[Inbreeding and serious mental illness in the first Spanish Bourbons]. / Consanguinidad y enfermedad mental grave en los primeros Borbones españoles.

INTRODUCTION: There is an argument about inbreeding as a risk factor in the development of major mental illnesses like bipolar disorder or schizophrenia. The genealogical trees of European royal dynasties represent an opportunity to study this relationship. Felipe V was the first Bourbon king to rule in Spain, who was thought to have possibly suffered a severe mental disorder. Felipe's son Fernando VI, also had a mental disease. Nevertheless Carlos III, Felipe V's son born from a different, unrelated mother, apparently showed no trace of such disorder. We hypothesize that consanguinity or inbreeding could explain the tendency in the acquiring of severe mental disorders. SUBJECTS AND METHODS:  Biographies of three Spanish Bourbon kings (Felipe V, Fernando VI and Carlos III) were analysed in order to evaluate if they were likely to have suffered from some mental disorder, according to DSM-5 and ICD-11 criteria. An inbreeding coefficient was determined with the PedPro Program. RESULTS:  Felipe V and Fernando VI could have been diagnosed with bipolar disorder, whereas Carlos III could have been diagnosed with a mild personality disorder. Both Felipe V and Fernando VI had a high inbreeding coefficient (0.091109 and 0.095023, respectively), while Carlos III had a lower one (0.038264). The inbreeding coefficient of siblings of couples of first grade cousins is 0.0625. CONCLUSIONS:  A high inbreeding coefficient is a risk factor in developing bipolar disorder. Felipe V and Fernando VI suffered from bipolar disorder. The analysis of genetic trees by the inbreeding coefficient is a valuable tool in the study of heredability of bipolar disorder. Endogamy accumulates pathogenic alleles and increases risk to suffer it. These kings had a high consanguinity which was an important risk factor to the illness. High consanguinity is a risk factor to suffer bipolar disorder.

TITLE: Consanguinidad y enfermedad mental grave en los primeros Borbones españoles.Introducción. Se discute si la consanguinidad es un factor de riesgo para sufrir trastorno bipolar o esquizofrenia. Los árboles genealógicos de las casas reales son una oportunidad para estudiarlo. Felipe V posiblemente sufrió un trastorno mental grave, como también su hijo Fernando VI. Sin embargo, Carlos III, también hijo de Felipe V, pero fruto de otro matrimonio, aparentemente no. Se mantiene la hipótesis de que la consanguinidad podría haber sido un factor de riesgo para ello. Sujetos y métodos. Se analizan las biografías de estos tres reyes para detectar si sufrieron algún trastorno mental de acuerdo con el DSM-5 y la CIE-11. Se estudia su coeficiente de consanguinidad mediante el programa PedPro con una base de datos de 25.776 individuos. Resultados. Felipe V y Fernando VI podrían haber sido diagnosticados de trastorno bipolar, mientras que Carlos III podría haberlo sido de un leve trastorno de la personalidad. Felipe V y Fernando VI tenían un coeficiente de consanguinidad elevado (0,091109 y 0,095023, respectivamente), mientras que en Carlos III era sólo de 0,038264. El coeficiente de los dos primeros es mayor que el de los hijos de primos hermanos (0,0625). Conclusiones. Felipe V y Fernando VI sufrieron un trastorno bipolar. El análisis de los árboles genéticos mediante el coeficiente de consanguinidad es una valiosa herramienta para el estudio de la heredabilidad del trastorno bipolar. La endogamia acumula alelos patógenos y el riesgo de sufrirlo. En estos sujetos, la alta consanguinidad fue un importante factor etiopatogénico de la enfermedad que sufrieron. Una elevada consanguinidad supone un factor de riesgo de sufrir trastorno bipolar.

