Point Of Rarity Research Articles

Reconstructing schizophrenia: Lessons from major mood disorders

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

Is our mistake trying to identify a “homogeneous” schizophrenia construct?

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

Retroverting schizophrenia

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

Clinical observations and neuroscientific evidence tell a similar story: Schizophrenia is a disorder of the self-other boundary

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

Reinventing schizophrenia: The rules of the game

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

Paradigm shift on the concept of schizophrenia that matches with both academic and clinical needs

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

Towards DSM 10: A bio-classification of developmental schizophrenia?

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

A useful construct to improve the lives of people with schizophrenia

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

The schizophrenia concept

The relationship between transdiagnostic, dimensional and categorical approaches to schizophrenia is under debate. We propose that if a categorical diagnosis of schizophrenia makes sense, points of rarity should be observable in causal risk factors, genetic or environmental, and/or the neural systems on which they impact. In our reading, the preponderance of the evidence supports the view that risk factors largely have a pleiotropic effect that is not restricted to schizophrenia. In cross-disorder neuroimaging studies, both structural and functional data likewise largely show transdiagnostic dimensional systems-level alterations, with the possible exception of hippocampal connectivity features linked to genetic risk. There is thus no clear neurobiological evidence to support the categorical construct of schizophrenia. Retaining this approach thus revolves primarily around clinical and pragmatic considerations.

Is there a symptomatic distinction between the affective psychoses and schizophrenia? A machine learning approach

Dubiety exists over whether clinical symptoms of schizophrenia can be distinguished from affective psychosis, the assumption being that absence of a “point of rarity” indicates lack of nosological distinction, based on prior group-level analyses. Advanced machine learning techniques, using unsupervised (hierarchical clustering) and supervised (regularized logistic regression algorithm and nested-cross-validation) were applied to a dataset of 202 patients with functional psychosis (schizophrenia n = 120, affective psychosis, n = 82). Patients were initially assessed with the Present State Examination (PSE), and followed up 2.5 years later, when DSM III diagnoses were applied (independent of initial PSE).Based on PSE syndromes, unsupervised learning discriminated depressive (approximately unbiased probability, AUP = 0.92) and mania/psychosis (AUP = 0.94) clusters. The mania/psychosis cluster further split into two groups - a mania (AUP = 0.84) and a psychosis cluster (AUP = 0.88). Supervised machine learning classified schizophrenia or affective psychosis with 83.66% (95% CI = 77.83% to 88.48%) accuracy. Area under the ROC curve (AUROC) was 89.14%. True positive rate for schizophrenia was 88.24% (95%CI = 81.05–93.42%) and affective psychosis 77.11% (95%CI = 66.58–85.62). Classification accuracy and AUROC remained high when PSE syndromes corresponding to affective symptoms (those that corresponded to the depressive and mania clusters) were removed. PSE syndromes, based on clinical symptoms, therefore discriminated between schizophrenia and affective psychosis, suggesting validity to these diagnostic constructs.

Psychopathology and classification in psychiatry.

The strengths and weaknesses of the 5th edition of the Diagnostic and Statistical Manual of the American Psychiatric Association are considered, and the likely form of the revised version of the International Classification of Disease, due to be released in the future is briefly considered. It is argued that there are a number of problems in the checklist approach to diagnosis: there are no points of rarity between common disorders, and that many disorders are rough groupings containing highly heterogeneous syndromes. The tendency to reify these disorders and to view them as independent entities, and to stretch the concept of co-morbidity to cover individuals who satisfy more than one of the diagnostic checklists is seen as being misleading as it gives a false air of precision. Two broadly similar solutions are proposed for an alternative approach to common mental disorders.

Porous Diagnostic Boundaries: A New Emphasis for the Bulletin

Porous Diagnostic Boundaries: A New Emphasis for the Bulletin

Diagnostic discontinuity in psychosis: a combined study of cortical gyrification and functional connectivity.

