Facing the Unknown: An Inductive Analysis of the Lived Experience of Medical Residents during the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic had significant repercussions for the everyday life and public health of society. Healthcare professionals were particularly vulnerable. Here, we interviewed medical residents about their lived experiences during the pandemic to offer a phenomenological analysis. To this end, we discuss their pandemic experiences considering Jaspers' "limit situation" concept - that is, a radical shift from their everyday experiences, to one causing them to question the basis of their very existence. METHODS: We interviewed 33 medical residents from psychiatry and other specialties from the Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP) who either (a) worked directly with COVID-19 patients or (b) provided psychiatric care to other healthcare professionals. Semi-structured interviews were developed using the Inductive Process to Analyze the Structure of lived Experience (IPSE). RESULTS: The descriptions of the lived experiences of medical residents during the pandemic were organized into four content themes: (a) existential defense, (b) limit situations during the COVID-19 pandemic, (c) changes in lived experience, and (d) new world meanings through lived experience. CONCLUSION: During the COVID-19 pandemic, medical residents experienced what can be thought of as a "limit situation," as they encountered the healthcare delivery challenges coupled with the social isolation imposed by the COVID-19 pandemic. These challenges included fear of infection and potential death, uncertainty about the future, and the emotional overload caused by the sharp increase in patient deaths. That said, after facing such a limit situation, residents reported feeling strengthened by this experience. This is consistent with the notion that when confronted with limit situations, we draw on our resources to overcome adversity and, in turn, reap existential gains. Health care providers might use these experiences to energize their own professional approach.

Perinatal and neonatal factors and mental disorders in children and adolescents: looking for the contributions of the early environment to common and dissociable aspects of psychopathology.

High rates of co-occurrence of mental disorders have been hypothesized to represent a result of common susceptibility to overall psychopathology. The purpose of this study is to test the hypothesis that commonalities among psychiatric disorders might be partially driven by sharable perinatal and neonatal environmental factors for mental disorders. Participants were 6-14 years of age children and their parents. Primary caregivers provided data on perinatal and neonatal information assessed retrospectively (n = 2231). Psychiatric disorders diagnoses were assessed using the Development and Well Being Behavior Assessment (DAWBA). We used bifactor models to disentangle common from dissociable aspects of psychopathology. These models allow modeling psychiatric disorders as the result of a common domain of psychopathology (p-factor) and three dissociable domains (fear, distress, and externalizing symptoms). Associations were tested using linear and tobit regression models. The p-factor was associated with male sex, low socioeconomic status, gestational smoking, gestational drinking, low levels of maternal education and presence of mental disorder in the mother. Associations with specific factors also emerged suggesting some risk factors might also have some role for fear, distress and externalizing factors. Our study supports the hypothesis that overall susceptibility to psychopathology might be partially driven by sharable perinatal and neonatal factors.

Threat and deprivation are associated with distinct aspects of cognition, emotional processing, and psychopathology in children and adolescents.

Exposure to childhood adversity has been consistently associated with poor developmental outcomes, but it is unclear whether these associations vary across different forms of adversity. We examined cross-sectional and longitudinal associations between threat and deprivation with cognition, emotional processing, and psychopathology in a middle-income country. The sample consisted of 2511 children and adolescents (6-17 years old) from the Brazilian High-Risk Cohort for Mental Conditions. Parent reports on childhood adversity were used to construct adversity latent constructs. Psychopathology was measured by the Child Behavior Checklist (CBCL) to generate a measure of general psychopathology (the "p" factor). Executive function (EF) and attention orienting toward angry faces were assessed using cognitive tasks. All measures were acquired at two time-points 3 years apart and associations were tested using general linear models. Higher levels of psychopathology were predicted by higher levels of threat cross-sectionally and longitudinally, and by deprivation longitudinally. For EF, worse performance was associated only with deprivation at baseline and follow-up. Finally, threat was associated with attention orienting towards angry faces cross-sectionally, but neither form of adversity was associated with changes over time in attention bias. Our results suggest that threat and deprivation have differential associations with cognitive development and psychopathology. Exposure to adversity during childhood is a complex phenomenon with meaningful influences on child development. Because adversity can take many forms, dimensional models might help to disentangle the specific developmental correlates of different types of early experience. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=uEU0L8exyTM.

Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study.

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Maternal distress, DNA methylation, and fetal programing of stress physiology in Brazilian mother-infant pairs.

Maternal prenatal psychosocial stress is associated with adverse hypothalamic-pituitary-adrenal axis (HPAA) function among infants. Although the biological mechanisms influencing this process remain unknown, altered DNA methylation is considered to be one potential mechanism. We investigated associations between maternal prenatal psychological distress, infant salivary DNA methylation, and stress physiology at 12 months. Mother's distress was measured via depression and anxiety in early and late pregnancy in a cohort of 80 pregnant adolescents. Maternal hair cortisol was collected during pregnancy. Saliva samples were collected from infants at 12 months to quantify DNA methylation of three stress-related genes (FKBP5, NR3C1, OXTR) (n = 62) and diurnal cortisol (n = 29). Multivariable linear regression was used to test for associations between prenatal psychological distress, and infant DNA methylation and cortisol. Hair cortisol concentrations in late pregnancy were negatively associated with two sites of FKBP5 (site 1: B = -22.33, p = .003; site 2: B = -15.60, p = .012). Infants of mothers with elevated anxiety symptoms in late pregnancy had lower levels of OXTR2 CpG2 methylation (B = -2.17, p = .03) and higher evening salivary cortisol (B = 0.41, p = .03). Furthermore, OXTR2 methylation was inversely associated with evening cortisol (B = -0.14, p-value ≤ .001). Our results are, to our knowledge, the first evidence that the methylation of the oxytocin receptor may contribute to the regulation of HPAA during infancy.

The association between duration of breastfeeding and the trajectory of brain development from childhood to young adulthood: an 8-year longitudinal study.

Breastfeeding has been associated with several short- and long-term health benefits, including positive cognitive and behavioral outcomes. However, the impact of breastfeeding on structural brain development over time remains unclear. We aimed to assess the association between breastfeeding duration in childhood and the developmental trajectory of overall cortical thickness, cortical area, and total intracranial volume during the transition from childhood to early adulthood. Participants included 670 children and adolescents with 1326 MRI scans acquired over 8 years from the Brazilian High-Risk Cohort for Mental Conditions (BHRCS). Breastfeeding was assessed using a questionnaire answered by the parents. Brain measures were estimated using MRI T1-weighted images at three time points, with 3-year intervals. Data were evaluated using generalized additive models adjusted for multiple confounders. We found that a longer breastfeeding duration was directly associated with higher global cortical thickness in the left (edf = 1.0, F = 6.07, p = 0.01) and right (edf = 1.0, F = 4.70, p = 0.03) hemispheres. For the total intracranial volume, we found an interaction between duration of breastfeeding and developmental stage (edf = 1.0, F = 6.81, p = 0.009). No association was found between breastfeeding duration and brain area. Our study suggests that the duration of breastfeeding impacts overall cortical thickness and the development of total brain volume, but not area. This study adds to the evidence on the potential impact of breastfeeding on brain development and provides relevant insights into the mechanisms by which breastfeeding might confer cognitive and mental health benefits.

Longitudinal associations between positive attributes and psychopathology and their interactive effects on educational outcomes.

