Developmental Psychobiology

Background: Alcohol and cannabinoids are frequently used during pregnancy, however their combined effects on offspring outcomes are currently under-investigated. In this study, co-exposure was compared to single-drug and drug-free exposures for influences on adult alcohol-seeking and cannabinoid system proteomics. Methods: Pregnant C57BL/6J mice received ethanol vapor (ALC), CP-55,940 (0.75 mg/kg; CB), both (ALC+CB), or neither on gestational days 12-15. Beginning on Postnatal Day 200, male and female offspring underwent home-cage ethanol drinking (N=108) and operant self-administration, progressive-ratio, extinction, and reinstatement testing (N=96). CNR1 and CNRIP1 protein abundance was quantified in the medial prefrontal cortex (mPFC) and dorsomedial striatum (N=57) and compared to within-subject drinking behaviors. Results: Prenatal CB exposure increased cumulative home-cage ethanol intake, primarily in males. At 40% ethanol under progressive-ratio schedules, ALC+CB males consumed more than all other male groups, whereas all exposed female groups consumed more than controls. ALC+CB males also showed greater extinction responding than all other male groups and greater reinstatement intake relative to baseline than CON and ALC males. ALC+CB increased mPFC CNR1 in males relative to all other groups, whereas CB and ALC+CB reduced mPFC CNR1 in females. Higher mPFC CNR1 was associated with fixed-ratio and 40% progressive-ratio intake, extinction, and reinstatement exclusively in males. Conclusions: Prenatal co-exposure produced a persistent male phenotype of enhanced ethanol seeking that was distinct from either exposure alone and accompanied by elevated mPFC CNR1. This behavioral and molecular convergence justifies future investigations manipulating corticostriatal cannabinoid signaling to attenuate exposure-induced ethanol consumption in late adulthood.

It is estimated that approximately fifty percent of the population will encounter at least one traumatic event during their lifetime; however, only six percent develop Posttraumatic Stress Disorder (PTSD), a trauma-related disorder characterized by persistent alterations in affect and cognition, including an exaggerated fear response. It is well established that females (9.7%) are more than twice as likely as males (3.6%) to be diagnosed with PTSD. Nevertheless, a significant challenge remains in understanding how the severity of traumas experienced in childhood versus adulthood influences PTSD development across sexes. To address this challenge effectively, the adoption of preclinical animal models that accurately reflect these key characteristics is crucial. The Stress Enhanced Fear Learning (SEFL) paradigm in rodents encapsulates some of these complexities associated with PTSD, such as persistent fear sensitization following exposure to acute trauma. This study investigates how stress severity and developmental timing affect the long-term maintenance of SEFL in male and female rats. Juvenile and adult rats were initially subjected to no stress (control, context only), low stress (1 footshock), moderate stress (3 footshocks), or high stress (15 footshocks), followed by an extinction session either one day (recent) or sixty days (remote) later. Subsequently, to evaluate SEFL in a new context, all subjects received a single footshock and were tested the following day. Shortly after stress induction, all groups displayed SEFL. Although the effects persisted for sixty days in adult males and juvenile females, even at the lowest stress level, they were significantly reduced in juvenile males and adult females. These findings offer novel insights into sex-related differences in the persistence of SEFL and introduce new considerations regarding how the timing of developmental stressors influences future threat encoding and fear responses.

Stressors experienced during the postnatal period may increase vulnerability to mental health disorders, including postpartum depression and anxiety. In rodents, maternal separation (MS) has been shown to alter behaviours in dams, but these observations have been made almost exclusively in rats and thus robust mouse models of postpartum mental health disorders using this stressor remain limited. Here we first examined, in mice, the effects of MS on maternal caregiving and on anxiety- and depressive-like behaviours. As stress-induced inflammatory activation in the gut-brain axis has been associated with behavioural alterations in non-postpartum contexts, changes in pro-inflammatory cytokines and tight junction proteins in the brain and intestinal tract were also examined. Female C57BL/6N mice were assigned to a No Separation (NS) or a MS condition that consisted of 3-hour daily separation sessions from postnatal days (P) 2 to 14. Maternal care behaviours were assessed on P3 and P7, followed by anxiety- and depressive-like behaviours on P22 and P23, and the collection of the medial prefrontal cortex (mPFC) and colon on P24 to determine the expression of selected genes. Caregiving patterns in MS dams fluctuated throughout the early postnatal period. Although behaviours and gene expression outcomes remained unchanged by MS, grooming time in the splash test was correlated with the expression of different genes in the mPFC. These findings suggest that C57BL/6 mouse dams may be less sensitive to the actions of MS on behaviour and on brain and intestinal markers of inflammation and barrier permeability, at least when examined shortly after weaning.

