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Center for integrated
molecular brain imaging
Association between Sensory Processing Sensitivity
and the 5-HTTLPR Short/Short Genotype
Cecilie L. Licht1, Erik L. Mortensen2, Gitte M. Knudsen1
1Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging (Cimbi), Copenhagen University Hospital Rigshospitalet, Denmark
2Department of Health Psychology, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark
Introduction
Associations between the common polymorphism in the
serotonin transporter (5-HTT) promoter 5-HTTLPR and the
personality traits Neuroticism and Harm Avoidance are
equivocal. The temperamental trait Sensory Processing
Sensitivity (SPS), which is characterized by increased
sensitivity to environmental stimuli (Aron and Aron, 1997)
and is related to Neuroticism and Openness (Smolewska et
al., 2006), may describe an underlying characteristic more
directly associated with 5-HTTLPR genotype. High levels of
SPS are found in 15-20% of the population and have in
fMRI studies been associated with enhanced neural
processing of detailed visual stimuli (Jagiellowicz et al.,
2011) and increased neural activation in response to happy
and sad faces (Acevedo et al., 2010). Several defining
characteristics of SPS, as reflected by items on the self-
report questionnaire, are similar to physiological
characteristics found in 5-HTTLPR short allele carriers,
including increased brain activation in response to
emotional stimuli (Canli et al., 2005), increased acoustic
startle response (Brocke et al., 2006), and increased
cortisol response to social evaluation (Way et al., 2010).
High levels of SPS may reflect an endophenotype
associated with the 5-HTTLPR short/short genotype.
Methods
Participants
Two-hundred healthy adult individuals (aged 18-88), included in the Cimbi
database between 2000 and 2010, completed NEO-PI-R and TCI
personality batteries at the time of inclusion. Blood samples were collected
and genotypes for the 5-HTTLPR polymorphism determined. In 2010, the
cohort (n = 169, 58.6% male) completed the questionnaires Highly
Sensitive Person (HSP) Scale and the Symptom Checklist-90R (SCL-
90R).
Questionnaires
NEO-PI-R – The Revised NEO Personality Inventory. A 240-item self-
report questionnaire providing a measure of the Five Factor Model:
Neuroticism, Extraversion, Openness to Experience, Agreeableness, and
Conscientiousness (Costa and McCrae, 1992).
Temperament and Character Inventory (TCI). A 240-item questionnaire
providing a measure of four dimensions of temperament (Harm
Avoidance, Novelty Seeking, Reward Dependence, and Persistence) and
three of character (Cloninger et al., 1994).
Highly Sensitive Person (HSP) Scale. A 27-item self-report questionnaire
providing a measure of Sensory Processing Sensitivity (HSP score) (Aron
and Aron, 1997) and the three facets Aesthetic Sensitivity (AES), Ease of
Excitation (EOE), and Low Sensory Threshold (LST) (Smolewska et al.,
2006). Examples of questions: ‘Do other people’s moods affect you?’, ‘Do
you startle easily?’, and ‘Does being very hungry create a strong reaction
in you, disrupting your concentration or mood?’ Items are rated on a 1-7
Likert scale, giving total scores in the range of 27-189. The present
dataset has scores in the range 27-138, mean ± SD of 92.6 ± 19.1, and a
Cronbach’s α of 0.86.
Revised Hopkins Symptom Checklist (SCL-90R). A 90-item self-report
questionnaire providing a measure of symptoms of distress and
psychopathology within the past week consisting of a Global Severity
Index (GSI) and scores for nine sub-scales of psychopathology (Derogatis
LR, 1994).
5-HTTLPR Genotyping
5-HTT gene-linked polymorphic region (5-HTTLPR, rs4795541). A 44 bp
insertion/deletion in the promoter region of the 5-HTT gene giving rise to
short (s) and long (l) alleles. Determined with a TaqMan 5’-exonuclease
allelic discrimination assay and ABI 7500 multiplex PCR (Applied
Biosystems). The three genotypes: l/l (n = 55, 32.5%), s/l (n = 82, 48.5%),
and s/s (n = 32, 18.9%) were in Hardy-Weinberg equilibrium (s allele
frequency: 43%, Χ
2
= 0.021, p = 0.883).
Statistical analysis
Performed in GraphPad Prism 5.04, GraphPad InStat 3.10, and
STATA/MP 10.1.
Conclusions
Sensory Processing Sensitivity was positively correlated
with female gender, psychological distress, and the
personality traits Neuroticism, Harm Avoidance, and
Openness, and negatively correlated with Extraversion.
