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PRISM casts revealing light on symptoms that cross diagnostic categories

The PRISM project is multidisciplinary, quantitative, biology-based and – above all – transdiagnostic in its search for clinical, behavioral, imaging, and genetic features shared by different disorders. This EU-funded drive to uncover common biological substrates is powered by the belief that the approach will provide insights to fuel drug discovery.

As a first step, researchers have been probing the biology of the social withdrawal that is strongly associated with schizophrenia, Alzheimer’s disease, and major depressive disorder (MDD). Although findings are preliminary, data indicate that social dysfunction is indeed a trait seen across disorders.

Moreover, evidence presented at ECNP 2020 Virtual by Ilja Saris (Amsterdam University Medical Center, The Netherlands), suggests that reduced social activity in MDD is linked to decreased functional connectivity in the Default Mode Network and, more specifically, in the rostromedial prefrontal cortex.1

Social dysfunction associated with reduced connectivity in the Default Mode Network

 

A paradigm shift in psychiatry

PRISM is part of a broad effort (also evident in the Research domain criteria, or RDoC approach2) to shift psychiatry from uncertain diagnoses based on subjective assessment of symptoms to diagnoses based on biological understanding and objectively assessed behavior.

Relevant to the latter, is the development of a smartphone app (called BEHAPP) for passive remote monitoring.

In another presentation at the PRISM Symposium, Martien Kas (University of Groningen, The Netherlands) described how BEHAPP reveals not only phone usage and messaging but also geolocation and extent of social interaction.3

Daily rhythms of activity, and the way patients (including those with schizophrenia) differ from healthy age-matched controls are already evident. And researchers have developed a framework for assessing neuropsychiatric phenotypes by using the smartphone app-based location data.4

Biobank data show sociability has a genetic component relevant to schizophrenia and MDD

Patients will benefit directly from digital technology that provides longitudinal, real-world  information, Professor Kas said. One clear aim is to develop ways of ensuring that relevant changes in behavior can be signaled to healthcare professionals or caregivers, allowing more timely intervention.  The PRISM project is said to have had excellent engagement from public and patients alike.

 

A tool for drug discovery

PRISM is also exploring the genetics underlying sociability and exploratory behavior both in rodent models and in large genome-wide association studies including more than 300,000 participants in the UK Biobank. This work, described by Hugh Marston (Boehringer Ingelheim, Biberach, Germany), has revealed the involvement of genetic loci (and hence potential drug targets) in known and novel pathways.5

Interestingly, the investigators reported that the genetic component to sociability revealed in their data seemed relevant to schizophrenia and MDD but not bipolar disease or Alzheimer’s.

PRISM researchers have begun discussion with the EMA about how transdiagnostic biomarkers of the kind they are discovering can be integrated into the regulatory pathway for the drugs that will hopefully be developed, Dr Marston said.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

This content does not necessarily represent the opinion of ECNP.
References

1. Saris IMJ et al. Scientific Reports 2020 Jan 13;10(1):194

2. Insel T et al. Am J Psychiatry 2010;167:748-51

3. van der Wee NJA, et al. Neuroscience and Biobehav Rev 2019;38-46

4. Jongs N et al. Transl Psychiatry 2020 Jul 1;10(1):211

5. Bralten J et al. bioRxiv 2019; doi: https://doi.org/10.1101/781195

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