepelin narrowed Kahlbaum's concept, dropping the phasic course, emphasizing positive psychotic symptoms and poor outcome. In his fourth to sixth editions, as he tried to integrate his three DP subtypes, he stressed, as suggested by Aschaffenburg and Schüle, the close clinical relationship between catatonia and hebephrenia and emphasized the bizarre and passivity delusions seen in catatonia, typical of paranoid DP., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In developing his mature concept of hebephrenic dementia praecox (DP) in his 4th (1893) through 6th textbook editions (1899), Kraepelin worked from the hebephrenic syndrome first described by Hecker (1871) and then carefully studied by his student Daraszkiewicz (1892). Working under Kraepelin's supervision, Daraszkiewicz followed Hecker in emphasizing several key features of hebephrenia (distinctive deteriorative course, importance of silliness and minimal positive psychotic symptoms) but expanded the syndrome to include cases developing severe dementia, rejected the link to prodromal depressive and manic phases, and reduced the emphasis on thought disorder. Daraszkiewicz proposed a soft subtyping of hebephrenia based on level of deterioration, which Kraepelin adopted in his 4th edition with an additional emphasis on severe positive psychotic symptoms. In his 5th edition, Kraepelin created a third subform with even more pronounced and bizarre delusions and hallucinations. In his 6th edition, which contained his first articulation of DP, Kraepelin eliminated his hebephrenia subforms presenting a single syndrome, which, compared to Hecker, included more emphasis on positive psychotic and catatonic symptoms and severe dementia. Kraepelin's paths to hebephrenic and paranoid DP differed in important ways. Paranoid DP was a de novo syndrome created by differentiation from paranoia. Hebephrenia, by contrast, evolved from a disorder created in the Kahlbaum/Hecker paradigm of the iterative study of clinical features, course and outcome. Kraepelin further implemented this approach in substantially reworking, over several drafts, the hebephrenic syndrome to fit into his emerging construct of dementia praecox.

This article uses the concept of "diagnosis infrastructures" to propose a framework for narrating the history of schizophrenia as a global category in the twentieth century. Diagnosis infrastructures include the material and architectural arrangements, legal requirements, and professional models that enable both the ways in which patients come to clinics and navigate the world of schizophrenia as well as the means through which clinicians organize their diagnostic work. These infrastructures constitute a framework for how schizophrenia has been identified as a disorder. This article explores three moments in the history of schizophrenia infrastructures in the twentieth century. The first is the German psychiatrist Kurt Schneider's discussion of first- and second-rank symptoms in the interwar period. The second is the research on criteria for defining schizophrenia within the framework of the WHO International Pilot Study of Schizophrenia at the turn of the 1970s. The third corresponds to the changing infrastructures of mental health care in the context of both global mental health and the changing landscape of schizophrenia research over the last decades.

Importance: First-rank symptoms (FRS), proposed by Kurt Schneider in 1939, subsequently became influential in schizophrenia diagnosis. We know little of their prehistory. How often were FRS described before 1939 and in which countries and time periods? Which FRS was most frequently noted?, Observations: Forty psychiatric texts from 37 authors, published 1810-1932, were identified that described FRS. In a systematic subsample, half of the textbooks examined contained such descriptions with little differences between countries or over time. Somatic passivity was most commonly noted, followed by thought insertion, thought withdrawal, and made actions. This pattern resembled that reported in recent studies of schizophrenia. A novel term-delusions of unseen agency-was seen in psychiatric texts and then found, from 1842 to 1905, in a range of official reports, and psychiatric, medical, and general audience publications. The Early Heidelberg School (Gruhle, Mayer-Gross, Beringer) first systematically described "self-disturbances" (Ichstörungen), many of which Schneider incorporated into FRS., Conclusions and Relevance: From the beginning of Western descriptive psychopathology in the early 19th century, symptoms have been observed later described as first-rank by Schneider. A term "delusion of unseen agency"-closely related to Schneider's first-rank concept-was popular in the second half of the 19th century and described in publications as prominent as the Encyclopedia Britannica and New England Journal of Medicine. The descriptions of these specific symptoms, with substantial continuity, over more than 2 centuries and many countries, suggest that an understanding of their etiology would teach us something foundational about the psychotic illness., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The Genain Quadruplets, a genetically identical group of sisters, all developed schizophrenia by their early 20s. Beginning in the 1950s, under the direction of David Rosenthal, they have been studied extensively with a number of neurobiological, neuroradiological and neurobehavioral measures at the Intramural Program of the National Institute of Mental Health (NIMH). A major focus of research interest has been the fact that they varied greatly in the severity of their illness. The present report emphasizes the important role that Monte Buchsbaum had in their evaluation, especially with respect to neuroradiology, during their second period of study at NIMH in the 1980s. It is of special interest that Buchsbaum et al. (1984) concluded "No strong relationship is shown between these (radiological) measures and illness severity or drug responsivity." The inference, therefore, is that the differences in illness severity among the sisters were not readily attributable to differences in the amount of damaged brain, at least as could be determined by the imaging methods available in the 1980s. The current report also summarizes the results of the other studies performed on the sisters in the 1980s, to which Monte Buchsbaum contributed., (Copyright © 2019. Published by Elsevier B.V.)

