Het plastische OCD brein: nieuwe aanknopingspunten voor preventie, vroeginterventie en innovatieve therapieën
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1 Het plastische OCD brein: nieuwe aanknopingspunten voor preventie, vroeginterventie en innovatieve therapieën Prof.dr. Odile A. van den Heuvel Psychiater VUmc
2 Emotional paradigms in OCD: Meta-Analysis dirt 23 studies focusing on emotional processing in OCD 9 symptom provocation (images) 6 emotional faces (images) 8 other (written symptom provocation/cognitive-emotional tasks) Total number of OCD patients: 514 Total number of healthy controls: 512 OCD > HC Increased activation in: bilateral amygdala symptom provocation > other paradigms unmedicated patients > medicated patients right putamen medicated patients > unmedicated patients subgenual ACC / OFC Thorsen et al., Biol Psych CNNI (in press)
3 Prediction Treatment Response Resting state fmri may be a useful tool in the future to predict response to CBT in OCD patients Higher degree centrality (= the number of links incident upon a node) in right basolateral amygdala predicts better response to CBT. Gottlich et al. 2015, Biol Psychology
4 pre-sma Hyperactivity in OCD + Siblings Stop Signal Task X SJ de Wit et al., 2012, Am J Psychiatry
5 dlpfc Hyperactivity/Inefficiency in OCD + Siblings N-back Task FE de Vries*, SJ de Wit* et al., 2014 Biol Psychiatry
6 Impaired Cognitive Reappraisal emotion regulation: main effect over all subjects (N=81) and all stimuli Contrast: fear regulate > attend p<.001, whole-brain uncorrected S.J. de Wit et al., 2015 Psychol Med
7 OCD Brain Imaging Consortium (OBIC) N=412 OCD N=368 controls GM: decreased volume: - dorsomedial PFC - IFG/insula increased volume: - cerebellum WM: decreased volume: - prefrontal WM - thalamus de Wit et al. 2014, Am J Psychiatry
8 Meta-analysis across Psychiatric Disorders N=193 studies = subjects 6 disorders: - Schizophrenia - Bipolar disorder - Major depressive disorder - Addiction - OCD - Anxiety Goodkind et al. JAMA Psych, 2015
9 Group x Age interactions effects in Striatum and Hippocampus In OCD patients (with increasing age): preservation of striatal volume more pronounced hippocampus volume reduction de Wit et al. 2014, Am J Psychiatry / Fouche et al Br J Psychiatry
10 Meta-analysis across Anxiety Disorders SDM Signed Differential Mapping Radua et al. Arch Gen Psych, 2010
11 From Anxiety to Compulsivity obsessive-compulsive spectrum disorders OCD and other anxiety disorders increased ventral circuit emotion / motivation decreased dorsal circuit cognition compulsivity control emotion regulation executive function
12 ENIGMA ENIGMA-OCD working group OCD Working Group
13 ENIGMA-OCD ENIGMA-OCD working group Subcortical Meta-Analysis - Adults Boedhoe et al (Am J Psychiatry)
14 ENIGMA-OCD ENIGMA-OCD working group Subcortical Meta-Analysis- Children Boedhoe et al (Am J Psychiatry)
15 ENIGMA-OCD ENIGMA-OCD working group Subcortical Volume OCD pallidum HC thalamus OCD HC
16 ENIGMA-OCD ENIGMA-OCD working group Cortical Meta-Analysis Adults (medicated OCD < controls) Boedhoe et al. 2018, Am J Psychiatry Decreased cortical thickness in frontal and temporal areas (d - 0.2, P FDR < 0.05)
17 ENIGMA-OCD ENIGMA-OCD working group Cortical Meta-Analysis Children (medicated OCD < controls) Boedhoe et al. 2018, Am J Psychiatry Decreased surface area in frontal, parietal, cingulate and occipital regions (d - 0.3, P FDR < 0.05)
18 ENIGMA-OCD ENIGMA-OCD working group Effects Medication Boedhoe et al., 2018 Am J Psych Med+ OCD (N=646) vs HC (N=1436) Unmed OCD (N=831) vs HC (N=1436) corticale dikte in frontale, temporale, parietale, en occipitale regio s Geen groepsverschil
19 Oorzaak versus Gevolg cause consequence early neurodevelopment neuroplastic changes due to chronic symptomatology and therapeutic interventions disease onset
20 Phenotype over the Lifespan anxiety compulsivity inhibition uncertainty obsessions goal-directed compulsions habits
