Genes and trauma - shaping the brain
towards psychopathology
Monica Aas, Clinical psychologist, PhD
Prinsiple investigator «stress under skin»
OUTLINE
• Childhood trauma and clinical features
of schizophrenia and bipolar disorders;
• Genes, biological processes and trauma
Main focus on this talk: BDNF and
trauma
Childhood trauma in patients with a
psychotic disorder and in healthy individuals
Childhood
Trauma %
Patients
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
60
GAF
score 55
50
45
Baseline
No Trauma
N=46
Trauma
N=43
Aas, M et al.2016
BMC Psych
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
15
Positive
14
symptoms
13
12
11
10
No Trauma
N=46
Trauma
N=43
Baseline
1 year follow-up
Time-Point: p˂0.001; Trauma: p=0.008;Interaction (Time X Trauma):N.S.
Figure 1. Age of onset in years (mean) and childhood abuse
28
Age at onset
25
p˂0.001
P˂0.001
23
20
18
0
1
2
3
Number of childhood trauma subtypes
Etain and Aas et al., Journal of Clin. Psychiatry. 2013
Frequency cannabis abuse %
%
Childhood Childhood Childhood Childhood
abuse=0
abuse=1 abuse=2 abuse=3
N=366
N=113
N=60
N=22
Aas, Psychological Medicine 2013
Childhood trauma and affective lability
CTQ / Affective Lability Scale (ALS)
N
ALS-18 total
Affective Lability Scale (ALS)
score
Total trauma
343 r=0.26, p˂0.001
Physical abuse
Sexual abuse
Emotional abuse
Emotional neglect
Physical neglect
343
343
343
343
343
r=0.04, p=0.45
r=0.22, p˂0.001
r=0.22, p˂0.001
r=0.20, p˂0.001
r=0.11, p=0.04
Aas M Psychological Medicine, 2016
9
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
Mainly animal studies
Brain
Stress vulnerabilty in schizophrenia?
• Do patients with schizophrenia have
compromised stress «buffers»?
Reduced BDNF in serum in schizophrenia
compared to healthy controls
p=0.004
Aas et al, In progress
Reduced BDNF RNA levels in schizophrenia
following childhood neglect
p=0.009
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
Normal BDNF
Val/val carriers
BDNF val66met
Aas et al 2014
Double hit
Low BDNF
Low BDNF
Met carriers
Met carriers
BDNF val66met BDNF val66met
+ trauma
No trauma
CA2-3 region, BDNF val66met and trauma
p=0.02
Normal BDNF
Low BDNF
Val/val carriers
Met carriers
BDNF val66met
BDNF val66met
No trauma
Aas et al 2014
Double hit
Low BDNF
Met carriers
BDNF val66met
+ trauma
BDNFval66met, sexual abuse and sMRI
10.00
Log lateral ventricle
9.50
p=0.003
9.00
> trauma median score
Aas,M., et al., 2013.
Prog Neuro. Biol
Psychiatry.
8.50
8.00
≤ trauma median score
Normal BDNF
Val/Val
Low BDNF
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
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!
[email protected]
Email: [email protected]
Oslo universitetssykehus HF
Klinikk psykisk helse og avhengighet
Seksjon for psykoseforskning/TOP
Ullevål sykehus, bygg 49
P.O. Box 4956 Nydalen
NO-0424 Oslo
Norway