The term "pseudoneurotic schizophrenia" was introduced in 1949 by Hoch and Polatin to describe apparently neurotic patients showing formal thought disorders, emotional dysregulation, and transient psychotic symptoms. Even if this diagnostic entity is no longer included in modern diagnostic systems, its evolution is intertwined with the history of schizophrenia in the 20th century. This article retraces the development of pseudoneurotic (or "borderline") schizophrenia in modern psychiatry, finding it a pioneering concept in psychopathology. In particular, we demonstrate that recent findings about the positive syndrome, good-outcome, type I "distress" subtype of schizophrenia (associated with high emotionality, including anxiety, depression, and sensitivity to stress) show surprising consistency with the clinical concept of pseudoneurotic schizophrenia. Finally, we discuss the historical development of pseudoneurotic schizophrenia in modern psychiatry as a meaningful example of the difficulty of confining severe psychological disturbances lying at the edge of full-blown schizophrenia within a widely accepted diagnostic category.

Purpose of Review: Emil Kraepelin, in 1899, proposed a dichotomy of psychiatric disorders into "dementia praecox," further called schizophrenia, and "manisch-depressives Irresein," now conceptualized as a bipolar disorder. The purpose of the review is to show both similarities and differences between disorders involved in this dichotomy, speaking for and against the idea., Recent Findings: On the molecular genetic side, there are data for both a genetic overlap and genetic differences between these two illnesses. Among pharmacological treatment, lithium, valproates, and carbamazepine present evidence for Kraepelinian dichotomy while atypical antipsychotics speak against this. The recent results for similarities and differences in the immune system, cognitive functions, and neurodevelopmental mechanisms have also been presented and discussed. As of 2019, the Kraepelinian dichotomy has been still partly valid although the results of recent clinical, neurobiological, and pharmacological studies provided a large number of data for an intermediate space between schizophrenia and bipolar disorder.

Twentieth-century psychiatry was transformed in the 1950s and 1960s by the introduction of powerful psychopharmaceuticals, particularly Chlorpromazine (Thorazine). This paper examines the reception of Chlorpromazine in the Soviet Union and its effect on the Soviet practice of psychiatry. The drug, known in the USSR by the name Aminazine, was first used in Moscow in 1954 and was officially approved in 1955. I argue that Soviet psychiatrists initially embraced it because Aminazine enabled them to successfully challenge the Stalin-era dogma in their field (Ivan Pavlov's 'theory of higher nervous activity'). Unlike in the West, however, the new psychopharmaceuticals did not lead to deinstitutionalisation. I argue that the new drugs did not disrupt the existing Soviet system because, unlike the system in the West, the Soviets were already dedicated, at least in theory, to a model which paired psychiatric hospitals with community-based 'neuropsychiatric dispensaries.' Chlorpromazine gave this system a new lease on life, encouraging Soviet psychiatrists to more rapidly move patients from in-patient treatment to 'supporting' treatment in the community.

In the first half of the 20th century, in most European countries, it was thought that cholinesterase and other drugs that counteract acetylcholine should reduce the manifestations of schizophrenia. In 1937, Fiamberti (1894-1970) introduced the transorbital method of lobotomy which established the use of acetylcholine shock treatment for curing the disturbances of schizophrenia. Accepting the idea that the psychic alterations of schizophrenia were caused by a pathological interruption of nerve conduction at a presumably cortical level, Fiamberti thought he could apply this to the clinical field using the properties of acetylcholine, an acetic ester of choline. Here, we examined, in detail, the contribution of Mario Fiamberti to acetylcholine therapy.

