Brussel, Jim van Os
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1 Brussel, Jim van Os
2 Onwetenschappelijke tweedeling Héél ernstig Mild Biologisch Sociaal Ahn, 2009 Fysische behandeling Psychische behandeling
3 Factor timing: Staging Neuroticism Plasticity Severity Depression
4 Factor timing: Staging Trait impulsivity Plasticity Severity Addiction
5 Factor timing: Staging Behavioural inhibition Plasticity Severity Anxiety disorder
6 Factor timing: Staging Cyclothymia Plasticity Severity Bipolar disorder
7 Factor timing: Staging Schizotypy Plasticity Severity Psychotic disorder
8 UHR Literature: Risk 30% Transition in 2 years 80% Schizo -conversion Almost all in 6 months UHR literature
9 You will transition to Schizo-diagnosis
10 Transformation Required? SICK CARE HEALTH CARE
11 Devastating Genetic Brain Disease Debilitating Neurological Disorder
12 BMJ, 2002 Communication Patients actively attempted to talk about the content of their psychotic symptoms in consultations. In response, doctors hesitated, responded with a question rather than with an answer, and smiled or laughed (when informal carers were present), indicating that they were reluctant to engage with patients' concerns about their psychotic symptoms.
13 Restricted Outcomes? Symptomatic recovery Delusions Hallucinations Cognition Motivation Mood Functional recovery Activities Social network Accomodation Personal recovery Experience of meaningful life being more than diagnosis
14 Wunderink et al, 2013, JAMA Psychiatr The Longterm AP Story
15 UHR literature UHR Literature: Interpretation
16 Fusar Poli et al, 2012 Transition Rate: Going Down?
17 What is an UHR Transition? psychosis 4 psychosis year transition rate: 20% 3 2 Anxiety / depression 1 Anxiety / depression 1 Fusar-Poli & Van Os, 2012
18 Psychopathology astrans-diagnostic Dimensions SCHIZ SzAFF DEPR ANX POP Cognition Affective dysregulation Psychosis UHR UHR?
19 Is Transition Relevant? To date, this is the longest follow-up study of an UHR sample. Poor functional outcome was associated with specific neurocognitive decrements, regardless of transition to psychosis.
20 Psychosis = Spectrum Schizophrenia 1% Any Psychotic Disorder 3.5% Psychotic Symptoms 7% (Non-clinical) Psychotic Experiences 15% Linscott & Van Os, Psychol Med, 2013
21 Psychosis as a Spectrum Psychotic experience Psychotic disorder Time
22 To Have An Open Mind Connectivity Slowing down
23 Slowing Down = Persistence = Flexibility
24 Prediction of Clinical Transition tipping point tipping point
25 Developmental Slowing Down Psychosis Level of psychosis Collip et al, Schiz Bull, 2008 Wigman et al, Schiz Bull, 2011 Cougnard et al, Psychol Med, 2007 Dominguez et al, 2010 Psychotic disorder Subclinical, schizotypal none birth adolescence adulthood old age
26 Mental Mechanism: Being Different
27 Persistence of Subthreshold Psychosis T0 Age yrs HAL / DEL ± 3000 T2 HAL / DEL 10 yr T3 HAL / DEL ± 2200 Psychotic disorder
28 Spauwen et al, Schizophrenia Research, 2003 Subthreshold Psychotic Experiences n=3024, aged yrs Cumulative Incidence Delusion 15.7% Hallucination 4.6%
29 Odd Ratio Persistence and Transition adolescents, aged years (EDSP). Expression of psychosis was assessed 4 times(t0 T3) over a period of 10 years. Clinical Outcome at T3 3 0 Dominguez et al, Schiz Bull, Level of Persistence over T0 -> T1->T2
