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3rd Newsletter (July, 2018) | Unsubscribe

I. Introduction by Prof. René Kahn

II. A Progress Report

III. Publications

IV. PSYSCAN in short: WP2 & WP5

V. Interview with a PSYSCAN Researcher

VI. The team

VII. PSYSCAN forthcoming meetings

VIII. PSYSCAN contact

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I. Introduction
by Prof. René Kahn

Prof. Celso Arango

Dear Reader

Welcome to the third PSYSCAN Newsletter!

We have made important progress since the last Newsletter. All the PSYSCAN Work Packages have worked hard to align with each other and to make sure that all the information that is collected from various sources is coming together. The PSYSCAN project enables us to combine clinical, cognitive and neuroimaging information to help us predict the transition or course of psychosis. This is a big step forward in adjusting treatment on an individual basis to provide adequate help for everyone suffering from this disease.

Work Package 2 has collected over 3,000 existing scans from centers all across the world, from subjects with psychosis, subjects at risk for psychosis, and controls. People have been very helpful in providing imaging data together with as much demographic and clinical data as possible to combine this information and start our first machine learning algorithms to analyse these data. The first publication is being prepared as we speak.

In our ongoing study in Work Package 5, we are collecting data from a population at ultra high risk for psychosis and data from a population who recently experienced a first episode of psychosis. We currently have 247 FEP patients, 113 UHR subjects, and 42 Healthy Controls in the study. At this moment, we have less than 6 months to include participants, so we ask all participating sites to keep up the good work!

Thanks to all who are working so hard to get and keep this project up and running. This Newsletter will bring you up to date on what has been happening and gives a little insight in the work that the different partners do to make PSYSCAN a successful project.

Best wishes,

René Kahn

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II. A progress report-WP5

FEP Cohort

  • 247 patients have been included in the FEP cohort.

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UHR Cohort

  • 119 patients have been included in the UHR cohort.

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III. Publications


Using neuroimaging to help predict the onset of psychosis.

Gifford G, Fusar-Poli P, Schnack HG, Kahn RS, Koutsouleris N, Cannon TD, McGuire P.

The aim of this review is to assess the potential for neuroimaging measures to facilitate prediction of the onset of psychosis. Research in this field has mainly involved people at ‘ultra-high risk’ (UHR) of psychosis, who have a very high risk of developing a psychotic disorder within a few years of presentation to mental health services. The review details the key findings and developments in this area to date and examines the methodological and logistical challenges associated with making predictions in an individual subject in a clinical setting.

Neuroimage. 2017 Jan 15;145 (Pt B):209-217. doi: 10.1016/j.neuroimage.2016.03.075


Long term outcomes of acute and transient psychotic disorders: The missed opportunity of preventive interventions.

Rutigliano G, Merlino S, Minichino A, Patel R, Davies C, Oliver D, De Micheli A, McGuire P, Fusar-Poli P.

BACKGROUND: Acute and transient psychotic disorders (ATPD) are characterized by an acute onset and a remitting course, and overlap with subgroups of the clinical high-risk state for psychosis. The long-term course and outcomes of ATPD are not completely clear.

METHODS: Electronic health record-based retrospective cohort study, including all patients who received a first index diagnosis of ATPD (F23, ICD-10) within the South London and Maudsley (SLaM) National Health Service Trust, between 1st April 2006 and 15th June 2017. The primary outcome was risk of developing persistent psychotic disorders, defined as the development of any ICD-10 diagnoses of non-organic psychotic disorders. Cumulative risk of psychosis onset was estimated through Kaplan-Meier failure functions (non-competing risks) and Greenwood confidence intervals.

RESULTS: A total of 3074 patients receiving a first index diagnosis of ATPD (F23, ICD-10) within SLaM were included. The mean follow-up was 1495 days. After 8-year, 1883 cases (61.26%) retained the index diagnosis of ATPD; the remaining developed psychosis. The cumulative incidence (Kaplan-Meier failure function) of risk of developing any ICD-10 non-organic psychotic disorder was 16.10% at 1-year (95%CI 14.83-17.47%), 28.41% at 2-year (95%CI 26.80-30.09%), 33.96% at 3-year (95% CI 32.25-35.75%), 36.85% at 4-year (95%CI 35.07-38.69%), 40.99% at 5-year (95% CI 39.12-42.92%), 42.58% at 6-year (95%CI 40.67-44.55%), 44.65% at 7-year (95% CI 42.66-46.69%), and 46.25% at 8-year (95% CI 44.17-48.37%). The cumulative risk of schizophrenia-spectrum disorder at 8-year was 36.14% (95% CI 34.09-38.27%).

