1. Preventing Psychotic Disorders by Early Detection and Intervention William R. McFarlane, M.D., Director Early Detection, Intervention and Prevention of Psychosis Program (EDIPPP) National Program Office Robert Wood Johnson Foundation Center for Psychiatric Research Maine Medical Center Research Institute and Spring Harbor Hospital Portland, Maine University of Vermont Tufts University Columbia University, College of Physicians and Surgeons

2. Collaborators William L. Cook, PhD Donna Downing, MS, OTR/L Anita Ruff, MPH Brenda Joly, PhD Kimberly Pukstas Diane Parham, O.T.R./L Karen Milner, MD Cameron Carter, MD Barbara Cornblatt, PhD Steven Adelsheim, MD Bentson McFarland, MD, PhD

3. Early detection and prevention in another illness “If you catch cancer at Stage 1 or 2, almost everybody lives. If you catch it at Stage 3 or 4, almost everybody dies. We know from cervical cancer that by screening you can reduce cancer up to 70 percent. We’re just not spending enough of our resources working to find markers for early detection.” ---Lee Hartwell, MD Nobel Laureate, Medicine President and Director, Hutchinson Center New York Times Magazine December 4, 2005, p. 56

4. Shortened productive lives Source: Mental Health Report of the Surgeon General

5. $10 million Lifetime costs for each new case of schizophrenia

6. 25 Years of life lost by people with schizophrenia due to all causes, including heart disease, cancer and suicide

7. Functioning as an effect of number of psychotic episodes

8. Empirical evidence for a relationship between a long DUP and a poor prognosis Johnstone et al. 1986: Many psychotic patients did not get appropriate treatment early, even when they sought help. Crow et al. 1986: DUP more important for the course than maintenance medication. Rabiner et al 1986: Long DUP was related to a poor one year outcome. Wyatt 1991,Opjordsmoen 1991: Earlier treatment predicted better course.

9. Effects of untreated initial psychosis Being psychotic is a personal disaster and the longer it lasts, the more it can become traumatic and stigmatizing. Being psychotic reduces cognitive and social function. They may lose contact with family and friends, fail school, or drop out of work. The longer the psychosis lasts, the more difficult it may be for the therapist to establish a good therapeutic relationship with the patient. Neurobiological deficit processes linked to symptom formation may possibly proceed unlimited as long as the patient is untreated.

10. Neurological disease (Cerebral AIDS, SLE, MS. etc.) Dementia praecox, deficit schizophrenia Chronic undifferentiated schizophrenia Paranoid schizophrenia Schizo-obsessive disorder. Schizo-affective disorder “NRG-1 disorder” Psychotic bipolar disorder Psychotic depressive disorder Severe agoraphobia time Validity of clinical differential diagnosis 0 High Premorbid period Defined Diagnosis Prodromal period Validity of diagnosis across phases of illness

11. Cognitive Deficits Affective Sx: Depression Social Isolation School Failure Biological Vulnerability: CASIS Brain Abnormalities Structural Biochemical Functional Disability Social and Environmental Triggers Increasing Positive symptoms Early Insults e.g. Disease Genes, Possibly Viral Infections, Environmental Toxins After Cornblatt, et al., 2005

12. NP Profile of Clinical High Risk (CHR) sample relative to Healthy Comparisons (HC)

13. Non-genetic biologic and psychosocial risk factors Prenatal infections (influenza, rubella, toxoplasma, herpes s.) Winter birth Prenatal toxic exposure (lead) Obstetrical complications Head trauma (perinatal to adolescence) Autoimmune (Rh incompatibility, thyroid, type 1 diabetes, celiac disease) Nutrition (starvation, omega-3 deficiency) Heavy metal exposure, maternal/fetal Heavy cannabis, other drug exposure Urban residence Exposure to trauma, with PTSD Negative emotional experience

14. Cortical volume reduction, in childhood-onset schizophrenia, ages 14-19

15. Expressed emotion Critical comments Hostility Over-involvement Warmth

16. Proportion of families with high EE in years following onset 14% 35% 50% Hooley, et al, 1995

17. Effects of genetic risk and family functioning on eventual schizophrenia- spectrum disorders * p < 0.001 **p = 0.582 G X E interaction: p=0.018 Tienari, Wynne, et al, BJM, 2004

