A randomized trial shows dose-frequency and genotype may determine the therapeutic efficacy of intranasal oxytocin.

BACKGROUND: The neuropeptide oxytocin is proposed as a promising therapy for social dysfunction by modulating amygdala-mediated social-emotional behavior. Although clinical trials report some benefits of chronic treatment, it is unclear whether efficacy may be influenced by dose frequency or genotype. METHODS: In a randomized, double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging trial (150 male subjects), we investigated acute and different chronic (every day or on alternate days for 5 days) intranasal oxytocin (24 international units) effects and oxytocin receptor genotype-mediated treatment sensitivity on amygdala responses to face emotions. We also investigated similar effects on resting-state functional connectivity between the amygdala and prefrontal cortex. RESULTS: A single dose of oxytocin-reduced amygdala responses to all face emotions but for threatening (fear and anger) and happy faces, this effect was abolished after daily doses for 5 days but maintained by doses given every other day. The latter dose regime also enhanced associated anxious-arousal attenuation for fear faces. Oxytocin effects on reducing amygdala responses to face emotions only occurred in AA homozygotes of rs53576 and A carriers of rs2254298. The effects of oxytocin on resting-state functional connectivity were not influenced by either dose-frequency or receptor genotype. CONCLUSIONS: Infrequent chronic oxytocin administration may be therapeutically most efficient and its anxiolytic neural and behavioral actions are highly genotype-dependent in males.

Serotonin and early life stress interact to shape brain architecture and anxious avoidant behavior - a TPH2 imaging genetics approach.

BACKGROUND: Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance. METHODS: The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). RESULTS: Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. CONCLUSIONS: The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.

Real-Time Functional Connectivity-Informed Neurofeedback of Amygdala-Frontal Pathways Reduces Anxiety.

BACKGROUND: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. METHODS: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after 3 days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. RESULTS: Training of the target, yet not the sham control, pathway significantly increased amygdala-vlPFC connectivity and decreased levels of anxiety. Stronger connectivity increases were significantly associated with higher anxiety reduction on the group level. At the follow-up, volitional control over the target pathway was maintained in the absence of feedback. CONCLUSIONS: The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel intervention to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.

A functional polymorphism of the OXTR gene is associated with autistic traits in Caucasian and Asian populations.

There is increasing evidence for associations between polymorphisms of the oxytocin receptor (OXTR) gene and autism spectrum disorder, but to date no study has established links with autistic traits in healthy subjects and potential cultural differences. The present research firstly investigated associations between three widely studied OXTR SNPs and autistic and empathic traits (rs53576 (G/A); rs2254298 (G/A); rs2268498 (T/C)) in two independent studies on male and female Caucasian (n = 537) and Chinese students (n = 280). Autistic and empathic traits were measured in all subjects in the two independent groups using the Autism -Spectrum Quotient (AQ) and the Interpersonal Reactivity Index (IRI) respectively, together with their sub-scales. For both sites, genotyping of the OXTR SNPs was conducted on buccal swab samples using a Cobas Z 480 Light Cycler following automated DNA extraction. Associations at the genotype level with autism trait scores were found in Caucasian subjects for rs2268498 only, with TT carriers having the lowest AQ scores compared with those carrying at least one C-allele. This finding was independently replicated in the Chinese sample although a smaller proportion carried the C-allele compared with the Caucasian sample. Some minor associations were found between empathy trait scores and the three SNPs but were not consistent between the samples. These findings show for the first time that the rs2268498 SNP localized in the promoter flanking region of the OXTR gene is associated with autistic traits in different ethnic/cultural groups. This provides further support for the role of the OXTR gene in relation to autism.

On the Willingness to Pay for social media/messenger services taking into account personality and sent/received messages among WhatsApp users.

