A Dyadic Nosology for Osteogenesis Imperfecta and Bone Fragility Syndromes 2024.

In 2023 following extensive consultation with key stakeholders, the expert Nosology Working Group of the International Skeletal Dysplasia Society (ISDS) published the new Dyadic Nosology for Genetic Disorders of the Skeleton. Some 770 entities were delineated associated with 552 genes. From these entities, over 40 genes resulting in distinct forms of Osteogenesis Imperfecta (OI) and Bone Fragility and/or Familial Osteoporosis were identified. To assist clinicians and lay stake holders and bring the considerable body of knowledge of the matrix biology and genomics to people with OI as well as to clinicians and scientists, a dyadic nosology has been recommended. This combines a genomic co-descriptor with a phenotypic naming based on the widely used Sillence nosology for the OI syndromes and the many other syndromes characterized in part by bone fragility.This review recapitulates and explains the evolution from the simple Congenita and Tarda subclassification of OI in the 1970 nosology, which was replaced by the Sillence types I-IV nosology which was again replaced in 2009 with 5 clinical groups, type 1 to 5. Qualitative and quantitative defects in type I collagen polypeptides were postulated to account for the genetic heterogeneity in OI for nearly 30 years, when OI type 5, a non-collagen disorder was recognized. Advances in matrix biology and genomics since that time have confirmed a surprising complexity both in transcriptional as well as post-translational mechanisms of collagens as well as in the many mechanisms of calcified tissue homeostasis and integrity.

The Influential Influenza: The "Russian Catarrh" Pandemic of 1781-1782.

The influenza pandemic of 1781-1782 was remarkably well-documented, with investigations and treatment records produced in Britain, France, Germany, Italy, and Russia. Everyone agreed that outbreak began in St. Petersburg in December 1781 and then spread across northern Europe, but the medical communities' consensus did not solve all issues. Two questions would inspire years of debate. The first concerned the transmission vector of the pandemic: was it the result of neo-Hippocratic, miasmatic, or contagionist exposure? This was perhaps the greatest concern of the late-eighteenth century, and multiple physicians hoped the latest influenza pandemic could provide an answer. The second was no less difficult - where did the disease originate? This was not only because geography affected both prophylactic measures and treatment options but also produced diplomatic and commercial consequences. Was a quarantine necessary, preventing commercial exchanges? Did the risk of infection result in peace negotiations being delayed, potentially extending the American Revolution and the ongoing naval conflict in the Atlantic? Even if a consensus could be reached that this was a "Russian" catarrh, this would not resolve the method of disease transmission. The pandemic of 1781-1782 was not a turning point in the arguments among neo-Hippocratic, miasmatic, and contagionist physicians, but rather reveals all three positions could be held simultaneously.

Historical and conceptual features of acute polymorphic psychosis: a myth of European psychiatry from bouffée délirante to ICD-11 acute and transient psychotic disorder.

This paper deals with the history and epistemology of acute polymorphic psychosis. We undertook a comparative study of short-lived psychotic disorders used in different European countries since the late nineteenth century. The theory of degeneration offered a speculative basis to conceptualization of conditions such as bouffée délirante, cycloid psychosis and reactive psychosis, but it seems likely that different factors contributed to the profusion of clinical concepts with adverse effects on both nomenclature and classification. The resulting picture suggests that earlier nosological concepts tend to converge on common descriptive features and challenge the diagnostic categories for short-lived psychotic disorders listed in modern symptom-based psychiatric classifications.

Fetal skeletal dysplasia cohort of a single tertiary referral center in Istanbul, Turkey.