18. Mutual causal effects: Patient symptoms and family interaction

19. Early prodrome Illusions Dread Insomnia Anorexia Social deficits Social & performance deficits Perceptual distortions Pervasive anxiety Withdrawal "Oddness" Functional deterioration Panic Misattribution High EE Late prodrome Psychosis Acute onset Biosocial causal interactions in late schizophrenic prodrome Critical comments CD, EOI Anxiety Structural Family/Social Physiological

20. Social networks in schizophrenia Family network size –diminishes with length of illness –decreases in the period immediately following a first episode –is smaller at the time of first admission Networks –buffer stress and adverse events –determine treatment compliance –predict relapse rate –correlate with coping skills and burden.

21. Is early intervention indicated prevention of psychotic disorders? Probably “Yes, we can?”

22. Trials of Indicated Prevention Buckingham, UK EDIE, UK German Research Network OPUS, Denmark TIPS, Norway, Denmark PACE, Australia PRIME, North America Omega-3 FAs, Austria PIER, Maine EDIPPP, USA

23. Psychosis prevention studies: One year rates for conversion to psychosis

24. Portland Identification and Early Referral (PIER) Reducing the incidence of major psychotic disorders in a defined population, by early detection and treatment: Indicated prevention

25. Project Overview

26. BIOLOGICAL RISK FACTORS Greater Portland Area Population 33O,OOO

27. Experimental Catchment Area: Vital statistics Population, 2007~340,000 Expected incidence, schizophrenia34 (10/100,000) Expected incidence, psychosis116 (34/100,000) Towns28 Public high schools25 Public middle schools23 Private schools, all types38 Colleges and universities4 Psychiatric inpatient beds134

28. Professional and Public Education Reducing stigma Information about modern concepts of psychotic disorders Increasing understanding of early stages of mental illness and prodromal symptoms How to get consultation, specialized assessments and treatment quickly Ongoing inter-professional collaboration

30. Youth Education Public service announcements by mainstream television and health information programs Interviews and spot announcements by youth television cable network 2-3 sessions on early warning signs as part of the obligatory 10 th grade health curriculum Widespread distribution of bookmarks and posters throughout catchment area schools, colleges, bookstores Art and literature contest Major publicity events during Mental Illness Awareness Week Youth oriented website: www.preventmentalillness.org

31. Welcome Mental illness Getting help About PIER Resources News Contact HomeHome | Contact Us | Disclaimer |Copyright©2005. Site by ACES Design - illustrations by Alan ClaudeContact UsDisclaimerACES Design

32. Family practitioners Pediatricians General Public Mental health clinicians Military bases and recruiters Clergy Emergency and crisis services College health services PIER Team Advertising School teachers, guidance counselors, nurses, social workers Employers

33. Family practitioners Pediatricians School guidance counselors, nurses, social workers Employers General Public Mental health clinicians Military bases and recruiters Clergy Emergency and crisis services College health services PIER Team

34. Clinical Strategies

35. Signs of prodromal psychosis Schedule of Prodromal Syndrome (SOPS), McGlashan, et al A clustering of the following: Changes in behavior, thoughts and emotions, with preservation of insight, such as: Heightened perceptual sensitivity To light, noise, touch, interpersonal distance Magical thinking Derealization, depersonalization, grandiose ideas, child-like logic Unusual perceptual experiences “Presence”, imaginary friends, fleeting apparitions, odd sounds Unusual fears Avoidance of bodily harm, fear of assault (cf. social phobia) Disorganized or digressive speech Receptive and expressive aphasia Uncharacteristic, peculiar behavior Satanic preoccupations, unpredictability, bizarre appearance Reduced emotional or social responsiveness “Depression”, alogia, anergia, mild dementia

36. Signs of prodromal psychosis Changes in behavior, thoughts and emotions, with preservation of insight, such as: Unusual perceptual experiences “Presence”, shadows, visual trails, ghosts Imaginary friends Fleeting apparitions Odd sounds Somatic illusions or hallucinations Heightened or dulled perceptions Vivid sensory experiences Sensations and thoughts located outside the body Frequent distortions or illusions Brief but frank hallucinations, minimal effect on behavior or thinking