Early-life adversity is associated with highly variable developmental outcomes, but identifying sources of this heterogeneity is difficult because variation in outcome is typically accompanied by variation in exposure. Animal models provide experimental leverage by standardizing features of the early environment while allowing variation in developmental experience and outcome to remain observable. Using a graded limited bedding and nesting model spanning normative rearing, moderate restriction, and severe scarcity, we asked what distinguishes social outcomes among animals exposed to the same resource restriction. Severe scarcity increased adverse maternal handling while leaving organized nurturing behaviors intact. Following the P8-P12 rearing manipulation, pups were tested outside the home cage in a P13 social approach assay. Severe scarcity reduced the proportion of pups that approached the dam, but outcomes varied substantially among scarcity litters. Greater typical maternal pup transport predicted greater approach, whereas a greater proportion of rough transport predicted poorer approach. Transport composition did not differ across rearing conditions, but its relationship with social behavior did. Amygdala intercalated-cell recruitment also covaried with social approach under severe scarcity despite limited condition-level differences in regional c-Fos. Plasma corticosterone differed across rearing conditions but did not covary detectably with the principal caregiving, behavioral, or neural measures. Maternal transport and intercalated-cell recruitment were not robustly associated, identifying separable experiential and neural correlates of behavioral variation. These findings show that standardizing an environmental constraint does not produce uniform developmental experience or outcome, and that caregiving experiences preserved across rearing conditions can distinguish social outcomes under severe scarcity.

Stressful experiences are a major risk factor for the development of neuropsychiatric disorders in vulnerable individuals. Identifying features that can distinguish stress-susceptible from resilient individuals remains a central goal in stress neurobiology. Due to the routine exclusion of female subjects from stress research or the use of male-defined criteria in behavioral characterization of subjects post-stress, female stress responses and vulnerability profiles remain poorly understood. This work aimed to gain a better understanding of sex-specific stress responses to social defeat stress. Here, we used a novel paired male-female social defeat paradigm and tracked subjects longitudinally in a ''two-hit'' design to evaluate responses to both acute social defeat stress (ASDS) and chronic social defeat stress (CSDS), and to determine how prior stress exposure influences subsequent vulnerability. We found that both ASDS and CSDS induces changes in social avoidance/approach behavior in males but not females, as measured by a classic social interaction ratio. Prior ASDS exposure enhanced susceptibility to subsequent CSDS most clearly in males, with females displaying specific changes in corner zone occupancy. Furthermore, we observed divergent anxiety profiles between males and females in a post-stress behavioral battery. Finally, females exhibited specific stress-related locomotor responses following ASDS. Together, these findings suggest that females may adopt distinct behavioral strategies following social defeat stress.

Courtship is an essential component of reproductive success for many species and many courtship behaviors, such as vocalization, are energetically demanding. In order to successfully balance investment in courtship with feeding and foraging, individuals must be aware of their current energy balance, and hormonal signals of energetic state have been found to influence social signal effort across a variety of species. Ghrelin is one hormone that plays an important role in regulating energy balance by signaling hunger and promoting feeding. Previous studies have investigated the role of ghrelin in courtship, aggression, and mating behavior. In this study, we build on prior work by investigating the effects of ghrelin on ultrasonic vocalizations (USV) and other courtship behaviors of male mice. We expand on previous research by observing ghrelin's effects over longer interactions, allowing us to understand how ghrelin impacts the dynamics of USV production over time. Our results show that while males initially vocally court females at a high rate regardless of treatment, ghrelin reduces overall USV production by increasing the rate of decline of vocalization. Surprisingly, despite its effects on vocal courtship, we found no significant differences in the production or timing of other, non-vocal, courtship behaviors. This study deepens our understanding of the role of hormones traditionally associated with controlling hunger and feeding in regulating social behaviors.

