Institute of Developmental Physiology

This narrative review synthesizes advances from the past 18 months on the etiology of autism spectrum disorder (ASD), integrating findings from genetics, neurobiology, environmental epidemiology, and developmental psychiatry. Given the profound clinical heterogeneity of ASD, improved etiologic clarity is essential for risk stratification, early identification, and targeted intervention. Extensive genomic and multiancestry studies are now further clarifying how both common polygenic and rare high-impact variants contribute to ASD. These studies reveal different patterns of genetic liability that underlie distinct ASD subgroups. In parallel, functional and multiomic research is highlighting shared pathways involving synaptic signaling, gene regulation, immune processes, and the balance between excitatory and inhibitory signals. Environmental research, especially on maternal immune activation and maternal metabolic factors, uses causal inference methods to clarify modest but plausible causal effects, tempering earlier claims. Longitudinal imaging and infant cohort studies continue to show that atypical connectivity and social-brain differences occur before behavioral diagnosis. Sex differences and global diversity underscore the need for etiology models to incorporate sex-specific genetic architecture and address significant gaps in ancestral representation. ASD arises from a dynamic interplay of genetic liability, early neurodevelopmental processes, and environmental exposures. Etiologic progress now depends on integrating multilevel and multiomic data - including genomic, transcriptomic, epigenetic, imaging, and epidemiologic information - toward stratified developmental models and better-tailored interventions.

We aimed to investigate the effects of EMs in the eye movement desensitization (EMD) process, as important part of EMDR, in reducing stress reactivity, PTSD symptoms, anxiety-depression symptoms, and improving quality of life and neurocognitive function, as compared to a retrieval-only condition, which involved the same procedures as EMD but excluded EMs, in Indonesian PTSD patients. Our research was a dismantling study that specifically examined the essential EMs component of EMDR. We followed the EMDR protocol when carrying out the EMD procedure. EMD is the initial stage of EMDR that does not involve the installation phase. We omitted the installation phase to achieve precise EMs effects during retrieval of traumatic memories. The results of our systematic review indicated that psychological treatment for PTSD did not affect most neurocognitive functions, except memory outcomes. The RCT, as presented in Chapters 4, 5, and 6, investigated the effect of EMD on the reduction of stress reactivity, PTSD symptoms, anxiety or depression symptoms, and the improvement of neurocognitive function in PTSD patients in comparison with retrieval-only conditions. We conducted a comparison of EMD with a retrieval-only control condition, which involved the same procedures as EMD but excluded EMs. Data collection occurred at baseline (T0), one week post-treatment (T1), one month (T2), and three months post-treatment (T3), with the exception of psychophysiological measures obtained at T0 and T1. In Chapter 4, it was described that no significant differences in stress reactivity between EMD and retrieval-only participants were found, as both groups showed a decreased HRV reactivity and accelerated HRV recovery at post- treatment in response to trauma scripts compared to neutral scripts. The study also did not find significant differences between EMD and retrieval-only in other physiological variables, such as HR, PEP, and circadian cortisol levels (area under the curve; AUC), and the cortisol awakening response (CAR) after treatment. In general, the physiological data indicated that EMs did not have an additive beneficial effect on the reduction of stress responses or the acceleration of recovery responses to traumatic memories in PTSD when compared to retrieval-only. There was one exception: a significant acceleration in HR recovery in response to the trauma script after treatment was found in the EMD condition, but not in the retrieval-only condition. Furthermore, in chapter 5, we reported no significant differences between the two groups in symptoms of PTSD, anxiety and depression and in quality of life. Finally, in chapter 6, the findings of our study indicated that there was no significant difference between the EMD and the retrieval-only conditions in terms of neurocognitive function. Our study findings did not support the hypothesis that EMs were more effective than retrieval-only in improving stress reactivity and stress response in PTSD patients, nor were EMs more effective in reducing PTSD symptoms, anxiety and depression symptoms, or in improving quality of life and neurocognitive functioning. Against expectations, the study's findings did not provide evidence to support the theory thatEMs have additional effects on the effectiveness of EMDR. Therefore, this studyconcludes that both EMD and retrieval-only interventions can be used to reduce stress reactivity, PTSD symptoms, and improve neurocognitive function in PTSD patients.

Both transcription and replication can take place simultaneously on the same DNA template, potentially leading to transcription-replication conflicts (TRCs) and topological problems. Here we asked which topoisomerase(s) is/are the best candidate(s) for sensing TRC. Genome-wide topoisomerase binding sites were mapped in parallel for all the nuclear topoisomerases (TOP1, TOP2A, TOP2B, TOP3A and TOP3B). To increase the signal to noise ratio (SNR), we used ectopic expression of those topoisomerases in H293 cells followed by a modified CUT&Tag method. Although each topoisomerase showed distinct binding patterns, all topoisomerase binding signals positively correlated with gene transcription. TOP3A binding signals were suppressed by DNA replication inhibition. This was also observed but to a lesser extent for TOP2A and TOP2B. Hence, we propose the involvement of TOP3A in sensing both head-on TRCs (HO-TRCs) and co-directional TRCs (CD-TRCs). In which case, the TOP3A signals appear concentrated within the promoters and first 20 kb regions of the 5' -end of genes, suggesting the prevalence of TRCs and the recruitment of TOP3A in the 5'-regions of transcribed and replicated genes.

