Jörg Strobel

Biomarkers of a five-domain translational substrate for schizophrenia and schizoaffective psychosis

BackgroundThe Mental Health Biomarker Project (2010–2014) selected commercial biochemistry markers related to monoamine synthesis and metabolism and measures of visual and auditory processing performance. Within a case–control discovery design with exclusion criteria designed to produce a highly characterised sample, results from 67 independently DSM IV-R-diagnosed cases of schizophrenia and schizoaffective disorder were compared with those from 67 control participants selected from a local hospital, clinic and community catchment area. Participants underwent protocol-based diagnostic-checking, functional-rating, biological sample-collection for thirty candidate markers and sensory-processing assessment.ResultsFifteen biomarkers were identified on ROC analysis. Using these biomarkers, odds ratios, adjusted for a case–control design, indicated that schizophrenia and schizoaffective disorder were highly associated with dichotic listening disorder, delayed visual processing, low visual span, delayed auditory speed of processing, low reverse digit span as a measure of auditory working memory and elevated levels of catecholamines. Other nutritional and biochemical biomarkers were identified as elevated hydroxyl pyrroline-2-one as a marker of oxidative stress, vitamin D, B6 and folate deficits with elevation of serum B12 and free serum copper to zinc ratio.When individual biomarkers were ranked by odds ratio and correlated with clinical severity, five functional domains of visual processing, auditory processing, oxidative stress, catecholamines and nutritional-biochemical variables were formed. When the strengths of their inter-domain relationships were predicted by Lowess (non-parametric) regression, predominant bidirectional relationships were found between visual processing and catecholamine domains. At a cellular level, the nutritional-biochemical domain exerted a pervasive influence on the auditory domain as well as on all other domains.ConclusionsThe findings of this biomarker research point towards a much-required advance in Psychiatry: quantification of some theoretically-understandable, translationally-informative, treatment-relevant underpinnings of serious mental illness. This evidence reveals schizophrenia and schizoaffective disorder in a somewhat different manner, as a conglomerate of several disorders many of which are not currently being assessed-for or treated in clinical settings. Currently available remediation techniques for these underlying conditions have potential to reduce treatment-resistance, relapse-prevention, cost burden and social stigma in these conditions. If replicated and validated in prospective trials, such findings will improve progress-monitoring and treatment-response for schizophrenia and schizoaffective disorder.

Impact of a psychiatric unit’s daily discharge rates on emergency department flow:

Objective: To investigate relationships between time spent in the emergency department (ED) in patients requiring admission to the psychiatric ward, the day of the week of presentation and the daily number of discharges from the psychiatric ward. Method: Retrospective analysis of patient flow as a function of day of week, time of day (a.m., p.m.), number of patients requiring admission and number of ward discharges over a one-year period, for all mental health related presentations to the ED of the Queen Elizabeth Hospital in Adelaide, South Australia, before their admission to the psychiatric inpatient facility. Results: The time spent by patients in the ED waiting for admission to the psychiatric ward was significantly greater on weekends. There were significantly fewer discharges from the psychiatric ward during weekends compared with weekdays. The average time spent by patients in the ED requiring admission to the psychiatric ward for those days when there were vacant beds was 17.9 hours (SD=14.5). More people presented to the ED with a psychiatric diagnosis in the afternoons. There was a significant inverse correlation between the time spent by patients in the ED requiring admission to the psychiatric ward per day and the number of discharges from the psychiatric ward per day. Conclusion: These findings demonstrate that patient flow is significantly slower on weekends because of fewer discharges from the ward, leading to longer times spent in the ED before ward transfer. Waiting times in the ED were very substantially greater than the proposed 4-hour target even when vacant beds were available, raising considerable doubt about that target being realistic for psychiatric patients.