The point of rarity in brain structure and function that separates the 2 major psychotic disorders--schizophrenia and bipolar disorder--is presently unknown. The aim of this study is to combine surface anatomical and functional imaging modalities to quantify the integrity of cortical connectivity in pursuit of the neural basis of the Kraepelinian "line of divide." We tested the hypothesis that multimodal brain regions show overlapping abnormalities in both disorders, while schizophrenia-specific defects are likely to be localized to sensory processing regions. Cortical folding patterns (gyrification) and functional connectivity hub architecture (degree centrality) were studied in a sample of 39 subjects with established schizophrenia, 20 subjects with psychotic bipolar disorder, and 34 healthy controls. We observed a significant difference between the 2 groups in both gyrification and functional connectivity of the visual processing regions. Further, the aberrant functional connectivity of the visual processing regions predicted persistent symptom burden better than the diagnostic information. Using a spatial similarity analysis, we observed that the degree of overlap between the 2 disorders was small (25%) for changes in cortical gyrification and modest (51%) for changes in functional connectivity measured during a cognitive task (n-back). In conclusion, our results suggest that prominent unimodal sensory processing deficits are more likely to be present in schizophrenia than in bipolar disorder. Further, connectivity-based neuroimaging measures appear to be better indicators of diagnostic discontinuity than the symptom-based clinical information.

Does testing for bimodality clarify whether the bipolar disorders are categorically or dimensionally different to unipolar depressive disorders?

It has been held that if bipolar disorder is categorically distinct, it should differentiate from unipolar depressive disorders by showing bimodality or a 'zone of rarity' in bipolar symptom scores. Two previous studies have failed to demonstrate bimodality. We undertook a third study. A total of 1106 patients attending the Black Dog Institute Depression Clinic completed the Mood Disorders Questionnaire (MDQ), in addition to undergoing clinical assessment by an Institute psychiatrist. The distributions of scores for the total number of hypomanic symptoms endorsed by unipolar and bipolar patients were both skewed, with the bipolar group endorsing a high number of hypomanic symptoms and the unipolar group endorsing few symptoms--and so giving the impression of an 'even' distribution generated by two quite distinctly differing sub-groups. However, formal statistical analyses involving mixed modelling provided no clear evidence that a bimodal distribution provided a better fit to the data than a unimodal one. Failure to statistically demonstrate a 'point of rarity' did not marry with visual inspection of the plotted data--which clearly suggested two groups putatively capturing those with bipolar and unipolar disorders respectively. The paper considers some limitations to the emphasis on 'bimodality' in differentiating potentially differing conditions.

Editorial: Categories and dimensions: reflections on obsessive-compulsive disorder (OCD)

Editorial: Categories and dimensions: reflections on obsessive-compulsive disorder (OCD)

Cognitive Enhancement: Promises and Perils

The potential use of drugs to enhance cognition, emotion, and executive function has engendered controversy despite the fact that few such agents exist today. Here, I provide a context for discussions based on medical, regulatory, and ethical concerns that have been raised by the possibility that enhancers will emerge from current efforts to discover drugs for neuropsychiatric disorders.

The failure of the schizophrenia concept and the argument for its replacement by hebephrenia: applying the medical model for disease recognition

The failure of the schizophrenia concept and the argument for its replacement by hebephrenia: applying the medical model for disease recognition

Cognitive Impairment in Schizophrenia and Affective Psychoses: Implications for DSM-V Criteria and Beyond

It has recently been suggested that the diagnostic criteria of schizophrenia should include specific reference to cognitive impairments characterizing the disorder. Arguments in support of this assertion contend that such inclusion would not only serve to increase the awareness of cognitive deficits in affected patients, among both clinicians and researchers alike, but also increase the "point of rarity" between schizophrenia and mood disorders. The aim of the current article is to examine this latter assertion in light of the recent opinion piece provided by Keefe and Fenton (Keefe RSE, Fenton WS. How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull. 2007;33:912-920). Through literature review, we explore the issue of whether cognitive deficits do in fact differentiate the major psychoses. The overall results of this inquiry suggest that inclusion of cognitive impairment criteria in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-V) would not provide a major advancement in discriminating schizophrenia from bipolar disorder and affective psychoses. Therefore, while cognitive impairment should be included in DSM-V, it should not dictate diagnostic specificity--at least not until more comprehensive evidence-based reviews of the current diagnostic system have been undertaken. Based on this evidence, we consider several alternatives for the DSM-V definition of cognitive impairment in schizophrenia, including (1) the inclusion of cognitive impairment as a specifier and (2) the definition of cognitive impairment as a dimension within a hybrid categorical-dimensional system. Given the state of current evidence, these possibilities appear to represent the most parsimonious approaches to the inclusion of cognitive deficits in the diagnostic criteria of schizophrenia and, potentially, of mood disorders.

