Biology subjects

Sindermann, C.

Publications and source records attributed to Sindermann, C..

5 recordsLinked to original sources

bioRxiv2019

Gene - Environment Interaction: A TPH2 polymorphism and early life stress shape brain architecture and anxious avoidant behavior

BackgroundEarly 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. MethodsThe 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). ResultsHigher 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. ConclusionsThe 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.

neuroscience↗

bioRxiv2019

Oxytocin modulation of self-other distinction is replicable and influenced by oxytocin receptor (OXTR) genotype

Intranasal oxytocin (OXT) has been associated with effects on diverse social-emotional domains in humans, however progress in the field is currently hampered by poor replicability. Limited statistical power and individual differences in biological factors, such as oxytocin receptor (OXTR) genetics, may have contributed to these variable findings. To this end, we present a pharmaco-genetic study aiming at (1) replicating previous findings suggesting that intranasal oxytocin (24 IU) blurs self-other distinction in a large sample of n = 170 male subjects, (2) determining whether variations in common receptor polymorphisms (rs237887, rs2268491, rs2254298, rs53576, rs2268498) influence sensitivity to oxytocins behavioral effects. Employing a validated oxytocin-sensitive trait judgment paradigm, we confirmed that it blurred self-other distinction in terms of decision time and subsequent memory. However, oxytocin only influenced decision time in rs53576 G carriers, whereas effects on memory performance were most pronounced in rs2268498 TT homozygotes. In summary, the current study replicates our previous findings showing that oxytocin blurs self-other distinction and suggests that sensitivity to its effects in this domain are receptor genotype dependent.

neuroscience↗

bioRxiv2018

Oxytocin effects on brain and behavior are influenced by dose-frequency and receptor genotype: therapeutic implications

BackgroundThere is considerable interest in therapeutic application of intranasal oxytocin in psychiatric disorders, but while clinical trials typically use daily dosing protocols it has not been established whether this is optimal or if there are moderating influences of oxytocin receptor genotype. MethodsIn a randomized, placebo-controlled pre-registered trial on 138 adult male subjects we investigated effects of single and repeated (24IU daily versus alternate days for 5 days) doses of oxytocin on two neural biomarkers (attenuated amygdala fear reactivity and increased intrinsic amygdala-prefrontal functional connectivity) and modulating effects of oxytocin receptor polymorphisms rs53576 and rs2254298 strongly associated with autism. ResultsFindings confirmed that after a single dose, amygdala responses to fear faces were reduced and its resting state connectivity with medial frontal cortex increased. Suppression of amygdala responses to fear faces was restricted to AA homozygotes of rs53576 and A+ carriers of rs2254298, whereas resting state effects were not genotype-dependent. Importantly, amygdala responses to fear faces were absent after daily oxytocin treatment but maintained after treatment every other day with infrequent dosing additionally resulting in reduced behavioral ratings of emotional arousal and intensity after 5 days. In contrast, oxytocin effects on intrinsic amygdala-prefrontal coupling were similar following daily or infrequent dose protocols after 5 days. ConclusionsOverall, results suggest that infrequent rather than daily doses of oxytocin may be more effective therapeutically and that its actions in reducing amygdala responses to fear are strongly genotype-dependent. The study was pre-registered at Clinical Trials.gov (NCT03610919).

neuroscience↗

bioRxiv2018

Oxytocin promotes lying for personal gain in a genotype-dependent manner

Society values honesty, since it fosters trust in others. Although we have a strong moral aversion to lying, particularly when it is self-serving, we nevertheless lie quite frequently and the biological basis for this is poorly understood. The hypothalamic neuropeptide oxytocin has been implicated in a number of anti-social as well as pro-social behaviours, including lying to benefit in-group members or in competitive situations. The aim of the present study was to investigate the effects of oxytocin administration on self-serving lying behaviour and possible moderating effects of genetic underpinnings of the oxytocin receptor. A total of 161 adult men participated in a randomized double-blind placebo-controlled between-subject intranasal oxytocin administration (24 International Units) study where self-serving lying was assessed using the die-in-a-cup paradigm. Additionally, contributions of polymorphisms in the oxytocin receptor gene were investigated using a haplotype approach. Results showed that while placebo-treated subjects behaved honestly across three successive rounds, oxytocin administration promoted self-serving lying, particularly in the third / last round and only to a certain degree (not to the maximum). Moreover, this effect of oxytocin was strongest in carriers of the GCG individual haplotype (rs237887-rs2268491-rs2254298) and non-carriers of the GT individual haplotype (rs53576-rs2268498) on the oxytocin receptor gene. Overall our findings demonstrate that oxytocin administration can promote self-serving lying when subjects are given repeated opportunities to lie and that these effects are moderated by genetic underpinnings of the oxytocin receptor.

genetics↗

bioRxiv2018

Real-time functional connectivity-based neurofeedback of amygdala-frontal pathways reduces anxiety

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 strategy 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. In a randomized within-subject sham-controlled design high anxious subjects (n = 26) underwent real-time fMRI-guided 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 three days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. Training of the target, yet not the sham-control, pathway significantly increased amygdala-vlPFC connectivity and decreased subjective anxiety levels. On the individual level stronger connectivity increases were significantly associated with anxiety reduction. At follow-up, volitional control over the target pathway and decreased anxiety level were maintained in the absence of feedback. The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel strategy 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.

clinical trials↗