We report on 314 fetal cases from 297 unrelated families with skeletal dysplasia evaluated in the postmortem period from 2000 to 2017 at a single clinical genetics center in Istanbul, Turkey. The definite diagnostic yield was 40% during the prenatal period, while it reached 74.5% when combined with postmortem clinical and radiological evaluation. Molecular analyses were performed in 25.5% (n: 76) of families, and 21 novel variants were identified. Classification according to International Skeletal Dysplasia Society-2019 revision revealed limb hypoplasia-reduction defects group (39) as the leading one, 24.5%, then followed by FGFR3 chondrodysplasias, osteogenesis imperfecta, and decreased mineralization and polydactyly-syndactyly-triphalangism groups 13.6, 11.1, and 8.9%, respectively. The inheritance pattern was autosomal recessive in 54% and autosomal dominant in 42.6% of index cases. The overall consanguinity rate of the cohort was 33%. The high prevalence of ultrarare diseases along with two or more unrelated autosomal recessive entities running in the same family was noteworthy. This study highlights the pivotal role of postmortem evaluation by an experienced clinical geneticist to achieve a high diagnostic yield in fetal skeletal dysplasia cohorts. The cohort is not only a representation of the spectrum of skeletal dysplasias in a population with a high consanguinity rate but also provides an ideal research group to work on to identify the unknowns of early fetal life.

Insomnia nosology: a systematic review and critical appraisal of historical diagnostic categories and current phenotypes.

Insomnia nosology has significantly evolved since the Diagnostic and Statistical Manual (DSM)-III-R first distinguished between 'primary' and 'secondary' insomnia. Prior International Classification of Sleep Disorders (ICSD) nosology 'split' diagnostic phenotypes to address insomnia's heterogeneity and the DSM nosology 'lumped' them into primary insomnia, while both systems assumed causality for insomnia secondary to health conditions. In this systematic review, we discuss the historical phenotypes in prior insomnia nosology, present findings for currently proposed insomnia phenotypes based on more robust approaches, and critically appraise the most relevant ones. Electronic databases PsychINFO, PubMED, Web of Science, and references of eligible articles, were accessed to find diagnostic manuals, literature on insomnia phenotypes, including systematic reviews or meta-analysis, and assessments of the reliability or validity of insomnia diagnoses, identifying 184 articles. The data show that previous insomnia diagnoses lacked reliability and validity, leading current DSM-5-TR and ICSD-3 nosology to 'lump' phenotypes into a single diagnosis comorbid with health conditions. However, at least two new, robust insomnia phenotyping approaches were identified. One approach is multidimensional-multimethod and provides evidence for self-reported insomnia with objective short versus normal sleep duration linked to clinically relevant outcomes, while the other is multidimensional and provides evidence for two to five clusters (phenotypes) based on self-reported trait, state, and/or life-history data. Some approaches still need replication to better support whether their findings identify true phenotypes or simply different patterns of symptomatology. Regardless, these phenotyping efforts aim at improving insomnia nosology both as a classification system and as a mechanism to guide treatment.

The 'discontinuity hypothesis' of depression in later life-clinical and research implications.

The term depression is overused as an umbrella term for a variety of conditions, including depressed mood and various psychiatric disorders. According to psychiatric diagnostic criteria, depressive disorders impact nearly all aspects of human life and are a leading cause of disability worldwide. The widespread assumption that different types of depression lie on a continuum of severity has stimulated important research on subthreshold depression in later life. This view assumes that depressed mood is a precursor of a depressive disorder. The present narrative review argues why in later life depressed mood might either (i) lie on a continuum with depressive disorders among people vulnerable for a depressive disorder or (ii) be an ageing-related epiphenomenon of underlying physical illnesses in people who are resilient to depressive disorders ('discontinuity hypothesis'). Three arguments are discussed. First, the course of depressed mood and depressive disorders differs across the life span. Second, screening instruments for depression have low predictive value for depressive disorders in later life. Third, a dose-response relationship has not been consistently found across different types of depression and detrimental health outcomes. Using the umbrella term depression may partly explain why pharmacological treatment is less effective with increasing age, and negative health-related outcomes might be overestimated. The discontinuity hypothesis may prevent pharmacological overtreatment of milder subtypes of depression and may stimulate comprehensive multidisciplinary assessment as well as the development of separate treatment algorithms for depressed mood and depressive disorders.

Were camptodactyly and boutonniere deformity considered pathological in late fifteenth century Italy? Evidence from the sculptures of Francesco di Simone Ferrucci (1437-1493).