21 Modellen voor OCD van den Heuvel et al. 2016, Eur Neuropsychopharmacology
22 Project 1 Global OCD project (funded by NIMH) PI: H. Blair Simpson, Columbia University, New York, USA PI Netherlands: Odile van den Heuvel Role NL: 1 of 5 sites worldwide, coordination of imaging PhD student: Niels de Joode Project members NL: Ton van Balkom, Neeltje Batelaan, Petra Pouwels, Chris Vriend, Merijn Eikelenboom Aim: to identify reproducible neuroimaging signatures those distinguish cognitive and clinical profiles of OCD Design: multi-center harmonized data-collection on clinical phenotype, neurocognitive profile and neuroimaging markers in 250 OCD patients, 250 healthy controls and 125 unaffected siblings Start: January 2018
23 Project 1 Global OCD project (funded by NIMH) Inclusion criteria: Ages Current DSM-5 criteria for OCD, with both obsessions and compulsions; OCD is the principal psychiatric problem (YBOCS score 16); Not on psychotropic medication (for at least 6 weeks; benzodiazepines / sleeping medication at least 1 week) No current cognitive behavioral therapy (exposure in vivo with response prevention) for their OCD symptoms (last 6 weeks) Project participation: 3 days assessment (2 clinical assessments and 1 MRI session) within 2 weeks time + 1 FU measurement (questionnaires only) More information: Niels de Joode > n.dejoode@vumc.nl
24 Aanknopingspunten voor Innovatie prevention Emotion regulation training limit chronicity Concentrated ET Neuromodulation (rtms/tdcs/dbs/surgery) early and effective treatment Prediction treatment response
25 Based on Gogtay et al. PNAS 2004;101: The dorsal prefrontal cortex (as part of the dorsal cognitive control circuit) is the last part of the brain reaching mature state. Brain Development
26 Project 2 Generation R (funded by NWO-ZonMW vidi) PI: Odile van den Heuvel PhD student: Cees Weeland Project members: Tonya White, Henning Tiemeier, Manon Hilligers Aims: > Identify the neural correlates of impaired cognitive control and early OCD symptoms in children > Identify the pre/perinatal environmental factors contributing to vulnerability and resilience Design: longitudinal design within Generation R study Start: May 2018 Inclusion: data already collected
27 Environmental and Genetic factors in Brain Development Generation R cohort Planned analyses in Generation R study (Rotterdam, The Netherlands), population-based birth cohort N>9000 pregnant women, N=350 children scanned at 6-8 yr, N>5000 children scanned at age 10 yr
28 Aanknopingspunten voor Innovatie prevention Emotion regulation training limit chronicity Concentrated ET Neuromodulation (rtms/tdcs/dbs/surgery) early and effective treatment Prediction treatment response
29 Project 3 7Tesla MRI (funded by NWO-ZonMW vidi) PI: Odile van den Heuvel PhD student: Niels de Joode Project members: Chris Vriend, Anouk Schrantee, Ton van Balkom, Chaim Huyser Aim: to understand the variation in thalamus and pallidum volume during the different stages of development and disease and how this relates to fluctuations in glutamate concentration. Design: cross-sectional lifespan approach, using high-resolution (7 Tesla) structural MRI (regions-of-interest: thalamus and pallidum) combined with dynamic MRS to measure state-dependent fluctuations in glutamate concentration and brain activation Start: mid 2018 Inclusion: broad range in developmental age (10-55 yr) and disease duration
30 Project 4 Inference Based Approach (funded by NWO) PI: Henny Visser (GGZ Centraal) PhD students: Emma Koenen (imaging) & Nadja Wolf (clinical) Project members: Ton van Balkom, Harold van Megen, Odile van den Heuvel, Patricia van Oppen Aim: who responds best to what? Design: multi-center randomized controlled non-inferiority trial comparing 20 sessions CBT to 20 sessions IBA with pre-posttreatment MRI Start: Autumn 2018 Inclusion: 200 OCD patients