We can trace, with high congruence, the clinical syndromes of depression and mania as described over the 20th century in psychiatric textbooks back to 1880 and to the earliest writing of Kraepelin published in 1883. However, this is not the case for Kraepelin's 2 delusional syndromes central to his overall nosology: Dementia Paranoides (later paranoid schizophrenia) and Paranoia. A detailed examination of 28 textbook descriptions of delusional psychoses from 1880 to 1900 reveals a diverse and partially overlapping set of syndromes with an admixture of symptoms and signs that would later be considered indicative of Dementia Paranoides and Paranoia. A similar pattern in seen in Kraepelin's own description of "Primäre Verrücktheit" from the first edition of his textbook (1883). No clear prototypes emerged in these textbooks or in Kraepelin's early writings for the 2 distinct delusional syndromes that would later evolve in his mature writings. Rather, the nosologic approach taken in these writings was symptom based and assumed that a viable diagnostic category could be constituted by including all delusional patients once those suffering from organic or mood disorders were excluded. While Kraepelin used the historical syndromes of mania and depression, with no appreciable change, as building blocks for his category of manic-depressive insanity, his nosologic system for the psychotic disorders-the syndromes of Dementia Praecox and Paranoia-was more innovative and without clear precedent in the prior psychiatric literature., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Current medical research has focused on diseases and their associated risk factors. As such, these factors are assumed to have a deleterious effect. An alternative hypothesis is that some of these risk factors would also increase the chance for an opposite, positive outcome. To test this hypothesis, we considered exceptional social achievement and schizophrenia as opposite outcomes. Sixty years ago, researchers in France collected data on socio-demographic factors associated with exceptional social achievement. As the number of female subjects in the original database was very limited, we restricted our analyses to men. We tested the odds of achieving prominence in the presence of factors known to be associated with an increased risk of schizophrenia, namely migration, urbanicity, seasonality of birth, birth order, and paternal age. Three of the five factors tested significantly increased the odds for exceptional social achievement (urban birth, being the first-born and father's age over 35). Our findings suggest that some of the factors that are currently considered as risk factors for schizophrenia could diversifying factors. Widening the focus of research to include all potential effects of factors associated with disease could have important consequences on our understanding of causal mechanisms and for designing public health interventions.

It is difficult to know precisely the history of a functional disease, unlike the natural history of infectious agents, tumour processes or poly-malformative syndromes. In the case of psychiatry, and especially schizophrenia and psychotic disorders, a retrospective look at artistic productions (writings and drawings) makes it possible to reconstitute a whole section of this pathological context. Through four medieval and modern examples, we will see how it is possible to do a paleo-psychiatry: Opicinus de Canistris (14 th c.), the Voynich manuscript (15 th c.), Hieronymus Bosch (15 th -16 th c.), and the Codex Seraphinianus (20 th c.)., (© 2018 L’Encéphale, Paris.)

Predictive prospective studies of schizophrenia date back to the late 1950s. At the turn of the Millennium, an Australian research group initiated programs of early detection of schizophrenia and early therapeutic intervention. The theoretical foundations of early schizophrenia detection usually remain unaddressed. In this paper, we focus on the issue of prediction of future schizophrenia in the general population on the basis of a symptomatic picture. Several notions used in this research program such as disease, symptom, and clinical staging derive from a medical model, which in our view is not entirely adequate for grasping the nature of schizophrenia. Schizophrenia is a spectrum of disorders with a shared core Gestalt comprising dis-order of selfhood and intersubjectivity. This core Gestalt has manifold manifestations, often predominantly in the existential or experiential domain. It is not feasible to apply medical concepts to this symptomatically poorly demarcated spectrum for which we do not know robust biological validators. Moreover, there is increasing evidence that the current DSM and ICD criteria of schizophrenia distort the original concept of schizophrenia and are formulated on a very high severity level. This often results in incorrect diagnoses of young help-seeking patients. In sum, it seems more appropriate to detect psychosis among already help-seeking patients than to implement detection programs in the general population. We discuss a reorientation of psychiatry towards more refined psychopathological knowledge and assessment that are needed in order to optimize the treatment of young help-seeking patients., (© 2018 L’Encéphale, Paris.)

A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (CGC-type) has significantly reduced promoter activity. A newly developed method for detecting ongoing positive selection was applied to the ST8SIA2 genomic region with the identification of an unambiguous sweep signal in a rather restricted region of 18 kb length surrounding the promoter. We also found that while the CGC-type emerged in anatomically modern humans in Africa over 100 thousand years ago, it has increased its frequency in Asia only during the past 20-30 thousand years. These findings support that the positive selection is driven by psychosocial stress due to changing social environments since around the last glacial maximum, and raise a possibility that schizophrenia extensively emerged during the Upper Paleolithic and Neolithic era., Competing Interests: The authors have declared that no competing interests exist.

