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Background: 22q11.2 deletion syndrome (22qDel) is a copy number variant that is associated with psychosis and other neurodevelopmental disorders. Adolescents who are at clinical high risk for psychosis (CHR) are identified based on the presence of subthreshold psychosis symptoms. Whether common neural substrates underlie these distinct high-risk populations is unknown. We compared functional brain measures in 22qDel and CHR cohorts and mapped the results to biological pathways., Methods: We analyzed 2 large multisite cohorts with resting-state functional magnetic resonance imaging data: 1) a 22qDel cohort (n = 164, 47% female) and typically developing (TD) control participants (n = 134, 56% female); and 2) a cohort of CHR individuals (n = 240, 41% female) and TD control participants (n = 149, 46% female) from the NAPLS-2 (North American Prodrome Longitudinal Study-2). We computed global brain connectivity (GBC), local connectivity (LC), and brain signal variability (BSV) across cortical regions and tested case-control differences for 22qDel and CHR separately. Group difference maps were related to published brain maps using autocorrelation-preserving permutation., Results: BSV, LC, and GBC were significantly disrupted in individuals with 22qDel compared with TD control participants (false discovery rate-corrected q < .05). Spatial maps of BSV and LC differences were highly correlated with each other, unlike GBC. In the CHR group, only LC was significantly altered versus the control group, with a different spatial pattern than the 22qDel group. Group differences mapped onto biological gradients, with 22qDel effects being strongest in regions with high predicted blood flow and metabolism., Conclusions: 22qDel carriers and CHR individuals exhibited different effects on functional magnetic resonance imaging temporal variability and multiscale functional connectivity. In 22qDel carriers, strong and convergent disruptions in BSV and LC that were not seen in CHR individuals suggest distinct functional brain alterations., (Copyright © 2024. Published by Elsevier Inc.)

Fathers play a crucial role in their children's socio-emotional and cognitive development. A plausible intermediate phenotype underlying this association is father's impact on infant brain. However, research on the association between paternal caregiving and child brain biology is scarce, particularly during infancy. Thus, we used magnetic resonance imaging (MRI) to investigate the relationship between observed father-infant interactions, specifically paternal sensitivity, and regional brain volumes in a community sample of 3-to-6-month-old infants (N = 28). We controlled for maternal sensitivity and examined the moderating role of infant communication on this relationship. T2-weighted MR images were acquired from infants during natural sleep. Higher levels of paternal sensitivity were associated with smaller cerebellar volumes in infants with high communication levels. In contrast, paternal sensitivity was not associated with subcortical grey matter volumes in the whole sample, and this was similar in infants with both high and low communication levels. This preliminary study provides the first evidence for an association between father-child interactions and variation in infant brain anatomy., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3- to 6-month-old infants (N = 39). In addition, we examined whether this relationship differed in male and female infants. We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes.

It has been suggested that the restricted, stereotyped and repetitive behaviours typically found in autism are underpinned by deficits of inhibitory control. The biological basis of this is unknown but may include differences in the modulatory role of neurotransmitters, such as serotonin, which are implicated in the condition. However, this has never been tested directly. We therefore assessed the modifying role of serotonin on inhibitory brain function during a Go/No-Go task in 14 adults with autism and normal intelligence and 14 control subjects that did not differ in gender, age and intelligence. We undertook a double-blind, placebo-controlled, crossover trial of acute tryptophan depletion using functional magnetic resonance imaging. Following sham, adults with autism relative to controls had reduced activation in key inhibitory regions of inferior frontal cortex and thalamus, but increased activation of caudate and cerebellum. However, brain activation was modulated in opposite ways by depletion in each group. Within autistic individuals depletion upregulated fronto-thalamic activations and downregulated striato-cerebellar activations toward control sham levels, completely 'normalizing' the fronto-cerebellar dysfunctions. The opposite pattern occurred in controls. Moreover, the severity of autism was related to the degree of differential modulation by depletion within frontal, striatal and thalamic regions. Our findings demonstrate that individuals with autism have abnormal inhibitory networks, and that serotonin has a differential, opposite, effect on them in adults with and without autism. Together these factors may partially explain the severity of autistic behaviours and/or provide a novel (tractable) treatment target., (© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.)

22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans, with a heterogenous clinical presentation including medical, behavioural and psychiatric conditions. Previous neuroimaging studies examining the neuroanatomical underpinnings of 22q11.2DS show alterations in cortical volume (CV), cortical thickness (CT) and surface area (SA). The aim of this study was to identify (1) the spatially distributed networks of differences in CT and SA in 22q11.2DS compared to controls, (2) their unique and spatial overlap, as well as (3) their relative contribution to observed differences in CV. Structural MRI scans were obtained from 62 individuals with 22q11.2DS and 57 age-and-gender-matched controls (aged 6-31). Using FreeSurfer, we examined differences in vertex-wise estimates of CV, CT and SA at each vertex, and compared the frequencies of vertices with a unique or overlapping difference for each morphometric feature. Our findings indicate that CT and SA make both common and unique contributions to volumetric differences in 22q11.2DS, and in some areas, their strong opposite effects mask differences in CV. By identifying the neuroanatomic variability in 22q11.2DS, and the separate contributions of CT and SA, we can start exploring the shared and distinct mechanisms that mediate neuropsychiatric symptoms across disorders, e.g. 22q11.2DS-related ASD and/or psychosis/schizophrenia.