Biomarker Case-Detection and Prediction with Potential for Functional Psychosis Screening: Development and Validation of a Model Related to Biochemistry, Sensory Neural Timing and End Organ Performance

The Mental Health Biomarker Project aimed to discover case-predictive biomarkers for functional psychosis. In a retrospective, cross-sectional study, candidate marker results from 67 highly characterized symptomatic participants were compared with results from 67 gender- and age-matched controls. Urine samples were analyzed for catecholamines, their metabolites, and hydroxylpyrolline-2-one, an oxidative stress marker. Blood samples were analyzed for vitamin and trace element cofactors of enzymes in catecholamine synthesis and metabolism pathways. Cognitive, auditory, and visual processing measures were assessed using a simple 45-min, office-based procedure. Receiver operating curve (ROC) and odds ratio analysis discovered biomarkers for deficits in folate, vitamin D and B6 and elevations in free copper to zinc ratio, catecholamines and the oxidative stress marker. Deficits were discovered in peripheral visual and auditory end-organ function, intracerebral auditory and visual processing speed and dichotic listening performance. Fifteen ROC biomarker variables were divided into five functional domains. Through a repeated ROC process, individual ROC variables, followed by domains and finally the overall 15 set model, were dichotomously scored and tallied for abnormal results upon which it was found that ≥3 out of 5 abnormal domains achieved an area under the ROC curve of 0.952 with a sensitivity of 84% and a specificity of 90%. Six additional middle ear biomarkers in a 21 biomarker set increased sensitivity to 94%. Fivefold cross-validation yielded a mean sensitivity of 85% for the 15 biomarker set. Non-parametric regression analysis confirmed that ≥3 out of 5 abnormally scored domains predicted >50% risk of caseness while 4 abnormally scored domains predicted 88% risk of caseness; 100% diagnostic certainty was reached when all 5 domains were abnormally scored. These findings require validation in prospective cohorts and other mental illness states. They have potential for case-detection, -screening, -monitoring, and -targeted personalized management. The findings unmask unmet needs within the functional psychosis condition and suggest new biological understandings of psychosis phenomenology.

Early effects of upgrading to a high bandwidth digital network for telepsychiatry assessments in rural South Australia.

There is some evidence that telehealth can increase access to specialist mental health services, thus resulting in better outcomes for patients. However, the wide scale use of telehealth in the provision of mental health services is often inhibited by reimbursement models, privacy, security and patient safety concerns along with interoperability and reliability problems. Despite the availability of reimbursement for telepsychiatry in Australia since 2002, only 0.06% of the psychiatric consultations provided between 2002 and 2011 were through telehealth. Telehealth was first used in mental health services in the country regions of South Australia in the mid 1990s. Increased recognition of the importance of access to high resolution videoconferencing led to plans for establishing a Digital Telehealth Network (DTN) in South Australia (SA). The SA Mental Health Act of 2010 permitted increased reliance on the use of videoconferencing, enabling clinical assessments to be undertaken for the purpose of confirming Mental Health Act orders. In SA, a psychiatrist must review an Involuntary Treatment Order (ITO) within 24 hours of a general practitioner (GP) making the ITO. This review may confirm or revoke the ITO. If the ITO is confirmed, the patient is admitted to one of the psychiatric units, all of which are situated in the state capital. Prior to the introduction of the DTN, rural patients who had been involuntarily detained by a GP would need to travel to the state capital for this review. However, a city-based psychiatrist can review the patients while they are still located in the country via videoconference over the DTN. Where the ITO is revoked, this avoids an unnecessary transfer of the patient to the city. The new SA Mental Health Act was the principal reason for upgrading the telehealth infrastructure, as high quality audio and video was thought to reduce the medico-legal risk to psychiatrists reviewing ITOs. It was also intended that the upgraded network would provide country mental health patients with faster access to consultant psychiatrists for general reviews and assessments. The DTN was established in rural SA starting in 2012. There are now over 160 videoconferencing units operating in over 80 health service sites, predominantly for telepsychiatry. We have examined whether the introduction of the DTN was associated with an increase in number of specialist assessments and whether this led to changes in mental health service provision for rural and remote patients. Emergency Department (ED) mental health presentations prior and post upgrading were obtained from hospital databases. Data relating to the number of conference calls and individual call records were extracted from the clinical information system used to record mental health encounters. Statistical analyses were performed using a standard package (SPSS version 17). Most sites on the DTN experienced an increase in bandwidth for videoconferencing from 128 to 512 kbit/s. The early indications are that this increased activity in rural mental health services. During the 12 months following the introduction of the DTN there was a 17% increase in the number of mental health assessments made by specialists through videoconferencing (from 2047 to 2318). There was a 46% increase, in the number of ITOs for rurally-based mental health patients reviewed by metropolitan based psychiatrists using videoconferencing (from 71 to 104) in the same period. During the first 12 months of the DTN operation, 9% of the ITOs for rurally-based mental health patients were revoked, thus avoiding unnecessary transportation of the patients to the capital city. During the 12 months following the introduction of the DTN there was a 26% reduction in mental health presentations to metropolitan EDs (from 249 to 186). However, this occurred in country hospital catchment areas where there had also been other local mental health changes, for example community based intermediate care and visiting psychiatrists, as well as telepsychiatry. The national Department of Health and Aging commissioned a review of the status of telehealth services in Australia in 2011. The report 6 documented telehealth services, both internationally and in Australia. It noted that: ‘‘even though telehealth has been utilized for decades, the take up of telehealth as a mainstream service is yet to be realized’’. Our findings suggest that the provision of better videoconferencing technology may lead to more widespread use of telepsychiatry. This may be particularly Journal of Telemedicine and Telecare 2015, Vol. 21(3) 174–175 ! The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1357633X15569955 jtt.sagepub.com