Consanguinidad y enfermedad mental grave en los primeros Borbones españoles / Inbreeding and serious mental illness in the first Spanish Bourbons

INTRODUCCIÓN: Se discute si la consanguinidad es un factor de riesgo para sufrir trastorno bipolar o esquizofrenia. Los árboles genealógicos de las casas reales son una oportunidad para estudiarlo. Felipe V posiblemente sufrió un trastorno mental grave, como también su hijo Fernando VI. Sin embargo, Carlos III, también hijo de Felipe V, pero fruto de otro matrimonio, aparentemente no. Se mantiene la hipótesis de que la consanguinidad podría haber sido un factor de riesgo para ello. SUJETOS Y MÉTODOS: Se analizan las biografías de estos tres reyes para detectar si sufrieron algún trastorno mental de acuerdo con el DSM-5 y la CIE-11. Se estudia su coeficiente de consanguinidad mediante el programa PedPro con una base de datos de 25.776 individuos. RESULTADOS: Felipe V y Fernando VI podrían haber sido diagnosticados de trastorno bipolar, mientras que Carlos III podría haberlo sido de un leve trastorno de la personalidad. Felipe V y Fernando VI tenían un coeficiente de consanguinidad elevado (0,091109 y 0,095023, respectivamente), mientras que en Carlos III era sólo de 0,038264. El coeficiente de los dos primeros es mayor que el de los hijos de primos hermanos (0,0625). CONCLUSIONES: Felipe V y Fernando VI sufrieron un trastorno bipolar. El análisis de los árboles genéticos mediante el coeficiente de consanguinidad es una valiosa herramienta para el estudio de la heredabilidad del trastorno bipolar. La endogamia acumula alelos patógenos y el riesgo de sufrirlo. En estos sujetos, la alta consanguinidad fue un importante factor etiopatogénico de la enfermedad que sufrieron. Una elevada consanguinidad supone un factor de riesgo de sufrir trastorno bipolar

INTRODUCTION: There is an argument about inbreeding as a risk factor in the development of major mental illnesses like bipolar disorder or schizophrenia. The genealogical trees of European royal dynasties represent an opportunity to study this relationship. Felipe V was the first Bourbon king to rule in Spain, who was thought to have possibly suffered a severe mental disorder. Felipe's son Fernando VI, also had a mental disease. Nevertheless Carlos III, Felipe V's son born from a different, unrelated mother, apparently showed no trace of such disorder. We hypothesize that consanguinity or inbreeding could explain the tendency in the acquiring of severe mental disorders. SUBJECTS AND METHODS: Biographies of three Spanish Bourbon kings (Felipe V, Fernando VI and Carlos III) were analysed in order to evaluate if they were likely to have suffered from some mental disorder, according to DSM-5 and ICD-11 criteria. An inbreeding coefficient was determined with the PedPro Program. RESULTS: Felipe V and Fernando VI could have been diagnosed with bipolar disorder, whereas Carlos III could have been diagnosed with a mild personality disorder. Both Felipe V and Fernando VI had a high inbreeding coefficient (0.091109 and 0.095023, respectively), while Carlos III had a lower one (0.038264). The inbreeding coefficient of siblings of couples of first grade cousins is 0.0625. CONCLUSIONS: A high inbreeding coefficient is a risk factor in developing bipolar disorder. Felipe V and Fernando VI suffered from bipolar disorder. The analysis of genetic trees by the inbreeding coefficient is a valuable tool in the study of heredability of bipolar disorder. Endogamy accumulates pathogenic alleles and increases risk to suffer it. These kings had a high consanguinity which was an important risk factor to the illness. High consanguinity is a risk factor to suffer bipolar disorder

Wild melancholy. On the historical plausibility of a black bile theory of blood madness, or hæmatomania.

Nineteenth-century art historian John Addington Symonds coined the term hæmatomania (blood madness) for the extremely bloodthirsty behaviour of a number of disturbed rulers like Ibrahim II of Ifriqiya (850-902) and Ezzelino da Romano (1194-1259). According to Symonds, this mental pathology was linked to melancholy and caused by an excess of black bile. I explore the historical credibility of this theory of 'wild melancholy', a type of melancholia that crucially deviates from the lethargic main type. I conclude that in its pure form Symonds' black bile theory of hæmatomania was never a broadly supported perspective, but can be traced back to the nosology of the ninth-century physician Ishaq ibn Imran, who practised at the Aghlabid court, to which the sadistic Ibrahim II belonged.

Goethe: A bipolar personality? Periodicity of affective states in Johann Wolfgang von Goethe as reflected by Paul Julius Möbius.

