Personal insult disrupts regulatory brain networks in violent offenders.

The failure to adequately regulate negative emotions represents a prominent characteristic of violent offenders. In this functional magnetic resonance imaging study, we used technical, nonsocial frustration to elicit anger in violent offenders (n = 19) and then increased the provocation by adding personal insults (social provocation). The aim was to investigate neural connectivity patterns involved in anger processing, to detect the effect of increasing provocation by personal insult, and to compare anger-related connectivity patterns between offenders and noncriminal controls (n = 12). During technical frustration, the offenders showed increased neural connectivity between the amygdala and prefrontal cortex compared to the controls. Conversely, personal insults, and thus increased levels of provocation, resulted in a significant reduction of neural connectivity between regions involved in cognitive control in the offenders but not controls. We conclude that, when (nonsocially) frustrated, offenders were able to employ regulatory brain networks by displaying stronger connectivity between regulatory prefrontal and limbic regions than noncriminal controls. In addition, offenders seemed particularly sensitive to personal insults, which led to increased implicit aggression (by means of motoric responses) and reduced connectivity in networks involved in cognitive control (including dorsomedial prefrontal cortex, precuneus, middle/superior temporal regions).

Sex-dependent multimodal response profiles to psychosocial stress.

INTRODUCTION: Sex differences in stress reactions are often reported in the literature. However, the sex-dependent interplay of different facets of stress is still not fully understood. Particularly in neuroimaging research, studies on large samples combining different indicators of stress remain scarce. MATERIALS AND METHODS: In a functional magnetic resonance imaging study, a sample of 140 healthy participants (67 females using oral contraceptives) underwent a standardized stress induction protocol, the ScanSTRESS. During the experiment, salivary cortisol and subjective ratings were obtained at multiple time points and heart rate was recorded. RESULTS: Sex differences emerged in different facets of the stress response:Women reacted with enhanced subjective feelings of stress and increases in heart rate, while men showed more pronounced neural activation in stress-related brain regions such as the inferior frontal gyrus and insula. Subjective feelings of stress and (para) hippocampal activity were negatively related in women,whereas a slightly positive association was observed in men. DISCUSSION: These results provide further insight in the sex-specific stress response patterns. Moreover, they emphasize the role of the hippocampus in the regulation of the stress response. This paves the way for the identification of sex-dependent vulnerability factors that can, in the future, be implemented in the prevention and treatment of stress-related disorders.

Accurate machine learning prediction of sexual orientation based on brain morphology and intrinsic functional connectivity.

BACKGROUND: Sexual orientation in humans represents a multilevel construct that is grounded in both neurobiological and environmental factors. OBJECTIVE: Here, we bring to bear a machine learning approach to predict sexual orientation from gray matter volumes (GMVs) or resting-state functional connectivity (RSFC) in a cohort of 45 heterosexual and 41 homosexual participants. METHODS: In both brain assessments, we used penalized logistic regression models and nonparametric permutation. RESULTS: We found an average accuracy of 62% (±6.72) for predicting sexual orientation based on GMV and an average predictive accuracy of 92% (±9.89) using RSFC. Regions in the precentral gyrus, precuneus and the prefrontal cortex were significantly informative for distinguishing heterosexual from homosexual participants in both the GMV and RSFC settings. CONCLUSIONS: These results indicate that, aside from self-reports, RSFC offers neurobiological information valuable for highly accurate prediction of sexual orientation. We demonstrate for the first time that sexual orientation is reflected in specific patterns of RSFC, which enable personalized, brain-based predictions of this highly complex human trait. While these results are preliminary, our neurobiologically based prediction framework illustrates the great value and potential of RSFC for revealing biologically meaningful and generalizable predictive patterns in the human brain.

A Systematic Review on Common and Distinct Neural Correlates of Risk-taking in Substance-related and Non-substance Related Addictions.