Interpersonal physiological synchrony (IPS) between interaction partners has been studied as a marker of social connectedness and coordination. However, little is known about how such interpersonal synchrony relates to the intrapersonal coordination of individuals' own autonomic systems during team interaction. The present study examined whether IPS and intrapersonal physiological synchrony (IAPS), defined as the within-person coordination of heart rate (HR), respiration, and electrodermal activity (EDA), function as competing or complementary regulatory processes. It also examined whether IAPS is state- or trait-like and whether teams high or low in both IPS and IAPS had better outcomes. Fifty five newly formed triads (N = 165; Mage = 23.87, 77% female) participated in a laboratory interaction including passive shared experiences and active collaborative tasks while continuous physiological activity was recorded. Synchrony within individuals and between team members was quantified using multidimensional recurrence quantification analysis. Across interaction segments, IAPS was positively associated with IPS in both HR and EDA, with stronger and more consistent associations during active teamwork versus during passive social contexts. These findings contradict a trade-off hypothesis and instead support a synergistic relationship between IAPS and IPS. IAPS exhibited state-like dynamics and sensitivity to features of the context, i.e., consistency within similar interaction contexts and higher in passive versus active social segments. Further, IAPS had limited associations with individual difference measures. Exploratory analyses indicated that teams characterized by both high IAPS and high IPS demonstrated more favorable outcomes, reflected in either higher objective task performance or greater perceived team efficacy depending on physiological modality. Together, these results suggest that effective team coordination is supported not only by IPS but also by the capacity to maintain coherent internal autonomic organization. They further highlight IAPS as a dynamic component of social functioning that merits exploration alongside interpersonal processes.

Disruptions to maternal behaviors that emerge during the peripartum period have been shown to have lasting physiological and behavioral consequences for offspring. In addition to effects on offspring, disrupted maternal behaviors have been associated with peripartum mood and anxiety disorders. Therefore, it is critical for the wellbeing of both mother and offspring to identify upstream risk factors for the disruption of maternal behavior. We have previously found that pubertal stress leads to a blunted hypothalamic-pituitary-adrenal (HPA) axis response in peripartum humans and mice. Given that dysfunction of the HPA axis is associated with both PMADs and disrupted maternal behavior, we examined how pubertal stress influenced maternal behavior throughout peripartum in mice using a pup retrieval test. We found that pubertal stress led to faster pup retrieval, but a less predictable pattern of maternal behavior, as well as a blunted HPA axis response during pregnancy. We also examined whether maternal pubertal stress influenced offspring behavior in adolescence and adulthood. We found sex-specific differences in risk-taking behavior during adolescence that are no longer present in adulthood. Finally, we used in situ hybridization to examine gene expression during pregnancy in the medial preoptic area of the hypothalamus, a region implicated in maternal behavior. Following pubertal stress, we found cell-type specific changes in the expression of genes necessary for the expression of maternal behavior. Collectively, these findings contribute to our understanding of upstream risk factors for peripartum disruptions to maternal behavior and the lasting effects of pubertal stress on both mother and offspring.

Oxytocin (OT) and vasopressin (AVP) are neuropeptide hormones involved in regulating animal social behavior and a broad spectrum of physiological processes. Although their distributions are well documented in neuroendocrine regions of the forebrain and midbrain, their expression in the hindbrain remains poorly understood. Here, we used immunohistochemistry to quantify OT and AVP immunoreactive puncta within three auditory brainstem nuclei, the lateral superior olive (LSO), the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB) in six wild-caught rodent species differing in sociality. We also quantified the volume of these nuclei and examined variation in total brain volume across species and sociality. OT and AVP puncta count differed among species and social groups. Group-living species exhibited higher OT and AVP puncta counts than monogamous and solitary species in the LSO and MNTB. In the MSO, OT puncta counts did not differ among social groups, whereas AVP puncta counts were higher in group-living than in monogamous and solitary species. Total brain volume and the volumes of the MNTB and MSO differed among species, but not across social groups, whereas LSO volume did not differ among species or sociality. These findings revealed sociality-related variation in OT and AVP immunoreactive puncta within auditory brainstem circuits and suggest that neuropeptide signaling within early auditory brainstem pathways may contribute to the neural integration of social and auditory information.

