Preventing Psychotic Disorders by Early Detection and Intervention

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. 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 Collaborators

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

11. Early Insults Social and Environmental Triggers e.g. Disease Genes, Possibly Viral Infections, Environmental Toxins Psychosis Increasing Positive symptoms Biological Vulnerability: CASIS Disability Cognitive Deficits Affective Sx: Depression Social Isolation School Failure Brain Abnormalities Structural Biochemical Functional 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 EEin years following onset 50% 35% 14% 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 + Family interaction Patient symptoms +

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

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 10th 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

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

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

34. Clinical Strategies

35. Signs of prodromal psychosisSchedule 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

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

48. Efficiency of identification: Diagnosis for those screened as at riskn = 780

49. Referral sources: Distribution

50. Screening and treatment entry