Both substance-related as well as non-substance-related addictions may include recurrent engagement in risky actions despite adverse outcomes. We here apply a unified approach and review task-based neuroimaging studies on substance-related (SRAs) and non-substance related addictions (NSRAs) to examine commonalities and differences in neural correlates of risk-taking in these two addiction types. To this end, we conducted a systematic review adhering to the PRISMA guidelines. Two databases were searched with predefined search terms to identify neuroimaging studies on risk-taking tasks in individuals with addiction disorders. In total, 19 studies on SRAs (comprising a total of 648 individuals with SRAs) and 10 studies on NSRAs (comprising a total of 187 individuals with NSRAs) were included. Risk-related brain activation in SRAs and NSRAs was summarized individually and subsequently compared to each other. Results suggest convergent altered risk-related neural processes, including hyperactivity in the OFC and the striatum. As characteristic for both addiction types, these brain regions may represent an underlying mechanism of suboptimal decision-making. In contrast, decreased DLPFC activity may be specific to SRAs and decreased IFG activity could only be identified for NSRAs. The precuneus and posterior cingulate show elevated activity in SRAs, while findings regarding these areas were mixed in NSRAs. Additional scarce evidence suggests decreased ventral ACC activity and increased dorsal ACC activity in both addiction types. Associations between identified activation patterns with drug use severity underpin the clinical relevance of these findings. However, this exploratory evidence should be interpreted with caution and should be regarded as preliminary. Future research is needed to evaluate the findings gathered by this review.

Identifying the duration of emotional stimulus presentation for conscious versus subconscious perception via hierarchical drift diffusion models.

To investigate subliminal priming effects, different durations for stimulus presentation are applied ranging from 8 to 30 ms. This study aims to select an optimal presentation span whichleads to a subconscious processing. 40 healthy participants rated emotional faces (sad, neutral or happy expression) presented for 8.3 ms, 16.7 ms and 25 ms. Alongside subjective and objectivestimulus awareness, task performance was estimated via hierarchical drift diffusion models. Participants reported stimulus awareness in 65 % of the 25 ms trials,in 36 % of 16.7 ms trials, and in 2.5 % of 8.3 ms trials.Emotion-dependent responses were reflected in decreased performance (drift rates, accuracy)during sad trials. The detection rate (probability of making a correct response) during 8.3 ms was 12.2 % and slightly above chance level (33.333 % for three response options) during 16.7 ms trials (36.8 %). The experiments suggest a presentation time of 16.7 ms as optimal for subconscious priming. An emotion-specific response was detected during 16.7 ms while the performanceindicates a subconscious processing.

Variability and symmetry of gait kinematics under dual-task performance of older patients with depression.

BACKGROUND: Depression in old age is associated with an increased fall risk. Especially in cognitively challenging situations, fall-promoting gait deviations could appear due to depression- and age-related cognitive deficits. AIM: This study investigates (i) whether there are differences in gait performance between depressed older patients and healthy controls and (ii) if gait patterns aggravate when performing a cognitive task whilst walking. METHODS: 16 depressed older patients (mean age: 73.1 ± 5.8 years) and 19 healthy controls (mean age: 73.3 ± 6.1 years) were included in the study. Spatiotemporal gait parameters (speed, stride length, swing time) and minimum toe clearance were recorded using a three-dimensional motion-capture system under a single- and a dual-task condition (counting backwards). RESULTS: After Bonferroni correction, depressed older patients showed significantly slower walking speed, shorter strides and smaller minimum toe clearance, as well as greater variability in stride length than healthy controls. Under the dual-task, gait performance deteriorated compared with single-task, with slower gait speed, shorter strides, and longer swing time. DISCUSSION: Slower walking speed and shorter steps of depressed patients may be a strategy to counteract their fall risk. Increased variability suggests a less stable gait pattern in patients, which could be a reason for their increased fall risk. CONCLUSIONS: Depression in old age has a strong effect on gait performance. Possible interventions that might prevent falls in this vulnerable group are discussed. The study was registered at Open Science Framework on May 18, 2021 (publicly accessible May 30, 2023).

[Implementation of a Pilot Project Supporting Parents Suffering from Cancer with Underage Children]. / Implementierung eines Modellprojektes zur phasenübergreifenden Unterstützung von krebskranken Eltern mit minderjährigen Kindern.

