31 May 2023
Improvements and personalisation of research and treatment in schizophrenia and psychosis-related disorders; observations from Schizophrenia International Research Society (SIRS) 2023 conference.
Earlier this month we had the pleasure of attending the Schizophrenia International Research Society (SIRS) conference in Toronto, Canada. We were delighted to present our recent findings from our meta-analysis comparing schizophrenia patients and healthy controls using the CANTAB battery, as well as learn about progression in the field and recommendations for future research. SIRS is the largest conference for schizophrenia and psychosis-related disorders and is a key hub to meet and learn from experts within the field. A wide range of topics were discussed, with our key takeaways from the conference listed below.
- Interventions and assessments for schizophrenia need to be updated into digital platforms to keep up with advances in technology such as through smartphone and virtual reality-based platforms.
- Novel pharmacological advancements in the treatment of schizophrenia are starting to stem away from the classical dopaminergic model and finding beneficial early effects.
- Continued growing interest in CANTAB for cognitive assessment in schizophrenia highlights the importance of using digital assessments in this therapeutic area.
- Standards for the collection and reporting of data are paramount for future progression in the field to reduce issues in reproducibility and the misreporting of findings.
- Early and personalised interventions are necessary to improve patient engagement and treatment outcomes with a large focus to include the patient’s own views and personal motivations into clinical decisions and treatment plans.
- Integration with other neurodevelopmental disorders highlights a new avenue of research to look for similarities and/or differences between patient groups to aid in our understanding of how mental illnesses present themselves in childhood.
1. Interventions and assessments for schizophrenia need to utilise digital platforms to keep up with advances in technology
A key theme we noticed at SIRS was the increased focus in using smartphone assessments to aid in the screening and continuous assessment of psychosis and its symptoms. In the current digital age, smartphones are more accessible to patient populations, with it estimated 97.4% of young first episode psychosis patients having access to one, and 95% of one sample demonstrating interest in using technology as part of their treatment journey and tracking. Most notably, a talk from Dr John Torous outlines the application of the mindLAMP app which provides a transparent, customisable and reproducible platform to help predict relapse in psychosis at an individual level. Data is collected from already available smartphone data (e.g. screen time, GPS movement and incoming/outgoing messaging) as well as allows the collection of sleep, cognitive and other biometric data. This provides a personalised threshold for relapse risk rather than relying on generalised clinical criteria alone. The future steps of mindLAMP is to integrate cognitive testing to help aid predictions of relapse.
Likewise, in terms of assessing functional capacity in psychosis patients, Dr Ventura advised on the use of the Virtual Realty Functional Capacity Assessment Tool (VRFCAT; Keefe et al., 2016). This tool acts as an alternative to standard assessments as it can provide realistic life-like experiences in assessing functional abilities in four different scenarios: i. following a recipe, ii. Taking a bus, iii. Shopping in a store, and iv. Managing currency. Here, the use of innovative digital technologies aids in capturing a more authentic representation of a patient’s functional outcomes than questionnaires and interviews alone.
In terms of cognitive assessment, Dr Danielle Pratt provided an excellent seminar on the comparison between a paper-and-pen and computerised versions of the digit symbol substitution test. When comparing performance between the Brief Assessment of Cognition and Schizophrenia version (paper-and-pen) to the computerised task version from Testmybrain, in a sample of 114 controls, 99 clinical high risk (CHR) cases with persistent symptoms and 97 with progressive symptoms, only the computerised version was able to differentiate between CHR groups. Similarly, the computerised version was more related to performance in motor function, which could be due to the format of the test (i.e. similar to that of a finger tapping test), whereas performance on the paper-and-pen task was more attributable to symptom scores. Performance on both tasks correlated well, as to be expected.
2. Novel pharmacological advancements in the treatment of schizophrenia
The goal to identify new pharmacological agents in the treatment of schizophrenia and psychosis was another key takeaway from the conference. Karuna presented initial findings from the phase 3 trial for KarXT, a novel intervention which targets muscarinic receptors rather than the traditional dopaminergic. The aim of this drug is to reduce symptoms while also being cognitively sparring and attain fewer detrimental side effects. In their 5-week trial, patients were either administered KarXT (n = 125) or placebo (n = 131). At the end of the trial there was an 8.4-point reduction in total Positive and Negative Syndrome Scale (PANSS) scores for the KarXT group, with this largely being driven by a reduction in positive symptoms rather than negative symptoms. Overall KarXT was well tolerated by the patient group.