WhatsApp has billions of users worldwide. Instead of paying a subscription fee, users provide their data for the use allowance. This data is used by Meta - the company behind WhatsApp - to obtain insights into user characteristics and monetize those insights. However, this data business model is among others criticized for fostering a loss of privacy that arises when platforms analyze user data, and for the use of design elements to attract users to the platform when they are not online or to extend their online time. Therefore, an increasing number of scientists are discussing whether other payment models are needed to overcome those disadvantages, like a monetary payment model. However, users would probably only pay for improved social media products. This paper provides an empirical basis for understanding the user perspective and, in particular, whether and how much users are willing to pay for improved social media products. For this, 2924 WhatsApp users' perspectives on this topic were investigated. They were asked whether and how much they are willing to pay money for a messenger/social media service when its quality would be improved. Variables potentially influencing Willingness to Pay (i.e., personality, sent/received messages) were studied as well. 47% of the participants were unwilling to pay for a healthier messenger service, and about a quarter were willing or stayed neutral. Further analysis revealed that more agreeable people were more willing to pay. Further: Higher Extraversion was associated with more sent/received messages, but the number of sent/received messages was not linked to Willingness to Pay. The present study shows that many users still are not willing to pay for social media (here messengers), which indicates that the advantages of paying for social media with money instead of with one's own data might need to be better communicated.

Examining the growth in willingness to pay for digital wellbeing services on social media: A comparative analysis.

In recent years, there has been a growing need for social media platforms to offer services that preserve and promote users' digital wellbeing, including better protection of personal data and balanced technology usage. However, the current business model of social media is often seen as in conflict with users' digital wellbeing. In 2020, a study investigated users' willingness to pay monetary fees for social media digital wellbeing services. In the present work, we replicated this study in Q4 of 2022, aiming to explore any changes in interest and willingness to pay for these services. In addition, we extended the replication by conducting qualitative analysis on participants' comments to gain deeper insight and identify reasons for payment and reasons for rejecting to pay. Data were collected from 262 participants through an online questionnaire. The survey focused on four services: better data protection, less use of data for marketing, aiding users in controlling their prolonged usage, and reducing fake news and radicalisation on social media. The results showed that the willingness to pay for these services was significantly higher in 2022 compared to the results published in 2020. Participants expressed concerns about the feasibility and fairness of the alternative business model, which requires users to pay for safety and support. Our findings suggest a growing interest in digital wellbeing services, emphasizing the need for social media platforms to assess the feasibility of alternative business models, identify user segments, and take measures to enhance consumers' trust, accordingly.

Salivary cortisol and alpha-amylase as stress markers to evaluate an individualized music intervention for people with dementia: feasibility and pilot analyses.

OBJECTIVES: We investigated salivary biomarkers of stress, more specifically, cortisol and alpha-amylase, to evaluate effects of individualized music listening (IML) in people with dementia. METHOD: Participants were N = 64 nursing home residents with dementia (meanage = 83.53 ± 7.71 years, 68.8% female). Participants were randomly assigned to either listening to their favorite music every other day for a period of six weeks (intervention), or standard care (control). Using the Saliva Children`s Swab (SCS), saliva was collected before, after, and 20 min after IML sessions at the beginning and end of the intervention period for the analysis of salivary alpha-amylase and cortisol. RESULTS: Using the SCS was feasible in people with dementia. Nevertheless, there was no effect of IML on salivary stress markers. DISCUSSION: Although using SCS was feasible, active patient engagement is required. Future studies need to corroborate findings in larger samples. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00015641, ISRCTN registry: ISRCTN59052178.

Patterns of neural activity in response to threatening faces are predictive of autistic traits: modulatory effects of oxytocin receptor genotype.