Psychopathology is associated with impaired learning and early termination of schooling, whereas positive attributes are associated with better educational outcomes. However, it is important to understand if and how psychopathology and positive attributes longitudinally impact each other so we could shed light on where to intervene to promote educational outcomes through these constructs. A large prospective school-based community cohort of youths (5-15 years of age, 45% female) were assessed and followed up for 3 years (n = 2010; 80% retention). We assessed the longitudinal impact of positive attributes (Youth Strength Inventory) and psychopathology (bifactor model of Strengths and Difficulties Questionnaire) using a cross-lagged panel model. We also used generalized mixed effects models to investigate how these both constructs predict school dropout and literacy, adjusting for confounders and testing their interaction. Positive attributes negatively predicted, and were negatively predicted by, the general factor of psychopathology and conduct problems in the cross-lagged panel model. Positive attributes (OR = 0.57, 95% CI [0.44, 0.73], p < 0.001) and specific conduct symptoms (OR = 2.33, 95% CI [1.64, 3.33], p < 0.001) predicted school dropout, whereas the general factor of psychopathology predicted lower literacy ability (ß = - 0.08, 95% CI [- 0.11, - 0.05], p < 0.001). However, the protective association of positive attributes on school dropout decreases as the general factor of psychopathology increases. These findings provide new evidence that positive attributes and psychopathology mutually influence each other over development and have interactive effects on educational outcomes.

Cognitive decline following acute viral infections: literature review and projections for post-COVID-19.

Recently, much attention has been drawn to the importance of the impact of infectious disease on human cognition. Several theories have been proposed, to explain the cognitive decline following an infection as well as to understand better the pathogenesis of human dementia, especially Alzheimer's disease. This article aims to review the state of the art regarding the knowledge about the impact of acute viral infections on human cognition, laying a foundation to explore the possible cognitive decline followed coronavirus disease 2019 (COVID-19). To reach this goal, we conducted a narrative review systematizing six acute viral infections as well as the current knowledge about COVID-19 and its impact on human cognition. Recent findings suggest probable short- and long-term COVID-19 impacts in cognition, even in asymptomatic individuals, which could be accounted for by direct and indirect pathways to brain dysfunction. Understanding this scenario might help clinicians and health leaders to deal better with a wave of neuropsychiatric issues that may arise following COVID-19 pandemic as well as with other acute viral infections, to alleviate the cognitive sequelae of these infections around the world.

Long-term stability of the cortical volumetric profile and the functional human connectome throughout childhood and adolescence.

There is compelling evidence showing that between-subject variability in several functional and structural brain features is sufficient for unique identification in adults. However, individuation of brain functional connectomes depends on the stabilization of neurodevelopmental processes during childhood and adolescence. Here, we aimed to (1) evaluate the intra-subject functional connectome stability over time for the whole brain and for large scale functional networks and (2) determine the long-term identification accuracy or 'fingerprinting' for the cortical volumetric profile and the functional connectome. For these purposes, we analysed a longitudinal cohort of 239 children and adolescents scanned in two sessions with an interval of approximately 3 years (age range 6-15 years at baseline and 9-18 years at follow-up). Corroborating previous results using short between-scan intervals in children and adolescents, we observed a moderate identification accuracy (38%) for the whole functional profile. In contrast, identification accuracy using cortical volumetric profile was 95%. Among the large-scale networks, the default-mode (26.8%), the frontoparietal (23.4%) and the dorsal-attention (27.6%) networks were the most discriminative. Our results provide further evidence for a protracted development of specific individual structural and functional connectivity profiles.

Promoting mother-infant relationships and underlying neural correlates: Results from a randomized controlled trial of a home-visiting program for adolescent mothers in Brazil.

Poverty and teenage pregnancy are common in low-and-middle-income countries and can impede the development of healthy parent-child relationships. This study aimed to test whether a home-visiting intervention could improve early attachment relationships between adolescent mothers and their infants living in poverty in Brazil. Analyses were conducted on secondary outcomes from a randomized controlled trial (NCT0280718) testing the efficacy of a home-visiting program, Primeiros Laços, on adolescent mothers' health and parenting skills and their infants' development. Pregnant youth were randomized to intervention (n = 40) or care-as-usual (CAU, n = 40) from the first trimester of pregnancy until infants were aged 24 months. Mother-infant attachment was coded during a mother-infant interaction when the infants were aged 12 months. Electrophysiological correlates of social processing (mean amplitude of the Nc component) were measured while infants viewed facial images of the mother and a stranger at age 6 months. Infants in the intervention group were more securely attached and more involved with their mothers than those receiving CAU at 12 months. Smaller Nc amplitudes to the mother's face at 6 months were associated with better social behavior at 12 months. Our findings indicate that the Primeiros Laços Program is effective in enhancing the development of mother-infant attachment.