30 Persistence and Transition: Mania % transition adolescents & young adults (EDSP). Expression of mania/depression was assessed 3 times(t1 T3) over a period of 10 years. Clinical Outcome at T3 0 Tijssen et al, Level of Persistence over T1 -> T2->T3
31 % Psychosis Persistence Psychosis Persistence and Environment Environmental load: cannabis + urbanicity + trauma Cohort 1 (n=7076; 3 years) Cohort 2 (n=3021; 10 years) Environmental load Cougnard et al, Psychol Med, 2007
32 Clustering people into diagnostic categories Connectivity S6 S5 S1 S4 S2 S3 S7 S8 Symptoms impacting on each other in relational Network or Interactome S5 S4 S7 S1 S3 S6 S2 S8 Correlated symptoms clustering in dimensions
33 Things Happen for a Reason in a Sequence Stress Stress Stress Insomnie Insomnie Insomnie Somber Hypomaan Paranoia Hartmann et al. Br J Psychiartry, 2013; Freeman et al. J Psychiatr Res 2010;44:
34 The Mood-Psychosis Network AETIOLOGY Perception TREATMENT Emotions Thought
35 van Rossum et al. Schizophrenia Bull 2011;37: ; Regeer et al. Psychol Med 2006;36: Connectivity Depression Psychosis 0,5 0,4 0,3 Effect size on psychotic experiences EDSP (n=3024) & NEMESIS (n=7076) Risk need for care 0,2 0,1 0 Number of depressive symptoms
36 Environmental Connectivity? EDSP=3021, interviewed 4 times over 10 years Depression Depression Trauma + Trauma excess Trauma relative risk: 1.91 Risk psychosis Risk psychosis Guloksuz et al, 2014
37 Environmental Connectivity? EDSP=3021, interviewed 4 times over 10 years Depression Depression Cannabis + Cannabis excess Cannabis relative risk: 3.76 Risk psychosis Risk psychosis Guloksuz et al, 2014
38 PSYCHOPATHOLOGY Affective Psychotic TIME S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10
39 PSYCHOPATHOLOGY Affective Psychotic TIME S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10
40 PSYCHOPATHOLOGY Affective Psychotic TIME S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10
41 PSYCHOPATHOLOGY Affective Psychotic TIME S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10 S1 S2 S3 S4 S5 S6 S7 S8 S9 S10
42 Mood Disorder and Subthreshold Psychosis EDSP Sample n=3021 / NEMESIS samples n= Psychotic disorder Delusions & Hallucinations: 80% Common mental disorder Delusions & Hallucinations: 30% General population Delusions & Hallucinations: 8%
43 Cross-dimensional Impact in MD Subclinical Mania NO IMPACT OUTCOME Subclinical Psychosis POOR OUTCOME Arch Gen Psychiatry, 2010
44 Psychotherapy and Sub-Psychosis in MD
45 Subclinical Psychosis and Mania and Outcome of Depression (n=120) Association with BDI SD improvement from baseline to FU 0.1 Week 8 Week 16 Week 26 Week 52 Week 104 Sub-Mania -0.1 Sub-Psychosis Wigman et al, Psychol Med, 2013 * Slower response * * Faster relapse
46 Ontogenesis Psychosis Hallucinatory Anomalies Genes Environment Delusional Meaning
47 Dutch G.R.O.U.P. Study Environmental exposures CASH interview psychosis 3-year follow-up Parents, n=919 Siblings, n=1057 Patients, n=1120 Controls, n=590
48 Ontogenesis Psychosis Hallucinatory anomaly Risk 0-100% Delusional Meaning 0 Sibling Control Smeets, Janssen & GROUP, submitted
49 Ontogenesis Psychosis Hallucinatory anomaly Risk? Delusional Meaning Trauma + Trauma - Smeets, Janssen & GROUP, submitted
50 Smeets et al, Schiz Bull, 2010 & Acta Psychiatr Scan, 2012 Hallucinatory-Delusional States: Outcome None Hal Del Hal+Del Depression 8.2% 24.7% 25.8% 39.7% Negative Sx 11.7% 15.4% 16.6% 21.5% 10-yr persistence 0.0% 14.2% 6.5% 33.1% Dysfunction % 35.8% 57.9% Caseness 1.2% 3.1% 7.0% 20.7% Help-seeking 0.1% 7.7% 8.7% 35.5%