Newron Pharmaceuticals’ poster presentation on Evenamide, an add-on antipsychotic treatment for patients with treatment-resistant schizophrenia, also provided novel insight for a sub-group of schizophrenia patients who do not typically respond to first- and second-line antipsychotic interventions. Evenamide is a selective inhibitor of voltage-gated sodium channels which normalises glutamate release, a neurotransmitter closely related to both treatment response and cognitive performance. Patients (n = 100) were assessed at 6 weeks, 6 months and at 1 year follow up. Improvements were observed at each timepoint in PANSS, Clinical Global Impression (CGI-S) and Strauss Carpenter Levels of Functioning (LOF) scores, with these all indicating gradual and sustained improvements. It will be interesting to see how Evenamide also contributes to improving cognitive deficits as this sub-population typically shows greater impairments than their antipsychotic-responsive counterparts.
3. Continued growing interest in CANTAB for cognitive assessment in schizophrenia
Our poster presenting the findings from the meta-analysis comparing schizophrenia and healthy controls was well received at the conference, with a growing interest in how the CANTAB battery could be used as an alternative to the current standard assessing cognitive performance in CIAS trials, the MATRICS Consensus Battery. Conference attendees were curious about our planned sensitivity analyses, including our current intention to restrict our sample to first episode psychosis and antipsychotic naïve cases to help reduce potential heterogeneity stemming from illness and treatment effects.
Dr Kristen Bojesen also presented a thought-provoking poster about the relationship between prefrontal glutamate levels and sustained attention measured using the Rapid Visual Information Processing (RVP) task. In their sample antipsychotic naïve patients (n = 54) and healthy controls (n = 55) were followed up at 6 weeks, 6 months, and 2 years, with the patient sample starting antipsychotic treatment following baseline assessment. Cognition assessed using the RVP and glutamate concentrations in the dorsal anterior cingulate cortex were measured at each visit. The patient sample performed significantly worse than healthy controls at each time point, as to be expected, with a strong association observed between prefrontal glutamate at baseline assessment (i.e., prior to antipsychotic medication) and at 2 years. We are delighted with the use of the RVP in this longitudinal design and significant positive associations seen with neurobiological markers of schizophrenia.
4. Standards for the collection and reporting of data are paramount for future progression in the field
An overarching theme of most talks from SIRS 2023 was how to improve the collection and reporting of data in psychosis trials, attributable to issues in reproducibility within the field. Dr Dost Ongur and Professor Mark Weiser both commented on the misreporting of results in psychiatric and clinical research. Dr Ongur compared the differences between medical and psychiatric journals in the standards to which they publish findings. His review found that medical journals tend to report clearer hypotheses, with higher reporting of p-values, confidence intervals and power calculations. A main takeaway from this talk was the importance of reporting power calculations to help understand the necessary sample sizes required as a guideline for future investigations.
Professor Weiser provided a review of research studies between 2000 – 2009 within the field of psychosis research to evaluate the quality of research and reporting of findings. The median timeline from a research group receiving funding to the publishing of outcomes was ~6 years, with negative findings (i.e. those reporting a non-significant effect) being less published (47%) than those finding a significant effect (positive). Key deviations from funding applications were also noted such as: inability to meet recruitment goals; reduced treatment periods; and the number of sub-groups and planned analyses changed. For research studies which published positive findings (64.7%), only 47% were replicated, highlighting a potential reproducibility issue within the field.
5. Early and personalised interventions are necessary to improve patient engagement and treatment outcomes
Early and personalised interventions have been of focus within the field for the past decade, with SIRS highlighting the importance of this from an array of talks and posters which were presented. With schizophrenia and psychosis being highly heterogeneous in their presentation and aetiology, it is unsurprising that formulating early detection and treatments on a case-by-case basis would aid in providing beneficial outcomes for this patient population.