Is cognitive impairment in schizophrenia ready for diagnostic prime time?

Is cognitive impairment in schizophrenia ready for diagnostic prime time?

The assessment of cognitive impairment would be a relevant addition to the criteria for diagnosing schizophrenia

The paper by Keefe reviews in a comprehensive and balanced way the findings on cognitive disturbances in schizophrenia. These disturbances are prevalent years before the psychotic breakdown, are only partially associated with acute psychotic symptoms, are more or less stable or can even increase over the longitudinal course of schizophrenia. In cross-sectional assessments, they are closely associated with social functioning and are more pronounced in patients diagnosed with schizophrenia than in those with (non-psychotic) affective disorders. All these are good reasons for Keefe to suggest that cognitive impairment should be included in the diagnostic criteria for schizophrenia. I fully agree with this suggestion. The inclusion of cognitive impairment would correspond very well to the traditional concept of dementia praecox/schizophrenia as proposed by Kraepelin and Bleuler. Kraepelin's term “dementia praecox” emphasized the importance of cognitive deterioration, although it alluded also to the change of personality in terms of negative symptoms. Similarly, Bleuler regarded cognitive alterations and negative symptoms as core symptoms of schizophrenia, while delusions and hallucinations were considered accessory symptoms. The predominance of positive symptoms in the concept of schizophrenia was established later on, especially with Schneider's concept of first-rank symptoms, and endorsed by our modern diagnostic systems, the DSM-IV and the ICD-10. The interest in the core symptoms of schizophrenia, including cognitive impairment, was revived by the introduction of second-generation antipsychotics, which are believed to have a somewhat stronger impact than older antipsychotics on both negative symptoms and cognitive disturbances 1. The focus on these core dimensions of schizophrenia could result in the development of drugs mainly targeted at cognitive deficit, but also able to treat positive symptoms. It is also important to stress that, in the context of the neurodevelopmental theory, cognitive disturbances are interpreted as being a vulnerability marker indicative of subtle brain alterations, and that modern neurogenetics applies cognitive impairment as an endophenotype 2–4. In the old days, the group of cognitive deficits consisted primarily of those disturbances which can be observed directly during psychiatric examination, such as deficits in attention and abstract thinking, thought blocking, incoherence, etc. These symptoms are still included in some schizophrenia rating scales, such as the Positive and Negative Syndrome Scale (PANSS). Nowadays, neurocognitive tests are able to assess cognitive impairment objectively and reliably and to describe the disturbances in verbal fluency, working memory, executive control, visual and verbal memory, and mental speed. There is no doubt that neurocognitive testing would be the proper way to diagnose cognitive deficits in schizophrenia. However, it should be kept in mind that, to my knowledge, thought disorders like thought blocking or incoherence are not covered by these tests. The question whether neurocognitive testing can be performed in the frame of routine care, as addressed by Keefe, is of course of great importance. Although several West European countries and the United States have a long tradition of psychological test assessments in the routine care of hospitalized patients, there are other regions of the world where this is not affordable. A categorical criterion, which is primarily based on clinical explorations of the patient and his relatives, might therefore be preferable. I think that a test battery specifically developed for the assessment of cognitive disturbances in schizophrenia, like the MATRICS 5, might complicate the test procedure in psychiatric hospitals or outpatient facilities. It seems more pragmatic to apply those neurocognitive test batteries which are used in the routine care of each facility. Of course, when it comes to research, an internationally standardized procedure like the MATRICS would be the best option. I definitely support Keefe's view that the inclusion of cognitive impairment in the diagnostic criteria for schizophrenia would enrich the diagnostic concept and hopefully contribute towards a better definition of a “point of rarity” between schizophrenia and affective psychosis. If DSM-V and ICD-11 follow a dimensional approach, including negative and cognitive symptoms as separate dimensions beside positive symptoms, it may be possible to achieve both a better differential diagnosis and a more powerful prognostic differentiation. I believe that such a dimensional approach, as an additional descriptive level to a categorical differentiation between schizophrenia and affective disorders or as a primarily syndromic classification of a broad psychosis category, could represent a fruitful improvement of our current diagnostic systems 6,7.