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

2. 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

3. 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

4. Childhood trauma and slower improvements rates over time in First-Episode psychosis65
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

5. 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.

6. P˂0.001 Age at onset Number of childhood trauma subtypes 28 25 23 2018
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?
Number of childhood trauma subtypes
Etain and Aas et al., Journal of Clin. Psychiatry. 2013

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

8. Age at onset Bipolar disorders
Aas, Psychological Medicine 2013

9. 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

10. 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

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

12. Champagne et al., 2009

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

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

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

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

18. 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

19. 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

20. 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., Prog Neuro. Biol Psychiatry.
8.50
8.00
Normal BDNF
Low BDNF
Val/Val Met carriers

21. 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,
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,
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,

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

23. Reduced resilience to stress in schizophrenia patients due to low neurogenesis  

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

27. 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!

28. Email: monica.aas@medisin.uio.no