PURPOSE OF REVIEW:This review examines how prenatal inflammation may contribute to psychiatric and neurodevelopmental disorders, with a focus on maternal immune activation, microglial programming, and epigenetic mechanisms. RECENT FINDINGS:Recent studies have found that inflammation during pregnancy is associated with changes in brain development and neurodevelopmental outcomes in children. Animal research indicates that maternal immune activation can cause long-lasting changes in gene expression, neural circuitry, and microglial activity. Two-hit models suggest that prenatal inflammation may prime microglia, making the brain more vulnerable to later stress, infections, or adversity. Interventions that target microglia, reduce inflammation, or provide enriched environments may reduce downstream behavioral and neurodevelopmental effects. SUMMARY:Inflammation in early life may increase the risk of psychiatric disorders by altering placental signals, fetal brain development, and neuroimmune regulation. Preventing inflammation during pregnancy and reducing stress and adversity after birth may help protect against later mental health problems.

Human parenting behaviors (HPBs)—including gaze, motherese, affectionate touch, and positive affect—are essential for child development and can be precisely measured during the first weeks of life (2–8 weeks) through microcoding of videotaped interactions. This study examined whether maternal exposure to adverse childhood experiences (ACEs) affects HPBs and whether postnatal depressive symptoms mediate this relationship. The sample included 272 mother–infant dyads from São Paulo, Brazil (mean maternal age: 27.2 ± 5.2 years, 67% with monthly income < US$317; infants: 48.5% female, mean age: 33 ± 19 days). Maternal ACEs and depressive symptoms were self-reported during pregnancy and postnatally, respectively. HPBs were assessed using the Coding Interactive Behavior (CIB) manual. Results showed that maternal ACEs were significantly associated with higher postnatal depressive symptoms (β = 0.665, p < 0.001), but neither a direct nor indirect association with HPBs was observed. These findings suggest that ACE-related disruptions in parenting may not manifest during the early weeks of life but could emerge later as caregiving demands increase. This study is among the few to use microcoded interaction analysis at this early stage of life and highlights the need for continued research into the complex pathways linking ACEs, maternal mental health, and parenting behaviors over time.

Halogenated flame retardants (HFRs) may disrupt thyroid hormone homeostasis, potentially affecting neurodevelopment in children. However, studies integrating multi-matrix HFR exposure assessment, thyroid function biomarkers, and multimodal neurodevelopmental outcomes in children remain limited. We examined associations of HFR exposures with thyroid function biomarker levels and, in turn, neurodevelopmental outcomes in children aged 8-12 years and evaluated thyroid function biomarkers as potential mediators. We utilized cross-sectional data within the prospective GESTation and Environment (GESTE) birth cohort in Canada. Among 167 children (57.5% female) with plasma HFRs and thyroid function biomarker data, 111 also provided stool samples, and 97-106 completed various attention-deficit/hyperactivity disorder-related trait scales, cognitive tests, and resting-state functional MRI. Higher plasma 2,2',4,4',5,5'-Hexabromodiphenyl ether (BDE-153) was associated with lower thyroid-stimulating hormone (TSH) (β = -0.20; 95% CI, -0.37 to -0.03), whereas higher stool 2,2',4,4'-Tetrabromodiphenyl ether (BDE-47) was associated with higher TSH (β = 0.14; 95% CI, 0.02 to 0.25). Higher TSH level was associated with lower block design score (β = -0.64; 95% CI, -1.17 to -0.11) and default mode network functional connectivity (β = -0.03; 95% CI, -0.05 to -0.01). Mediation analysis suggested an indirect effect of TSH in the association between stool BDE-47 and block design score (β = -0.14; 95% CI, -0.37 to -0.01). However, none of these associations above remained statistically significant after controlling for the false discovery rate. Despite the potential relationships between HFR exposures and TSH alterations that are linked to neurodevelopmental outcomes in school-aged children, the inconsistent results of HFRs from various studies suggest further evidence is needed to reveal the complex relationship.