The concept of autism has changed across time, from the Bleulerian concept, which defined it as one of several symptoms of dementia praecox, to the present-day concept representing a pervasive development disorder. The present theoretical contribution to this special issue of EJN on autism introduces new theoretical ideas and discusses them in light of selected prior theories, clinical examples, and recent empirical evidence. The overall aim is to identify some present challenges of diagnostic practice and autism research and to suggest new pathways that may help direct future research. Future research must agree on the definitions of core concepts such as autism and psychosis. A possible redefinition of the concept of autism may be a condition in which the rationale of an individual's behaviour differs qualitatively from that of the social environment due to characteristic cognitive impairments affecting reasoning. A broad concept of psychosis could focus on deviances in the experience of reality resulting from impairments of reasoning. In this light and consistent with recent empirical evidence, it may be appropriate to redefine dementia praecox as a developmental disorder of reasoning. A future challenge of autism research may be to develop theoretical models that can account for the impact of complex processes acting at the social level in addition to complex neurobiological and psychological processes. Such models could profit from a distinction among processes related to (i) basic susceptibility, (ii) adaptive processes and (iii) decompensating factors involved in the development of manifest illness., (© 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Early experiences and indications are reported that psychopharmacotherapy, particularly as prophylactic long-term medication for prevention of relapses, has led to an increased recognition of social determinants of the course of illness, especially in schizophrenic patients. As a result, institutions combining both social and psychopharmacological treatment have developed, e. g., in Berlin beginning with "Phönix" a transition home ("Übergangsheim") in 1956 to a catamnesis for long-term outpatient treatment of schizophrenic patients in 1957, a social service in 1960, a day and night hospital in 1962 up to a university department of social psychiatry in 1972 with a rich spectrum of facilities for a step by step rehabilitation of mentally ill patients. In comparison with well-known humanistic sources of German psychiatric reform, some less well-known sources based on psychopharmacotherapeutic experiences that need further historical elaboration are considered. Questions include: 1. how psychiatric pharmacotherapy has influenced the development of social psychiatry in Germany, 2. whether the pioneering spirit of the 1950s, initiated by new treatment with psychotropic drugs has influenced or fostered the development of social psychiatry in Germany, 3. whether retardation of the development of social psychiatry in Germany (as opposed to England, France, and Canada and possibly related to its post-war international isolation) has been overcome not least by the new scientific development of psychopharmacology that has encouraged renewal of international contacts. In any case the possible influence of psychopharmacotherapy should not be missing in an overall view of the development of social psychiatry in Germany.

How deep are the historical roots of our concept of major depression (MD)? I showed previously that psychiatric textbooks published in 1900-1960 commonly described 18 characteristic depressive symptoms/signs that substantially but incompletely overlapped with the current DSM (Diagnostic and Statistical Manual of Mental Disorders) MD criteria. I here expand that inquiry to the key years of 1880-1900 during which our major diagnostic categories of manic-depressive illness (MDI) and dementia praecox were developed. I review the symptoms of depression/melancholia in 28 psychiatric textbooks and 8 other relevant documents from this period including monographs, reviews and the first portrayal of melancholia Kraepelin in 1883. Descriptions of melancholia in the late nineteenth and twentieth century textbooks closely resembled each other, both reporting a mean of 12.4 characteristic symptoms, and emphasizing core features of mood change and alterations in cognitive content and psychomotor behavior. The detailed monographs, reviews and the early description of Kraepelin were more thorough, reporting a mean of 16.6 of these characteristic symptoms. These nineteenth century texts often contained phenomenologically rich descriptions of changes in mood and cognition, loss of interest and anhedonia and emphasized several features not in DSM including changes in volition/motivation, posture/facial expression and derealization/depersonalization. In the early nineteenth century, melancholia was often defined primarily by delusions or as the initial phase of a unitary psychosis transitioning to mania and then dementia. By 1880, the concept of depression as an independent mood disorder with characteristic symptoms/signs and a good prognosis had stabilized. Kraepelin incorporated this syndrome into his diagnostic concept of MDI, changing its name to 'Depressive States', but did not alter its underlying nature or clinical description.