CONCLUSIONS: Individuals with ATPD have a very high risk of developing persistent psychotic disorders and may benefit from early detection and preventive treatments to improve their outcomes.

Eur Psychiatry. 2018 May 19;52:126-133. doi: 10.1016/j.eurpsy.2018.05.004.


Evidence That Environmental and Familial Risks for Psychosis Additively Impact a Multidimensional Subthreshold Psychosis Syndrome.

Pries LK, Guloksuz S, Ten Have M, de Graaf R, van Dorsselaer S, Gunther N, Rauschenberg C, Reininghaus U, Radhakrishnan R, Bak M, Rutten BPF, van Os J.

Background: The observed link between positive psychotic experiences (PE) and psychosis spectrum disorder (PSD) may be stronger depending on concomitant presence of PE with other dimensions of psychopathology. We examined whether the effect of common risk factors for PSD on PE is additive and whether the impact of risk factors on the occurrence of PE depends on the co-occurrence of other symptom dimensions (affective dysregulation, negative symptoms, and cognitive alteration).

Method: Data from the Netherlands Mental Health Survey and Incidence Study 2 were used. Risk factors included childhood adversity, cannabis use, urbanicity, foreign born, hearing impairment, and family history of affective disorders. Logistic regression models were applied to test (1) the additive effect of risk factors (4 levels) on PE and (2) the moderating effects of symptom dimensions on the association between risk factors (present/absent) and PE, using additive interaction, expressed as the interaction contrast ratio.

Results: Risk factors were additive: the greater the number of risk factors, the greater the odds of PE. Furthermore, concomitant presence of the other symptom dimensions all increased the impact of risk factors on PE. After controlling for age, sex, and education, only affective dysregulation and negative symptoms remained significant moderators; only affective dysregulation remained a significant moderator if all dimensions were adjusted for each other.

Conclusions: Risk factors may not be directly associated with PE but additively give rise to a multidimensional subthreshold state anticipating the multidimensional clinical syndrome. Early motivational and cognitive impairments in the context of PE may be reducible to affective dysregulation.

Schizophr Bull. 2018 Apr 25. doi: 10.1093/schbul/sby051.


Child Maltreatment and Clinical Outcome in Individuals at Ultra-High Risk for Psychosis in the EU-GEI High Risk Study.

Kraan TC, Velthorst E, Themmen M, Valmaggia L, Kempton MJ, McGuire P, van Os J, Rutten BPF, Smit F, de Haan L, van der Gaag M; EU-GEI High Risk Study.

Background: Child maltreatment has been associated with a wide range of mental disorders in adulthood. Whether child maltreatment is specifically associated with psychosis risk in individuals at ultra-high risk (UHR) for psychosis, or leads to a general vulnerability for overall psychopathology in the UHR stage remains unclear. The present study examines the association between child maltreatment and transition to psychosis and other mental disorders.

Methods: The sample consisted of 259 UHR individuals from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Participants were followed-up for 2 years to assess clinical outcome. Clinical outcome was assessed at 6 months, 12 months, and 24 months after baseline. Child maltreatment before the age of 17 years was assessed at baseline.

Results: Our findings show that a history of emotional abuse was associated with an increased risk for transition to psychosis (OR = 3.78, 95% CI = 1.17 to 12.39, P = .027). Apart from psychosis, a history of physical abuse was associated with depressive disorder (OR = 4.92, 95% CI = 2.12 to 11.39, P = .001), post-traumatic stress disorder (OR = 2.06, 95% CI = 1.10 to 3.86, P = .023), panic disorder (OR = 2.00, 95% CI = 1.00 to 3.99, P = .048) and social phobia (OR = 2.47, 95% CI = 1.18 to 5.16, P = .016) at follow-up.