This paper aims to investigate the character and etiological basis of German poet Johann Wolfgang von Goethe's mental disorder. From 1898, German neuropsychiatrist Paul Julius Möbius developed the hypothesis that Goethe's work provided several hints for the notion that the German poet suffered from a distinct bipolar disorder. The paper investigates Möbius's psychopathographic study on Goethe and his hypothesis of a mood periodicity in Goethe against the mirror of modern concepts. Möbius came to the conclusion that Goethe's illness was bipolar in character and became visible at intervals of seven years and lasted for about two years. The majority of Möbius's contemporary psychiatric colleagues (Emil Kraepelin, Max Isserlin, Ernst Kretschmer, Josef Breuer) supported this view which has still not been convincingly challenged. In present-day terms, Möbius's hypothesis can be best mirrored as a subclinical foundation of mood disorder. Furthermore, with his extensive study, Möbius disproved the common notion that Goethe had suffered from an illness as the result of a syphilitic infection.

[Carl Wernicke (1848-1905) and the "Wernicke-Kleist-Leonhard school". Connections to "Erlangen School" of psychiatry]. / Carl Wernicke (1848­1905) und die "Wernicke-Kleist-Leonhard Schule". Beziehungen zur "Erlanger Schule" der Psychiatrie.

BACKGROUND: To celebrate Carl Wernicke's 170th anniversary, the paper aims at analysing possible connections of Wernicke and his "Wernicke-Kleist-Leonhard (WKL) school" to the "Erlangen school" of psychiatry. METHODS: Relevant primary and secondary literature as well as archival material were examined to test the hypothesis. RESULTS: Wernicke's efforts to realise his nosological system in clinical practice were continued by his pupil Karl Kleist (1879-1960). After Wernicke's tragic early death Kleist worked under Gustav Specht's "Erlangen school of psychiatry". Karl Leonhard (1904-1988), who worked under Specht as well as under Kleist, continued Wernicke's and Kleist's research and ended up with a very differentiated classification of endogenous psychoses. DISCUSSION: Specht's "Erlangen school" of psychiatry can be regarded as a link in the development of the "Wernicke-Kleist-Leonhard school". Wernicke's description of "anxiety psychosis" motivated Specht to study the emotion of anxiety in "manic-depressive disorder". Specht's study again stimulated Leonhard's concept of "anxiety-happiness psychosis". Generally, Specht's intensive focus on bipolarity has influenced Leonhard's concept of cycloid psychoses. Specht's description of "pathologic affect" had an impact on Leonhard's concept of "affect-laden paraphrenia". CONCLUSION: Modern methods of neuro-imaging open a new perspective to Wernicke's localisation theory. The natural-scientific-philosophical "double orientation" of the WKL school motivates an increased integration of philosophical elements (ethics, religiosity, spirituality) in the field of psychiatry, psychosomatic medicine and psychotherapy.

A half-century of participant observation in psychiatry. Part II: Affective disorders. / Pól wieku obserwacji uczestniczacej w psychiatrii. Czesc II. Choroby afektywne.

The last half-century, thanks to the efforts of outstanding researchers, brought about great progress in the pathogenesis and clinics of affective illnesses. The catecholamine and serotonin hypothesis delineated in the 1960s have retained significant merit. Since the 1990s, the theories have pointed on excessive immune activation and impairment of neuroplasticity under stress. Since the 1970s, asystematic subclassification of unipolar and bipolar affective disorder has proceeded. Epidemiological studies of the last half-century indicated a significantly higher prevalence of depression compared with previous decades. The 21st century brought evidence for agreater frequency of various forms of bipolar affective disorder. During the last 50years, the etiopathogenesis, diagnosis and treatment of affective disorders were my favorite and fascinating clinical and research topics. This initiated in 1970 when I began my work in the Department of Psychiatry, Medical Academy in Poznan, on account of the introduction of lithium salts for the treatment of these disorders. In 1976-1977, I received afellowship of the National Institutes of Health at the University of Pennsylvania in Philadelphia and participated in research that elucidated the mechanism of lithium transport across cell membranes. I carried out the studies on the pathogenesis of affective disorders for more than 40 years afterward. They concerned abnormalitiesof transport across cell membranes, the activity of stress system, excessive pro-inflammatory activation, molecular genetics, dysfunctions of cognition and neurotrophins, especially the brain-derived neurotrophic factor (BDNF). Atthe beginning of the 21st century, I coordinated two Polish epidemiological projects DEP-BI and TRES-DEP. For my research on bipolar disorders, I received many international awards. I am also the author of the book The faces of manic-depressive illness which had three Polish editions as well as English and Russian versions.

[Psychiatric disorder of Sylvia Plath].