OBJECTIVE: Families with one parent suffering from cancer are exposed to extraordinary emotional and organizational burdens, affecting underaged children. To help coordinated access to social and logistic support options and thus reduce the stress on family members, the project Brückenschlag was founded. The aim of this paper was to evaluate the implementation of this pilot project following the healthcare utilization model by Andersen. METHODS: A cross-sectional observational study was conducted using a mixed-method approach. Semi-structured written expert surveys (n=10) and secondary analysis of routine data of the care model (n=171 families) were combined. RESULTS: Quantitative secondary analysis: The participating families had 1-7 children (median (m) 2, range (s) 6). In 66% of the cases, the mother was affected by cancer, in 20% the diseased parent was in a single parent household. The communication structure in these families was rated "limited" to "rather open". Of the total of 171 contacts (study period 9/14 to 11/17), 133 families made use of Brückenschlag; 59.2% of the contacts were made by psycho-oncologists and the social services department of the hospital. If the contact was initiated by the patients themselves or by psycho-oncologists, a guidance was established significantly more frequently (significance of chi-squared test 0.047). Qualitative analysis: There was a lack of awareness and coordination of existing support services and a lack of family resources to use existing support offers. Both the desired and the established support fell primarily in the area of organizational support. Brückenschlag improved networking and took on a navigating function for the families. CONCLUSION: The data collected indicate that in families, matching the German average in their socio-demographic characteristics, a great need for organizational support develops as soon as one parent becomes sick with cancer. The model project Brückenschlag creates an access to support services for families with one parent suffering from cancer.

Male brain processing of the body odor of ovulating women compared to that of pregnant women.

Female chemical signals underlie the advertising of sexual receptivity and fertility. Whether the body odor of a pregnant woman also has a signaling function with respect to male behavior is yet to be conclusively established. This study examines how the body odors of ovulating and pregnant women differentially affect the behavior of heterosexual men. Body odor samples were collected from 5 pregnant women and 5 matched controls during ovulation. In a double-blind functional magnetic resonance imaging design, 18 heterosexual men were exposed to female body odors during ovulation (OV) and pregnancy (PRG) while being required to indicate the attractiveness of concurrently presented female portrait images. The participants were also required to indicate whether they assumed a depicted woman was pregnant. While neither OV nor PRG altered the perceived attractiveness of a presented face, the men tended to identify the women as pregnant while exposed to a PRG body odor. On the neural level, OV activated a network of the frontotemporal and limbic regions, while PRG activated the superior medial frontal gyrus. The results suggest that the detection of sexual availability activates the male brain regions associated with face processing and reward/motivation, whereas sensing pregnancy activates a region responsible for empathy and prosocial behavior. Thus, the female body odor during pregnancy likely helps foster circumstances conducive to the future care of offspring while the body odor advertising sexual availability promotes mating behavior. The brains of heterosexual men may be capable of unconsciously discriminating between these two types of olfactory stimuli.

Supramodal neural networks support top-down processing of social signals.

The perception of facial and vocal stimuli is driven by sensory input and cognitive top-down influences. Important top-down influences are attentional focus and supramodal social memory representations. The present study investigated the neural networks underlying these top-down processes and their role in social stimulus classification. In a neuroimaging study with 45 healthy participants, we employed a social adaptation of the Implicit Association Test. Attentional focus was modified via the classification task, which compared two domains of social perception (emotion and gender), using the exactly same stimulus set. Supramodal memory representations were addressed via congruency of the target categories for the classification of auditory and visual social stimuli (voices and faces). Functional magnetic resonance imaging identified attention-specific and supramodal networks. Emotion classification networks included bilateral anterior insula, pre-supplementary motor area, and right inferior frontal gyrus. They were pure attention-driven and independent from stimulus modality or congruency of the target concepts. No neural contribution of supramodal memory representations could be revealed for emotion classification. In contrast, gender classification relied on supramodal memory representations in rostral anterior cingulate and ventromedial prefrontal cortices. In summary, different domains of social perception involve different top-down processes which take place in clearly distinguishable neural networks.

The association of the 5-HTTLPR polymorphism and the response to different stressors in healthy males.

