TY - JOUR
T1 - Relationship of the serotonin transporter gene promoter polymorphism (5-HTTLPR) genotype and serotonin transporter binding to neural processing of negative emotional stimuli
AU - Schneck, Noam
AU - Miller, Jefvrey M.
AU - Delorenzo, Christine
AU - Kikuchi, Toshiaki
AU - Sublette, M. Elizabeth
AU - Oquend, Maria A.
AU - Mann, J. John
AU - Parsey, Ramin V.
N1 - Publisher Copyright:
© 2015 Elsevier B.V.
PY - 2016/1/15
Y1 - 2016/1/15
N2 - Background The lower-expressing (S′) alleles of the serotonin transporter (5-HTT) gene promoter polymorphism (5-HTTLPR) are linked to mood and anxiety related psychopathology. However, the specific neural mechanism through which these alleles may influence emotional and cognitive processing remains unknown. We examined the relationship between both 5-HTTLPR genotype and in vivo 5-HTT binding quantified via PET with amygdala reactivity to emotionally negative stimuli. We hypothesized that 5-HTT binding in both raphe nuclei (RN) and amygdala would be inversely correlated with amygdala reactivity, and that number of S′ alleles would correlate positively with amygdala reactivity. Methods In medication-free patients with current major depressive disorder (MDD; N=21), we determined 5-HTTLPR genotype, employed functional magnetic resonance imaging (fMRI) to examine amygdala responses to negative emotional stimuli, and used positron emission tomography with [11C]DASB to examine 5-HTT binding. Results [11C]DASB binding in RN and amygdala was inversely correlated with amygdala response to negative stimuli. 5-HTTLPR S′ alleles were not associated with amygdala response to negative emotional stimuli. Limitations Primary limitations are small sample size and lack of control group. Conclusions Consistent with findings in healthy volunteers, 5-HTT binding is associated with amygdala reactivity to emotional stimuli in MDD. 5-HTT binding may be a stronger predictor of emotional processing in MDD as compared with 5-HTTLPR genotype.
AB - Background The lower-expressing (S′) alleles of the serotonin transporter (5-HTT) gene promoter polymorphism (5-HTTLPR) are linked to mood and anxiety related psychopathology. However, the specific neural mechanism through which these alleles may influence emotional and cognitive processing remains unknown. We examined the relationship between both 5-HTTLPR genotype and in vivo 5-HTT binding quantified via PET with amygdala reactivity to emotionally negative stimuli. We hypothesized that 5-HTT binding in both raphe nuclei (RN) and amygdala would be inversely correlated with amygdala reactivity, and that number of S′ alleles would correlate positively with amygdala reactivity. Methods In medication-free patients with current major depressive disorder (MDD; N=21), we determined 5-HTTLPR genotype, employed functional magnetic resonance imaging (fMRI) to examine amygdala responses to negative emotional stimuli, and used positron emission tomography with [11C]DASB to examine 5-HTT binding. Results [11C]DASB binding in RN and amygdala was inversely correlated with amygdala response to negative stimuli. 5-HTTLPR S′ alleles were not associated with amygdala response to negative emotional stimuli. Limitations Primary limitations are small sample size and lack of control group. Conclusions Consistent with findings in healthy volunteers, 5-HTT binding is associated with amygdala reactivity to emotional stimuli in MDD. 5-HTT binding may be a stronger predictor of emotional processing in MDD as compared with 5-HTTLPR genotype.
KW - Biological Markers
KW - Brain Imaging
KW - Depression
KW - Functional MRI
KW - Genetics
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U2 - 10.1016/j.jad.2015.10.047
DO - 10.1016/j.jad.2015.10.047
M3 - Article
C2 - 26561939
AN - SCOPUS:84946600651
VL - 190
SP - 494
EP - 498
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
SN - 0165-0327
ER -