Prediction and prevention of psychotic disorders? Ultra High Risk research: background and recent developments

1. Prediction and prevention of psychotic disorders?Ultra High Risk research: background and recent developments Associate Professor Alison Yung ORYGEN Research Centre University of Melbourne, Australia

2. Alison Yung Barnaby Nelson Gregor Berger Lisa Phillips Elizabeth Cosgrave Cathy Greenwood Smith Magenta Simmons Chris Pantelis Danny Kelly Lisa O’Dwyer George Patton Patrick McGorry Hok Pan Yuen Paul Amminger Shona Francey Ilona Di Bella John Koutsogiannis Denis Velakoulis Carrie Stanford Susanne Jones Natalie Kobilek Henry Jackson Any many more……… People involved

5. “The best hope now for the prevention of schizophrenia lies with indicated preventive interventions targeted at individuals manifesting precursor signs and symptoms who have not yet met full criteria for diagnosis. The identification of individuals at this early stage, coupled with the introduction of pharmacological and psychosocial interventions, may prevent the development of the full-blown disorder” • Mrazek and Haggerty (1994)

6. Can we predict and prevent psychotic disorder? • We know that psychotic disorders, such as schizophrenia, are almost always preceded by a prodromal phase

7. sys treatment psychosis DUP prodrome time

8. Characteristics of the initial psychotic prodrome • 1993 literature review and retrospective study of patients with first episode psychosis

9. Prodromal symptoms • Non -specific symptoms eg depressed mood, anxiety, sleep disturbance • Subthreshold or attenuated psychotic symptoms - more proximal to psychosis onset • Behavioural changes eg social withdrawal, deterioration in role functioning - could be the result of a number of underlying causes eg depression, other prodromal phenomena or frank psychosis

10. Prodromal symptoms • About 25 % of individuals experienced suicidal thoughts, self harm and forensic behaviour • Period of psychosocial decline and of health damaging behaviours

11. Subthreshold psychotic symptoms, distress and serious functional decline occur before frank psychosis • Need for care ≠ threshold psychotic disorder

12. Recognising the ‘prodrome’ prospectively • A “prodrome” is difficult to recognise prospectively because of its non-specific symptoms

13. sys Threshold for diagnosis of psychosis ? time

14. True Positive sys Threshold for diagnosis of psychosis psychosis prodrome time

15. False positive sys Threshold for diagnosis of psychosis resolving symptoms time

16. False false positive sys Threshold for diagnosis of psychosis symptoms resolved with intervention time

17. How do we identify those truly experiencing a prodrome? • Prodrome is a retrospective concept • Definitive “diagnosis” only after psychosis onset • Prospectively can only use the term At Risk Mental State (ARMS)

18. At Risk Mental State sys Threshold for diagnosis of psychosis ? time

19. “We want to know… what to ask to split clearly between the people who are having trouble in living and the people who are in grave risk of serious psychosis” • Harry Stack Sullivan (1938)

22. How do we identify those truly experiencing a prodrome? • Combine risk factors • And/or use those symptoms which seem to be more specific or more proximal to the time of psychosis onset

23. Combining risk factors(‘close-in strategy’) • Age 14 - 30 (age range at highest risk for onset of a psychotic disorder) • plus ARMS with one (or more) of the following features

24. Group 1 • Attenuated psychotic features • Overvalued ideas, perceptual distortions • Duration - at least one week, not longer than 5 years • Frequency - at least twice per week • Recency - in the last year

25. Group 2 • BLIPS: Brief Limited Intermittent Psychotic Symptoms • Frank psychotic features • Either resolve spontaneously within 7 days • Or occur very infrequently - less than twice per week • Recency - in the last year • Can be drug induced

26. Group 3 • Family history of psychotic disorder in a first degree relative • Or schizotypal PD • PLUS non-specific ARMS symptoms • Duration - at least one month, not longer than 5 years • Associated with significant decline in functioning

27. Setting • PACE Clinic established • Youth friendly and easily accessible health service • Located at Highpoint Shopping Centre and previously Centre for Adolescent Health • “Personal Assessment and Crisis Evaluation”

28. PACE referrals March 1995 - January 1999

29. Results - transition to psychosis • 29 of the 104 (28%) subjects had developed by 6 month follow up point psychosis. • By 12 months 36 (34.6 %) subjects had developed psychosis • 5 subjects developed psychosis after 12, 15, 18, 25 and 28 months • Total developing psychosis thus far: 41 subjects (39.4% of sample)

30. Survival curve of proportion remaining non-psychotic

31. Transition to full blown psychosis - by centre

32. UHR criteria in different populations • UHR criteria applied to a help-seeking sample of people aged 14 - 25 presenting to a mental health service for young people • Assessed by Triage service as not psychotic

33. UHR in general adolescent sample • From April - October 2003 • 207 individuals presented • 149 agreed to research assessment (72% response rate)

34. UHR in general adolescent sample • Of these 149, 43 met UHR criteria at baseline, 106 did not

35. UHR in general adolescent sample

36. UHR in general adolescent sample - 6 month follow up • Transition rate = 11.6%. • UHR+ status: • PPV 0.116 • Sensitivity 0.833 • Specificity 0.734 • NPV 0.991 • UHR+ status at baseline was significantly associated with psychosis at 6 month follow up (Fisher’s exact two tailed p= 0.008).

37. UHR in general adolescent sample - 2 year follow up • 2 more developed psychotic disorder • 1 was UHR positive at baseline, 1 UHR negative

38. UHR in general adolescent sample

39. UHR in general adolescent sample - 2 year follow up • Transition rate = 14%. • UHR+ status: • PPV 0.14 • Sensitivity 0.75 • Specificity 0.738 • NPV 0.981 • UHR+ status at baseline was significantly associated with psychosis at 2 year follow up (Fisher’s exact two tailed p= 0.008).

40. So…? • UHR criteria still predict onset of psychosis within short time frame • Transition rate much lower than in the previous PACE group, and most other UHR centres • (only 11% at 6 months, 14% at 2 yrs)

41. More alarmingly… • Transition rate in PACE also seems to have declined recently

42. Reduction in transition rate

43. Reduction in transition rate

44. Effect of year on transition rate after adjusting for:

45. So year is still a significant predictor of transition even after adjusting for symptoms and functioning • However it was no longer significant after adjusting for duration of symptoms prior to coming to PACE.

47. Schizophrenia Frank psychotic symptoms Psychotic-like experiences associated with distresshelp-seeking, decreased functioning, comorbidity Psychiatric disorders with “incidental” PLEs

48. But there’s more …. • Psychotic experiences are actually quite common in the community

49. Community studies • Van Os et al: 17.5% of people in the NEMESIS study reported “psychotic-like experiences” at some time in their lives • Eaton et al ECA • Poulton et al: 14.7% of children aged 11 • Hanssen 83 of 4067 (2%) developed new psychotic experiences over the course of 2 years

50. Schizophrenia Frank psychotic symptoms Psychotic-like experiences associated with distresshelp-seeking, decreased functioning, comorbidity Psychiatric disorders with “incidental” PLEs Non-distressing PLEs No psychiatric symptoms