51 Morrison et al, 2013 What is UHR Transition?
52 Psychosis is a Trans-Diagnostic Dimension
53 Daily Life Ambulatory Phenotypes Exercise sensitive Stress-reactive 24-hrs BP monitoring Preserved nocturnal dip
54 Zelfmonitoring en Zelfmanagement JAMA, 2014
55 How to capture affective states? Fluctuating affective responses to environment Experiment 1 Van Os et al, Nature, day
56 Experience Sampling Technology PsyMate I PsyMate II
57 Positive affect Voices Stress Negative affect Paranoia Company Beep 1 Experience Sampling Method (ESM) DAY 1 DAY 2 Beep 2 Beep 3 Beep 4 DAY 3 DAY 4 DAY 5 DAY 6 DAY X (day 4 in detail) Beep 5 Beep 6 Beep 7 Beep 8 Beep 9 Beep 10
58 Critical Slowing Down: Paranoia PATIENT A Level of Paranoia PATIENT B Level of Paranoia
59 Personal Prediction: n=1 RCT 0,4 Negative Affect Autocorrelation 0,35 0,3 0,25 0,2 0,15 0,1 0,05 Wichers et al, in prep 0
60 Prediction of Clinical Transition 30 days Mood AR(1) Van de Leemput et al, PNAS, 2014
61 Interventions at the HUB: MindMaastricht RCT Sample: 130 participants with mood disorders 6 days Experience Sampling Mindfulness Training Control 6 days Experience Sampling FU 6 months FU 12 months Geschwind et al, J. Consulting & Clinical Psychology, 2011
62 Positive Emotions Daily-Life Reward Intervention Flow of Daily Life
63 Positive Emotions PA Persistence over Time Flow of Daily Life
64 Selfmonitoring-Feedback-Treatment Lancet, 2011
65 Emotional resilience in depression: RCT Sample: 102 subjects with depression or residual symptoms PsyMate feedback TAU + PsyMate + feedback Baseline PsyMate Pseudo-intervention TAU + PsyMate Post PsyMate Control TAU Depressive symptoms FU 1,2,3 & 6 months Kramers et al, World Psychiatry, 2014
66 Results REMOD PsyMate Intervention Trial Control PsyMate only PsyMate + feedback Kramers et al, World Psychiatry, 2014
67 The Depression-Psychosis Network AETIOLOGY Perception TREATMENT Affect Thought
68 Precision Diagnosis in Psychiatry? Van Os et al, WORLD PSYCHIATRY, June 2013
69
70 Fin
71
72 Professional Guidelines Vroege Psychose Effect size CBT: Effect size medications:
73 Effect size CBT: Effect size medications: ES CBT: 0.4 ES meds: 0.2 ES CBT: 0.1 ES meds: 0.1 ES CBT: 0.8 ES meds: 0.2 ES CBT: 0.2 ES meds: 0.8
74 Traditional Biological Psychiatry Diagnosis Biological Test Kapur, Insel et al, Mol Psychiatry, 2012
75 Biology: hardware alterations? Lesions in the neural substrate
76 Mental: software alterations? maladaptive operating rules acquired by environmental programming
77 Van Os et al, Nature, 2010 Learned Environment: Top-down cortical processing Learning Expectation Representation social world Affectively meaningful Facts Motivation Interaction Actual Environment: bottom-up sensory input
78 Experimental Medicine Environment / Treatment Brain mechanisms G E Mind mechanisms Psychopathology
79 TCA: Stress Sensitivity Reducing or Reward-Repairing? 70 Depressed Patients Imipramine Placebo Baseline: ESM, HAMD Week 6: ESM, HAMD Wichers et al, Neuropsychopharmacology, 2009
80 effect negative activities on NA effect positive activities on PA Response contingent on change in reward change in stress-sensitivity in responders versus nonresponders after treatment (TCA or placebo) change in reward experience in responders versus non-responders after treatment (TCA or placebo) 0,25 0,1 0,2 0,15 0,1 0,05 non-responders responders 0,08 0,06 0,04 0,02 non-responders responders 0 baseline week 6 0-0,02 baseline week 6 χ2 = 0.27, B = 0.010, p = 0.6 χ2 = 10.1, B = 0.036, p = Wichers et al, Neuropsychopharmacology, 2009
81 ? Kapur, 2003
