Association between Sensory Processing Sensitivity
and the 5-HTTLPR Short/Short Genotype
Center for integrated
molecular brain imaging

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

AMethods
ParticipantsTwo-hundred healthy adult individuals (aged 18-88), included in the Cimbi
database between 2000 and 2010, completed NEO-PI-R and TCIpersonality batteries at the time of inclusion. Blood samples were collected
and genotypes for the 5-HTTLPR polymorphism determined. In 2010, thecohort (n = 169, 58.6% male) completed the questionnaires Highly
Sensitive Person (HSP) Scale and the Symptom Checklist-90R (SCL90R).

B

SPS versus Neuroticism

Harm Avoidance

Neuroticism

r = 0.40
p < 0.0001

r = 0.39
p <0.0001

10050

20

1000050

1000150

50100

DSPS versus Extraversion

200150HSP Score

HSP Score

Cr = - 0.17p = 0.025

Total HSPAESEOELSTNeuroticism

0.39***

0.10

0.42***

0.30***

Extraversion-0.24**-0.27***SPS versus Harm Avoidance
30

150-0.17*

0.15

Openness

0.18*

0.47***-0.01

Conscientiousness-0.01a-0.02a-0.04a-0.10aAgreeableness

0.12a

0.07a

0.06a

0.17a*-0.08

Table 2. Correlations between Sensory Processing Sensitivity facets
and personality traits of the Five Factor Model. The facets Ease ofExcitation (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’scorrelation coefficients. aSpearman correlation coefficient. n = 165. * p <0.05, ** p < 0.01, *** p < 0.001.

SPS versus Openness

200r = 0.18p = 0.023

EOE Score and 5-HTTLPR Short/Short Genotype
Gender_Age_SCL-90R GSI

10050100500050100150

HSP Score

0050100150

HSP Score

Figure 2. Correlations between Sensory Processing Sensitivity and associatedpersonality 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.

Residual EOE Score-1001020150

OpennessExtraversion

150-.50.5
Residual 5-HTTLPR Short/Short Genotype1Pcorr = 0.17 p = 0.036

Figure 5. Ease of Excitation (EOE) is associated with 5-HTTLPR Short/
Short Genotype when taking gender, age, and psychological distressinto 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.

HS P Score and 5-HTTL PR Short/Short G enotype
Gender_A ge_SC L-90R GSI40Associations between the common polymorphism in theserotonin transporter (5-HTT) promoter 5-HTTLPR andthe personality traits Neuroticism and Harm Avoidance areequivocal. 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 (Smolewskaet al., 2006), may describe an underlying characteristic
more directly associated with 5-HTTLPR genotype. Highlevels of SPS are found in 15-20% of the population andhave in fMRI studies been associated with enhanced
neural processing of detailed visual stimuli (Jagiellowicz etal., 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 physiologicalcharacteristics found in 5-HTTLPR short allele carriers,
including increased brain activation in response toemotional 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.

-20

Introduction

Revised Hopkins Symptom Checklist (SCL-90R). A 90-item self-reportquestionnaire providing a measure of symptoms of distress andpsychopathology within the past week consisting of a Global Severity
Index (GSI) and scores for nine sub-scales of psychopathology (DerogatisLR, 1994).

20

1Figure 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.

Statistical analysis

HS P Sco re a nd 5 -HTTL PR Sho rt/Sh ort G en otyp e
Ge nd er_A ge_ SC L-90 R GSI_ NEO-40
SPS and Gender

HSP Score0.5
Residual 5-HT TLP R S hort/Short Genotype1Pcorr = 0.20 p = 0 .01 1Figure 4. Sensory Processing Sensitivity is associated with 5-HTTLPR Short/ShortGenotype 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.