Embedding research into clinical practice: the Services, Pathways Access - Research and Knowledge (SPARK) study.

Niranjan Bidargaddi, Geoffrey Schrader, Cynthia Piantadosi, Robert Adams, Bronwyn Ryan, Jennifer Williams, and Jorg Strobel

Monte Carlo Simulations Demonstrate Algorithmic Interventions Over Time Reduce Hospitalisation in Patients With Schizophrenia and Bipolar Disorder

Non-adherence with pharmacologic treatment is associated with increased rates of relapse and rehospitalisation among patients with schizophrenia and bipolar disorder. To improve treatment response, remission, and recovery, research efforts are still needed to elucidate how to effectively map patient’s response to medication treatment including both therapeutic and adverse effects, compliance, and satisfaction in the prodromal phase of illness (ie, the time period in between direct clinical consultation and relapse). The Actionable Intime Insights (AI2) application draws information from Australian Medicare administrative claims records in real time when compliance with treatment does not meet best practice guidelines for managing chronic severe mental illness. Subsequently, the AI2 application alerts clinicians and patients when patients do not adhere to guidelines for treatment. The aim of this study was to evaluate the impact of the AI2 application on the risk of hospitalisation among simulated patients with schizophrenia and bipolar disorder. Monte Carlo simulation methodology was used to estimate the impact of the AI2 intervention on the probability of hospitalisation over a 2-year period. Results indicated that when the AI2 algorithmic intervention had an efficacy level of (>0.6), over 80% of actioned alerts were contributing to reduced hospitalisation risk among the simulated patients. Such findings indicate the potential utility of the AI2 application should replication studies validate its methodologic and ecological rigour in real-world settings.

Characteristics of patients seen by visiting psychiatrists through Medicare in a rural community mental health service with an established telemedicine service

Objective: We aimed to determine characteristics of patients receiving Medicare-funded face-to-face consultations by psychiatrists in a rural service with an established telemedicine service. Methods: For this study, 55 case-managed patients from four rural community mental health teams in South Australia provided information through questionnaires regarding psychological symptoms, quality of life, body mass index (BMI) and gave access to their Medicare data. Results: In a logistic regression, it was found that being younger was more likely associated with a Medicare psychiatric consultation (p<0.05). Participants with at least one recorded visit to a Medicare psychiatrist consultation also tended to have lower levels of psychological distress at the end of the 4-year period, have a higher BMI, and more general practitioner consultations. Conclusion: The study provides clinicians and policy makers with preliminary information on the subtle differences in clinical profile of patients seen by Medicare-funded psychiatrists within an established state-managed telepsychiatry service.