Mother-child similarity in brain morphology: A comparison of structural characteristics of the brain\u27s reading network

Background: Substantial evidence acknowledges the complex gene-environment interplay impacting brain development and learning. Intergenerational neuroimaging allows the assessment of familial transfer effects on brain structure, function and behavior by investigating neural similarity in caregiver-child dyads. Methods: Neural similarity in the human reading network was assessed through well-used measures of brain structure (i.e., surface area (SA), gyrification (lG), sulcal morphology, gray matter volume (GMV) and cortical thickness (CT)) in 69 mother-child dyads (children\u27s age~11 y). Regions of interest for the reading network included left-hemispheric inferior frontal gyrus, inferior parietal lobe and fusiform gyrus. Mother-child similarity was quantified by correlation coefficients and familial specificity was tested by comparison to random adult-child dyads. Sulcal morphology analyses focused on occipitotemporal sulcus interruptions and similarity was assessed by chi-square goodness of fit. Results: Significant structural brain similarity was observed for mother-child dyads in the reading network for lG, SA and GMV (r = 0.349/0.534/0.542, respectively), but not CT. Sulcal morphology associations were non-significant. Structural brain similarity in lG, SA and GMV were specific to mother-child pairs. Furthermore, structural brain similarity for SA and GMV was higher compared to CT. Conclusion: Intergenerational neuroimaging techniques promise to enhance our knowledge of familial transfer effects on brain development and disorders

Atypical dorsolateral prefrontal activity in females with conduct disorder during effortful emotion regulation

BACKGROUND: Conduct disorder (CD), which is characterized by severe aggressive and antisocial behavior, is linked to emotion processing and regulation deficits. However, the neural correlates of emotion regulation are yet to be investigated in adolescents with CD. Furthermore, it remains unclear whether CD is associated with deficits in emotional reactivity, emotion regulation, or both. METHODS: We used functional magnetic resonance imaging to study effortful emotion regulation by cognitive reappraisal in 59 female adolescents 15 to 18 years of age (30 with a CD diagnosis and 29 typically developing (TD) control adolescents). RESULTS: Behaviorally, in-scanner self-report ratings confirmed successful emotion regulation within each group individually but significant group differences in emotional reactivity and reappraisal success when comparing the groups (CD < TD). Functional magnetic resonance imaging results revealed significantly lower activation in left dorsolateral prefrontal cortex and angular gyrus in CD compared with TD adolescents during emotion regulation, but no group differences for emotional reactivity. Furthermore, connectivity between left dorsolateral prefrontal cortex and the bilateral putamen, right prefrontal cortex, and amygdala was reduced in CD compared with TD adolescents during reappraisal. Callous-unemotional traits were unrelated to neural activation, but these traits correlated negatively with behavioral reports of emotional reactivity. CONCLUSIONS: Our results demonstrate reduced prefrontal brain activity and functional connectivity during effortful emotion regulation in female adolescents with CD. This sheds light on the neural basis of the behavioral deficits that have been reported previously. Future studies should investigate whether cognitive interventions are effective in enhancing emotion-regulation abilities and/or normalizing prefrontal and temporoparietal activity in female adolescents with CD

Empathy deficits, callous‐unemotional traits and structural underpinnings in autism spectrum disorder and conduct disorder youth

Distinct empathy deficits are often described in patients with conduct disorder (CD) and autism spectrum disorder (ASD) yet their neural underpinnings and the influence of comorbid Callous‐Unemotional (CU) traits are unclear. This study compares the cognitive (CE) and affective empathy (AE) abilities of youth with CD and ASD, their potential neuroanatomical correlates, and the influence of CU traits on empathy. Adolescents and parents/caregivers completed empathy questionnaires (N = 148 adolescents, mean age = 15.16 years) and T1 weighted images were obtained from a subsample (N = 130). Group differences in empathy and the influence of CU traits were investigated using Bayesian analyses and Voxel‐Based Morphometry with Threshold‐Free Cluster Enhancement focusing on regions involved in AE (insula, amygdala, inferior frontal gyrus and cingulate cortex) and CE processes (ventromedial prefrontal cortex, temporoparietal junction, superior temporal gyrus, and precuneus). The ASD group showed lower parent‐reported AE and CE scores and lower self‐reported CE scores while the CD group showed lower parent‐reported CE scores than controls. When accounting for the influence of CU traits no AE deficits in ASD and CE deficits in CD were found, but CE deficits in ASD remained. Across all participants, CU traits were negatively associated with gray matter volumes in anterior cingulate which extends into the mid cingulate, ventromedial prefrontal cortex, and precuneus. Thus, although co‐occurring CU traits have been linked to global empathy deficits in reports and underlying brain structures, its influence on empathy aspects might be disorder‐specific. Investigating the subdimensions of empathy may therefore help to identify disorder‐specific empathy deficits