The experience of stress is related to individual wellbeing and vulnerability to psychopathology. Therefore, understanding the determinants of individual differences in stress reactivity is of great concern from a clinical perspective. The functional promotor polymorphism of the serotonin transporter gene (5-HTTLPR/rs25531) is such a factor, which has been linked to the acute stress response as well as the adverse effect of life stressors. In the present study, we compared the impact of two different stress induction protocols (Maastricht Acute Stress Test and ScanSTRESS) and the respective control conditions on affective ratings, salivary cortisol levels and cognitive performance. To this end, 156 healthy young males were tested and genotyped for the 5-HTTLPR/rs25531 polymorphism. While combined physiological and psychological stress in the MAST led to a greater cortisol increase compared to control conditions as well as the psychosocial ScanSTRESS, subjective stress ratings were highest in the ScanSTRESS condition. Stress induction in general affected working memory capacity but not response inhibition. Subjective stress was also influenced by 5-HTTLPR/rs25531 genotype with the high expression group showing lower stress ratings than lower expression groups. In line with previous research, we identified the low expression variant of the serotonin transporter gene as a risk factor for increased stress reactivity. While some dimensions of the human stress response may be stressor specific, cognitive outcomes such as working memory performance are influenced by stress in general. Different pathways of stress processing and possible underlying mechanisms are discussed.

The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group.

BACKGROUND: In contrast to cisgender persons, transgender persons identify with a different gender than the one assigned at birth. Although research on the underlying neurobiology of transgender persons has been accumulating over the years, neuroimaging studies in this relatively rare population are often based on very small samples resulting in discrepant findings. AIM: To examine the neurobiology of transgender persons in a large sample. METHODS: Using a mega-analytic approach, structural MRI data of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity) were analyzed. OUTCOMES: Structural brain measures, including grey matter volume, cortical surface area, and cortical thickness. RESULTS: Transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), we observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined. CLINICAL TRANSLATION: The outcomes of this large-scale study may provide a normative framework that may become useful in clinical studies. STRENGTHS AND LIMITATIONS: While this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites. CONCLUSION: Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype. Mueller SC, Guillamon A, Zubiaurre-Elorza L, et al. The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group. J Sex Med 2021;18:1122-1129.

Predictive Pattern Classification Can Distinguish Gender Identity Subtypes from Behavior and Brain Imaging.

The exact neurobiological underpinnings of gender identity (i.e., the subjective perception of oneself belonging to a certain gender) still remain unknown. Combining both resting-state functional connectivity and behavioral data, we examined gender identity in cisgender and transgender persons using a data-driven machine learning strategy. Intrinsic functional connectivity and questionnaire data were obtained from cisgender (men/women) and transgender (trans men/trans women) individuals. Machine learning algorithms reliably detected gender identity with high prediction accuracy in each of the four groups based on connectivity signatures alone. The four normative gender groups were classified with accuracies ranging from 48% to 62% (exceeding chance level at 25%). These connectivity-based classification accuracies exceeded those obtained from a widely established behavioral instrument for gender identity. Using canonical correlation analyses, functional brain measurements and questionnaire data were then integrated to delineate nine canonical vectors (i.e., brain-gender axes), providing a multilevel window into the conventional sex dichotomy. Our dimensional gender perspective captures four distinguishable brain phenotypes for gender identity, advocating a biologically grounded reconceptualization of gender dimorphism. We hope to pave the way towards objective, data-driven diagnostic markers for gender identity and transgender, taking into account neurobiological and behavioral differences in an integrative modeling approach.

What determines violent behavior in men? Predicting physical, psychological, and sexual violent offending based on classification and regression tree analysis.

Despite compelling evidence that victimization and offending co-occur, it remains unclear what types of victimization are linked to specific forms of perpetration. Here we examined the relationship between physical, psychological, and sexual violence with respect to influencing variables including mental health, risk-taking behaviors, and coping strategies. Data from 5385 men were collected as part of an epidemiological study on violence experience. A classification and regression tree analysis identified the main predictors of violence perpetration and classified violent offending into high- and low-risk groups. Results indicate that violence is best predicted by previous exposure to violence and polyvictimization. Physical violence is best predicted by prior exposure to physical violence and this is further influenced by the frequency of and the age at which violence was experienced. Drug use was a strong predictor of physical and psychological violence. The latter is best predicted by a history of polyvictimization, the severity and the originator of violence. Sexual violence is strongly predicted by one's sexual violence experience. Other factors such as demographic characteristics are less predictive. Our results may contribute to the development of early prevention and intervention approaches that account for different risk factors. The significance of violence exposure suggest that intervention measures must focus on victims of early and prolonged experience of violence. On the strength of the link between drug use and violence, exposure to violence should be considered in drug prevention and intervention and vice versa.