The development of social-cognitive abilities during adolescence is vital for the formation of positive lasting social relationships outside the family. A better understanding of the development of adolescent social-cognitive abilities can potentially foster positive social relationships, heighten resilience, and improve general well-being and mental health for adolescents. Research in the past decade has provided strong evidence that social-cognitive abilities and their underlying neural functions are still under development during adolescence. However, the specific developmental trajectories of distinct social-cognitive abilities, and individual differences relating to their development have not yet been established. The aim of the current dissertation was to further our understanding of the development of specific social-cognitive abilities during adolescents and how they shape and are shaped by the peer environment. Overall, the present dissertation confirms that adolescence is a period of continued social-cognitive development. The precise developmental trajectories depend on the specific social-cognitive process and show individual differences, depending on factors such as the peer environment and gender. Our results demonstrate a bidirectional interaction in which social-cognitive abilities shape and are shaped by the peer context during adolescence. As such, the present dissertation confirms that the combination of adolescents’ social reorientation and continued maturation of the neural networks of the social brain present unique opportunities for adolescents’ social-cognitive development and highlights the role of the peer context in influencing positive or negative developmental trajectories.

IntroductionIn the USA, Black birthing people and infants experience disproportionately worse pregnancy-related health outcomes. The causes for these disparities are unknown, but evidence suggests that they are likely socially and environmentally based. Efforts to identify the determinants of these racial disparities are urgently needed to elucidate the highest priority targets for intervention. The Birth and Beyond (BABY) study evaluates how micro-level (eg, interpersonal and family) and macro-level (eg, neighbourhood and environmental) risk and resiliency factors transact to shape birth person-infant health, and underlying psychobiological mechanisms.Methods and analysisThe BABY study will follow 350 Black families (birthing parents, non-birthing parents and infants) from pregnancy through the first postpartum year, with research visits during pregnancy and at infant ages 6 and 12 months. Research visits comprise a combination of interview about a range of recent and life course stress and resiliency exposures and supports, psychophysiological (sympathetic, parasympathetic and adrenocortical) assessment and behavioural observations of parent–infant coregulatory behaviours. Spatial analyses are completed by mapping parent current and past residential addresses onto archival public data (eg, about neighbourhood quality and racial segregation). Finally, EMRs are abstracted for information about birthing parent relevant medical history, pregnancy conditions and infant birth outcomes. Analyses will evaluate the risk and resiliency mechanisms that contribute to pregnancy and birth-related outcomes for Black birthing people and their infants, and the protective role of individual, familial, cultural, and community supports.Ethics and disseminationThe BABY study has been approved by the Institutional Review Board at Albany Medical Centre. The study team consulted with local organisations and groups comprised of stakeholders and community leaders and continues to do so throughout the study. Research results will be disseminated with the scientific and local community as appropriate.

Workers who do monotonous and repetitive work in a static position often complain about fatigue and decreased work efficiency. Some studies indicate that to improve muscle fatigue, resistance strength training can be used. To investigate the effect of 4-week inertial training on shoulder muscles' strength and muscles' fatigue resistance 44 female workers with disabilities were examined. The participants were randomized into the training group (T) (N = 32) and the control group (C) (N = 12). Before the training and after that shoulder muscles' strength were tested at the start and at the end of the workday (Monday and Friday). The participants were asked to complete questionnaire concerning their fatigue at work (T and C), inertial training and work efficiency (T). The work performed during the last day of the workweek, i.e., Friday (before training) resulted in a significant decrease in shoulder muscles' strength in T and C. Muscle strength achieved at the end of the workweek (Friday afternoon) was significantly lower than achieved at the start of the workweek (Monday morning) in both tested groups (before training). Moreover, inertial training resulted in a significant increase in shoulder muscles' strength in T; 34-74% for different muscles. No changes in muscles' strength were noted in C. Increased muscle strength in T following inertial training effectively prevented muscle fatigue. After training the differences in shoulder muscles' strength noted in T during different times of the workday and workweek were insignificant. Moreover, 4-week inertial training increased significantly the work efficiency of women from T by 4%; no changes were noted in C. Inertial training was well tolerated by the participants. Using inertial training in women with disabilities to prevent shoulder muscles' fatigue during the workday and workweek is recommended. Med Pr Work Health Saf. 2024;75(2):113-122.

