Experience in context. Mood. Psychotic Symptoms Daily stress. Daily stress

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1 Experience in context Psychotic reactivity to stress: Linking phenomenology, biology and genetics Inez Myin-Germeys Prof. of Ecological Psychiatry Center for Contextual Psychiatry The Experience Sampling Method Beep 1 Emotional Reactivity to stress Beep 2 DAY 1 Beep 3 DAY 2 DAY 3 DAY 4 (day 4 in detail) DAY 5 DAY 6 Beep 4 Beep 5 Beep 6 Beep 7 Daily stress Mood ü 10 times a day Beep 8 ü 6 consecutive days ü at random moments Beep 9 Beep 10 Myin-Germeys et al, 2009; Wichers et al., 2009; Delespaul, 1995 Emotional reactivity to daily life stress Direct effect on psychosis? 42 Patients, β=0.22 Negative affect 47 Relatives, β=0.09 Daily stress Psychotic Symptoms 49 Controls, β=0.05 STRESS Myin-Germeys et al., Arch Gen Psych

2 Biological reactivity to daily life stress? Activity-related stress and psychosis Psychosis intensity Patients, β= Relatives, β=0.16 Controls, β= Increase in activity-related stress Myin-Germeys et al., Psych Med 2005 Cortisol and psychosis? Cortisol reactivity in daily life Blunted awakening response stress Increased cortisol level mood symptoms Role of Antipsychotic medication Cortisol levels over the ESM sampling moments Cortisol Cortisol Reactivity to daily stress mean cortisol, nmol/l In healthy siblings 3,5 3,4 3,3 3,2 3,1 3 2,9 2,8 2,7 2,6 * Daily stress Cortisol 1 controls siblings Collip et al., Psych Med,

3 cortisol levels Cortisol reactivity to stress momentary symptoms Cortisol Cortisol Psychotic symptoms Negative affect subjectively appraised stressfulness of event p=0.03 p=0.004 p= Collip et al., Psych Med 2012 Collip et al., Psych Med, 2011 HPA-axis -> increased stress-reactivity? Pituitary volume 20 patients, 38 healthy siblings, 33 controls The pituitary? Pituitary volume Controls (n=32) Siblings (n=37 Patients (n=20) β = P = 0.69 Habets et al., Psych Med, 2012 Pituitary volume & emotional stress-reactivity Emotional stress-reactivity and pituitary volume 20 patients, 38 healthy siblings, 33 controls Emotional stress-reactivity 0.45 negative affect Controls Siblings Patients Daily hassles Emotional reactivity to stress 0.40 Low volume Medium volume High volume P=0.00 Habets et al., Psych Med,

4 HPA-axis -> increased stress-reactivity? Group differences in hippocampal volume The hippocampus? 20 patients, 38 healthy siblings, 33 controls * * * Collip et al., Psych Med, 2013 Hippocampal volume and emotional stress-reactivity Emotional stress-reactivity & hippocampal volume 20 patients, 38 healthy siblings, 33 controls Daily hassles negative affect Emotional reactivity to stress Collip et al., Psych Med, 2013 Hippocampal volume and Biological stress-reactivity Biological stress-reactivity (cortisol) 38 healthy siblings, 33 controls cortisol Daily hassles Biological reactivity to stress Collip et al., Psych Med,

5 Montreal Imaging Stress Task Dopamine, stress, and psychosis Psychosis Stress Psychosis & Stress hyper hypo Pruessner et al., 2004, Am J Psych Dopamine & stress in humans Stress task associated with: Dopamine & stress in siblings High stress PsychoEc reacevity to stress and vmpfc dopamine Prefrontal dopamine release controls relatives Lataster et al., Neuromage 2011, Schiz Bull 2014 Lataster et al., Schiz bull, 2014 Dopamine & stress in siblings Stress-reactivity Hernaus et al., J Abn Psychol,

6 And now in unmedicated patients? And now in unmedicated patients? Hernaus et al, TranslaEona Psychiatry, 2015 Hernaus et al, TranslaEona Psychiatry, 2015 So,. What about genes?? Psychosis hyper hypo Negative affect Hallucinations Hallucinations Delusions Stress Delusions Caspi et al, 2005 Candidate gene: Catechol-O-methyltransferase gene Stress and psychosis: ESM function in the DA neurotransmission In 31 patients & 25 controls Val Val Met Val Met Met COMT High activity homozygote COMT Advantage in processing of aversive stimuli Egan et al., 2001, Stein et al., 2006, Mier et al., 2010 COMT Low activity homozygote Advantage in memory and attention tasks Effect size of event stress on NA breakdown of dopamine (particularly PFC) Van Winkel et al, Am J Med Genet B

7 Stress and psychosis: ESM In 90 patients & 127 controls Met/Met 0,8 Val/Met Val/Val 0,6 0,4 0,2 le as a an t np Ve ry u le as Un p nt an t ea s ra l Bi t un pl Ne ut pl - 0,2 ea s nt an t 0 Bi t P = 0.002; χ2 = 16.9 Pl ea sa Effect size of event stress on NA Stress and psychosis: ESM Collip et al., CNS 2011 Collip et al., CNS 2011 Stress and psychosis: experimental Stress and psychosis: experimental approach In 14 sibs and 12 healthy controls Negative affect Hallucinations Hallucinations Delusions Stress Delusions Hernaus et al, Plos One 2013 Stress and psychosis: experimental approach In 14 sibs and 12 healthy controls Experience in context Hernaus et al, Plos One

8 Centre for Contextual Psychiatry Prof. Ruud van Winkel Dr. Uli Reininghaus Dr. Martine van Nierop Dr. Maude Schneider Zuzana Kasanova Thomas Vaessen Annelie Klippel Henrietta Steinhart Yori van der Steen Maastricht University Prof. Therese van Amelsvoort Ass. Prof. Wolfgang Viechtbauer Dr. Machteld Marcelis Dr. Johan Lataster Dr. Dina Collip Dr. Dennis Hernaus University of Montreal, Canada Prof. Jens Pruessner Dr. Linda Booij KU Leuven Prof. Koen van Laere Dr. Jenny Ceccarini University of Aachen Prof. Felix Mottaghy Dr. Alexander Winz 8