The neurodevelopmental hypothesis of schizophrenia has become a paradigm broadly accepted in today's research in schizophrenia and its spectrum. This article traces the historical development of the neurodevelopmental hypothesis of schizophrenia up until the time of its explicit formulation in 1987, by Weinberger and by Murray and Lewis, with a main focus on the seminal contribution of Barbara Fish to its conception and elaboration., (© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

We review the changing conceptions of schizophrenia over the past 50 years as it became understood as a disorder of brain function and structure in which neurocognitive dysfunction was identified at different illness phases. The centrality of neurocognition has been recognized, especially because neurocognitive deficits are strongly related to social and role functioning in the illness, and as a result neurocognitive measures are used routinely in clinical assessment of individuals with schizophrenia. From the original definitions of the syndrome of schizophrenia in the early 20th century, impaired cognition, especially attention, was considered to be important. Neurocognitive impairments are found in the vast majority of individuals with schizophrenia, and they vary from mild, relatively restricted deficits, to dementia-like syndromes, as early as the first psychotic episode. Neurocognitive deficits are found in the premorbid phase in a substantial minority of pre-teenage youth who later develop schizophrenia, and they apparently worsen by the prodromal, high-risk phase in a majority of those who develop the illness. While there is limited evidence for reversibility of impairments from pharmacological interventions in schizophrenia, promising results have emerged from cognitive remediation studies. Thus, we expect cognitive interventions to play a larger role in schizophrenia in the coming years. Moreover, because youth at risk for schizophrenia can be identified by an emergent high-risk syndrome, earlier interventions might be applied in a pre-emptive way to reduce disability and improve adaptation. The notion of schizophrenia as a developmental neurocognitive disorder with stages opens up a window of possibilities for earlier interventions. (JINS, 2017, 23, 881-892).

The history of psychosurgery is filled with tales of researchers pushing the boundaries of science and ethics. These stories often create a dark historical framework for some of the most important medical and surgical advancements. Dr. Robert G. Heath, a board-certified neurologist, psychiatrist, and psychoanalyst, holds a debated position within this framework and is most notably remembered for his research on schizophrenia. Dr. Heath was one of the first physicians to implant electrodes in deep cortical structures as a psychosurgical intervention. He used electrical stimulation in an attempt to cure patients with schizophrenia and as a method of conversion therapy in a homosexual man. This research was highly controversial, even prior to the implementation of current ethics standards for clinical research and often goes unmentioned within the historical narrative of deep brain stimulation (DBS). While distinction between the modern practice of DBS and its controversial origins is necessary, it is important to examine Dr. Heath's work as it allows for reflection on current neurosurgical practices and questioning the ethical implication of these advancements.

Current conceptualizations of schizophrenia have been introduced over centuries and continue to progress in recent decades. Symptoms have been divided into several domains, contrasting negative and positive symptoms which are different in their nature, onset, progression and response to treatment. An account of the different historical changes of the concept – essentially nosographic – has led to models attempting to integrate findings for each dimension of the disorder. This paper reviews the history of negative symptoms in diagnosis and how different approaches have been utilised to consider negative symptoms in the concept of schizophrenia. The paper also bridges various international classifications which have evolved and modified the role of negative symptoms in their diagnostic criteria for schizophrenia, which highlights the challenge of defining this disease.

Both within clinical and wider societal discourses, the term 'schizophrenia' has achieved considerable potency as a signifier, privileging particular conceptual frames for understanding and responding to mental distress. However, its status has been subject to instability, as it has lacked indisputable biological correlates that would anchor its place within the canon of medical diagnosis. Informed by a semiotic perspective, this paper focuses on its recent history: how 'schizophrenia' has been claimed, appropriated and contested-and how this connects with its earlier history of signification. It also explores how the dominance of this signifier has influenced the ways in which people with the diagnosis may find themselves constructed in their interactions with professionals, family and wider society, and hence how they may come to see themselves. It is argued that, from a point in the 1990s when 'schizophrenia' had achieved an almost iconic status, the term is now subject to greater instability, with concerns and challenges being raised from both within and outside psychiatry. On the one hand, this uncertainty has triggered a 'calls to arms' from those within the psychiatric establishment who see diagnoses such as 'schizophrenia' as crucial to their professional identity and status. On the other hand, this has created spaces for new conversations and alliances between elements within neurology, psychiatry, social work and other professions, and between these and service users. Some of these conversations are casting doubt on the validity and utility of 'schizophrenia' as a construct, and are beginning to posit alternative regimes of signification., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

The German poet Hölderlin, assumed to have suffered from schizophrenia, in fact has been the victim of a combined calomel and cantharidine intoxication administered by his physician Autenrieth. This new theory explains much better his behavioural changes and also his neurological and other concomitant symptoms; it can be tested by analysing a very few of his hairs for the presence of these compounds.