| 1. |
- Furmark, Tomas, et al.
(författare)
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A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety
- 2008
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 28:49, s. 13066-74
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Tidskriftsartikel (refereegranskat)abstract
- Placebo may yield beneficial effects that are indistinguishable from those of active medication, but the factors underlying proneness to respond to placebo are widely unknown. Here, we used functional neuroimaging to examine neural correlates of anxiety reduction resulting from sustained placebo treatment under randomized double-blind conditions, in patients with social anxiety disorder. Brain activity was assessed during a stressful public speaking task by means of positron emission tomography before and after an 8 week treatment period. Patients were genotyped with respect to the serotonin transporter-linked polymorphic region (5-HTTLPR) and the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene promoter. Results showed that placebo response was accompanied by reduced stress-related activity in the amygdala, a brain region crucial for emotional processing. However, attenuated amygdala activity was demonstrable only in subjects who were homozygous for the long allele of the 5-HTTLPR or the G variant of the TPH2 G-703T polymorphism, and not in carriers of short or T alleles. Moreover, the TPH2 polymorphism was a significant predictor of clinical placebo response, homozygosity for the G allele being associated with greater improvement in anxiety symptoms. Path analysis supported that the genetic effect on symptomatic improvement with placebo is mediated by its effect on amygdala activity. Hence, our study shows, for the first time, evidence of a link between genetically controlled serotonergic modulation of amygdala activity and placebo-induced anxiety relief.
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| 2. |
- Henningsson, Susanne, 1977, et al.
(författare)
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A randomized placebo-controlled intranasal oxytocin study on first impressions and reactions to social rejection
- 2021
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Ingår i: Biological Psychology. - : Elsevier BV. - 0301-0511 .- 1873-6246. ; 164
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Tidskriftsartikel (refereegranskat)abstract
- Oxytocin is central to pair-bonding in non-human animals. We assessed effects of intranasal oxytocin on bond formation between two opposite-sex strangers. In a double-blind placebo-controlled design, 50 pairs of one man and one woman received oxytocin or placebo spray intranasally. After treatment, they played a social interaction game, followed by tasks designed to measure first impressions of the opposite-sex co-participant, and a virtual ball-tossing game (cyberball), designed to measure reactions to rejection by the co-participant. We found no evidence that intranasal oxytocin can improve first impressions of an opposite-sex stranger, and some Bayesian support against this hypothesis. For rejection sensitivity, we observed a sex-and-context-dependent drug effect on post-ostracism mood ratings, consistent with recent studies indicating that interindividual variation and social context can interact with intranasal oxytocin effects. Further research is needed to determine the generalisability of these findings, i.e. if oxytocin can improve first impressions in humans under different conditions.
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| 3. |
- Henningsson, Susanne, 1977, et al.
(författare)
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Association between polymorphisms in NOS3 and KCNH2 and social memory
- 2015
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Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-4548 .- 1662-453X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Social memory, including the ability to recognize faces and voices, is essential for social relationships. It has a large heritable component, but the knowledge about the contributing genes is sparse. The genetic variation underlying inter-individual differences in social memory was investigated in an exploratory sample (n = 55), genotyped with a chip comprising approximately 200,000 single nucleotide polymorphisms (SNPs), and in a validation sample (n = 582), where 30 SNPs were targeted. In the exploratory study face identity recognition was measured. The validation study also measured vocal sound recognition, as well as recognition of faces and vocal sounds combined (multimodal condition). In the exploratory study, the 30 SNPs that were associated with face recognition at puncorrected < 0.001 and located in genes, were chosen for further study. In the validation study two of these SNPs showed significant associations with recognition of faces, vocal sounds, and multimodal stimuli: rs1800779 in the gene encoding nitric oxide synthase 3 (NOS3) and rs3807370 in the gene encoding the voltage-gated channel, subfamily H, member 2 (KCNH2), in strong linkage disequilibrium with each other. The uncommon alleles were associated with superior performance, and the effects were present for men only (p < 0.0002). The exploratory study also showed a weaker but significant association with (non-emotional) word recognition, an effect that was independent of the effect on face recognition. This study demonstrates evidence for an association between NOS3 and KCNH2SNPs and social memory.
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| 4. |
- Hovey, Daniel, et al.
(författare)
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Emotion recognition associated with polymorphism in oxytocinergic pathway gene ARNT2
- 2018
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Ingår i: Social Cognitive & Affective Neuroscience. - : Oxford University Press (OUP). - 1749-5024 .- 1749-5016. ; 13:2, s. 173-181
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Tidskriftsartikel (refereegranskat)abstract
- The ability to correctly understand the emotional expression of another person is essential for social relationships and appears to be a partly inherited trait. The neuropeptides oxytocin and vasopressin have been shown to influence this ability as well as face processing in humans. Here, recognition of the emotional content of faces and voices, separately and combined, was investigated in 492 subjects, genotyped for 25 single nucleotide polymorphisms (SNPs) in eight genes encoding proteins important for oxytocin and vasopressin neurotransmission. The SNP rs4778599 in the gene encoding aryl hydrocarbon receptor nuclear translocator 2 (ARNT2), a transcription factor that participates in the development of hypothalamic oxytocin and vasopressin neurons, showed an association that survived correction for multiple testing with emotion recognition of audio-visual stimuli in women (). This study demonstrates evidence for an association that further expands previous findings of oxytocin and vasopressin involvement in emotion recognition.
