Genes and trauma - shaping the brain towards psychopathology Monica Aas, Clinical psychologist, PhD Prinsiple investigator «stress under skin»

Genes, biological processes and trauma OUTLINE Childhood trauma and clinical features of schizophrenia and bipolar disorders; Genes, biological processes and trauma Main focus on this talk: BDNF and trauma

Church & Aas under review Childhood trauma in patients with a psychotic disorder and in healthy individuals Patients Childhood Trauma % Controls (Study, N=900) Cohens d=1.27 P<0.001 Church & Aas under review

Childhood trauma and slower improvements rates over time in First-Episode psychosis 65 No Trauma N=46 60 GAF score Trauma N=43 55 50 Aas, M et al.2016 BMC Psych 45 Baseline 1 year follow-up Time-Point: p˂0.001; Trauma: p=0.002; Interaction (Time X Trauma): p=0.005

PANSS positive symptoms (FEP) 16 No Trauma N=46 15 Positive symptoms 14 Trauma N=43 13 12 11 10 Baseline 1 year follow-up Time-Point: p˂0.001; Trauma: p=0.008;Interaction (Time X Trauma):N.S.

P˂0.001 Age at onset Number of childhood trauma subtypes 28 25 23 20 18 Det vi ser her, er hvordan det å ha opplevd barndomstraumer henger sammen med debutalder for bipolar lidelse. Her har en undersøkt ulike former for barndomstraumer, og delt dette inn i 3 kategorier, f.eks. fysiske traumer, emosjonelle traumer og seksuelle traumer. De som ikke hadde opplevd barndomstraumer, hadde en gjennomsnittlig debutalder på ca. 26 år. De som hadde opplevd en form for barndomstraumer, hadde en debutalder på straks under 23 år, mens for de som hadde opplevd 3 ulike former for traumer hadde en debutalder på ca. 20 år. Debut-aldersforskjellen var altså ca. 7 år for de som hadde opplevd mange former for traumer og de som ikke hadde opplevd traumer i det hele tatt. Alternative forklaringer? 0 1 2 3 Number of childhood trauma subtypes Etain and Aas et al., Journal of Clin. Psychiatry. 2013

% Frequency cannabis abuse % Childhood abuse=0 N=366 Childhood abuse=1 Aas, Psychological Medicine 2013

Age at onset Bipolar disorders Aas, Psychological Medicine 2013

Childhood trauma and affective lability CTQ / Affective Lability Scale (ALS) Affective Lability Scale (ALS)   N ALS-18 total score Total trauma 343 r=0.26, p˂0.001 Physical abuse r=0.04, p=0.45 Sexual abuse r=0.22, p˂0.001 Emotional abuse Emotional neglect r=0.20, p˂0.001 Physical neglect r=0.11, p=0.04 Aas M Psychological Medicine, 2016

Patients with Childhood Trauma reported Positive Faces as less positive, p=0.05 Cohens d=0.2 Patients with Childhood Trauma reported Negative Faces as more negative, p ≤0.01; Cohens d=0.8 Aas, M et al., Psych Med 2016

Early stress/ Childhood trauma Clinical features and behavior Genes Cells Brain Mainly animal studies

Champagne et al., 2009

Stress vulnerabilty in schizophrenia? Do patients with schizophrenia have compromised stress «buffers»?

Reduced BDNF in serum in schizophrenia compared to healthy controls Aas et al, In progress

Reduced BDNF RNA levels in schizophrenia following childhood neglect Aas,M., et al., 2014

  Reduced resilience to stress in SZ and BD due to high levels of childhood trauma and low BDNF

BDNF RNA Levels, BDNF val66met and trauma p=0.008 Double hit Normal BDNF Low BDNF Low BDNF Val/val carriers BDNF val66met Met carriers BDNF val66met No trauma Met carriers BDNF val66met + trauma Aas et al 2014

CA2-3 region, BDNF val66met and trauma p=0.02 Double hit Normal BDNF Low BDNF Low BDNF Val/val carriers BDNF val66met Met carriers BDNF val66met No trauma Met carriers BDNF val66met + trauma Aas et al 2014

BDNFval66met, sexual abuse and sMRI 10.00 Log lateral ventricle ≤ trauma median score > trauma median score 9.50 p=0.003 9.00 Aas,M., et al., 2013. Prog Neuro. Biol Psychiatry. 8.50 8.00 Normal BDNF Low BDNF Val/Val Met carriers

Childhood trauma is associated with lower cognitive performance Aas, M., Dazzan, P., Fisher, et al., (2011). Childhood trauma and cognitive function in first-episode affective and non-affective psychosis. Schizophr Res 129, 12-9. Aas, M., Dazzan, P., Mondelli, V., et al., (2014). A Systematic Review of Cognitive Function in First-Episode Psychosis, Including a Discussion on Childhood Trauma, Stress, and Inflammation. Front Psychiatry 4, 182. Aas, M., Haukvik, U. K., Djurovic, S., et al., (2013). BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses. Prog. Neuropsychopharmacol. Biol. Psychiatry 46C, 181-188. Aas, M., Navari, S., Gibbs, A., Mondelli, V. et al., (2012a). Is there a link between childhood trauma, cognition, and amygdala and hippocampus volume in first-episode psychosis? Schizophr. Res 137, 73-79. Aas, M., Steen, N. E., Agartz, I., et al., (2012b). Is cognitive impairment following early life stress in severe mental disorders based on specific or general cognitive functioning? Psychiatry Res 198, 495-500

Cognitive impairments in First-Episode Psychosis Aas, Frontiers, 2014

Reduced resilience to stress in schizophrenia patients due to low neurogenesis  

Reduced resilience to stress in SZ due to compromised habituation to stress

Thank you for your attention! Acknowledgement Funding: Stress under skin, South-Eastern Norway Health Authority, NARSAD and SCNP Young Scientist award to M Aas. Thanks to: The researchers at NORMENT Thank you for your attention! Monica.aas@medisin.uio.no

Email: monica.aas@medisin.uio.no