An integrative analysis of 5HTT-mediated mechanism of hyperactivity to non-threatening voices

Chen, Chenyi; Martínez, Róger Marcelo; Liao, Tsai Tsen; Yang, Chung‐May; Cheng, Yawei

doi:10.1038/s42003-020-0850-3

Cited by 7 publications

(6 citation statements)

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“…In the same vein, although justice sensitivity was not found to be significantly associated with the permissibility of harm, it was found to be modulated by anxiety and implicit moral attitudes, both of which were intercorrelated with the 5-HTT polymorphism. These results show ecological and gene–environmental interactions and help explain why Han Chinese participants exhibit a higher proportion of the S/S genotype and a lower frequency of the L/L genotype than that observed in Caucasian populations, where the S allele was seen as conferring less susceptibility toward anxiety in Asian people ( Chen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 74%

“…First, several studies have observed a significant interaction between the 5-HTT polymorphism and early-life environment on the modulation of behavior and psychological factors (including education) ( Assary et al, 2018 ), which this study did not consider. Nevertheless, this study makes use of a portion of the same sample, and utilizing the same procedures, as other studies ( Chen et al, 2020 ). Second, the sample for those homozygous for the L allele is quite small; thus, replication studies with a greater sample size are warranted.…”

Section: Discussionmentioning

confidence: 99%

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The Multifaceted Effects of Serotonin Transporter Polymorphism (5-HTTLPR) on Anxiety, Implicit Moral Attitudes, and Harmful Behaviors

et al. 2020

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Morality is fundamentally human in nature. Regardless, and even when moral norms seem to work toward the common goal of human cooperation, which morally contentious behaviors are permitted and which are prohibited vary across populations. Because of this occurrence, much scientific debate has revolved around the notion that this phenomenon might be explained by the interaction between genes and environment. Alongside, whether the principles cementing the bases of morality are intuition- or reason-based is another question that has been raised. However, previous research addressing these topics used explicit measures to probe moral attitudes, thus being the participants able to intentionally modify or disguise their honest responses. What’s more, while the 5-HTT gene was found to be associated with anxiety, morality, and even cultural structures, a single genotype–phenotype linkage cannot be established without considering the multifaceted effects of the 5-HTT gene on gene–behavior interactions. In order to explore the role of genetics on modeling moral attitudes and behaviors, we genotyped the 5-HTTLPR in 114 healthy volunteers and subsequently assessed their explicit justice sensitivity (Justice Sensitivity Inventory) and moral permissibility judgments, as well as their implicit moral attitudes [moral implicit association task (mIAT)]. Results revealed that 5-HTTLPR short-allele carriers had significantly lower mIAT reaction times when answering correctly and were less compliant on harming another person even when harm or death would inevitably occur anyway to this other individual. With these preliminary results, we can first see how it does not have to be a matter of vouching for a rationalist versus an intuitionist model of moral judgment, but rather being moral judgment an outcome of the different variants of the 5-HTTLPR polymorphism affecting the way in which individuals engage contrastingly with moral issues.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

The Multifaceted Effects of Serotonin Transporter Polymorphism (5-HTTLPR) on Anxiety, Implicit Moral Attitudes, and Harmful Behaviors

et al. 2020

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“…Compared to CTL, ASC individuals with anxiety showed significantly more negative correlations of the amygdala signal with those of the superior parietal cortex, hippocampus, and fusiform gyrus during explicit threat processing, whereas more positive correlations with the mPFC, inferior frontal cortex, temporal pole, and hippocampus, during implicit threat processing. This amygdala‐centered dysconnectivity could help explain the high level of anxiety comorbid with ASC and support the transdiagnostic neurobiological nature of anxiety (Chen et al, 2020; Herrington et al, 2016; Herrington, Maddox, McVey, et al, 2017; Top Jr. et al, 2016). On one hand, the existing significantly stronger negative couplings with the superior parietal cortex during explicit threat might explain the reduced amygdala reactivity toward explicit fear in ASCs.…”

Section: Discussionmentioning

confidence: 73%

“…Anxiety is the most prevalent co-occurring mental illness in individuals with a diagnosis for an autism spectrum disorder (ASD) (Rodgers & Ofield, 2018). Recent studies have postulated an underlying universal mechanism of anxiety which involves a hyper-or-elevated level of arousal at baseline even to nonthreatening stimuli, and that is mediated by gene expression (Chen et al, 2020;Top Jr. et al, 2016). Previous conceptualizations concerning the neuropathological changes central to the impairments in social interaction incurred by ASD individuals have emphasized amygdala dysfunction as one of its causes (Amaral et al, 2003;Baron-Cohen et al, 2000;Schultz, 2005).…”

Section: Introductionmentioning

confidence: 99%

An amygdala‐centered hyper‐connectivity signature of threatening face processing predicts anxiety in youths with autism spectrum conditions