Representations of disease in Renaissance paintings have been discussed in medical literature, in the context of historical epidemiology, as potential sources of information about the incidence and appearance of particular conditions in earlier times. The present study seeks to show how Renaissance art can also contribute to historical nosology by casting light on the question of whether particular conditions recognized as abnormal today were understood as pathological in the past. The hands of two Renaissance Madonna figures are examined in sculptures produced by Francesco di Simone Ferrucci (1437-1493). Because the Virgin Mary was considered physically perfect by believers, and because Francesco was a successful producer of devotional sculptures for a wide audience, it is highly probable that any abnormal conditions found in the hands of Madonnas sculpted by him would not have been regarded as pathological at the time. The sculptures examined appear to depict camptodactyly and boutonniere deformity in the hands of Madonna figures. These uncommon conditions are also found in Renaissance artworks that show other individuals of high social status, but their presence in the hands of the Madonna gives the strongest indication that they were not considered pathological, due to religious belief in the Virgin's physical perfection. Examination of Madonna figures in late fifteenth century Renaissance art can contribute to historical nosology by identifying abnormal conditions that were not regarded as pathological at the time. The examples of such conditions identified in the present study are camptodactyly and boutonniere deformity.

Towards a New Classification of Cardiomyopathies.

PURPOSE OF REVIEW: The aim of this paper is to briefly summarise the clinical approach to disease notation for cardiomyopathies and to highlight its limitations with respect to the integration of new knowledge about aetiology. RECENT FINDINGS: The paper uses the recently advocated concept of arrhythmogenic cardiomyopathy as an example of the limitations of current classification systems. At present, there is no single classification system that meets the needs of all potential users, whether they are basic scientists, clinicians, patients or families. The classical cardiomyopathy subtypes still have utility, but future disease notation needs to be modified to take into account the new and more complete phenotypes and aetiologies.

Probing the overarching continuum theory: data-driven phenotypic clustering of children with ASD or ADHD.

The clinical validity of the distinction between ADHD and ASD is a longstanding discussion. Recent advances in the realm of data-driven analytic techniques now enable us to formally investigate theories aiming to explain the frequent co-occurrence of these neurodevelopmental conditions. In this study, we probe different theoretical positions by means of a pre-registered integrative approach of novel classification, subgrouping, and taxometric techniques in a representative sample (N = 434), and replicate the results in an independent sample (N = 219) of children (ADHD, ASD, and typically developing) aged 7-14 years. First, Random Forest Classification could predict diagnostic groups based on questionnaire data with limited accuracy-suggesting some remaining overlap in behavioral symptoms between them. Second, community detection identified four distinct groups, but none of them showed a symptom profile clearly related to either ADHD or ASD in neither the original sample nor the replication sample. Third, taxometric analyses showed evidence for a categorical distinction between ASD and typically developing children, a dimensional characterization of the difference between ADHD and typically developing children, and mixed results for the distinction between the diagnostic groups. We present a novel framework of cutting-edge statistical techniques which represent recent advances in both the models and the data used for research in psychiatric nosology. Our results suggest that ASD and ADHD cannot be unambiguously characterized as either two separate clinical entities or opposite ends of a spectrum, and highlight the need to study ADHD and ASD traits in tandem.

Toward a new nosology of neurodegenerative diseases.

New "omic" technologies are revealing shared and distinct biological pathways within and across neurodegenerative diseases (NDDs), allowing a better understanding of endophenotypes that exceeds the boundaries of the current diagnostic criteria. Moreover, a diagnostic framework is needed that can accommodate the co-pathology and the clinical overlap and heterogeneity of NDDs. Apart from dissecting the reasons for a revolution in how we conceive NDD, this article aims to prompt a change in how we diagnose and classify NDD, drafting a general scheme for a new nosology. As identifying a cause is the key to using the term "disease" properly, we propose using a tridimensional classification based on three axes: (1) etiology or pathogenic mechanism, (2) pathology markers and molecular biomarkers, (3) anatomic-clinical; and three hierarchical levels of etiology: (1) genetic/sporadic (2) cellular pathways and processes, and function of fluidic brain systems, and (3) risk factors.