Neuroendocrine Stress Response in Female and Male Youths With Conduct Disorder and Associations With Early Adversity

Objective: Conduct disorder (CD) involves aggressive and antisocial behavior and is associated with blunted cortisol stress response in male youths. Far less is known about cortisol stress responsivity in female youths with CD or other neuroendocrine responses in both sexes. Although CD is linked to early adversity, the possibility that neuroendocrine alterations may mediate the relationship between early adversity and CD has not been systematically investigated. Method: Within the European FemNAT-CD multi-site study, salivary cortisol, testosterone, the testosterone/cortisol ratio, oxytocin, and psychological stress response to a standardized psychosocial stress test (the Trier Social Stress Test [TSST]), together with common pre- and postnatal environmental risk factors, were investigated in 130 pubertal youths with CD (63% female, 9-18 years of age) and 160 sex-, age-, and puberty-matched healthy controls (HCs). Results: The TSST induced psychological stress in both CD and HCs. In contrast, female and male youths with CD showed blunted cortisol, testosterone, oxytocin, and testosterone/cortisol stress responses compared to HCs. These blunted stress responses partly mediated the relationship between environmental risk factors and CD. Conclusion: Findings from this unique sample, including many female youths with CD, provide evidence for a widespread attenuated stress responsivity of not only stress hormones, but also sex hormones and neuropeptides in CD and its subgroups (eg, with limited prosocial emotions). Results are the first to demonstrate blunted neuroendocrine stress responses in both female and male youths with CD. Early adversity may alter neuroendocrine stress responsivity. Biological mechanisms should be investigated further to pave the way for personalized intervention, thereby improving treatments for CD.</p

Identifying cortical structure markers of resilience to adversity in young people using surface-based morphometry

Previous research on the neurobiological bases of resilience in youth has largely used categorical definitions of resilience and voxel-based morphometry methods that assess gray matter volume. However, it is important to consider brain structure more broadly as different cortical properties have distinct developmental trajectories. To address these limitations, we used surface-based morphometry and data-driven, continuous resilience scores to examine associations between resilience and cortical structure. Structural MRI data from 286 youths (Mage = 13.6 years, 51% female) who took part in the European multi-site FemNAT-CD study were pre-processed and analyzed using surface-based morphometry. Continuous resilience scores were derived for each participant based on adversity exposure and levels of psychopathology using the residual regression method. Vertex-wise analyses assessed for correlations between resilience scores and cortical thickness, surface area, gyrification and volume. Resilience scores were positively associated with right lateral occipital surface area and right superior frontal gyrification and negatively correlated with left inferior temporal surface area. Moreover, sex-by-resilience interactions were observed for gyrification in frontal and temporal regions. Our findings extend previous research by revealing that resilience is related to surface area and gyrification in frontal, occipital and temporal regions that are implicated in emotion regulation and face or object recognition

Testing the Ecophenotype Model:Cortical Structure Alterations in Conduct Disorder With Versus Without Childhood Maltreatment