Autistic individuals generally demonstrate impaired emotion recognition but it is unclear whether effects are emotion-specific or influenced by oxytocin receptor (OXTR) genotype. Here we implemented a dimensional approach using an implicit emotion recognition task together with functional MRI in a large cohort of neurotypical adult participants (N = 255, male = 131, aged 17-29 years) to establish associations between autistic traits and neural and behavioral responses to specific face emotions, together with modulatory effects of OXTR genotype. A searchlight-based multivariate pattern analysis (MVPA) revealed an extensive network of frontal, basal ganglia, cingulate and limbic regions exhibiting significant predictability for autistic traits from patterns of responses to angry relative to neutral expression faces. Functional connectivity analyses revealed a genotype interaction (OXTR SNPs rs2254298, rs2268491) for coupling between the orbitofrontal cortex and mid-cingulate during angry expression processing, with a negative association between coupling and autistic traits in the risk-allele group and a positive one in the non-risk allele group. Overall, results indicate extensive emotion-specific associations primarily between patterns of neural responses to angry faces and autistic traits in regions processing motivation, reward and salience but not in early visual processing. Functional connections between these identified regions were not only associated with autistic traits but also influenced by OXTR genotype. Thus, altered patterns of neural responses to threatening faces may be a potential biomarker for autistic symptoms although modulatory influences of OXTR genotype need to be taken into account.

Linking primary emotional traits to ideological attitudes and personal value types.

The present study aimed at investigating associations of both ideological attitudes and personal value types with the personality traits derived from the Affective Neuroscience Theory (ANT). For that, data of N = 626 (n = 403 men, n = 220 women, n = 3 identifying as neither a man nor a woman) participants of an online survey in the German language were analyzed. Relations of primary emotional traits derived from the ANT with Right-Wing Authoritarianism (RWA), Social Dominance Orientation (SDO), and personal value types, such as the higher-order value type dimensions "Conservation-Openness to Change" and "Self-Enhancement-Self-Transcendence", were examined by means of correlational analyses and structural equation modeling. Results revealed among others relations between low SEEKING, high ANGER and high RWA. Low CARE and high ANGER were associated with high SDO. Moreover, FEAR was related to the higher-order value type dimension ranging from Conservation to Openness to Change. ANGER was associated with the higher-order value type dimension ranging from Self-Enhancement to Self-Transcendence. The present results do not only expand knowledge on the personality traits associated with ideological attitudes and personal value types. Beyond this, considering the neuroanatomical, functional, and neurochemical correlates of the primary emotional traits SEEKING, ANGER, CARE, and FEAR, the present results may provide a roadmap for forthcoming studies aiming at examining biological correlates of ideological attitudes and personal value types, such as those works in the field of political neuroscience.

A central serotonin regulating gene polymorphism (TPH2) determines vulnerability to acute tryptophan depletion-induced anxiety and ventromedial prefrontal threat reactivity in healthy young men.

Serotonin (5-HT) has long been implicated in adaptive emotion regulation as well as the development and treatment of emotional dysregulations in mental disorders. Accumulating evidence suggests a genetic vulnerability may render some individuals at a greater risk for the detrimental effects of transient variations in 5-HT signaling. The present study aimed to investigate whether individual variations in the Tryptophan hydroxylase 2 (TPH2) genetics influence susceptibility for behavioral and neural threat reactivity dysregulations during transiently decreased 5-HT signaling. To this end, interactive effects between TPH2 (rs4570625) genotype and acute tryptophan depletion (ATD) on threat reactivity were examined in a within-subject placebo-controlled pharmacological fMRI trial (n = 51). A priori genotype stratification of extreme groups (GG vs. TT) allowed balanced sampling. While no main effects of ATD on neural reactivity to threat-related stimuli and mood state were observed in the entire sample, accounting for TPH2 genotype revealed an ATD-induced increase in subjective anxious arousal in the GG but not the TT carriers. The effects were mirrored on the neural level, such that ATD specifically reduced ventromedial prefrontal cortex reactivity towards threat-related stimuli in the GG carriers. Furthermore, the ATD-induced increase in subjective anxiety positively associated with the extent of ATD-induced changes in ventromedial prefrontal cortex activity in response to threat-related stimuli in GG carriers. Together the present findings suggest for the first time that individual variations in TPH2 genetics render individuals susceptible to the anxiogenic and neural effects of a transient decrease in 5-HT signaling.