OBJECTIVE:The COVID-19 pandemic was associated with a worldwide increase in hospitalizations among adolescents with anorexia nervosa (AN). The factors contributing to this remain unclear and may include alterations in healthcare systems and/or clinical factors. This study examined the possibility that pandemic-related stress led to more severe illness in adolescents with AN. METHODS:Participants included adolescents with AN and healthy controls (HC) enrolled in a longitudinal study between 2017 and 2022. Illness severity and response to treatment were compared between individuals enrolled pre-COVID-19 and mid-COVID-19, with HC providing an additional reference for community levels of mood, anxiety, and eating symptoms. Exposure to COVID-19-related stress was assessed systematically, and the effect on illness severity was evaluated. RESULTS:There were no significant differences in age, body mass index (BMI), or eating disorder/depression/anxiety severity between individuals who presented for evaluation of AN pre-COVID-19 (n = 60) versus mid-COVID-19 (n = 31). Illness duration was shorter in the mid-COVID-19 group (Mmid-COVID = 0.30 ± 0.35 vs. Mpre-COVID = 0.83 ± 1.07 years, t88 = 2.62, p = 0.01). Duration of restrictive eating was also shorter in the mid-COVID-19 group (Mmid-COVID = 1.4 ± 1.1 years vs. Mpre-COVID = 2.4 ± 2.1 years, t88 = 2.36, p = 0.02). Individuals with AN and HC showed similar levels of COVID-related stress, and there was little association between COVID-19-related stress and symptom severity or response to treatment. DISCUSSION:This study suggests that while the pandemic led to increased incidence and hospitalizations for AN, there may have been less impact on overall illness severity and treatment response. For some, pandemic-related circumstances might have influenced hospitalization rates more than the level of pandemic-related stress.

OBJECTIVES:In the context of the Cannabis Antenatal and Neurodevelopment of Babies (CAN-B) cohort study, we describe our experience identifying the most effective recruitment strategy to meet enrolment objectives by comparing interest, enrolment rates, and cost-efficiency across multiple approaches. METHODS:From May 2022 to August 2025, at the obstetrical ultrasound unit of Sherbrooke University Hospital Center (CHUS), 4 recruitment strategies were successively implemented: (1) a study flyer given by care providers (May-September 2022), (2) recruitment by phone (October-November 2022); (3) a study flyer given by care providers or part time in-person study presentation by research team (December 2022-May 2023), and (4) full time in-person presentation of the study by the research team (June 2023-August 2025). Interest, enrolment rate and cost-effectiveness were compared. RESULTS:At CHUS, which has approximately 3000 annual births, 185 participants were enrolled, including 115 pregnant cannabis users. The proportion of cannabis users among women approached ranged from 7% to 17%. The fourth strategy yielded the highest enrolment rate (3 cannabis users/month) with high interest (71%), compared with strategies 1 (2/month;100% interest), 2 (1/month; 64% interest), and 3 (2/month; 55% interest). Recruitment by phone was the costliest despite suboptimal performance. Although the first strategy was the least costly, the fourth was retained due to superior recruitment outcomes. CONCLUSIONS:Our experience demonstrates that pregnant women, including cannabis users, are interested in clinical research. Implementing an active recruitment strategy that enables direct interaction between research staff and pregnant women can increase both interest and enrolment rates.

Diffusion MRI (dMRI) provides a powerful, non-invasive window into white matter (WM) development. Yet, most existing processing pipelines are not well-suited to the rapidly evolving neurophysiology of the pediatric brain. Here, we introduce sf-pediatric, a scalable, end-to-end, age-adaptable dMRI pipeline that integrates normative models of brain diffusivities to enable optimal subject-specific analysis from birth through 18 years old. Leveraging normative trajectories derived from nearly 2,000 participants from six cohorts, sf-pediatric dynamically calibrates diffusion priors, template selection, segmentation, and WM atlases based on the subject′s age. By incorporating automatic quality control into a portable, tested, containerized, open-access, and press-button framework across computing environments, sf-pediatric provides a robust pipeline for large-scale pediatric dMRI studies. We validated this approach by showing improved local modeling and cortical fanning while preserving reproducibility and the ability to derive brain-behavior relationships. Additionally, we demonstrated robust recovery of known developmental trajectories of WM microstructure and connectome-derived network organization. ### Competing Interest Statement Author MD is a co-founder and shareholder at Imeka Solutions Inc (www.imeka.ca). All other authors declare no financial or non-financial competing interests. Canadian Institutes of Health Research, https://ror.org/01gavpb45, 493956

Prospective prediction of mental health risk in adolescence can facilitate early preventive interventions. Here, using psychosocial questionnaires and neuroimaging measures from over 11,000 children in the Adolescent Brain and Cognitive Development Study, we trained neural network models to stratify general psychopathology risk. The model trained on current symptoms accurately predicted which participants would convert into the highest psychiatric illness risk group in the following year (area under the receiver operating characteristic curve = 0.84). The model trained solely on potential etiologies or disease mechanisms achieved an area under the receiver operating characteristic curve of 0.75 without relying on the child's current symptom burden. Sleep disturbances emerged as the most influential predictor of high-risk status, surpassing adverse childhood experiences and family mental health history. Including neuroimaging measures did not enhance predictive performance. These findings suggest that artificial intelligence models trained on readily available psychosocial questionnaires can effectively predict future psychiatric risk while highlighting potential targets for intervention. This is a promising step toward artificial intelligence-based mental health screening for clinical decision support systems.