Higher levels of Sensory Processing Sensitivity were
associated with the serotonin transporter 5-HTTLPR
short/short genotype, when taking gender, age,
psychological distress, and the personality traits
Neuroticism, Extraversion, and Openness into account.
In particular, this association was evident for Ease of
Excitation, a facet of Sensory Processing Sensitivity.
Neuroticism and Harm Avoidance were not associated
with the 5-HTTLPR short/short genotype, or with 5-
HTTLPR short allele carrier status.
Thus, the trait Sensory Processing Sensitivity describes a
psychological profile associated with homozygotic status
of a common polymorphism in the serotonin system.
References
Acevedo B, Aron A, and Aron E (2010). American Psychological Association Annual Convention, Symposium 2273.
Aron EN and Aron A (1997). J Pers Soc Psychol 73, 345-68.
Brocke B, Armbruster D, Muller J, Hensch T, Jacob CP, Lesch KP et al. (2006). Mol Psychiatry 11, 1106-12.
Canli T, Omura K, Haas BW, Fallgatter A, Constable RT, and Lesch KP (2005). PNAS 102, 12224-9.
Cloninger CR, Przybeck TR, Svrakic DM, and Wetzel RD (1994). Center for Psychobiology of Personality, Missouri.
Costa PT and McCrae RR (1992). Psychological Assessment Resources, Odessa, Florida.
Derogatis LR (1994). Administration, Scoring, and Procedures Manual, 3rd ed. National Computer Systems,
Minneapolis, Minnesota.
Jagiellowicz J, Xu X, Aron A, Aron E, Cao G, Feng T, and Weng X (2011). SCAN 6, 38-47.
Smolewska KA, McCabe SB, and Woody EZ (2006). Pers Indiv Differ 40, 1269-79.
Way BM and Taylor SE (2010). Biol Psychiatry 67, 487-92.
Acknowledgements
The Lundbeck Foundation and the Sawmill Owner Jeppe Juhl and Wife Ovita
Juhl Memorial Foundation are acknowledged for financial support.
Contact: cecilie.licht@nru.dk
Figure 1. Influence of gender and psychological distress on
Sensory Processing Sensitivity. A) Females have higher HSP
score than males (99.8 ± 2.2 vs. 87.6 ± 1.8, p < 0.0001, Student’s t
test, n = 169). B) Global Severity Index (GSI) on the SCL-90R
measure of psychological distress is positively correlated with HSP
score (Spearman’s r = 0.42, p < 0.0001, n = 165).
Figure 2. Correlations between Sensory Processing Sensitivity and associated
personality traits. A) Neuroticism is correlated with HSP score (Pearson’s r = 0.39, p <
0.0001). B) Harm Avoidance is correlated with HSP score (Spearman’s r = 0.40, p < 0.0001).
C) Extraversion is negatively correlated with HSP score (Pearson’s r = -0.17, p = 0.025). D)
Openness is correlated with HSP score (Pearson’s r = 0.18, p = 0.023). Reward Dependence
is correlated with HSP score (Pearson’s r = 0.26, p = 0.0007, data not shown). n = 164-165.
Figure 3. Sensory Processing Sensitivity is not associated with 5-HTTLPR Short/
Short Genotype when taking gender, age, and psychological distress into account.
Partial regression plot of HSP score vs. 5-HTTLPR s/s genotype (s/s = 1, s/l or l/l = 0),
(pcorr = 0.15, p = 0.056). Model: adj. R2 = 27.4%, n = 164. 5-HTTLPR s/s: coeff. = 6.21, se
= 3.23.
Table 1. Comparison of associations of Sensory Processing Sensitivity, Neuroticism,
and Harm Avoidance with 5-HTTLPR Short allele. Values are partial correlation
coefficients for 5-HTTLPR short allele status with each personality trait taking gender, age
(SPS only), and psychological distress (SCL-90R GSI) into account. Models in bottom
section include the personality traits listed in parentheses to test each personality trait’s
association with 5-HTTLPR s/s genotype independent of associated traits. n = 161-164. *p <
0.05.
Table 2. Correlations between Sensory Processing Sensitivity facets
and personality traits of the Five Factor Model. The facets Ease of
Excitation (EOE) and Low Sensory Threshold (LST) are correlated with
Neuroticism and negatively correlated with Extraversion. The facet Aesthetic
Sensitivity (AES) is correlated with Openness. Values are Pearson’s
correlation coefficients. aSpearman correlation coefficient. n = 165. * p <
0.05, ** p < 0.01, *** p < 0.001.