Chen

Martínez

et al. 2021

Autism Research

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Anxiety is exceedingly prevalent among individuals with an autism spectrum condition (ASC). While recent literature postulates anxiety as a mechanism encompassing an underlying amygdala-related elevated baseline level of arousal even to nonthreatening cues, whether this same mechanism contributes to anxiety in those with an ASC and supports the transdiagnostic nature of anxiety remains elusive. In this case-control study of 51 youths (26 ASC), we assessed autism and anxiety via the Autism-Spectrum Quotient and the State-Trait Anxiety Inventory, respectively. Hemodynamic responses, including amygdala reactivity, to explicit and implicit (backwardly masked) perception of threatening faces were acquired using functional Magnetic Resonance Imaging (fMRI). For explicit fear, ASC individuals showed significantly greater negative correlations between the amygdala and the attentional deployment-parietal network. For implicit fear, ASC individuals showed significantly stronger correlations of the amygdala with the prefrontal networks, temporal pole, and hippocampus. Additionally, an fMRIbased neurologic signature for anxiety in ASCs was identified via the LibSVM machine learning model using amygdala-centered functional connectivity during the emotional processing of explicit and implicit stimuli. Hypervigilance to implicit threat in ASCs comorbid with anxiety might exacerbate explicit threat reactivity; hence the use of attentional avoidance patterns to restrict affective hyperarousal for explicitly perceived socioemotional stimuli. Consequently, developing an attention-independent behavioral/neural marker identifying anxiety in ASCs is highly warranted. Lay SummaryThis study identifies a dissociation of amygdala reactivity dependent on explicit and implicit threat processing. Implicit anxiety in individuals with an autism spectrum condition (ASC) could outweigh explicitly induced threat. When explicitly perceiving socioemotional stimuli, ASC individuals with anxiety might use attentional avoidance patterns to restrict affective hyperarousal.K E Y W O R D S amygdala, autism spectrum condition (ASC), explicit, implicit, threat Yu-Chun Chen and Chenyi Chen contributed equally to this study.

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“…anxiety might involve a hyper-or-elevated baseline level of arousal to neutral stimuli[8,15,35,36], we further conducted detailed comparisons between explicit and implicit conditions to fearful and neutral faces (EF − IF; EN − IN), respectively. A two-way ANOVA with one within-subject variable (emotion: Neutral vs.…”

mentioning

confidence: 99%

Unmasking Anxiety in Autism: Explicit and Implicit Threatening Faces Dissociate Amygdala-centered Functional Connectivity

Chen

Liu

et al. 2020

Preprint

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Background: Anxiety is the most prevalent comorbidity in individuals diagnosed with autism spectrum disorder (ASD). Amygdala reactivity to explicit and implicit threat processing is predictive of anxiety-related symptomatology. The neural mechanisms underlying the link between anxiety and ASD remains elusive. Methods: In this fMRI study, we recruited young adults with ASD (N = 31) and matched them with controls, then proceeded to assess their autistic and anxiety traits by the use of the Autism-Spectrum Quotient (AQ) and the State-Trait Anxiety Inventory (STAI-S), respectively; and scanned their hemodynamic responses, including amygdala, in response to explicit and implicit (backwardly masked) perception of threatening faces. Results: As compared to controls, the amygdala reactivity in ASD subjects was significantly lower to explicit threat, but comparable for implicit threat. The correlations of the amygdala reactivity with the AQ and STAI-S were dissociated depending on threat processing (explicit or implicit). Furthermore, the amygdala in ASD relative to controls had a more negative functional connectivity with the superior parietal cortex, fusiform gyrus, and hippocampus for explicit threat, whereas a more positive connectivity with the medial prefrontal cortex, temporal pole, and hippocampus for implicit threat. Conclusion: In ASD, the transmission of socially relevant information along dorsal and ventral neural pathways centered on the amygdala is dissociated depending on explicit and implicit threat processing. This dissociation, ascribed to their failure to compromise pre-existing hyperarousal, might contribute to anxiety in ASD.

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An integrative analysis of 5HTT-mediated mechanism of hyperactivity to non-threatening voices

Cited by 7 publications

References 73 publications

The Multifaceted Effects of Serotonin Transporter Polymorphism (5-HTTLPR) on Anxiety, Implicit Moral Attitudes, and Harmful Behaviors

The Multifaceted Effects of Serotonin Transporter Polymorphism (5-HTTLPR) on Anxiety, Implicit Moral Attitudes, and Harmful Behaviors

An amygdala‐centered hyper‐connectivity signature of threatening face processing predicts anxiety in youths with autism spectrum conditions

Unmasking Anxiety in Autism: Explicit and Implicit Threatening Faces Dissociate Amygdala-centered Functional Connectivity

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