BACKGROUND:Material and emotional hardship during pregnancy can shape early brain development and behavior in infants. This study used the COVID-19 pandemic as a natural context in which such hardships were widespread, particularly in low-resource settings. METHODS:This cohort study examined associations between pandemic-related maternal emotional distress and material hardship during pregnancy and early neurodevelopmental outcomes in infants. A total of 235 mother-infant dyads from low-resource healthcare settings in Brazil were enrolled during the COVID-19 pandemic. Maternal hardships were assessed using a COVID-19-specific questionnaire, which included self-reported COVID-19 exposure/infection. Infant neurodevelopment was evaluated via MRI at 2-6 weeks of age and behavioral assessments at 14 months using the Bayley Scales of Infant Development. RESULTS:Material hardship was associated with reduced hippocampal volumes in the left (pfdr = .008) and right (pfdr = .025) hemispheres. Among female infants, material hardship was linked to lower functional connectivity between the right hippocampus and the right rostral anterior cingulate cortex (p = .004). Smaller hippocampal volumes correlated with weaker gross motor skills at 14 months (r = .23; p = .02). Maternal emotional distress and self-reported COVID-19 exposure/infection were not significantly associated with infant neurodevelopmental outcomes. CONCLUSIONS:Material hardship may adversely affect early neurodevelopment, particularly hippocampal structure and connectivity, with potential downstream effects on motor skills. These findings underscore the importance of addressing material hardship during the perinatal period to support infant brain health and development.

Cortisol, a key biomarker of hypothalamus–pituitary–adrenal (HPA) axis activity, is central to early stress regulation and neurodevelopment. While prior studies have linked maternal and infant cortisol to child outcomes, less is known about their synchrony during early infancy, a time of rapid neuroendocrine development. In this longitudinal study, we examined cortisol coupling and the correlation with maternal adverse childhood experiences (ACEs) in 305 mother–infant dyads from São Paulo, Brazil. Salivary cortisol was collected at 1 month (32.3 days) and 6 months postpartum. We assessed intra- and interindividual cortisol dynamics and coupling using bivariate latent change score modeling. Maternal and infant cortisol were positively correlated at baseline (r = 0.319, p < 0.001) and at 6 months (r = 0.208, p = 0.003), suggesting early attunement that diminishes over time. Mothers and infants showed negative self-feedback, where higher baseline cortisol predicted smaller changes (mothers: B = -0.654; infants: B = -0.615; both p < 0.001). Maternal ACEs predicted elevated maternal cortisol at baseline (B = 0.126, p = 0.026) but did not affect the rate of change. These findings reveal early HPA synchrony and gradual decoupling, and highlight the lasting effects of maternal adversity on postpartum stress physiology.

Survival rates for pediatric posterior fossa tumor patients have improved due to advances in chemotherapy and irradiation treatment. Despite reduced irradiation in current treatment methods, many survivors experience cognitive impairment, learning difficulties, and academic delays that are secondary to emerging deficits in intelligence, attention, memory, and processing speed. Posterior fossa tumor survivors between the ages of 6 and 17 were recruited at four sites across North America and between 1 and 10 years posttreatment for either M0 posterior fossa medulloblastoma without dissemination or posterior fossa low-grade astrocytoma without relapse or evidence of residual disease. Resting state functional magnetic resonance imaging was analyzed using independent component analysis, and connectivity between brain regions were quantified. Significant effect of tumor diagnosis on independent component analysis based functional connectivity in the visual network and sensory motor network (p < .05) were observed. Significant interactions were found between the right cuneus, tumor type, and processing speed (p = .0137), and fine motor functioning in the dominant hand (p = .0181). Significant interactions were documented between the left lingual gyrus and tumor type on processing speed (p = .0075) and fine motor functioning in the nondominant hand (p = .0306). There was a significant interaction of the right superior parietal lobe and tumor type on emotion regulation (p = .0218). This research supports neuroimaging techniques identifying medulloblastoma survivors who are at risk and experiencing cognitive difficulties posttreatment. Specific brain regions were identified that are impacted by treatment, which provides insight into the cognitive domains that should be targeted in intervention and will be important for cognitive remediation programs for this population.

