Download Molecular genetics in psychological science: personality

Molecular genetics in
psychological science:
personality and beyond
Prof. Dr. Christian Montag
Department of Molecular Psychology
Institute of Psychology and Education
Ulm University, Ulm, Germany
Talk at the University of Belgrade, Serbia
22nd October 2015
Genetics play a crucial
role in human behavior …
Polderman et al. (2015), Nature Genetics
frequency
frequency
Many genetic variations influence
complex psychological phenotypes
low
Openness to Experience
high
Openness to Experience
Today’s talk …
… demonstrates that personality psychology
in combination with molecular genetics is interesting
for a lot of (clinical) research fields!
Apolipoprotein Genetics,
Personality
and Cognition
Oxytocin Genetics,
Personality and
Social Cognition
2/3
1/3
First, some
introductory words.
Some word on Dementia
•
Degenerative disorder of the human brain with
short comings in the areas of short term
memory, language and motoric skills, but also
changes in personality.
•
Besides the most well known form, namely
Alzheimer’s, there are several additional forms
of other dementias. Alzheimer’s is with 50-60%
the most important form of dementia.
Alois Alzheimer
•
Latin: Morbus Alzheimer
(morbus = disease)
•
1901 Alois Alzheimer
described the first case of this
disease. The patient was 50
year old Auguste Deter.
•
Two forms of Alzheimer’s are
known: the familial form of
Alzheimer’s (presenile, also
called ‚real’ Alzheimer‘s) and
the late sporadic occurring
form of Alzheimer’s (senile
form of Alzheimer’s)
Alois Alzheimer (1864-1915)
Symptoms of Alzheimer’s
•
Decline of cognitive functions (in
particular cognitive functions in
the area of memory and
language)
•
(Profound) problems in everyday
life
•
Changes in drive and affect (in
response to recognizing one’s
own deficits)
•
Brain scans show reductions in
parietal- and temporal lobes, in
the CSF one observes amyloid
plaques and tau proteins
Bild von
http://nursebuddy.co/living-with-somebody-who-has-alzheimers-disease-7-tips-for-family-carers/
Epidemiology of
Alzheimer’s disease
•
Currently 1.2 million Germans suffer
from Alzheimer’s.
•
In year 2050 about 3 million will
suffer from Alzheimer’s in Germany.
•
Every year about 200.000 patients
get the diagnosis of Alzheimer’s.
•
About 70% of dements are helped
by their families at home.
•
There is still no cure for Alzheimer’s.
Beyreuther et al. (2002), Demenzen (S. 23)
Amyloid Precursor Protein
•
•
APP is an impor tant par t of the
membrane.
APP exerts neuroprotective effects (by
strengthening neurotrophic activity), the
molecular mechanism are not completely
understood until now.
•
APP is split by the enzymes α- und βsecretase.
•
Reduction of α- and increase of βsecretase are associated with an
increase of amyloid derivates with
neurotoxic potency.
•
β-amyloid plaque can be observed first
in the isokortex of Alzheimer patients,
later on in the hippocampus.
Split by enzyme gamma (2)
resulting in A beta 42
A
be
ta
42
42 42
4
42 2
42
Plaques (3)
Split by enzymes
alpha and beta (1)
Cell Membran
A
P
P
10-15 years before the onset of Alzheimers an
aggregation of β-amyloid plaques at the outer
parts of nerve cells can be observed.
So, let’s move to
molecular genetics
APOE polymorphism(s)
taken from http://www.athero.org/images/comm340.jpg
Apolipoprotein E
•
ε4 variation of the APOE gene is a risk factor for both early
and in particular late Alzheimer’s!
•
The gene product APOE plays a crucial role as a
lipidtransporter protein in the catabolism of membrane
lipide aswell as regulator in cholesterine uptake!
•
In late Alzheimer disease the onset of Alzheimer’s is
reduced in term of years for each copy of ε4 years by 5-9
years.
•
The ε4 variation is associated with higher plaques of
βA4 molecules.
Risk to get Alzheimer’s depending
on the APOE genotypes
Geno-
type
ε2/ε2
ε2/ε3
ε2/ε4
ε3/ε3
ε3/ε4
2.6 times
3.2 times
Disease
40% less 40% less
average
more
more
Risk
likely
likely
risk
likely
likely
ε4/ε4
14.9
times
more
likely
Numbers from http://www.alzdiscovery.org/cognitive-vitality/what-apoe-means-for-your-health
But APOE genetics alone …
Mayeux et al. (1998), New England Journal of Medicine
APOE and intelligence
•
„The more common rs429358
allele is (T). If the allele is (C)
and the same chromosome
also harbors the rs7412(C)
allele, the combination is
known as an APOE-ε4
allele.“ (Source SNPedia)
•
Results from a GWAS study by
Davies et al. (2015) indicate
that one SNP of the well known
APOE polymorphism
combination is associated with
i n d i v i d u a l d i ff e re n c e s i n
cognitive functions
Dar-Nimrod et al. (2012), American Journal of Geriatric Psychiatry
If APOE4 + Neuroticism/
Extraversion is a risk constellation
for cognitive decline in elderly
persons …
Getting the gene samples and personality
screening from a large adolescent sample
29.10.2013 in Bonn.