Objective: Women with premenstrual syndrome (PMS) experience affective lability, irritability, depressed mood, and anxiety during the late luteal phase of the menstrual cycle. Stress reactivity may contribute to the development of these symptoms, yet neural correlates remain unexplored. We examined neural, behavioral and endocrine stress responses across menstrual cycle phases in women with and without PMS. Methods: 26 women with PMS and 24 women without PMS participated in two fMRI sessions, during the mid-follicular (days 5 to 11) and late-luteal phases (days -7 to -1). Participants completed the Montreal Imaging Stress Task (MIST). Subjective stress ratings and salivary cortisol were collected at six time points before and after stress induction. Stress-related brain activation was assessed using whole-brain and region-of-interest analyses. Results: Subjective stress ratings increased as expected from before to after the MIST, with no group or phase differences. Salivary cortisol was significantly higher during the mid-follicular phase, with no group effect or significant pre-post MIST difference. While the stress task elicited activation patterns in stress-related regions, whole-brain analysis revealed no significant effects of group (PMS vs. no PMS) or menstrual cycle phase (follicular vs. luteal) on the neural stress response. Considering premenstrual symptom severity as a predictor revealed significant group-by-symptom severity interactions in the right inferior frontal gyrus and the right superior temporal gyrus. Conclusion: Using a within-subject repeated-measures design, we found neural responses to psychosocial stress to be stable across menstrual cycle phases. Individual differences in symptom severity may nevertheless be associated with differences in stress-related brain activation.

Modest positive associations between episodic memory performance and whole hippocampal and hippocampal subfield volumes have been reported in numerous prior studies. A smaller number of studies have reported associations between hippocampal volume and performance on tests of non-mnemonic cognition. The present study examined whether these associations were evident in a lifespan sample of cognitively healthy adults. Of particular interest was whether any identified associations were sensitive to age, and whether associations between subfield volumes and mnemonic and non-mnemonic performance were subfield dependent. We acquired high-resolution T1- and T2-weighted structural images from 163 adults (18-87 years of age). Participants also undertook a comprehensive neuropsychological test battery and an in-scanner test of source memory. Principal components analysis was employed to reduce the neuropsychological test scores to 5 cognitive components. Two components reflected memory performance while the other three reflected different aspects of non-mnemonic cognition. Hippocampal subfields (Cornu Ammonis (CA)1, CA2-3, dentate gyrus (DG) and subiculum) were segmented and measured with the Automated Segmentation of Hippocampus Subfields (ASHS) package. Source memory performance was selectively associated across participants with CA2-3 volume. By contrast, both mnemonic and non-mnemonic component scores derived from the test battery were associated exclusively with the volume of the DG. All associations were age-invariant. The findings indicate that different cognitive domains can be dissociated by virtue of their associations with different hippocampal subfields. Of importance, these associations appear to be life-long and hence are unlikely to reflect individual differences in age-related decline in structural integrity.

We investigated how auditory and visual presentation of small numerical magnitudes and non- numerical magnitudes are passively processed at the neural level. Earlier research suggests automatic processing of quantities occurs rapidly in the brain. However, there are no studies on passive, pre-attentive change detection of magnitudes utilizing mismatch negativity (MMN) across sensory modalities in same participants, important to understand amodal processing of magnitudes. We recorded EEG in passive auditory and visual multi-feature oddball and control paradigms from the same adult individuals (N=104/105, respectively). In the auditory paradigm, the standard stimulus was a 2-part sound, while the deviant stimuli varied in frequency, intensity, gap length, and number of sounds (1-part and 3-part stimuli). In the visual paradigm, the standard stimulus was a dot array containing two medium-sized dots, while the deviant stimuli varied in numerosity (1 or 3 dots) and dot size (small or large). The results for the auditory paradigm showed significant MMN across all features, including comparisons with deviant-alone control stimuli, except for the 2-part vs. 1-part contrast. The results for the visual paradigm suggested differences in processing across all features apart from large and medium-size stimuli. These results replicate earlier MMN findings that the brain distinguishes pre-attentively changes in sound frequency, amplitude and gap. Auditorily presented small numerical magnitudes also showed pre-attentive processing but less robustly to the contrast 2 vs. 1. Visual pre-attentive processing of small numerical magnitudes was also observed. Together these findings could be interpreted to support the existence of abstract, pre- attentive processing of numerical magnitudes. Highlights* Auditory and visual processing of numerical and non-numerical magnitudes was examined with EEG * Auditory non-numerical magnitudes and medium vs. small dots replicated earlier MMN studies * aMMN and vMMN showed pre-attentive processing of changes in small numerosities 2 vs. 3 and 2 vs. 1 * 2 vs. 1 tone processing was less robust than 2 vs. 3 or the processing of the visual contrasts * The brain processes changes in small non-symbolic magnitudes pre-attentively