Sylvia Plath was one of the most famous American poets in the twentieth century. Plath was diagnosed with depression after her first suicide attempt when she was 20 years old. Her major depression (without psychotic symptoms) recurred several times. Plath never had a manic episode, but there were probable hypomanic periods in her life. She died by violent suicide when she was 30. Sylvia Plath took a bottle of sleeping pills and stuck her head in a gas oven. Several factors may have contributed to Plath's psychiatric disorder and suicide. The author reviews the etiological factors and course of psychiatric disorder based on the Unabridged Journals of Sylvia Plath and the literature. Her family history was positive and her premorbid personality was vulnerable to depression. There were histrionic, narcissistic and borderline features in her personality. The probable diagnoses of Plath were bipolar II. affective disorder and mixed personality disorder.

120th Anniversary of the Kraepelinian Dichotomy of Psychiatric Disorders.

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.

[Visna of Egill Skallagrimsson].

Considering the changes in moral principles, human behavior and behavioral values through the ages, in Egill Skallagrimsson's Saga, Egill presents us with altered mental status. This is in terms of what at present is considered symptoms of an anti-social personality, and bipolar affective disorder. Egill Skallagrimsson is considered one of the most famous Vikings in the Icelandic Sagas. Archaeological findings mentioned in Egill's Saga indicate disfigurement of his skull, which has led many authors to suggest that Egill suffered from skeletal dysplasia. The primary assumption in the literature is that Egill Skallagrimsson was affected by Paget's disease of bone. This consideration is additionally based on the scholar's interpretation of the Saga text. The unique storytelling style in the Saga of Egill Skallagrimsson is evident; however, the question of the story's truthfulness remains open. In this article, we investigate Egill Skallagrimsson's assumed Paget's disease of bone, based on the physical and mental symptoms disclosed in the Saga of Egill Skallagrimsson. Associated with the assumption, the author's hermeneutics of Egill's Saga in the context of modern-day knowledge of Paget's disease of bone, brings forward the probability estimate to the range of permille. In Scandinavian folklore and mythology, a tale by Saxo Grammaticus of a notorious shield-maiden named Visna, reminds of Egill, as noted by Snorri Sturluson. Hence, in reference to Egill Skallagrimsson's mental status and physical appearance as listed in Egill's Saga, the authors recommend the name for his condition to be "Visna of Egill Skallagrimsson".

Showers: from a violent treatment to an agent of cleansing.

In the early nineteenth century, physicians designed the first manufactured showers for the purpose of curing the insane. Sustained falls of cold water were prescribed to cool hot, inflamed brains, and to instil fear to tame impetuous wills. By the middle of the century showers had appeared in both asylums and prisons, but shower-related deaths led to their decline. Rather than being abandoned, however, the shower was transformed by the use of warm water to economically wash the skins of prison and asylum populations. In stark contrast to an involuntary, deliberately unpleasant treatment, by the end of the century the shower was a desirable product for the improvement of personal hygiene and population health.

Views from an asylum: a retrospective case note analysis of a nineteenth century asylum.

PURPOSE: To investigate whether lifelong admission to psychiatric asylum care was usual practice before community psychiatric care was introduced. METHODS: Historical archives (1838-1938) for 50 patients at the Northampton General Lunatic Asylum in England were studied. Regression analyses were performed to investigate associations between predictor variables (age, gender, marital status, social class) and outcomes (diagnoses, length of stay and admission outcomes). RESULTS: 30 patients (70%) were discharged into the community. 15 (31%) patients were admitted longer than 1 year. Diagnosis of mania was significantly higher in patients who were married. Trend associations were observed for melancholia being diagnosed in higher social class patients and monomania being diagnosed in unmarried patients. No associations were found between predictor variables and length of stay or admission outcomes. CONCLUSIONS: These findings challenge the myth that asylum incarceration was a usual practice before the advent of community care. Most patients were discharged from psychiatric asylum hospital within a year of admission even before the advent of psychotropic medication.

A History of the Pharmacological Treatment of Bipolar Disorder.

In this paper, the authors review the history of the pharmacological treatment of bipolar disorder, from the first nonspecific sedative agents introduced in the 19th and early 20th century, such as solanaceae alkaloids, bromides and barbiturates, to John Cade's experiments with lithium and the beginning of the so-called "Psychopharmacological Revolution" in the 1950s. We also describe the clinical studies and development processes, enabling the therapeutic introduction of pharmacological agents currently available for the treatment of bipolar disorder in its different phases and manifestations. Those drugs include lithium salts, valproic acid, carbamazepine, new antiepileptic drugs, basically lamotrigine and atypical antipsychotic agents (olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, asenapine, cariprazine and lurasidone). Finally, the socio-sanitary implications derived from the clinical introduction of these drugs are also discussed.