Existential depression: A meaningful diagnostic entity?

OBJECTIVE: To examine the construct of existential depression and whether it represents a distinct diagnostic entity. METHOD: Descriptive psychopathology and phenomenology are used to define the characteristics of existential depression and for comparison with other presentations of low mood. RESULTS: Existential depression can be differentiated from other forms of depression by careful appraisal of symptomatology. Drawing attention to this, and likewise other distinguishable yet under-recognised forms of depression, may help stimulate interest in further research on the classification of mood disorders with the prospect of greater diagnostic specificity and more precise treatment matching. CONCLUSION: Existential depression is a clinically discernible diagnostic entity.

The essentialism of early modern psychiatric nosology.

Are psychiatric disorders natural kinds? This question has received a lot of attention within present-day philosophy of psychiatry, where many authors debate the ontology and nature of mental disorders. Similarly, historians of psychiatry, dating back to Foucault, have debated whether psychiatric researchers conceived of mental disorders as natural kinds or not. However, historians of psychiatry have paid little to no attention to the influence of (a) theories within logic, and (b) theories within metaphysics on psychiatric accounts of proper method, and on accounts of the nature and classification of mental disorders. Historically, however, logic and metaphysics have extensively shaped methods and interpretations of classifications in the natural sciences. This paper corrects this lacuna in the history of psychiatry, and demonstrates that theories within logic and metaphysics, articulated by Christian Wolff (1679-1754), have significantly shaped the conception of medical method and (psychiatric) nosology of the influential nosologist Boissier De Sauvages (1706-1767). After treating Sauvages, I discuss the method of the influential nosologist William Cullen (1710-1790), and demonstrate the continuity between the classificatory methods of Sauvages and Cullen. I show that both Sauvages and Cullen were essentialists concerning medical diseases in general and psychiatric disorders in particular, contributing to the history of conceptions of the ontology and nature of mental disorders.

Classic Text No. 136 'On the question of unitary psychosis', by Harry Marcuse (1926).

In his article 'On the question of unitary psychosis' (1926), Harry Marcuse (1876-1931) undertook a thought experiment in which he challenged clinical psychiatrists to entertain the possibility that the concept of unitary psychosis could be a useful diagnostic and nosological tool. Drawing on the psychology of Friedrich Jodl (1849-1914) and contemporary notions of energeticism, Marcuse proposed a non-empirical, 'analytic' method of overcoming growing dissatisfaction with Kraepelinian categories in the 1910s and 1920s.

Neurodevelopmental disorders and neurodiversity: definition of terms from Scotland's National Autism Implementation Team.

Adults with neurodevelopmental disorders frequently present to, but fit uneasily into, adult mental health services. We offer definitions of important terms related to neurodevelopmental disorders through unifying research data, medical and other viewpoints. This may improve understanding, clinical practice and development of neurodevelopmental disorder pathways within adult mental health services.

Galenic syndromes: combinations of mental state and personality disorders too closely entwined to be separated.

Many mental disorders are linked to personality, but this is rarely recognised in clinical practice. It is suggested here that when the links are very close, the two can be joined. Galenic syndromes are so named because Galen was the first physician to recognise the links between personality and disease.

The Hierarchical Taxonomy of Psychopathology (HiTOP) in psychiatric practice and research.

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

Using major depression polygenic risk scores to explore the depressive symptom continuum.

BACKGROUND: Major depression (MD) is often characterised as a categorical disorder; however, observational studies comparing sub-threshold and clinical depression suggest MD is continuous. Many of these studies do not explore the full continuum and are yet to consider genetics as a risk factor. This study sought to understand if polygenic risk for MD could provide insight into the continuous nature of depression. METHODS: Factor analysis on symptom-level data from the UK Biobank (N = 148 957) was used to derive continuous depression phenotypes which were tested for association with polygenic risk scores (PRS) for a categorical definition of MD (N = 119 692). RESULTS: Confirmatory factor analysis showed a five-factor hierarchical model, incorporating 15 of the original 18 items taken from the PHQ-9, GAD-7 and subjective well-being questionnaires, produced good fit to the observed covariance matrix (CFI = 0.992, TLI = 0.99, RMSEA = 0.038, SRMR = 0.031). MD PRS associated with each factor score (standardised ß range: 0.057-0.064) and the association remained when the sample was stratified into case- and control-only subsets. The case-only subset had an increased association compared to controls for all factors, shown via a significant interaction between lifetime MD diagnosis and MD PRS (p value range: 2.23 × 10-3-3.94 × 10-7). CONCLUSIONS: An association between MD PRS and a continuous phenotype of depressive symptoms in case- and control-only subsets provides support against a purely categorical phenotype; indicating further insights into MD can be obtained when this within-group variation is considered. The stronger association within cases suggests this variation may be of particular importance.