Worry is an important contributor to anxiety and depressive disorders, particularly in adolescence. Underlying changes in brain networks are thought to drive development of pathological worry, yet the degree to which neural correlates of worry vary by age is unknown. Here, we use multivariate pattern analysis (MVPA) to investigate individual variance in brain activity during worry in a cross-sectional sample of adolescents and adults varying in worry symptoms. Participants (n=69; ages 12-31) completed a personalized worry-induction fMRI task. Brain activity was averaged across k=268 brain regions from the Shen atlas. Participants also completed self-reports assessing trait worry (PSWQ), anxiety (SCARED), and depression (MFQ) severity. A random-forest model was trained on estimated parameters from worry vs. neutral blocks using leave-one-subject-out cross-validation. Age and symptomatology measures were correlated with model performance metrics. The overall cross-validated model had accuracy=66.71%, balanced accuracy=62.61%, sensitivity=80.43%, and specificity=44.78%. Trial-level accuracy increased with in-scanner worry ratings regardless of condition (b =0.62, p<.001). Accuracy (r=0.30, p=.01) and balanced accuracy (r=0.31, p=.01) significantly correlated with age but did not relate to symptom severity. Brain patterns associated with worry become more differentiated across adolescence, suggesting that neural processes of worry consolidate across this period. Thus, early adolescence may be an opportune time for interventions to alter worry, but interventions adapted from adult populations may require tailoring for adolescent patients.

Childhood adversity is robustly linked to differences in amygdala and hippocampal volume. However, findings across studies have been inconsistent and contradictory. This inconsistency stems partly from the many reasonable but arbitrary choices that researchers make when operationalizing brain regions, stress exposure, and covariates. To deal with this variability, we applied a multiverse analysis approach using adolescent data from the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) study to evaluate how multiple analytic choices influence the relationships between stress and hippocampal/amygdala volume. Our primary analysis crossed three region-of-interest operationalizations (left, right, total), four intracranial volume scaling methods, and multiple sociodemographic covariates. Greater lifetime stress severity was associated with smaller amygdala volume across 72% of specifications, and with smaller hippocampal volume across 52% of specification models. Statistical significance was strongly influenced by the region of interest. Our secondary multiverse analysis tested six operationalizations of stress exposure (total/acute/chronic x count/severity). This analysis found that the laterality pattern in the primary analysis was not strongly influenced by stress operationalization. These findings demonstrate the robustness of the stress-medial temporal lobe association and identify specific analytic choices (i.e. hemisphere operationalization) that most strongly drive the variability observed in previous literature. Our study is one of the first that utilized multiverse analysis for adversity-neuroimaging research, and provides a strong framework for evaluating and interpreting inconsistent findings.

Early environmental conditions can have long-lasting effects on survival and reproductive fitness. Using a 23 year-long monitoring data set of captive mouse lemur's life history traits, we tested a relationship between maternal allocation to offspring (N = 1365) and their adulthood survival. Maternal characteristics such as age or body condition did not affect allocation to offspring whatever the litter size (1 to 3). Although birth mass depended on size and composition of the litters, mouse lemur survival was highly correlated with body mass acquired after weaning in both sexes, through potential sibling competition. Moreover, female's reproductive success correlated with this body mass and was consistently associated with increased longevity. These findings suggest the presence of a silver spoon effect under constant captive conditions. However, cumulative effects of genetic and adulthood social conditions strongly interact to affect adult survival. Deaths related to intra- or inter-sexes aggressive social interactions may outweigh effect of early environment and therefore minimize the silver-spoon effect on captive mouse lemur's survival. However, having a high body mass after weaning appeared to be a determinant factor in individual survival for mouse lemurs.

