SHIP-Ergebnisse: Psychische Aspekte - Hans J. Grabe, 2020
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SHIP-Ergebnisse:
Psychische Aspekte
Hans J. Grabe, 2020
3 / 14.05.2020 Hans Grabe
4 / 14.05.2020 Blausen.com staff (2014)
Kortikale Dicke der grauen Substanz
bei Menschen mit Depression
Compared to adult HC, adults with
MDD showed lower cortical thickness
in the bilateral medial OFC, cingulate
cortex, insula and temporal lobes, but
no surface area alterations.
Schmaal et al., 2016
2018 6 / 14.05.2020
SHIP-LEGENDE
Zusammenhang von
Kindesmisshandlungen und Depression (F32.0-F33.3)
Childhood Trauma
Questionnaire Lebenszeitprä-
none-mild versus valenz
moderate-severe Prävalenz Depression OR
3.9
Emotionaler Missbrauch 3.8 % 45.2 %
(2.5-6.3)
2.1
Körperlicher Missbrauch 4.7 % 28.0 %
(1.3-3.3)
2.02
Sexueller Missbrauch 3.6 % 31.7 %
(1.3-3.3)
2.1
Emotionale Vernachlässigung 12.6 % 26.8 %
(1.6-2.8)
1.3
Körperliche Vernachlässigung 16.9 % 19.7 %
(1.1-1.8)
Missbrauch insgesamt: 9.0% Vernachlässigung insgesamt: 21.9%
7 / 14.05.2020
8 / 14.05.2020
Depression: •12-Monatsprävalenz: 8-12 % •Kosten: 106 mrd. € /Jahr in der EU
"Study of Health in Pomerania" (SHIP) Since 1997 (N=4310), SHIP-0,-1, LEGEND, -2, -3 Since 2007 (N=4421), SHIP-TREND -0, -1 10 / 14.05.2020
CHARGE*-Consortium on Depression
*Cohorts for Heart and Aging Research in Genomic
Cohort Anzahl Teilnehmer Instrument
Framingham Heart Study 4956 CES-D
Cardiovascular Health Study 3155 CES-D
Rotterdam Study 1 3791 CES-D
Rotterdam Study 2 2093 CES-D
ARIC1 393 CES-D
ARIC2 614 CES-D
ERF 1297 CES-D
InChianti 1052 CES-D
Health ABC 1654 CES-D
BLSA 764 CES-D
SHIP 1384 BDI-II
AGES 2855 GDS
MONICA/KORA3 1433 PHQ
MONICA/KORA4 1807 PHQ
ARIC 8918 Maastricht Questionnaire
Total incl. further samples 51258
Imputation to 2.4 mill SNPs according to standard methods.
Hek et al., Biol Psychiatry, 2013
Significance level: P1*10E-512 / 14.05.2020
Neuronal growth regulator 1 (NEGR1) is a
glycosylphosphatidylinositol-anchored
membrane protein that mediates neural
cell communication and synapse formation.
It influences axon extension and synaptic
plasticity in cortex, hypothalamus, and
hippocampus, and modulates synapse
formation in hippocampus via regulation of
neurite outgrowth. Association to BMI.
13 / 14.05.202014 / 14.05.2020
OLFM4 (olfactomedin 4) has diverse
functions outside the CNS including
myeloid precursor cell differentiation,
innate immunity, anti-apoptotic effects, gut
inflammation, and is over-expressed in
diverse common cancers. Many
olfactomedins also have roles in
neurodevelopment and synaptic function.
LRFN5(leucine rich repeat and fibronectin
type III domain containing 5) encodes
adhesion-like molecules involved in
synapse formation
15 / 14.05.2020There are independent associations with
major depression at both the 5’ and the 3’
ends of RBFOX1(1.7 Mb, RNA binding
protein fox-1 homolog 1). This
convergence makes it a strong candidate
gene. Fox-1 regulates the expression of
thousands of genes, many of which are
expressed at synapses and enriched for
autism-related genes.
16 / 14.05.202017 / 14.05.2020
18 / 14.05.2020 Hans Grabe
19 / 14.05.2020 Hans Grabe
20 / 14.05.2020 Hans Grabe
21 / 14.05.2020 Hans Grabe
Hans Grabe
23 / 14.05.2020
Multi-level Systems Approach
Psychische Erkrankung
Max Ernst (1926)
24Welche weiteren Risikofaktoren gibt es
und welches sind die Langzeitfolgen von
Kindesmisshandlung?
25 / 14.05.2020 Hans Grabe26 / 14.05.2020
Medical relevance - ACE Study
N=17337, Dong et al., 2004 Circulation 28 / 14.05.2020 Hans Grabe
Missbrauch und
Hirnstruktur
.
29 / 14.05.202030 / 14.05.2020
Women ≤ 65y abuse (emotional+ physical + sexual) ROI-Analysis significant gray matter (GM) decrease in: L Hipp/Parahipp: 709 Vx (p
Women ≤ 65y neglect (physical) ROI-Analysis significant gray matter (GM) decrease in: L Hippo/parahippo : 1246Vx 32 / 14.05.2020
Dysregulation of HPA-axis in
depressive disorders
Dysregulation of HPA-axis in depression especially in humans with
childhood maltreatment (Heim et al. 2004, 2008)
Nestler EJ, et al. Neuron 2002;34(1):13-25. Nestler 2002FKBP5 gene codes for FK506 binding protein 51
(FKBP5), a co-chaperone of hsp90 which
regulates the glucocorticoid receptor (GR)
sensitivity
TT-Genotype = relative cortisol resistance of target tissues (Binder, 2009)FKBP5 x childhood trauma - MDD (n=2157)
30
20
rs1360780
CC CT TT
odds ratio for MDD
2 3 4 5 6 7 89
1
Klengel et al., 2012
none/mild moderate/severe
physical abuse
Appel et al., 2011Abused/Non-abused: FKBP5 TT- versus CT/CC
Gene x Exposure
on brain
Abused n=319 non-abused n=1507
36 / 14.05.2020
Grabe et al., 2016Abuse:
FKBP5 TT-
versus
CT/CC
1886 voxels
L insula
L temporal pole, sup. gyrus
L hippocampus
L middle temporal gyrus
L superior temporal gyrus
L putamen
799 voxels
L olfactory cortex
R putamen
R hippocampus
R caudate nucleus
R pallidum
R amygdala
R
37 /olfactory
14.05.2020 cortex Grabe et al., 2016Multi-level Systems Approach Max Ernst (1926) 38
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