82 Mood Disorder and Subthreshold Psychosis EDSP Sample n=3021 / NEMESIS samples n= Psychotic disorder Delusions & Hallucinations: 80% Common mental disorder Delusions & Hallucinations: 30% General population Delusions & Hallucinations: 8%
83 Nature, 2010 Environmental Effects
84 Environmental Connectivity? EDSP=3021, interviewed 4 times over 10 years Depression Depression Urbanicity + Urbanicity excess Urbanicity relative risk: 2.46 Risk psychosis Risk psychosis Guloksuz et al, 2014
85 ESM dynamics underlying Psychotic Symptoms Wigman et al, PLoS ONE, 2013 Slowing Down Flexibility A 30 min t-1 60 min 90 min 30 min 60 min 90 min t t-1 t negative context B positive context trauma negative affect genes positive affect Paranoid state momentary transfer + Paranoid state Paranoid state momentary transfer Non-paranoid state 30 min t-1 60 min 90 min t 30 min 60 min 90 min t-1 t
86 Environmental Connectivity? EDSP=3021, interviewed 4 times over 10 years Depression Depression E + Excess relative risk E Risk psychosis Risk psychosis Guloksuz et al, 2014
87 MBCT impacts on PArelated momentary outcomes: RCT Geschwind et al, J. Consulting & Clinical Psychology, 2011
88 Wigman et al, PLos ONE, 2013 Childhood Trauma and Micro-level Momentary Persistence Non-Persistence phenotype: NO SYMPTOM Level of paranoia moment 1 moment 2 moment 3 moment 4 moment 5 moment 6 moment 7 Level of paranoia Persistence phenotype: SYMPTOM moment 1 moment 2 moment 3 moment 4 moment 5 moment 6 moment 7
89 Dynamics underlying Psychotic Symptoms Wigman et al, PLoS ONE, 2012 Persistence Non-transfer 30 min 60 min 90 min 30 min 60 min 90 min t-1 t t-1 t A negative context B positive context negative affect genes positive affect Paranoid state momentary transfer + Paranoid state Paranoid state momentary transfer Non-paranoid state 30 min 60 min 90 min t-1 t 30 min 60 min 90 min t-1 t
90 Critical Slowing Down: Stress-Sensitivity PATIENT A Level of NA Level of NA PATIENT B
91 Affective S1 S5 S2 S4 S6 S3 S10 S7 S8 Psychotic S9
92 Affective S1 S5 S2 S4 S6 S3 S10 S7 S8 Psychotic S9
93 Affective S1 S5 S2 S4 S6 S3 S10 S7 S8 Psychotic S9
94 Affective S1 S5 S2 S4 S6 S3 S10 S7 S8 Psychotic S9
95 Things Happen for a Reason in a Sequence Stress Stress Stress Insomnia Insomnia Insomnia Irritable Hypomanic Paranoid Hartmann et al. Br J Psychiartry, 2013; Freeman et al. J Psychiatr Res 2010;44:
96 Prediction of Clinical Transition tipping point tipping point
97 Momentary Transfer Dynamics PLoS ONE 2013
98 Paranoia Reduction in Paranoia Collip et al, PLoS ONE, 2013 Flow of Daily Life
99 Crucial Connection in the Psychosis Network Hallucinatory Experience Genes Environmen t Delusional Meaning
100 Dutch G.R.O.U.P. Study Parents, n=919 Siblings, n=1057 Patients, n=1120 Controls, n=590
101 Ontogenesis Psychosis Hallucinatory anomaly Risk 0-100% Delusional Meaning Cannabis + Cannabis - Smeets, Janssen & GROUP, in press
102 Ontogenesis Psychosis Hallucinatory anomaly Risk 0-100% Delusional Meaning Trauma + Trauma - Smeets, Janssen & GROUP, in press
103 An Open Mind
104 Psychosis as a Transdiagnostic Dimension COMMON MENTAL DISORDERS SCHIZ SzAFF DEPR ANX POP Psychosis
105 Ontogenesis Psychosis Hallucinatory anomaly Risk 0-100% Delusional Meaning Family history+ Family history - Smeets, Janssen & GROUP, in press
106 Years Weeks Episodic variation Symptom variation Low resolution, Nomothetic low intensity Hours Momentary variation High Idiographic resolution, high intensity
107 The Psychopathology Interactome Kendler et al, 2010; Borsboom et al, 2010; Goedkoop et al, 2013 Latent Construct Hallu Delusion Mood Motivation Cogn DSM5 schizophrenia