Conclusion: Our findings suggest that in the UHR stage child maltreatment is a pluripotent risk factor for developing psychosis, depressive disorder, post-traumatic stress disorder (PTSD), panic disorder, and social phobia in adulthood.

Schizophr Bull. 2018 Apr 25. doi: 10.1093/schbul/sby051.

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IV. PSYSCAN in short: WP2 & WP5

Work Package 2: Legacy Data Fusion

Prof. Mc-Guire

WP2 is led by Prof. McGuire and its main objectives are to collect existing neuroimaging, genetic, clinical and cognitive data to identify candidate measures for prediction of outcomes.

King's College London is responsible for WP2. Each partner collaborating in PSYSCAN will contribute legacy data to WP2 of the above-mentioned modalities; these different datasets will be merged with common parameters in order to perform mega-analyses of new, larger samples. This approach will permit analyses of datasets an order of magnitude larger than those studied to date. The results from WP2 will guide the initial development of machine learning algorithms for the WP5 dataset.

Work Package 5: Discovery and Validation of the PSYSCAN Tool

Work package 5 (WP5) is led by Prof. René Kahn and its main objective is to develop a quantitative and objective tool for the prediction of the course and outcome of psychosis at an individual level. This will be achieved by combining the predictive values of measures of psychopathology, brain structure and function, cognition and biological markers in blood.

330 participants who are at clinical high risk (CHR) for developing psychosis, 465 patients who experienced a first episode of psychosis (FEP), and 150 healthy controls will be included in this study. At baseline, psychopathology will be examined using questionnaires and interviews, brain structure and function are measured with Magnetic Resonance Imaging (MRI), cognition will be assessed using a computerized battery of neuropsychological tests, and blood samples are drawn to determine levels of genetic and immune parameters. Participants are followed up for one year (FEP patients and healthy controls) or two years (CHR subjects), and assessments are repeated at certain time points. Using state-of-the-art machine learning techniques, we will extract discriminative information from our high-dimensional data set in order to predict psychosis outcome at the level of the individual. Examples of predictions are the transition to psychosis of UHR participants or the recovery of FEP patients. Data will be used to develop a quantitative and objective tool that will enable healthcare professionals to tailor psychiatric care to the particular needs of each patient.


Prof. René Kahn
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V. Interview with a PSYSCAN Researcher
Dieuwke Siegmann Today we interview Dieuwke Siegmann, one of the psychologists working in the PSYSCAN team in Amsterdam.

Dieuwke is involved in PSYSCAN as a researcher since 2016. The Amsterdam team has recruited so far 40 FEP, 21 UHR participants, and 15 HCs into the study and we wanted to talk with her today about her feelings about PSYSCAN, her experience with the patients enrolled at her site and her insights into research on first-episode

1. How did you become involved in PSYSCAN?

During my Master degree Clinical Psychology I started getting interested in psychosis spectrum disorders. That´s why I started my Psychology internship at the AMC, at the department Early Psychosis in September 2015. After my graduation in 2016, Lieuwe de Haan contacted me about the PSYSCAN study. In September 2016, I became involved in PSYSCAN as research employee, which is my current position.

2. Could you describe us how the Amsterdam PSYSCAN team is organised and your experience with the project so far?

The team consists of the Principal Investigator (Lieuwe de Haan), Jana Barkhof and me. Jana Barkhof has joined the team as a research employee in November 2017, and is responsible for the recruitment and assessments of the Healthy Controls. However, she also helps me to manage the follow-up visits for FEP and UHR participants, which I’m very grateful for! Lastly, I’m responsible for the UHR and FEP participants; recruitment, planning, baseline and follow-up assessments (including blood draw and MRI-scan). On Wednesdays and Fridays we plan the baseline and follow-up assessments including the MRI scans. On Tuesdays I recruit participants at the early psychosis department and plan all the assessments.
Our team has recruited so far 40 FEP participants (2 to go), 21 UHR participants (4 to go) and 15 HC participants (0 to go). The most outstanding practical difficulty for us would be time management, because we usually have several assessments a day (sometimes including MRI scan, which we conduct ourselves), which can be quite challenging.