The genealogy of the clinical syndrome of mania: signs and symptoms described in psychiatric texts from 1880 to 1900.

In 1800, mania was conceptualized as an agitated psychotic state. By 1900, it closely resembled its modern form. This paper reviews the descriptions of mania in Western psychiatry from 1880 to 1900, when Kraepelin was training and developing his concept of manic-depressive illness. Psychiatric textbooks published 1900-1960 described 22 characteristic manic symptoms/signs the presence of which were recorded in 25 psychiatric textbooks and three other key documents published 1880-1900. Descriptions of mania in these nineteenth century textbooks closely resembled those in the twentieth century, recording a mean (s.d.) of 15.9 (2.3) and 17.0 (2.3) of the characteristic symptoms, respectively (p = 0.12). The frequency with which individual symptoms were reported was substantially correlated in these two periods (r = +0.64). Mendel's 1881 monograph, Kraepelin's first description of mania in 1883 and the entry for mania in Tuke's Dictionary of Psychological Medicine (1892) described a mean (s.d.) of 19 (1.7) of these characteristic symptoms. These descriptions of mania often contained phenomenologically rich descriptions of euphoria, hyperactivity, grandiosity, flight of ideas, and poor judgment. They also emphasized several features not in DSM criteria including changes in character, moral standards and physical appearance, and increased sense of humor and sexual drive. Fifteen authors described key symptoms/signs of mania most reporting elevated mood, motoric hyperactivity and accelerated mental processes. By 1880, the syndrome of mania had been largely stabilized in its modern form. In the formation of his concept of manic-depressive illness, Kraepelin utilized the syndrome of mania as described in the psychiatric community in which he was trained.

Understanding the experience of women admitted to a psychiatric hospital in Sydney with psychosis or mania following childbirth after World War II (1945-1955).

In the present study, we investigated a unique set of historical health-care records of women admitted to a psychiatric hospital in Sydney, Australia with a diagnosis of psychosis or mania after childbirth in the post-World War II (WWII) period, from 1945 to 1955. This research is part of a larger project examining how the descriptions of these women documented in the health-care records from 1885 to 1975 affected their treatment and the outcome of their admission. In the present paper, we report on the findings from an intensive examination of the post WWII documents. Eighteen health-care records from a psychiatric facility (Gladesville Hospital) were identified from admission registers housed in the State Records Office of New South Wales in 2014. Although seven records had been destroyed, 11 were transcribed verbatim. The records contain demographic information; descriptions of the women's signs and symptoms on admission; and information about the women before, during, and after their admission found in letters from relatives or medical staff. A content analysis of admission information showed how the women were described by health-care professionals, but a textual analysis of the records revealed that there were other factors that could have contributed to the women's condition, which might not have been taken into consideration when treatment and care were devised. The present study demonstrates the value of investigating historical health-care records to understand how prevailing attitudes and practices might affect diagnosis and treatment.

The Role of Dr. Francis Willis in the Madness of George III.

In the well-known story of the illness of King George III, what is often overlooked is the part played by Dr. Francis Willis, an inconspicuous doctor who with great success ran an asylum in Lincolnshire. In November 1788, he was called to attend the King whose mania was becoming uncontrollable. Because of his interventions there was a slow but marked improvement. The King's recovery in 1789 increased Willis' reputation and expanded his practice.

The genealogy of major depression: symptoms and signs of melancholia from 1880 to 1900.

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.

'Details on the Establishment of Doctor Willis, for the Cure of Lunatics' (1796).

The 'mad-doctor' Dr Francis Willis achieved national and international celebrity following his successful treatment of King George III's first major episode of insanity in 1788-9. At the time of his summons to attend the King, Willis was a well-established provincial practitioner and madhouse proprietor. An anonymous French visitor published a description of Willis's Lincolnshire madhouse and his therapeutic practices in 1796. The translated text of the full article provides a unique insight into the work of a key figure in the historical development of psychological medicine. The accompanying Introduction summarizes Francis Willis's career as a mad-doctor and uses salient information from the original text to place him and his madhouse practice within a contemporary context.