Background. Studying the functional state of the body of adolescents when they preform cognitive activity using electronic devices is of great importance due to the introduction of information and computer technologies into the educational process. Identifying the characteristics of the reactivity of students’ bodies when performing cognitive activities in a digital environment will contribute to both optimization of learning and health protection.The aim. To study the autonomic regulation of heart rate, electrodermal activity, cerebral circulation and the level of cortisol in saliva when adolescents performed a cognitive test on electronic devices (tablet, laptop) and on paper.Materials and methods. Using analysis of heart rate variability, electrodermal activity, rheoencephalography and enzyme-linked immunosorbent determination of cortisol in saliva, цe examined 48 adolescents while performing a cognitive activity on electronic devices.Results. When adolescents perform cognitive activity using electronic devices, we can register changes in heart rate variability, electrodermal activity and cerebral circulation. Cognitive activity in a digital environment causes an increase in sympathetic effect ontheheart rate with adecrease inparasympathetic activity, anincrease inthe integrative indicator ofgalvanic skin response, invascular tone and adecrease in the cerebral blood flow intensity. One in four adolescents experiences anticipatory stimulation of the endocrine system before taking a cognitive test. Correlation analysis revealed alarge number of correlations between the studied indicators both in the initial state and during cognitive activity.Conclusion. A large number of correlations, both in the initial state and during the cognitive test, between heart rate variability and cortisol concentration, cerebral circulation parameters indicate the preservation of a rigid system of neurovegetative and humoral regulation of heart rate when using electronic devices compared to paper-based media.

Adolescence is an important developmental period for learning who can and cannot be trusted, and how to adapt one’s trust behavior in response to others’ reciprocal behavior. The main objective of this thesis was to create more insight into the development of adolescent trust behavior and to explain individual differences in trust behavior and the related neural activity. The development of initial trust behavior and the development of adaptive trust behavior were investigated. Furthermore, in the chapters described in this thesis, factors within the individual, e.g., gender, personality traits, symptoms of psychopathology, and perspective-taking abilities, and factors from one’s social environment, e.g., social embeddedness within social networks, were used to predict individual differences in trust behavior. Collectively, the results presented in this thesis indicate that adolescence is an important developmental period for trust behavior. First, increased levels of initial trust behavior were found throughout adolescence. Second, adolescents showed stronger adaptive trust behavior with age when interacting with untrustworthy others, and they showed age-related increases in average trust behavior when the partner behaved in a trustworthy manner. This suggests that learning who can be trusted and responding adaptively to the partner develops throughout adolescence. Adaptive trust behavior was also elicited by contextual factors, as adolescents showed they were able to overcome incorrect prior expectations about the partner and adjust their trust behavior in response to the partner’s actual behavior. The increased dlPFC and superior parietal gyrus activity that was found when interacting with this partner might tentatively suggest that cognitive control processes underlie these adaptive trust behavior processes. Furthermore, the results of this thesis indicated no support for a relationship between trust behavior and personality traits, symptoms of psychopathology, and perspective-taking abilities. The results did show that individual differences in adolescent trust behavior and the related neural activity can be explained by gender and the position within a social network. Boys showed a stronger developmental increase in initial trust behavior throughout adolescence compared to girls. Furthermore, the centrality of one´s social network position was positively related to levels of initial trust and to caudate activity, tentatively indicating increased expectancy violation when interacting with untrustworthy others.

SummaryGerminal zone (GZ) exit is at the top of a cascade of events promoting the maturation of neurons and their assembly into neuronal circuits. Developing neurons and their progenitors must interpret varied niche signals like morphogens, guidance molecules, extracellular matrix, or adhesive cues to navigate GZ occupancy. How newborn neurons integrate multiple cell-extrinsic niche cues with their cell-intrinsic machinery in exiting a GZ is unknown. We establish cooperation between cell polarity-regulated adhesion and Netrin-1 signaling comprises a coincidence detection circuit repelling maturing neurons from their GZ. In this circuit, the Partitioning defective 3 (Pard3) polarity protein and Junctional adhesion molecule-C (JAM-C) adhesion protein promote, while the Seven in absentia 2 (Siah2) ubiquitin ligase inhibits, Deleted in colorectal cancer (DCC) receptor surface recruitment to gate differentiation linked repulsion to GZ Netrin-1. These results demonstrate cell polarity as a central integrator of adhesive- and guidance cues cooperating to spur GZ exit.Highlights-Netrin1 expressed in the cerebellar GZ ranges from an attractive to repulsive cue depending on differentiation status or extracellular matrix context.-Modulation of DCC expression levels impacts the nature of the Netrin1 response and GZ occupancy status.-Siah2, Pard3, and JamC function to modulate responsiveness to purified Netrin1 and cooperate with Dcc to regulate GZ exit.-Pard3 and JamC promote both basal and Netrin1 stimulated DCC surface recruitment to control GZ exit and Netrin1 repulsion