10050

p < 0.0001
0MaleB

FemaleSPS and Psychological Distress
2.0r = 0.42p < 0.0001

SCL-90R GSI

1.51.0Sensory Processing Sensitivity

5-HTTLPRShort/Short

5-HTTLPR Short
Allele Carrier

0.15 (p = 0.056)

na050

100150HSP Score

Figure 1. Influence of gender and psychological distress onSensory Processing Sensitivity. A) Females have higher HSP
score than males (99.8 ± 2.2 vs. 87.6 ± 1.8, p < 0.0001, Student’s ttest, n = 169). B) Global Severity Index (GSI) on the SCL-90R
measure of psychological distress is positively correlated with HSPscore (Spearman’s r = 0.42, p < 0.0001, n = 165).

Contact: cecilie.licht@nru.dk

Higher levels of Sensory Processing Sensitivity wereassociated 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 ofExcitation, a facet of Sensory Processing Sensitivity.
Neuroticism and Harm Avoidance were not associatedwith the 5-HTTLPR short/short genotype, or with 5HTTLPR short allele carrier status.
Thus, the trait Sensory Processing Sensitivity describes
a psychological profile associated with homozygotic
status of a common polymorphism in the serotoninsystem.

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)

naHarm Avoidance (Sensory Processing Sensitivity)-0.15 (p = 0.066)

na

Cloninger CR, Przybeck TR, Svrakic DM, and Wetzel RD (1994). Center for Psychobiology of Personality, Missouri.

Sensory Processing Sensitivity (Neu., Ext., Ope.)

0.20 (p = 0.011)*

naCosta PT and McCrae RR (1992). Psychological Assessment Resources, Odessa, Florida.

0.50.01

Sensory Processing Sensitivity was positively correlatedwith female gender, psychological distress, and thepersonality traits Neuroticism, Harm Avoidance, andOpenness, and negatively correlated with Extraversion.

-.51500.5
Residual 5-HTTLPR Short/Short GenotypePcorr = 0.23 p = 0.004

Conclusions

Performed in GraphPad Prism 5.04, GraphPad InStat 3.10, andSTATA/MP 10.1.

A-.5Figure 6. Ease of Excitation (EOE) is associated with 5-HTTLPR Short/Short Genotype when taking gender, age, psychological distress, andthe personality traits Neuroticism, Extraversion, and Openness intoaccount. 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.

Residual HSP Score-200205-HTT gene-linked polymorphic region (5-HTTLPR, rs4795541). A 44 bp
insertion/deletion in the promoter region of the 5-HTT gene giving rise toshort (s) and long (l) alleles. Determined with a TaqMan 5’-exonuclease
allelic discrimination assay and ABI 7500 multiplex PCR (AppliedBiosystems). 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 allelefrequency: 43%, Χ2 = 0.021, p = 0.883).

Residual EOE Score-100100.5
Residual 5-HTTLPR S hort/Short GenotypePcorr = 0.15 p = 0.056

405-HTTLPR Genotyping-.5-20Highly Sensitive Person (HSP) Scale. A 27-item self-report questionnaire
providing a measure of Sensory Processing Sensitivity (HSP score) (Aronand Aron, 1997) and the three facets Aesthetic Sensitivity (AES), Ease ofExcitation (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 presentdataset has scores in the range 27-138, mean ± SD of 92.6 ± 19.1, and a
Cronbach’s α of 0.86.

Gender_Age_SCL-90R GSI_NEO-40

Temperament and Character Inventory (TCI). A 240-item questionnaire
providing a measure of four dimensions of temperament (HarmAvoidance, Novelty Seeking, Reward Dependence, and Persistence) andthree of character (Cloninger et al., 1994).

EOE Score and 5-HTTLPR Short/Short Genotype-60

NEO-PI-R – The Revised NEO Personality Inventory. A 240-item selfreport questionnaire providing a measure of the Five Factor Model:
Neuroticism, Extraversion, Openness to Experience, Agreeableness, andConscientiousness (Costa and McCrae, 1992).

Residual HSP Score-20
020

Questionnaires

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.

Derogatis LR (1994). Administration, Scoring, and Procedures Manual, 3rd ed. National Computer Systems,Minneapolis, Minnesota.

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.

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 OvitaJuhl Memorial Foundation are acknowledged for financial support.