3. What are your recommendations for recruiting a high number of UHR and FEP participants in PSYSCAN?

To recruit a high number of UHR participants is, in my opinion, only possible by working together with other institutions and research teams. That is why we recently started collaboration with Arkin (institution for general psychiatry), so that patients with a high PQ score (Prodromal Questionnaire) are referred to the AMC to perform a CAARMS assessment. Patients with a UHR status are asked to join the study. We also work closely together with other research teams at the Early Psychosis Department, to combine follow-up assessments from different studies to minimise the potential burden for participants.
For the recruitment of FEP participants I think it is very important to work closely together with the clinical team and have frequent contact with the staff (nurses and psychiatrists). I think it's very important that the staff is research-minded and understands the purposes of the study.

4. Which are, in your opinion, the main clinical questions that still demand answer in FEP and UHR treatment and research?

Although much research has been already done, I think it is still important to investigate which predictive factors determine the onset to psychosis (after a UHR diagnosis) and which pathways, comorbid symptoms or combination of (predictive) factors lead to crossing the psychosis threshold. Also, in clinical practice, it's important to understand more of the process of a first episode of psychosis, to offer patients more detailed advice of prognosis, treatment and lifestyle.

5. Which are, in your opinion, the main positive aspects of the PSYSCAN project?

For me as a psychologist and research assistant, one of the main positive aspects of PSYSCAN is the regular contact with the participants. Most of the participants are very happy to attend the follow-up assessments, which is very encouraging. Additionally it is very satisfying to see that most of the participants are doing so well!

6. Which are your plans and expectations for the future?

I am very motivated to include the last FEP and UHR participants and to finish the follow-up assessments. Although psychosis still remains an interesting topic for me, in the future I'd like to extend my skills and knowledge about mental illness and be more involved in the diagnosis and treatment of mental illnesses in a broader sense.

Thank you very much for your help, Dieuwke! We hope that your team will keep on contributing with the project as successfully as they have done so far.

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VI. The team

FEP Cohort

MAP FEP COHORT

UHR Cohort

MAP UHR COHORT
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VII. PSYSCAN meetings
Last April we had an amazing PSYSCAN meeting during the SIRS conference in Florence including most of the principal investigators or their representatives and many of the PSYSCAN researchers. We were able to discuss interesting aspects about the project, ongoing issues, challenges and also the most rewarding moments. We were happy to award the following sites:
PSYSCAN meeting

General Assembly
The next PSYSCAN General Assembly will take place in London on the afternoon of the 26th October 2018.

More details will be sent out soon but please save the date in your diaries.
PSYSCAN meeting

EC reporting
The current reporting period will end on the 31st July. Scientific and financial reports need to be submitted to the EC 60 days after this date.
  • The scientific reports will be written by work package leaders only.
  • All sites (except subcontractors) need to submit a financial report, detailing expenditure in the current period.
  • If you have any questions about reporting, please contact Holly Elphinstone (holly.elphinstone@kcl.ac.uk)
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VIII. Contact details
Coodinator
Philip McGuire
Institute of Psychiatry, Psychology, and Neuroscience
King's College, London
16 De Crespigny Park
London SE5 8AF
United Kingdom
Phone: +44 207 848 0355
Email: philip.mcguire@kcl.ac.uk
Research Programme Coordinator
Kate Merritt
Institute of Psychiatry, Psychology, and Neuroscience
King's College, London
16 De Crespigny Park
London SE5 8AF
United Kingdom
Email: a.a.t.s.reinders@kcl.ac.uk
Project Finance and Legal Manager
Holly Elphinstone
Institute of Psychiatry, Psychology, and Neuroscience
King's College, London
16 De Crespigny Park
London SE5 8AF
United Kingdom
Phone: +44 (0)207 848 0927
Email: holly.elphinstone@kcl.ac.uk
Project Manager FEP
Erika van Hell
Brain Center Rudolf Magnus
Department of Psychiatry, A01.126
University Medical Center Utrecht
PO Box 85500
3504 GA Utrecht
The Netherlands
Phone: +31 (0)88 7556369
Email: H.H.Vanhell-2@umcutrecht.nl
Project Manager UHR
Stefania Tognin
Institute of Psychiatry, Psychology, and Neuroscience
King's College, London
16 De Crespigny Park
London SE5 8AF
United Kingdom
Email: stefania.tognin@kcl.ac.uk
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