31 Project 5 Intensive Exposure Therapy (funded by Norwegian grant) PI: Gerd Kvale & Bjarne Hansen (Bergen, Norway) PhD student: Anders Lillevik Thorsen Project members: Odile van den Heuvel, Stella de Wit, e.a. Question: which neural biomarkers predict good treatment response and maintained remission? Design: pre-post intensive ET MRI + 3 months FU MRI Start: data collection completed ( ) Analyses starting ( )
32 Aanknopingspunten voor Innovatie prevention Emotion regulation training limit chronicity Concentrated ET Neuromodulation (rtms/tdcs/dbs/surgery) early and effective treatment Prediction treatment response
33 Transcranial Magnetic Stimulation
34 Modulation Treatment Response Controls: Low-frequency rtms vs. placebo (= inhibition) OCD patients: High-frequency rtms vs. placebo (= stimulation) Emotion / Motivation Cognition Ventral ventral frontal-striatal & limbic circuits Dorsal dorsal frontal-striatal circuit
35 repetitive Transcranial Magnetic Stimulation (rtms) day 1 fmri during emotion regulation paradigm version 1 SPM: Single subject analysis reappraise > attend stimulation coordinates day 2 20 min rtms treatment fmri during (1 Hz, 10 Hz or sham) emotion regulation paradigm using neuronavigation version 2 a.s.a.p. repeated measures analyses day 1 versus day 2, 1 st level 2 nd level group analysis
36 Effect of rtms on Habituation OCD patients: Sham: No decrease in state anxiety (day 2 vs day 1) in response to exposure 10 Hz DLPFC: Decreased state anxiety at day 2 (habituation) controls: Sham: Decreased state anxiety at day 2 (vs day 1) in response to exposure 1 Hz DLPFC: Less habituation S.J. de Wit et al., 2015, Psychol Med
37 Project 6 Transcranial Magnetic Stimulation (funded by NWO-ZonMW vidi) PI: Odile van den Heuvel PhD student: Sophie Fitzsimmons Project members: Ysbrand van der Werf, Dilene van Campen, Neeltje Batelaan Aim: to compare the mechanisms of effect between two different stimulation protocols, i.e., targeting the dorsal cognitive control circuit (DLPFC-rTMS) and the sensorimotor circuit (SMA-rTMS) to determine the role of glutamate in the rtms-induced changes to establish the effects of rtms on the ability to profit from behavioural therapy (exploratory analysis) Design: RCT (3 stimulation conditions) with pre-post EEG and MRI low-frequency SMA-rTMS (n=25), high-frequency DLPFC-rTMS (n=25), and placebo stimulation (n=25) Start: Summer 2018 Inclusion: 75 adult OCD patients who did not respond sufficiently to behavioural therapy and medication.
38 Acknowledgements Info: Global OCD Project Columbia University, New York, USA: H. Blair Simpson and team VU university medical center, Amsterdam, NL: Odile van den Heuvel and team NIMHANS, Bangalore, India: Janardhan Reddy and team Sao Paulo, Brazil: Euri Miguel and team Cape Town, South Africa: Dan Stein and team Funding: NIMH (R01MH ) Section Neuropsychiatry, Vumc, Amsterdam Ysbrand van der Werf, Chris Vriend, Dilene van Campen, Kathleen Thomaes, Hein van Marle, Stella de Wit, Froukje de Vries, Sonja Rutten, Premika Boedhoe, Tim van Balkom, Ires Ghielen, Merijn Joling, Christa van der Heijden, Inga Aarts, Niels de Joode (NIMH / 7 Tesla MRI-MRS), Sophie Fitzsimmons (TMS), Emma Koenen (IBA), Cees Weeland (Generation R) In collaboration with GGZinGeest (Ton van Balkom, Neeltje Batelaan, Merijn Eikelenboom, Patricia van Oppen, Aartjan Beekman, Jan Smit, Brenda Penninx), GGZ Centraal (Henny Visser) and NOCDA. The OCD Team, Bergen, Norway Gerd Kvale, Bjarne Hansen, Anders Likkevik Thorsen Lifespan approach in OCD In collaboration: Generation R (Tonya White, Henning Tiemeier, Manon Hilligers), Spinoza centrum (Anouk Schrantee). Funding: NWO ZonMW VIDI ( ) ENIGMA: Paul Thompson (PI ENIGMA), Neda Jahanshad Derrek Hibar, Lianne Schmaal & Dick Veltman ENIGMA OCD working group: Dan Stein (co-chair), Premika Boedhoe + collaborators from >30 sites (Netherlands, UK, Sweden, Spain, China, Korea, Japan, Brazil, South Africa, Switzerland, USA, Canada, India, Italy, Germany) Funding ENIGMA: 1. NIH: BD2k (Big Data) U54 EB Neuroscience Campus Amsterdam (NCA)
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