Revisiting the concept of bipolar depression: comparison of diagnostic validators between melancholic and non-melancholic episodes.

The current definition of bipolar disorder derives with minimal changes from one that emerged through expert consensus in the late 1970s, and the topic of its validity tended to be neglected in the literature. The aim of this exploratory study was to compare patients with bipolar disorder with a history of melancholic and non-melancholic depressive episodes in a series of external diagnostic validators. One hundred eight subjects were categorized as melancholic or non-melancholic in relation to their history of depressive episodes through the clinician-rated Sydney Melancholia Prototype Index (SMPI). The external validators used were clinical-demographic variables, family history of bipolar disorder, neurocognitive performance and functional outcome. There were 43.5% of the patients with a history of melancholia and 56.5% of non-melancholic depression. Non-melancholic depressions were overrepresented in females, while melancholic depressions had a female:male ratio closer to unity. Patients with melancholia had more history of BD in first-degree relatives and better functional outcome than those with non-melancholic depression. There were no differences between groups regarding neurocognitive performance. Results tended to be unchanged when controlled for confounders. Our preliminary results highlight the inherent heterogeneity in the current concept of bipolar depression, and suggest the need for further clinical research to elucidate its validity.

Clinical Situations in Which the Diagnosis of Autism is Debatable: An Analysis and Recommendations.

The "autism spectrum disorder" (ASD) construct and its current diagnostic criteria have led to the inclusion of increasingly heterogeneous and decreasingly atypical individuals under its definition. This broad category, based on the polymorphic clinical expression of common genetic variants underpinning the risk of autism, is likely beneficial for certain individuals. However, determining the boundaries between ASD and typical individuals, as well as those with other neurodevelopmental conditions, remains an issue of which the importance is growing with the increase in ASD prevalence. We identified four clinical contexts associated with a questionable, poorly justified, or unhelpful ASD diagnosis: (1) those in which diagnostic instruments raise uncertainties, (2) in the context of a subclinical presentation, (3) when early autistic signs tend to fade away during development, and (4) when comorbidities are prominent. We argue that in certain cases, a diagnosis of ASD may not be the most suitable, timely, or helpful medical act and provide recommendations for clinical practice when facing such situations.

Conceptual Issues in Acute and Transient Psychotic Disorders.

Short-lived psychotic disorders as currently listed under "acute and transient psychotic disorder," ICD-11 Classification of Mental, Behavioural, and Neurodevelopmental Disorders, and "brief psychotic disorder," Diagnostic and Statistical Manual of Mental Disorders (DSM-5), constitute a point of divergence in the classification of psychotic disorders between the 2 diagnostic systems, which reveals the lack of knowledge about these conditions. Whether this is due to conceptual shortcomings inherent to the categories themselves and which spill over onto research or reflects a mismatch between the diagnostic criteria used and research techniques needs clarification. This study aimed to examine conceptual issues involved in the development of the above categories and shows that little continuity exists between earlier nosological concepts such as bouffée délirante, cycloid psychosis, and reactive psychosis and modern descriptive categories used to classify short-lived psychotic disorders. It seems likely that shortcomings in terms of symptom completeness, specificity, and heterogeneity, in addition to changes in definition and diagnostic criteria in successive DSM and ICD versions, have hampered empirical research, making it difficult to enhance the understanding of these conditions and achieve a closer concordance between the 2 classificatory systems.