108 Trauma and Network Connectivity T I M E STRESS LOW MOOD ANXIETY AVOIDANCE PSYCHOSIS t0 t1 t 2 t3 t4 t5
109 Prediction of Clinical Transition 1 YEAR Van de Leemput et al, PNAS, 2014
110 Symptoms: spectrum of human variation Patient Nonpatient sub-symptoms psychosis negative anxiety depression
111 Network: Things Happen for a Reason Insomnia Low mood Error-prone (Adult) Stresssensitivity Early Trauma Paranoia Negative selfevaluation Hartmann et al. Br J Psychiartry, 2013; Freeman et al. J Psychiatr Res 2010;44:
112 Novel Diagnostic Approach Wigman et al. PLoS ONE 8(3): e doi: /journal.pone
113 Stages of Severity & Specificty Wigman et al, PLoS One, 2013 Stage 1 Stage 2 Stage 3
114 Classic Paradigm: Unsuccesful? DSM Cases (Super)normal controls Versus
115 Approximate Replication Sampling Test Processing Analyses Reporting Study 1 Replication 1 Replication 2 Replication 3 Maxwell, 2004
116 Dimensional Extended Phenotypes Threshold behavioural expression risk Disorder threshold Frequency Liability R D
117 Munich EDSP Study Young People T0 Age yrs HAL / DEL ± 3000 T2 HAL / DEL 10 yr T3 HAL / DEL ± 2200 Lieb, Isensee, Von Sydow & Wittchen, Eur. Add. Res., 2000
118 Spauwen et al, Schizophrenia Research, 2003 Subtheshold Psychosis: Aberrant Salience n=3024, aged yrs Cumulative Incidence Delusion 15.7% Hallucination 4.6%
119 Precision Diagnosis HUB Positive + event event Irritable Low Paranoia Van Os et al, World Psychiatry, 2013
120 The complexity of psychiatry Gene-environment interplay Extended phenotypes Diagnoses fuzzy sets
121 Mental Illnesses are Continua What is ill? well ill
122 Mental Illnesses are Continua What is ill? well ill
123 Symptoms and Subthreshold expression of liability Patient Nonpatient sub-symptoms psychosis negative cognitive depression
124 Stage of non-specific mental distress STRESS WORRY ANERGIA ANERGIA DYSPHORIA WORRY AVOLITION ANERGIA Early treatment ANXIOUS SLOW ABERRANT SALIENCE ANXIOUS LOW HALLUCINATIONS AVOIDANCE GUILT DELUSIONS LOW PANIC Stage of specific mental syndrome Van Os, Am J Psychiatry, 2013 Anxiety Syndrome Mood Syndrome Psychosis Syndrome
125 Van Os et al, Nature, 2010 Learned Environment: Top-down cortical processing Learning Expectation Representation social world Affectively meaningful Facts Motivation Interaction Actual Environment: bottom-up sensory input
126 mhealth Zelf-kwantificatie Technologie PsyMate I PsyMate II
127
128 Hoge resolutie zelfmonitoring Functionele reactiviteit Positievereactiviteit Depressieve reactiviteit Morgen Psychotische -reactiviteit Avond
129 Crucial Connection in the Psychosis Network Hallucinatory Experience Genes Environment Delusional Meaning
130 New Diagnostic Paradigms in Medicine Continuous ambulatory monitoring of: Blood pressure Muscle tone EEG Plasma glucose
131 Psychosis as a Transdiagnostic Dimension SCHIZ SzAFF DEPR ANX POP Psychosis Linscott & Van Os, 2010, 2013
132 Kessler, JAMA Psychiatry, 2010 Trauma and Anxiety/Depression CAs in a maladaptive family functioning (MFF) cluster (parental mental illness, substance abuse disorder, and criminality; family violence; physical abuse; sexual abuse; and neglect) were the strongest correlates of disorder onset CAs are associated with 44.6% of all childhood onset disorders and with 25.9% to 32.0% of lateronset disorders.
133 Smeets et al, Schiz Bull, 2010 & Acta Psychiatr Scan, 2012 Subthreshold Delusions and Hallucinations General Population Samples (NL, TUR, GER) Combined Hallucinations and delusions expected Combined Hallucinations and delusions observed 25 (1.0) 78 (3.1)
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