The personalisation of functional outcome assessments and notions around illness recovery was discussed in Dr Joseph Ventura’s seminar outlining the differences between objective and subjective rating scales. Objective measures of functional outcomes are useful for clinical decision making, and correlate with illness insight, however these are bounded by what society deems as ‘acceptable’ functioning. In contrast, subjective measures such as the Heinrich’s quality of life scale provide additional data to complete the snapshot of a patient’s functioning. Subjective assessments also consider the importance of other factors which could impede functioning and engagement in treatment plans: self-perception, well-being stigma and self-acceptance, however, due to their lack of objectivity they are limited in their use for clinical decision making alone. Similarly, clinical (objective) versus personal (subjective) recovery was also discussed with the latter providing subjective accounts from the patient to understand their goals for personal growth and engagement in positive recovery-oriented services. Both objective and subjective tools provide important insight into recovery, but it is important to understand what each patient deems as important in their own recovery.
Motivation was also highlighted as an important variable for how an individual may differ in how they engage and respond to treatment. Helen Thai’s talk detailed that autonomous (extrinsic) and intrinsic motivation are key for improving treatment engagement. Their scoping review of cross-sectional studies (n = 21) found higher baseline motivation being associated with better treatment engagement and functioning, with any fluctuations observed during treatment to be associated with treatment response. In Randomised Controlled Trials (RCTs) providing motivation-based interventions it was identified that continual application of motivation skills throughout treatment were more beneficial than a standalone session. Here, Helen concludes that these interventions will be of clinical benefit for patient groups who struggle with engagement in treatment and have poorer treatment response.
The aforementioned mindLAMP app presented by Dr Torous, which utilises within-smartphone data, as well as sleep, sociability and activity parameters, also aims to personalise treatment plans to detect relapse risk for patients at an individual level. This tool also aims to provide an earlier indication of potential risk of relapse prior to patients reaching a peak threshold (i.e. when symptoms are high or close to presentation). However, Dr Torous did specify that these tools, albeit helpful, should work in conjunction with standard clinical measures and tools, rather than replace them.
6. Integration with other neurodevelopmental disorders
A new aspect for SIRS this year was the consideration of the role of other neurodevelopmental disorders in their presentation and overlap with psychotic disorders. Previously in the field there was some debate over whether schizophrenia was a neurodegenerative or neurodevelopmental disorder, with the inclusion of talks surrounding the therapeutic area of autism spectrum disorders (ASDs) suggesting a leniency toward the neurodevelopmental rhetoric. Within this dedicated symposium, five speakers presented mixed findings of social cognitive deficits, symptoms and neurobiological mechanisms and the homo/heterogeneity between schizophrenia spectrum disorders (SSDs) and ASDs.
Dr. Lindsay Oliver provided evidence of comparability between SSDs and ASDs. There are already known similarities in social cognition impairments in both groups, however, previous studies have typically looked at them in parallel rather than in conjunction. Likewise, this research typically uses cohorts with differing demographics meaning there are too many uncontrolled variables for consistent comparison. Dr Lindsay’s study aimed to determine overlap between SSDs and ASDs by completing a systematic review and meta-analysis. The results, which focused on emotional processing measures, showed similar cognitive impairment between the groups. However, Dr Lindsay admits that further studies with larger sample sizes, consistent batteries and outcome measures are needed to confirm the results and identify any similarities or differences between the disorders.
Dr Tim Ziermans presented their findings from an 8-year follow-up study focusing on attenuated positive symptoms. The analysis, which compared Schizotypal Personality Questionnaire – Brief Revised (SPQ-BR) scores from 30 ASD individuals to a normative sample, provided moderate evidence that positive symptoms were lower in ASD individuals during childhood, suggesting that the use of positive symptoms and cognitive markers in childhood as a predictor of psychosis in ASD individuals is limited, highlighting the need for better markers of ASD in childhood.
Whilst the addition of potential overlap with other neurodevelopmental disorders to this symposium highlights the importance of this topic, further research is needed.