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| 5. |
- Karlsson, Sara, 1980, et al.
(författare)
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Social memory associated with estrogen receptor polymorphisms in women
- 2016
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Ingår i: Social Cognitive & Affective Neuroscience. - : Oxford University Press (OUP). - 1749-5016 .- 1749-5024. ; 11:6, s. 877-883
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Tidskriftsartikel (refereegranskat)abstract
- The ability to recognize the identity of faces and voices is essential for social relationships. Although the heritability of social memory is high, knowledge about the contributing genes is sparse. Since sex differences and rodent studies support an influence of estrogens and androgens on social memory, polymorphisms in the estrogen and androgen receptor genes (ESR1, ESR2, AR) are candidates for this trait. Recognition of faces and vocal sounds, separately and combined, was investigated in 490 subjects, genotyped for 10 single nucleotide polymorphisms (SNPs) in ESR1, four in ESR2 and one in the AR. Four of the associations survived correction for multiple testing: women carrying rare alleles of the three ESR2 SNPs, rs928554, rs1271572 and rs1256030, in linkage disequilibrium with each other, displayed superior face recognition compared with non-carriers. Furthermore, the uncommon genotype of the ESR1 SNP rs2504063 was associated with better recognition of identity through vocal sounds, also specifically in women. This study demonstrates evidence for associations in women between face recognition and variation in ESR2, and recognition of identity through vocal sounds and variation in ESR1. These results suggest that estrogen receptors may regulate social memory function in humans, in line with what has previously been established in mice.
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| 6. |
- Westberg, Lars, 1973, et al.
(författare)
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Variation in the Oxytocin Receptor Gene Is Associated with Face Recognition and its Neural Correlates
- 2016
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Ingår i: Frontiers in Behavioral Neuroscience. - : Frontiers Media SA. - 1662-5153. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- The ability to recognize faces is crucial for daily social interactions. Recent studies suggest that intranasal oxytocin administration improves social recognition in humans. Oxytocin signaling in the amygdala plays an essential role for social recognition in mice, and oxytocin administration has been shown to influence amygdala activity in humans. It is therefore possible that the effects of oxytocin on human social recognition depend on mechanisms that take place in the amygdala a central region for memory processing also in humans. Variation in the gene encoding the oxytocin receptor (OXTR) has been associated with several aspects of social behavior. The present study examined the potential associations between nine OXTR polymorphisms, distributed across the gene, and the ability to recognize faces, as well as face-elicited amygdala activity measured by functional magnetic resonance imaging (fMRI) during incidental encoding of faces. The OXTR 3' polymorphism rs7632287, previously related to social bonding behavior and autism risk, was associated with participants ability to recognize faces. Carriers of the GA genotype, associated with enhanced memory, displayed higher amygdala activity during face encoding compared to carriers of the GG genotype. In line with work in rodents, these findings suggest that, in humans, naturally occurring endogenous modulation of OXTR function affects social recognition through an amygdala-dependent mechanism. These findings contribute to the understanding of how oxytocin regulates human social behaviors.
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| 7. |
- Furmark, Tomas, et al.
(författare)
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Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder.
- 2009
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Ingår i: Journal of psychiatry & neuroscience : JPN. - : Canadian Medical Association. - 1488-2434 .- 1180-4882. ; 34:1, s. 30-40
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although the amygdala is thought to be a crucial brain region for negative affect, neuroimaging studies do not always show enhanced amygdala response to aversive stimuli in patients with anxiety disorders. Serotonin (5-HT)-related genotypes may contribute to interindividual variability in amygdala responsiveness. The short (s) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) and the T variant of the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene have previously been associated with amygdala hyperresponsivity to negative faces in healthy controls. We investigated the influence of these polymorphisms on amygdala responsiveness to angry faces in patients with social anxiety disorder (SAD) compared with healthy controls. METHODS: We used positron emission tomography with oxygen 15-labelled water to assess regional cerebral blood flow in 34 patients with SAD and 18 controls who viewed photographs of angry and neutral faces presented in counterbalanced order. We genotyped all participants with respect to the 5-HTTLPR and TPH2 polymorphisms. RESULTS: Patients with SAD and controls had increased left amygdala activation in response to angry compared with neutral faces. Genotype but not diagnosis explained a significant portion of the variance in amygdala responsiveness, the response being more pronounced in carriers of s and/or T alleles. LIMITATIONS: Our analyses were limited owing to the small sample and the fact that we were unable to match participants on genotype before enrollment. In addition, other imaging techniques not used in our study may have revealed additional effects of emotional stimuli. CONCLUSION: Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD. Emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT-related genes into account.
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