37. Signs of prodromal psychosis Changes in behavior, thoughts and emotions, with preservation of insight, such as: Unusual fears Marked guardedness, distrustful Fear of assault (not social phobia) Avoidance of bodily harm Somatic delusions Severe nihilism Persistent persecutory self-referential thoughts Paranoia Extreme guilt, fear of harming others Bizarre obsessional preoccupations Fears of mind-reading Frank delusions, without full conviction

38. Signs of prodromal psychosis Changes in behavior, thoughts and emotions, with preservation of insight, such as: Disorganized or digressive speech and thoughts Receptive aphasia: “Can’t understand others.” Expressive aphasia: “Can’t be understood.” Odd, circumstantial, tangential, paralogical speech Overly simple speech Loss of gist of conversation, poor abstracting Rigid, concrete, almost autistic thinking Loosening of associations Marked vagueness, lack of clarity of subjects and objects Racing speech Stereotyped ideas, speech Over-elaborate speech Poor problem-solving

39. Signs of prodromal psychosis 2. Significant deterioration in functioning –Unexplained decrease in work or school performance –Decreased concentration and motivation –Decrease in personal hygiene –Decrease in the ability to cope with life events and stressors 3. Social withdrawal –Loss of interest in friends, extracurricular sports/hobbies –Increasing sense of disconnection, alienation –Family alienation, resentment, increasing hostility, paranoia

40. Family-aided Assertive Community Treatment (FACT): Clinical and functional intervention Rapid, crisis-oriented initiation of treatment Psychoeducational multifamily groups Case management using key Assertive Community Treatment methods –Integrated, multidisciplinary team; outreach PRN; rapid response; continuous case review Supported employment and education –Collaboration with schools, colleges and employers

41. Family-aided Assertive Community Treatment (FACT): Clinical and functional intervention Cognitive assessments used in school or job Low-dose atypical antipsychotic medication –aripiprazole 10-20 mg, quetiapine 300-600 mg, olanzapine 2.5-7.5 mg, risperidone 0.25-3 mg Mood stabilizers, as indicated by symptoms: –Mood stabilizing drugs: lamotrigine 50-150 mg, valproate 500- 1500mg, lithium by blood level SSRIs, with caution, especially with aripiprazole and/or a family history of manic episodes

42. Key clinical strategies in family intervention specific to prodromal psychosis Strengthening relationships and creating an optimal, protective home environment: –Reducing intensity, anxiety and over-involvement –Preventing onset of negativity and criticism –Adjusting expectations and performance demands –Minimizing internal family stressors Marital stress Sibling hostility Conceptual and attributional confusion and disagreement

43. Key clinical strategies in family intervention specific to prodromal psychosis Strengthening relationships and creating an optimal, protective home environment: –Buffering external stressors Academic and employment stress Social rejection at school or work Cultural taboos Entertainment stress Romantic and sexual complications

44. Key clinical strategies in family intervention specific to prodromal psychosis Individualized, responsive education for single families Little discussion of atrophic aspects of brain functioning emphasis on transient, stress-induced hyperactivity in some brain areas and some biochemical systems Accelerated recovery, reentry and rehabilitation Emphasis on careful forward progress. –"Slow down personal and career advancement, until stability and motivation returns."

45. PIER: Outcomes after one year of treatment Data for 148 at-risk cases from the first 6 years intake: May 7, 2001- September 6, 2007

46. Community Education and Training: Results Outreach events325 Public schools and colleges trained100% Professionals trained7270 Bookmarks distributed>70,000 Resource guides distributed>1400 Website hits (2005-2007)1,071/day Website sessions (2005-2007)56.3/day Total hits (2005-2007)>500,000 Surveys: Awareness of PIER in area, 2001 vs. 2007 8% vs. 19%

47. Figure 1. Disposition of all contacts with PIER, 5/7/2001-9/1/2007 All contacts N=1333 Case Referrals N=1103 Referred Elsewhere N=240 (30.8%) No further contact required N=51 (6.5%) Contact withdrawn N=85 (10.9%) In catchment area N=921 Screened for formal assessment N=404 (51.8%) Completed SIPS N=271 (67.1%) Met SOPS criteria N=148 (54.6%) Declined treatment N=10 (6.8%) Dropped out in < 3 months N=22 (14.9%) Treated > 3 months N=118 (79.7%) Referred Elsewhere N= 74 (18.3%) Request for presentation N=50 Request for information N=180 Presumed Psychotic N=47 (11.6%) Contact withdrawn or did not complete SIPS N=9 (2.2%) Age 12-35 N=780 Did not meet SOPS criteria N=94(34.7%) Psychotic by POPS criteria N=32 (11.8%)

