Linking heart rate variability to psychological health and brain structure in adolescents with and without conduct disorder

AimsHeart rate variability (HRV) measures have been suggested in healthy individuals as a potential index of self-regulation skills, which include both cognitive and emotion regulation aspects. Studies in patients with a range of psychiatric disorders have however mostly focused on the potential association between abnormally low HRV at rest and specifically emotion regulation difficulties. Emotion regulation deficits have been reported in patients with Conduct Disorder (CD) however, the association between these emotion regulation deficits and HRV measures has yet to be fully understood. This study investigates (i) the specificity of the association between HRV and emotion regulation skills in adolescents with and without CD and (ii) the association between HRV and grey matter brain volumes in key areas of the central autonomic network which are involved in self-regulation processes, such as insula, lateral/medial prefrontal cortices or amygdala.MethodsRespiratory sinus arrhythmia (RSA) measures of HRV were collected from adolescents aged between 9–18 years (693 CD (427F)/753 typically developing youth (TD) (500F)), as part of a European multi-site project (FemNAT-CD). The Inverse Efficiency Score, a speed-accuracy trade-off measure, was calculated to assess emotion and cognitive regulation abilities during an Emotional Go/NoGo task. The association between RSA and task performance was tested using multilevel regression models. T1-weighted structural MRI data were included for a subset of 577 participants (257 CD (125F); 320 TD (186F)). The CerebroMatic toolbox was used to create customised Tissue Probability Maps and DARTEL templates, and CAT12 to segment brain images, followed by a 2 × 2 (sex × group) full factorial ANOVA with RSA as regressor of interest.ResultsThere were no significant associations between RSA and task performance, neither during emotion regulation nor during cognitive regulation trials. RSA was however positively correlated with regional grey matter volume in the left insula (pFWE = 0.011) across all subjects.ConclusionRSA was related to increased grey matter volume in the left insula across all subjects. Our results thus suggest that low RSA at rest might be a contributing or predisposing factor for potential self-regulation difficulties. Given the insula’s role in both emotional and cognitive regulation processes, these brain structural differences might impact either of those

Identifying structural brain markers of resilience to adversity in young people using voxel-based morphometry

There is increasing evidence that resilience in youth may have a neurobiological basis. However, the existing literature lacks a consistent way of operationalizing resilience, often relying on arbitrary judgments or narrow definitions (e.g., not developing PTSD) to classify individuals as resilient. Therefore, this study used data-driven, continuous resilience scores based on adversity and psychopathology to investigate associations between resilience and brain structure in youth. Structural MRI data from 298 youth aged 9–18 years (M$_{age}$ = 13.51; 51% female) who participated in the European multisite FemNAT-CD study were preprocessed using SPM12 and analyzed using voxel-based morphometry. Resilience scores were derived by regressing data on adversity exposure against current/lifetime psychopathology and quantifying each individual’s distance from the regression line. General linear models tested for associations between resilience and gray matter volume (GMV) and examined whether associations between resilience and GMV differed by sex. Resilience was positively correlated with GMV in the right inferior frontal and medial frontal gyri. Sex-by-resilience interactions were observed in the middle temporal and middle frontal gyri. These findings demonstrate that resilience in youth is associated with volume in brain regions implicated in executive functioning, emotion regulation, and attention. Our results also provide evidence for sex differences in the neurobiology of resilience

Unmet Needs in Children With Attention Deficit Hyperactivity Disorder—Can Transcranial Direct Current Stimulation Fill the Gap? Promises and Ethical Challenges

Attention deficit hyperactivity disorder (ADHD) is a disorder most frequently diagnosed in children and adolescents. Although ADHD can be effectively treated with psychostimulants, a significant proportion of patients discontinue treatment because of adverse events or insufficient improvement of symptoms. In addition, cognitive abilities that are frequently impaired in ADHD are not directly targeted by medication. Therefore, additional treatment options, especially to improve cognitive abilities, are needed. Because of its relatively easy application, well-established safety, and low cost, transcranial direct current stimulation (tDCS) is a promising additional treatment option. Further research is needed to establish efficacy and to integrate this treatment into the clinical routine. In particular, limited evidence regarding the use of tDCS in children, lack of clear translational guidelines, and general challenges in conducting research with vulnerable populations pose a number of practical and ethical challenges to tDCS intervention studies. In this paper, we identify and discuss ethical issues related to research on tDCS and its potential therapeutic use for ADHD in children and adolescents. Relevant ethical issues in the tDCS research for pediatric ADHD center on safety, risk/benefit ratio, information and consent, labeling problems, and nonmedical use. Following an analysis of these issues, we developed a list of recommendations that can guide clinicians and researchers in conducting ethically sound research on tDCS in pediatric ADHD

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