Total HSP AES EOE LST
Neuroticism 0.39*** 0.10 0.42*** 0.30***
Extraversion -0.17* 0.15 -0.24** -0.27***
Openness 0.18* 0.47*** -0.01 -0.08
Conscientiousness -0.01a-0.02a-0.04a-0.10a
Agreeableness 0.12a0.07a0.06a0.17a*
5-HTTLPR
Short/Short
5-HTTLPR Short
Allele Carrier
Sensory Processing Sensitivity 0.15 (p = 0.056) na
Neuroticism -0.04 (p = 0.628) 0.03 (p = 0.704)
Harm Avoidance -0.10 (p = 0.202) -0.10 (p = 0.210)
Sensory Processing Sensitivity (Neuroticism) 0.18 (p = 0.026)* na
Sensory Processing Sensitivity (Harm Avoidance) 0.18 (p = 0.025)* na
Neuroticism (Sensory Processing Sensitivity) -0.08 (p = 0.325) na
Harm Avoidance (Sensory Processing Sensitivity) -0.15 (p = 0.066) na
Sensory Processing Sensitivity (Neu., Ext., Ope.) 0.20 (p = 0.011)* na
0 50 100 150
0
50
100
150 r = 0.39
p <0.0001
SPS versus Neuroticism
HSP Score
Neuroticism
A
0 50 100 150
0
10
20
30 r = 0.40
p < 0.0001
SPS versus Harm Avoidance
HSP Score
Harm Avoidance
B
0 50 100 150
0
50
100
150
200 r = - 0.17
p = 0.025
SPS versus Extraversion
HSP Score
Extraversion
C
0 50 100 150
0
50
100
150
200 r = 0.18
p = 0.023
SPS versus Openness
HSP Score
Openness
D
Figure 4. Sensory Processing Sensitivity is associated with 5-HTTLPR Short/Short
Genotype when taking gender, age, psychological distress, and the personality traits
Neuroticism, Extraversion, and Openness into account. Partial regression plot of HSP
score vs. 5-HTTLPR s/s genotype (s/s = 1, s/l or l/l = 0), (pcorr = 0.20, p = 0.011). Model:
adj. R2 = 38.4%, n = 161. 5-HTTLPR s/s: coeff. = 7.56, se = 2.93.
Figure 5. Ease of Excitation (EOE) is associated with 5-HTTLPR Short/
Short Genotype when taking gender, age, and psychological distress
into account. Partial regression plot of EOE score vs. 5-HTTLPR s/s
genotype (s/s = 1, s/l or l/l = 0), (pcorr = 0.17, p = 0.036). Model: adj. R2 =
30.0%, n = 164. 5-HTTLPR s/s: coeff. = 3.25, se = 1.54.
Figure 6. Ease of Excitation (EOE) is associated with 5-HTTLPR Short/
Short Genotype when taking gender, age, psychological distress, and
the personality traits Neuroticism, Extraversion, and Openness into
account. Partial regression plot of EOE score vs. 5-HTTLPR s/s genotype
(s/s = 1, s/l or l/l = 0), (pcorr = 0.23, p = 0.004). Model: adj. R2 = 40.4%, n =
161. 5-HTTLPR s/s: coeff. = 4.09, se = 1.41.
SPS and Gender
Male Female
0
50
100
150
p < 0.0001
HSP Score
A
B
0 50 100 150
0.0
0.5
1.0
1.5
2.0
r = 0.42
p < 0.0001
SPS and Psychological Distress
HSP Score
SCL-90R GSI
-60 -40 -20 0 20 40
Residual HSP Score
-.5 0 .5 1
Residual 5-HTTLPR Short/Short Genotype
Pcorr = 0.15 p = 0.056
Gender_Age_SCL-90R GSI
HSP Score and 5-HTTLPR Short/Short Genotype
-40 -20 0 20 40
Residual HSP Score
-.5 0 .5 1
Residual 5-HTTLPR Short/Short Genotype
Pcorr = 0.20 p = 0.011
Gender_Age_SCL-90R GSI_NEO
HSP Score and 5-HTTLPR Short/Short Genotype
-20 -10 0 10 20
Residual EOE Score
-.5 0 .5 1
Residual 5-HTTLPR Short/Short Genotype
Pcorr = 0.23 p = 0.004
Gender_Age_SCL-90R GSI_NEO
EOE Score and 5-HTTLPR Short/Short Genotype
-20 -10 0 10 20
Residual EOE Score
-.5 0 .5 1
Residual 5-HTTLPR Short/Short Genotype
Pcorr = 0.17 p = 0.036
Gender_Age_SCL-90R GSI
EOE Score and 5-HTTLPR Short/Short Genotype