Bernd Lachmann
Rayna Sariyska
23.11.2013 in Bonn.
Diagnostics of late onset Alzheimer
genetics and personality
N = 531 participants
(n = 172 males, n = 358 females)
mean-age: 21.57, SD = 3.50
All persons filled in NEO-FFI.
Genotype distribution was in HWE: χ2 = 3.537, df = 3, p > 0.05
Geno-
type
ε2/ε2
ε2/ε3
ε2/ε4
ε3/ε3
ε3/ε4
ε4/ε4
Numbers
6
63
7
351
96
8
Montag, Kunz, Axmacher, Sariyska, Lachmann & Reuter (2014), BMC Neuroscience
Diagnostics of Alzheimer
genetics and personality
Montag, Kunz, Axmacher, Sariyska, Lachmann & Reuter (2014), BMC Neuroscience
What about APOE
genetics and cognitive
functions in adolescence?
Large scale genotyping of Alzheimer’s
risk genetic variations in adolescents
•
•
Nikolai Axmacher (Bochum) and
my group recruited hundreds of
young students for genotyping
Alzheimer’s risk variants
Then we invited participants after
á priori genotyping with equal
sizes for Alzheimer’s risk variation
•
All participants underwent brain
imaging to study grid cell activity
•
Grid cells in the entorhinal cortex
are the first to loose functionality
in Alzheimers
Cell
ε3/ε3
ε3/ε4
males
18
18
females
19
20
Frequencies
Grid cell* activity depending on
APOE genotypes in adolescences
*cell group
of the entorhinal cortex
activated while navigating
Kunz, Schröder, Lee, Montag, Lachmann, Sariyska, Reuter, Stirnberg, Stöcker, Messing-Floeter, Fell, Doeller & Axmacher (2015), Science
Kunz, Schröder, Lee, Montag, Lachmann, Sariyska, Reuter, Stirnberg, Stöcker, Messing-Floeter, Fell, Doeller & Axmacher (2015), Science
Molecular genetics of
prosocial behavior
Oxytocin and
social cognition
•
Oxytocin is a nonapeptide
classically investigated in the
context of motherhood (e. g.
lactation)
•
Males also produce oxytocin, so
oxytocin needs to have further
functions
•
Kosfeld et al. (2005) observed
that the nasal administration of
oxytocin is associated with
elevated trust behavior in the
economic trust game.
•
Also links to empathy!
Kosfeld et al. (2005), Nature
Investigation of the oxytocin
receptor gene revealed …
… a special role of rs2268498 for social cognition!
rs2268498 and emotion
detection abilities
Melchers, Montag, Markett & Reuter (2013), Behavioral Neuroscience
rs2268498 and the
Interpersonal Perception Task
Who won the game
of one-on-one
basketball?
a) the man on the left
b) the man on the right
Melchers, Montag, Felten & Reuter (2015), Social Neuroscience
rs2268498 and brain activity
O‘Connell et al. (2012) show,
that TT carrier show higher
activity in the inferior occipital
gyrus when processing fearful
faces
Thank you, Jeremy :-)
O‘Connell, Whalley, Mukherjee, Stanfield, Montag, Hall & Reuter (2012), Journal of Behavioral and Brain Science
Some future directions
Oxytocin & direct gaze
Three way interaction on amygdala: gene by oxytocin/placebo by gaze
Montag, Sauer, Reuter & Kirsch (2013)
European Archives of Psychiatry and Clinical Neuroscience
Vasopressin
•
Another very important
neuropeptide represent
vasopressin.
•
Arginine-Vasopressin (AVP)
could counteract fear (or
anxiety) effects by
strengthening the PFC activity
as a top-down fear/anxiety
regulator.
•
Investigation of rs11174811 on
the AVPR1a gene (located on
chromosome 12q) in the
context of anxiety.
New questionnaire to disentangle anxiety and fear:
Reuter & Montag’s rRST-Q
Reuter, Cooper, Smillie, Markett & Montag (2015), Frontiers in Systems Neuroscience
Impact of AVPR1a s11174811 on anxiety
(Behavioral Inhibition System)
Reuter, Cooper, Smillie, Markett & Montag (2015), Frontiers in Systems Neuroscience
Getting Ekman and Panksepp together:
a neuroscientific framework to study the
molecular basis of facial expression
Montag & Panksepp (under review)
Panksepp (2011), PLoSOne
PsychoNeuroInformatics
N = 100
Genes
Structural brain scans
resting state fMRI
tracking real
behavior
Ya Fei Chen & Mei Li
Nikolai
Axmacher
Beijing University of Civil Engineering and Architecture
Jaak Panksepp
Washington State
Martin Reuter
Universität Bonn
Universität Bochum
Stefan
Schneider
Deutsche
Sporthochschule, Köln
Thanks.
Bernd
Alexander Rayna
Lachmann Markowetz Sariyska
Universität Ulm
Universität Bonn
Chun-Bo Li
Shanghai Mental
Health Center
Universität Ulm
The Menthal Team: Computer Science meets Psychology