The influence of semantic associations on sentence production in schizophrenia: an fMRI study.

One of the most prominent symptoms of schizophrenia is thought disorder, which manifests itself in language production difficulties. In patients with thought disorders the associations are loosened and sentence production is impaired. The determining behavioral and neural mechanisms of sentence production are still an important subject of recent research and have not yet been fully understood. The aim of the current study was to examine the influence of associative relations and distractor modalities on sentence production in healthy participants and participants with schizophrenia. Therefore, reaction times and neural activation of 12 healthy subjects and 13 subjects with schizophrenia were compared in an adapted picture word interference paradigm (PWI). No significant group differences were found, neither on the behavioral nor on the neural level. On the behavioral level, for the entire group incremental sentence processing was found, i.e. processing of the second noun only starts after the first noun was processed. At the neural level, activation was discovered in the bilateral caudate nuclei and the cerebellum. Those activations could be related to response enhancement and suppression as well as to the modulation of cognitive processes.

Mental health in refugees and asylum seekers (MEHIRA): study design and methodology of a prospective multicentre randomized controlled trail investigating the effects of a stepped and collaborative care model.

The sudden arrival of culturally diverse asylum seekers and refugees into Germany has created a strong demand for recognizing and appropriately treating those suffering from mental health issues. Due to many systemic, organizational, cultural and socio-linguistic barriers, psychiatric treatment of refugees is posing a major challenge to Germany's mental health care system. Thus, there is a need for alternative models that allow for increased access to adequate, effective and efficient culturally sensitive mental health care services. Here, we describe the Mental Health in Refugees and Asylum Seekers (MEHIRA) project, a multicentre randomized controlled trial investigating a stepped collaborative care model (SCCM) for providing mental health treatment in this vulnerable population. The proposed SCCM aims to decrease the aforementioned barriers. Adult and adolescent participants will be screened for depressive symptoms and matched to appropriate psychological interventions, including group-level interventions (START intervention, Empowerment/Gender-sensitive/Peer to peer), and other innovative, digital treatment approaches (Smartphone application). The therapeutic effect of the SCCM will be compared to TAU (treatment-as-usual). All interventions have been designed to be culturally sensitive, and offered in two different languages: Arabic and Farsi. The outcome of this study may contribute significantly to future clinical and legal guidelines in developing parallel and efficient new structures of treatment. Collected data will inform primary and secondary mental health care providers with recommendations concerning the design and implementation of effective treatment models and programmes. Guidelines and recommendations may also potentially be adopted by other host countries, developing countries and also in humanitarian aid programmes.

[Evaluation of a peer-helper project for mental health stabilization of refugees]. / Evaluation eines Laienhilfeprojekts zur psychischen Stabilisierung von Geflüchteten.

STUDY GOAL: This article presents the results of a pilot project to support mentally affected refugees by trained peer helpers. The evaluation aims to assess the necessity, usefulness and effectiveness of the project. METHODS: External agents as well as those involved in this project were interviewed with the help of validated and self-designed instruments and the results subjected to statistical analysis. The sample consisted of 197 refugees living in camps, 18 peer helpers participating in the project, as well as 16 social workers and administrators of twelve refugee shelters. RESULTS: More than half of the refugee sample reported having psychological problems. Peer-help, which consisted primarily of individual consultations, was rated positively by the refugees. 58.5 % severely affected refugees were reassigned to standard health care. Trained peer helpers rated peer training, coordination and supervision as good. The psychological burden of peer helpers did not change during the project. Social workers and administrators of the refugee shelters evaluated the peer-helper project as helpful. CONCLUSION: The pilot project appears to be necessary and useful. Mentally affected refugees benefit from the low-level help offer with trained peers providing valuable, native-speaker assistance. Good training, coordination and supervision as framework conditions allow the successful use of peer helpers to support mentally affected refugees effectively.

Distinct modes of top-down cognitive processing in the ventral visual cortex.