Introduction: With global warming, heatwaves are increasing in severity, affecting species worldwide. Recent studies show associations between heat exposure in pregnancy and adverse birth outcomes such as preterm birth, low birthweight and stillbirth across multiple species. This suggests potentially conserved mechanisms such as maternal inflammation, dehydration and changes in placental physiology in response to heat exposure. Moreover, the gestational timing of antenatal heat likely impacts the type and severity of outcome, yet this is not fully understood. Methods: We conducted a scoping review of studies on heat exposure and pregnancy outcomes in humans and other animals, to identify common mechanisms and temporal dynamics of effects. Temperature-, trimester- and species- specific patterns were reviewed across 197 studies and ten species (human, cow, sheep, pig, goat, rat, mouse, guinea pig, lizard and rabbit). Results: Qualitative trends indicate that high temperatures are associated with adverse birth outcomes. In particular, third trimester exposure increases risk of preterm birth and low birthweight. Many studies emphasise placental involvement in adverse outcomes and point to potential aberrations in placental physiology or cortisol signaling pathways. Conclusions: Overall, literature presents that heat exposure increases risk of adverse birth outcomes across studies, and taxa. Understanding the relationship between heat exposure and adverse birth outcomes, as well as the mechanisms and timing, is vital for informing public health policies and creating mitigating strategies for expecting mothers.

In utero alcohol exposure (IUE) can alter mammary development and increase mammary tumor susceptibility in experimental models. However, most previous studies have relied on carcinogen-induced or genetically tumor-prone models, leaving it unresolved whether prenatal alcohol exposure produces mammary developmental and molecular changes before the introduction of an oncogenic challenge. Here, we addressed this question using non-tumorigenic C57BL/6 mice. Pregnant dams received a Lieber-DeCarli liquid diet containing 1.7% (v/v) ethanol or an isocaloric control diet from gestational day 11 to 19, and mammary glands from female offspring were examined during puberty (postnatal day 40, PND40) and young adulthood (PND70). At PND40, IUE enhanced mammary ductal morphogenesis, increased terminal end bud numbers, and elevated epithelial proliferation. These developmental alterations persisted at PND70, with increased lateral branching and proliferative activity. IUE also altered mammary epithelial composition, expanding the basal/myoepithelial compartment and the CD24highCD49fhigh mammary repopulating unit/stem cell-enriched population. Mammary epithelial cells from IUE-exposed offspring exhibited increased colony-forming cells (CFCs), mammosphere formation, and 3D Matrigel growth, indicating enhanced stem/progenitor-associated activity. At the molecular level, IUE increased ER; expression and phosphorylation together with Cyclin D1, c-Myc, E2F1, and Bcl-2, and enhanced AKT, ERK, and STAT3 phosphorylation, IL-6 expression, and SOX2 at PND40. Importantly, major components of this signaling phenotype remained altered at PND70, including ER;-associated signaling, AKT/ERK activation, and IL-6/STAT3 signaling, whereas the pubertal increase in SOX2 was not sustained. Together, these findings demonstrate that prenatal alcohol exposure induces profound and persistent histomorphological, cellular, and signaling alterations in the mammary gland in the absence of a carcinogenic challenge or genetically introduced oncogenic driver. These results identify intrinsic developmental reprogramming of normal mammary tissue as a potential basis through which prenatal alcohol exposure may modify subsequent responses to tumor-promoting or other environmental challenges.

The phenotype of a focal individual can be affected not only by the individuals own genes (direct genetic effects, DGE) but also by genes of other individuals it interacts with (indirect genetic effects, IGE). Better understanding IGE can help better understand the impact and mechanisms of social effects. Here, we investigated, in laboratory mice, the modulation of IGE by genetic background of the focal individual (social epistasis) and by sex. We focused on IGE arising from Epha4, a gene that has been associated with the individuals own stress-related and social behaviours (i.e. DGE) and the stress-coping behaviour and wound healing of the other mice in the cage (i.e. IGE). Among four different genetic backgrounds for focal mice, significant IGE from Epha4 were detected in CBA females only. A formal model selection analysis was consistent with the modulation of IGE by the similarity of the genetic backgrounds of the focal mouse and its Epha4 cage mate, as well as by sex. Observations of fighting in cages of males with dissimilar genetic backgrounds suggested aggression might underpin these modulatory effects, which prompted to us to expand the conceptual framework describing the mechanisms of social epistasis. Thus, our results strengthen the emerging view that IGE are not fixed properties of social genotypes but can depend on the genetic and sex context of interacting individuals, revealing an underexplored layer of their genetic architecture.