48. Efficiency of identification: Diagnosis for those screened as at risk n = 780 Referred for another disorder31440.2% Prodromal14819.0% Psychosis7910.1% Any psychiatric illness58969.4%

49. Referral sources: Distribution Non-mental health sources52.3% Tertiary sources21.5% Mental health sources26.2%

50. Screening and treatment entry Referrals780100.0% SIPS Completed27134.8% Met SOPS Criteria14854.6% Declined treatment 106.8% Dropped out <3 Months 2214.9% Treated sample11678.4%

51. Demographics of the treated sample Males (age range 12 - 27) 53.4% Females (age range 12 - 24)46.6% Average age16.5 DSM-IV Substance abuse disorder 15%

52. Treated cases converting to psychosis within 12 months (n = 93) Cases not converted72 77.4% Cases converted, 1-6 days 5 5.4% Cases converted, 7-30 days 7 7.5% SOPS psychosis conversions 5 5.4% Schizophrenic disorder 4 4.3% Total SOPS conversions 9 9.7%

53. SOPS scores at baseline and 12 months p<.001 n=94

55. Overall functioning: Baseline and 12 months N=94; p<.01

57. Components of expressed emotion: Prodromal vs. chronic phase All differences, prodromal vs. chronic: p<0.01

58. Difference in Initial Admissions Portland vs. 3 Maine Urban Areas, Ages 12-25 Incidence difference, mean: Portland vs 3 urban areas: 65/100,000 % of Portland baseline: 60%

59. Difference in Initial Admissions Rates for Psychosis Portland minus 3 Maine urban areas, Ages 12-25 PIER begins

60. Differences In Initial Admission Rates/100,000 For All Psychoses, Ages 12-35, 1994-2000 Vs. 2001-2007: Portland Vs. Control Catchment Areas In Maine

61. Incidence in Portland and 3 urban areas All Psychosis, ages 12-25 r = -0.53

62. First admissions to Maine hospitals for a psychotic or major mood disorder, 1990-2007 Ages 12-25 Source: MHDO data, analyzed by Maine Health Information Center and Maine Medical Center Research Institute

63. Hospitalization costs avoided* Portland vs. 3 other Maine cities Cases not admitted Days in hospital Hospital daily rate Annual costs avoided 200236.810$900$331,200 36.813$1,600$765,440 Average: 2001-2007 62.710$900$564,300 62.713$1,600$1,304,160 200789.510$900$805,500 89.513$1,600$1,861,600 *Savings from avoided initial hospitalizations in Portland. Cost estimates based on incidence rate differences (i.e., resulting fewer cases) between greater Portland and the other 3 Maine urban areas. Amounts are based on time period—2002, 2007 or the average for 2001-2007—days in hospital for first admission and daily rate in dollars. Population based on US Census estimates for the respective years.

64. Differences between treated prodromal and post-psychotic states Prodromal young persons have manifested: Maintenance of insight (prevention of loss) Continued ego-dystonic response to psychotic symptoms High acceptance of, and adherence to, treatment Low rates of substance abuse More open to discontinuing heavy drug and alcohol abuse Less resistance to family inclusion by patient Higher motivation to continue schooling and/or work More trusting and grateful therapeutic relationships Higher sensitivity to treatments Higher likelihood of improving course of functioning

65. Conclusions Public education is influencing attitudes, knowledge and behavior. Accurate referrals are coming from outside the mental health system. Treatment is blocking the final common pathway to psychosis. Medication at low doses is adequate but appears essential for prevention of imminent, and perhaps later, psychosis. Very low conversion rates and functional improvement accompany comprehensive treatment (~15%; ~5% for schizophrenic disorders). A substantial proportion of the incident population can be identified and prevented from developing psychosis.

66. PIER Sponsors PIER has been made possible with the generous support of: Robert Wood Johnson Foundation National Institute of Mental Health Center for Mental Health Services (SAMHSA) State of Maine Maine Health Access Foundation Bingham Fund Betterment Fund Brain Foundation American Psychiatric Foundation UnumProvident Foundation Wrendy Haines Fund