Top-down cognitive control leads to changes in the sensory processing of the brain. In visual perception such changes can take place in the ventral visual cortex altering the functional asymmetry in forward and backward connections. Here we used fixation-related evoked responses of EEG measurement and dynamic causal modeling to examine hierarchical forward-backward asymmetry, while twenty-six healthy adults performed cognitive tasks that require different types of top-down cognitive control (memorizing or searching visual objects embedded in a natural scene image). The generative model revealed an enhanced asymmetry toward forward connections during memorizing, whereas enhanced backward connections were found during searching. This task-dependent modulation of forward and backward connections suggests two distinct modes of top-down cognitive processing in cortical networks. The alteration in forward-backward asymmetry might underlie the functional role in the cognitive control of visual information processing.

Audio-visual and olfactory-visual integration in healthy participants and subjects with autism spectrum disorder.

The human capacity to integrate sensory signals has been investigated with respect to different sensory modalities. A common denominator of the neural network underlying the integration of sensory clues has yet to be identified. Additionally, brain imaging data from patients with autism spectrum disorder (ASD) do not cover disparities in neuronal sensory processing. In this fMRI study, we compared the underlying neural networks of both olfactory-visual and auditory-visual integration in patients with ASD and a group of matched healthy participants. The aim was to disentangle sensory-specific networks so as to derive a potential (amodal) common source of multisensory integration (MSI) and to investigate differences in brain networks with sensory processing in individuals with ASD. In both groups, similar neural networks were found to be involved in the olfactory-visual and auditory-visual integration processes, including the primary visual cortex, the inferior parietal sulcus (IPS), and the medial and inferior frontal cortices. Amygdala activation was observed specifically during olfactory-visual integration, with superior temporal activation having been seen during auditory-visual integration. A dynamic causal modeling analysis revealed a nonlinear top-down IPS modulation of the connection between the respective primary sensory regions in both experimental conditions and in both groups. Thus, we demonstrate that MSI has shared neural sources across olfactory-visual and audio-visual stimulation in patients and controls. The enhanced recruitment of the IPS to modulate changes between areas is relevant to sensory perception. Our results also indicate that, with respect to MSI processing, adults with ASD do not significantly differ from their healthy counterparts.

Externalization Errors of Olfactory Source Monitoring in Healthy Controls-An fMRI Study.

Using a combined approach of functional magnetic resonance imaging (fMRI) and noninvasive brain stimulation (transcranial direct current stimulation [tDCS]), the present study investigated source memory and its link to mental imagery in the olfactory domain, as well as in the auditory domain. Source memory refers to the knowledge of the origin of mental experiences, differentiating events that have occurred and memories of imagined events. Because of a confusion between internally generated and externally perceived information, patients that are prone to hallucinations show decreased source memory accuracy; also, vivid mental imagery can lead to similar results in healthy controls. We tested source memory following cathodal tDCS stimulation using a mental imagery task, which required participants to perceive or imagine a set of the same olfactory and auditory stimuli during fMRI. The supplementary motor area (SMA) is involved in mental imagery across different modalities and potentially linked to source memory. Therefore, we attempted to modulate participants' SMA activation before entering the scanner using tDCS to influence source memory accuracy in healthy participants. Our results showed the same source memory accuracy between the olfactory and auditory modalities with no effects of stimulation. Finally, we found SMA's subregions differentially involved in olfactory and auditory imagery, with activation of dorsal SMA correlated with auditory source memory.

Genetic and epigenetic regulatory mechanisms of the oxytocin receptor gene (OXTR) and the (clinical) implications for social behavior.

Oxytocin and the oxytocin receptor (OXTR) play an important role in a large variety of social behaviors. The oxytocinergic system interacts with environmental cues and is highly dependent on interindividual factors. Deficits in this system have been linked to mental disorders associated with social impairments, such as autism spectrum disorder (ASD). This review focuses on the modulation of social behavior by alterations in two domains of the oxytocinergic system. We discuss genetic and epigenetic regulatory mechanisms and alterations in these mechanisms that were found to have clinical implications for ASD. We propose possible explanations how these alterations affect the biological pathways underlying the aberrant social behavior and point out avenues for future research. We advocate the need for integration studies that combine multiple measures covering a broad range of social behaviors and link these to genetic and epigenetic profiles.