Background:Childhood maltreatment is common in youths with conduct disorder (CD), and both CD and maltreatment have been linked to neuroanatomical alterations. Nonetheless, our understanding of the contribution of maltreatment to the neuroanatomical alterations observed in CD remains limited. We tested the applicability of the ecophenotype model to CD, which holds that maltreatment-related psychopathology is (neurobiologically) distinct from psychopathology without maltreatment.Methods:Surface-based morphometry was used to investigate cortical volume, thickness, surface area, and gyrification in a mixed-sex sample of participants with CD (n = 114) and healthy control subjects (HCs) (n = 146), ages 9 to 18 years. Using vertexwise general linear models adjusted for sex, age, total intracranial volume, and site, the control group was compared with the overall CD group and the CD subgroups with (n = 49) versus without (n = 65) maltreatment (assessed by the Children’s Bad Experiences interview). These subgroups were also directly compared.Results:The overall CD group showed lower cortical thickness in the right inferior frontal gyrus. CD youths with a history of maltreatment showed more widespread structural alterations relative to HCs, comprising lower thickness, volume, and gyrification in inferior and middle frontal regions. Conversely, CD youths with no history of maltreatment only showed greater left superior temporal gyrus folding relative to HCs. When contrasting the CD subgroups, those with maltreatment displayed lower right superior temporal gyrus volume, right precentral gyrus surface area, and gyrification in frontal, temporal, and parietal regions.Conclusions:Consistent with the ecophenotype model, findings indicated that CD youths with versus without maltreatment differ neurobiologically. This highlights the importance of considering maltreatment history in neuroimaging studies of CD and other disorders

White matter microstructure of the extended limbic system in male and female youth with conduct disorder

BackgroundPrevious studies of conduct disorder (CD) have reported structural and functional alterations in the limbic system. However, the white matter tracts that connect limbic regions have not been comprehensively studied. The uncinate fasciculus (UF), a tract connecting limbic to prefrontal regions, has been implicated in CD. However, CD-related alterations in other limbic tracts, such as the cingulum and the fornix, have not been investigated. Furthermore, few studies have examined the influence of sex and none have been adequately powered to test whether the relationship between CD and structural connectivity differs by sex. We examined whether adolescent males and females with CD exhibit differences in structural connectivity compared with typically developing controls.MethodsWe acquired diffusion-weighted magnetic resonance imaging data from 101 adolescents with CD (52 females) and 99 controls (50 females). Data were processed for deterministic spherical deconvolution tractography. Virtual dissections of the UF, the three subdivisions of the cingulum [retrosplenial cingulum (RSC), parahippocampal and subgenual cingulum], and the fornix were performed and measures of fractional anisotropy (FA) and hindrance-modulated orientational anisotropy (HMOA) were analysed.ResultsThe CD group had lower FA and HMOA in the right RSC tract relative to controls. Importantly, these effects were moderated by sex – males with CD significantly lower FA compared to male controls, whereas CD and control females did not differ.ConclusionsOur results highlight the importance of considering sex when studying the neurobiological basis of CD. Sex differences in RSC connectivity may contribute to sex differences in the clinical presentation of CD

Does the Relationship between Age and Brain Structure Differ in Youth with Conduct Disorder?

Conduct disorder (CD) is characterised by persistent antisocial and aggressive behaviour and typically emerges in childhood or adolescence. Although several authors have proposed that CD is a neurodevelopmental disorder, very little evidence is available about brain development in this condition. Structural brain alterations have been observed in CD, and some indirect evidence for delayed brain maturation has been reported. However, no detailed analysis of age-related changes in brain structure in youth with CD has been conducted. Using cross-sectional MRI data, this study aimed to explore differences in brain maturation in youth with CD versus healthy controls to provide further understanding of the neurodevelopmental processes underlying CD. 291 CD cases (153 males) and 379 healthy controls (160 males) aged 9–18 years (Mage = 14.4) were selected from the European multisite FemNAT-CD study. Structural MRI scans were analysed using surface-based morphometry followed by application of the ENIGMA quality control protocols. An atlas-based approach was used to investigate group differences and test for group-by-age and group-by-age-by-sex interactions in cortical thickness, surface area and subcortical volumes. Relative to healthy controls, the CD group showed lower surface area across frontal, temporal and parietal regions as well as lower total surface area. No significant group-by-age or group-by-age-by-sex interactions were observed on any brain structure measure. These findings suggest that CD is associated with lower surface area across multiple cortical regions, but do not support the idea that CD is associated with delayed brain maturation, at least within the age bracket considered here.</p

Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9-18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed