Realising stratified psychiatry using multidimensional signatures and trajectories

BACKGROUND: Stratified or personalised medicine targets treatments for groups of individuals with a disorder based on individual heterogeneity and shared factors that influence the likelihood of response. Psychiatry has traditionally defined diagnoses by constellations of co-occurring signs and symptoms that are assigned a categorical label (e.g. schizophrenia). Trial methodology in psychiatry has evaluated interventions targeted at these categorical entities, with diagnoses being equated to disorders. Recent insights into both the nosology and neurobiology of psychiatric disorder reveal that traditional categorical diagnoses cannot be equated with disorders. We argue that current quantitative methodology (1) inherits these categorical assumptions, (2) allows only for the discovery of average treatment response, (3) relies on composite outcome measures and (4) sacrifices valuable predictive information for stratified and personalised treatment in psychiatry. METHODS AND FINDINGS: To achieve a truly ‘stratified psychiatry’ we propose and then operationalise two necessary steps: first, a formal multi-dimensional representation of disorder definition and clinical state, and second, the similar redefinition of outcomes as multidimensional constructs that can expose within- and between-patient differences in response. We use the categorical diagnosis of schizophrenia—conceptualised as a label for heterogeneous disorders—as a means of introducing operational definitions of stratified psychiatry using principles from multivariate analysis. We demonstrate this framework by application to the Clinical Antipsychotic Trials of Intervention Effectiveness dataset, showing heterogeneity in both patient clinical states and their trajectories after treatment that are lost in the traditional categorical approach with composite outcomes. We then systematically review a decade of registered clinical trials for cognitive deficits in schizophrenia highlighting existing assumptions of categorical diagnoses and aggregate outcomes while identifying a small number of trials that could be reanalysed using our proposal. CONCLUSION: We describe quantitative methods for the development of a multi-dimensional model of clinical state, disorders and trajectories which practically realises stratified psychiatry. We highlight the potential for recovering existing trial data, the implications for stratified psychiatry in trial design and clinical treatment and finally, describe different kinds of probabilistic reasoning tools necessary to implement stratification

Enhancing Trial Delivery in Parkinson’s Disease: Qualitative Insights from PD STAT

Background: Recruitment and retention of participants in clinical trials for Parkinson’s disease (PD) is challenging. A qualitative study embedded in the PD STAT multi-centre randomised controlled trial of simvastatin for neuroprotection in PD explored the motivators, barriers and challenges of participants, care partners and research staff. Objective: To outline a set of considerations informing a patient-centred approach to trial recruitment, retention, and delivery. Method: We performed semi-structured interviews and focus groups with a subset of trial participants and their care partners. Quantitative and qualitative data were obtained through surveys circulated among the 235 participants across 23 UK sites at the beginning, middle and end of the 2-year trial. We also interviewed and surveyed research staff at trial closure. Results: Twenty-seven people with PD, 6 care partners and 9 researchers participated in interviews and focus groups. A total of 463 trial participant survey datasets were obtained across three timepoints, and 53 staff survey datasets at trial closure. Trial participants discussed the physical and psychological challenges they faced, especially in the context of OFF state assessments, relationships, and communication with research staff. Care partners shared their insights into OFF state challenges, and the value of being heard by research teams. Research staff echoed many concerns with suggestions on flexible, person-centred approaches to maximising convenience, comfort, and privacy. Conclusion: These considerations, in favour of person-centred research protocols informed by the variable needs of participants, care partners and staff, could be developed into a set of recommendations for future trials

Anais Nin: A case study of personality disorder and creativity

Anais Nin, diarist and author of autobiographical novellas and erotica, and gregarious socialite, was known for her exotic persona and stormy personal life. The concept of personality disorder and the underlying assumption of the buffering capacity that personality affords to stressors are discussed. Against this background, evidence drawn from Nin's diaries, short stories and two biographies suggests that she conformed to the diagnostic criteria of histrionic personality disorder (HPD), with comorbid borderline and narcissistic features, and numerous Axis I symptoms. The proposed origin of the overall dysfunctional histrionic pattern is attributed to her early developmental history, and the maladaptive cognitive mechanisms of dissociation and repression inferred from her writings and shown to conform to the HPD pattern. Finally, it is argued that while Nin may not have displayed the classic divergent cognitive style thought to underlie the association between schizotypy and creativity, her HPD psychopathology was pivotal in shaping her creative products, most famous of which is her diary. (C) 2009 Elsevier Ltd. All rights reserved.</p

Anais Nin: A case study of personality disorder and creativity

Anais Nin, diarist and author of autobiographical novellas and erotica, and gregarious socialite, was known for her exotic persona and stormy personal life. The concept of personality disorder and the underlying assumption of the buffering capacity that personality affords to stressors are discussed. Against this background, evidence drawn from Nin's diaries, short stories and two biographies suggests that she conformed to the diagnostic criteria of histrionic personality disorder (HPD), with comorbid borderline and narcissistic features, and numerous Axis I symptoms. The proposed origin of the overall dysfunctional histrionic pattern is attributed to her early developmental history, and the maladaptive cognitive mechanisms of dissociation and repression inferred from her writings and shown to conform to the HPD pattern. Finally, it is argued that while Nin may not have displayed the classic divergent cognitive style thought to underlie the association between schizotypy and creativity, her HPD psychopathology was pivotal in shaping her creative products, most famous of which is her diary. (C) 2009 Elsevier Ltd. All rights reserved.</p

doi:10.1016/j.neuropsychologia.2009.01.002

a b s t r a c t This study sought to disambiguate the impact of Parkinson&apos;s disease (PD) on cognitive control as indexed by task set switching, by addressing discrepancies in the literature pertaining to disease severity and paradigm heterogeneity. A task set is governed by a rule that determines how relevant stimuli (stimulus set) map onto specific responses (response set). Task set switching may entail reconfiguration in either or both of these components. Although previous studies have shown that PD patients are impaired at switching between stimuli, in the present study not all patients were impaired at switching entire task sets, that is, both stimulus and response sets: compared with controls, patients with unilateral signs (Hoehn &amp; Yahr Stage I) demonstrated intact switching, even following withdrawal from dopaminergic medication, while bilaterally affected Stage II patients were impaired. The parametric measure of Unified Parkinson&apos;s Disease Rating Scale (UPDRS) score predicted increasing switch costs within the patient group. These findings suggest that switching entire task sets may be a function of extrastriatal, possibly nondopaminergic pathology which increases as the disease progresses