The putamen plays a key role in motor control, learning, and cognition, with abnormal putamen volumes associated with neuropsychiatric disorders. Using data from the ABCD study, we performed a genome wide association study (GWAS) of putamen volumes, followed by replication and pathway enrichment analyses. We next evaluated the shared genetic architecture of putamen volume and neuropsychiatric disorders-including depression, schizophrenia, Parkinson's, ADHD, bipolar, and OCD- using SNP associations from this and prior GWASs. We identified 199 genome-wide significant SNP associations in White participants. Most identified SNPs were in gene regulatory regions and in the neuronal growth-linked genes, DCC and DSCAM . Sixteen of the most significant associations observed in Whites were replicated in non-White participants. Twenty-one SNPs from prior GWASs of putamen volumes were also replicated in our ABCD GWAS analysis, including five of the top eight SNPs. There was considerable genetic heterogeneity between White and non-White participants in putamen-linked SNPs with significant differences between the minor allele frequencies across the two groups (Wilcoxon rank-sum test Exact prob < 0.0001). We identified a key pathway ( REACTOME_DSCAM_INTERACTIONS) associated with putamen volume that involves DSCAM gene, netrin-1 protein and/or DCC gene. In addition, 28 unique SNPs from prior GWASs of neuropsychiatric disorders were strongly associated with putamen volume at Bonferroni-corrected significance, while 40 SNPs shared by at least three disorders were associated with putamen volume at a 0.05 threshold. Our findings provide deeper insights into the shared genetic architecture and cross-population differences in genetic associations of putamen volume.

OBJECTIVES:Here we present Healthy MiNDS, a cohort of mothers and their newborns in São Paulo, Brazil, designed to investigate how maternal adverse childhood experiences (ACEs) intergenerationally affect child behavior and neurodevelopment, while exploring underlying biological mechanisms. METHODS:The study included seven encounters, beginning with the enrollment of women at 25-39 weeks of gestation from a low-resource area, based on their high or low exposure to ACEs. Their newborns were followed through the first 2 years of life. Biospecimens (e.g. maternal and cord blood, hair, saliva, placenta) were collected before/during childbirth and at follow-up visits. Newborns underwent non-sedated brain MRI scans and were regularly assessed for behavior, mother-child interactions, and home environment. RESULTS:We enrolled 626 mothers, with 60% of those who provided ACEs information (n = 603) reporting three or more ACEs, and 545 mother-child dyads. We obtained 303 MRI scans and 333 placental samples, among other biospecimens. Enrollment and the 6-month follow-up are complete, while the 14-, 18-, and 24-month visits are ongoing for active dyads. CONCLUSION:The Healthy MiNDS data allows for testing associations between maternal ACEs, prenatal inflammation and stress, placental biology, and offspring brain-behavior development in a population highly exposed to ACEs.

Adverse childhood experiences (ACEs) can influence parenting behaviours and have lasting effects on child development. This study investigated how maternal ACEs affect mind-mindedness during interactions between 69 Brazilian mothers and their six-month-old infants, and the role of stress in this relationship. Maternal vocalisations were coded for appropriate and non-attuned mind-related comments according to the Mind-Mindedness Coding Manual. The number of maternal ACEs was assessed using the CDC-Kaiser ACE Study Questionnaire. Current stress, postnatal depression, depression, anxiety, adverse life events, and resilience were assessed using the Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Depression Scale Patient Health Questionnaire, Generalized Anxiety Disorder, the Inventory of Major Life Events, and the Resilience Scale, respectively. General Linear Models analysed associations between variables. The results showed no direct link between ACEs and mind-mindedness. However, stress moderated the relationship between maternal ACEs and appropriate mind-related comments. These findings suggest that maternal exposure to ACEs affects how mothers interpret their infants' mental states, particularly under stress. Understanding these relationships can guide interventions to support maternal mental health and foster positive parent-infant interactions, potentially preventing the intergenerational transmission of trauma.

Depression and suicide are leading global causes of disability and death and are highly familial. Family and individual history of depression and suicide are associated with neurobiological differences including decreased white matter connectivity. However, this has been shown for individual regions, not considering that changes in connectivity may reverberate throughout the brain network. Furthermore, suicide and depression are correlated, but distinct psychological constructs. We use graph theory models to account for the network structure of the brain with high levels of specialization and integration and examine whether they differ by family history of depression or of suicidality within a three-generation longitudinal family study with well-characterized clinical histories. Clinician interviews across three generations were used to classify family risk of depression and suicidality. Then, we created weighted network models using 108 cortical and subcortical regions of interest for 96 individuals using diffusion tensor imaging derived fiber tracts. Global and local summary measures (clustering coefficient, characteristic path length, and global and local efficiencies) and network-based statistics were utilized for group comparison of family history of depression and, separately, of suicidality, adjusted for personal psychopathology. Clustering coefficient and local efficiency were associated with concurrent clinical symptoms. Network-based statistics showed hypoconnected cortical-subcortical subnetworks in individuals with high family risk of depression (including prefrontal and putamen regions) and of suicidality (prefrontal, thalamus and precuneus), after controlling for personal psychopathology. Family history of depression and of suicidality are associated with hypoconnectivity between subcortical and cortical regions, suggesting brain-wide impaired information processing, even in those personally unaffected.