Background: Childhood trauma is a well-established risk factor for adverse mental health outcomes, yet large-scale cross-national evidence from the Arab region remains limited. This study examined the prevalence of childhood trauma and its associations with multiple transdiagnostic outcomes across 17 Arab countries. Methods: A cross-sectional online survey was conducted between September and October 2025 among 6,181 adults from 17 Arab countries. Childhood trauma was assessed using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Transdiagnostic mental health outcomes included depression, anxiety, posttraumatic stress symptoms (PTSS), maladaptive behavior, and social/functional impairment. Descriptive statistics, Pearson correlations, and multiple linear regression analyses were performed via IBM SPSS Statistics. Confirmatory factor analysis and structural equation modeling were conducted via R (Lavaan) to evaluate a second-order latent construct representing global childhood trauma. Results: Childhood trauma was widely reported across the sample, with physical neglect and emotional neglect emerging as the most frequently endorsed domains. All trauma domains were significantly associated with poorer mental health outcomes (p < .001). In regression analyses adjusted for demographic factors, emotional abuse emerged as the strongest predictor of depression ({beta} = .472, p < .001) and PTSS ({beta} =.439, p < .001). Structural equation modeling supported a second-order global trauma construct, which showed strong associations with depression ({beta} = .70), anxiety ({beta} = .64), PTSS ({beta} = .68), maladaptive behavior ({beta} = .68), and social impairment ({beta} = .67). This latent factor showed strong associations with all mental health outcomes, explaining substantial variance in depression (R2 = .52), anxiety (R2 = .43), and PTSS (R2 = .48). The structural model demonstrated borderline-to-acceptable fit (CFI = .899, TLI = .890, RMSEA = .058, SRMR = .085), supporting the hypothesized latent structure while indicating scope for further model refinement. Conclusions: Childhood trauma is highly prevalent across the Arab region and is strongly associated with multiple dimensions of psychological distress, highlighting the urgent need for trauma-informed prevention, screening, and early intervention programs in the Arab region.

A central premise of developmental neuroscience is that mature behaviour emerges through reciprocal interactions between infants spontaneous actions, neural activity, and environmental experience. Yet, much human neuroimaging research relies on highly controlled, repetitive paradigms designed to minimize behavioural variability, obscuring the very brain-behaviour dynamics that drive developmental change. Here, we introduce a naturalistic functional near-infrared spectroscopy (fNIRS) paradigm that exploits, rather than suppresses, natural variability in infants behaviour to investigate cortical changes associated with behavioural development. Continuous video coding of spontaneous infant behaviour was combined with finite impulse response (FIR) modelling to estimate behaviour-specific hemodynamic responses associated with reach-to-grasp, hand-to-mouth, and vocalization behaviours while accounting for temporally overlapping hemodynamic responses by treating extraneous behaviours as nuisance regressors. From 6 to 13 months of age, reach-to-grasp and vocalizations increased in frequency, while all three behaviours shortened in duration. Critically, developmental changes in cortical activation were behaviour-specific. During reach-to-grasp movements, bilateral posterior parietal activity decreased with age. In contrast, during hand-to-mouth and vocalizations, somatomotor and premotor activity increased with age. Cortical activity was also related to individual variation in the frequency and duration of these behaviours, indicating that cortical recruitment remained coupled to behavioural variation independent of age. These findings reveal behaviour-specific patterns of cortical reorganisation during infant development and establish a methodological framework for linking spontaneous behaviour to cortical activity in freely behaving infants. More broadly, this approach enables direct investigation of cortical development as it unfolds through naturalistic interactions among behaviour, neural activity, and experience. Significance StatementContinuous self-generated interactions with the environment play a critical role in driving infant brain development, yet neuroimaging research often examines infants while sleeping or in highly constrained and repetitive tasks. Here, we show that spontaneous infant behaviour can instead be leveraged to provide the temporal variability needed to resolve behaviour-specific cortical responses in freely behaving infants. By combining continuous behavioural coding with data-driven finite impulse response (FIR) modelling of overlapping hemodynamic responses, we identified behaviour-specific developmental differences in cortical recruitment without tightly constraining the infants behaviour. This novel approach expands developmental neuroimaging beyond sleeping or trial-based paradigms and demonstrates how naturally occurring behavioural variability can become a useful feature of fNIRS experimental design. More broadly, it generates new opportunities to directly test theories of neurobehavioural development in more ecologically valid settings.