Risk factors for obsessive-compulsive symptoms. Follow-up of a community-based youth cohort.

Environmental factors are at least as important as genetic factors for the development of obsessive-compulsive symptoms (OCS), but the identification of such factors remain a research priority. Our study aimed to investigate the association between a broad scope of potential risk factors and OCS in a large community cohort of children and adolescents. We evaluated 1877 participants and their caregivers at baseline and after 3 years to assess various demographic, prenatal, perinatal, childhood adversity, and psychopathological factors. Mean age at baseline was 10.2 years (SD 1.9) and mean age at follow-up was 13.4 years (SD 1.9). Reports of OCS at baseline and follow-up were analyzed using latent variable models. At preliminary regression analysis, 15 parameters were significantly associated with higher OCS scores at follow-up. At subsequent regression analysis, we found that eight of these parameters remained significantly associated with higher follow-up OCS scores while being controlled by each other and by baseline OCS scores. The significant predictors of follow-up OCS were: lower socioeconomic status (p = 0.033); lower intelligence quotient (p = 0.013); lower age (p < 0.001); higher maternal stress level during pregnancy (p = 0.028); absence of breastfeeding (p = 0.017); parental baseline OCS (p = 0.038); youth baseline anxiety disorder (p = 0.023); and youth baseline OCS scores (p < 0.001). These findings may better inform clinicians and policymakers engaged in the mental health assessment and prevention in children and adolescents.

Cognitive performance in children and adolescents at high-risk for obsessive-compulsive disorder.

BACKGROUND: Cognitive performance has been studied in adults with obsessive-compulsive symptoms (OCS) and in adult relatives of patients with obsessive-compulsive disorder (OCD) Meanwhile, few studies have been conducted with children under the same conditions. This study compared the neurocognitive domains previously associated with dysfunction in OCD, especially visuoconstructive ability, visuospatial memory, executive functions, and intelligence, in children and adolescents at high risk (HR) for OCD (n = 18) and non-OCD controls (NOC) (n = 31). METHODS: For the HR group, we considered the first-degree relatives of patients with OCD that present OCS, but do not meet diagnostic criteria for OCD. Psychiatric diagnosis was assessed by experienced clinicians using the Structured Clinical Interview for DSM-IV and OCS severity was measured by the Yale-Brown Obsessive-Compulsive Scale. Neurocognitive assessment was performed with a comprehensive neuropsychological battery. Performance on the cognitive domains was compared between groups using Multivariate Analysis of Variance, whereas performance on the neuropsychological variables was compared between groups using independent t-tests in a cognitive subdomain analysis. RESULTS: The cognitive domain analysis revealed a trend towards significance for impairments in the motor and processing speed domain (p = 0.019; F = 3.12) in the HR group. Moreover, the cognitive subdomain analysis identified a statistically significant underperformance in spatial working memory in the HR group when compared to the NOC group (p = 0.005; t = - 2.94), and a trend towards significance for impairments in non-verbal memory and visuoconstructive tasks in the HR group. CONCLUSIONS: Our results suggest impairments in spatial working memory and motor and processing speed in a non-clinical sample of HR participants. Considering the preliminary nature of our findings, further studies investigating these neurocognitive domains as potential predictors of pediatric OCD are warranted.

Relationships between childhood maltreatment, impairment in executive functions and disruptive behavior disorders in a community sample of children.

Evidence points to an independent relationship among childhood maltreatment, impairments in executive functions (EF) and disruptive behavior disorders (DBD). However, it is still not fully understood how these three factors are interrelated. This study evaluated the association between childhood maltreatment and DBD testing the role of EF performance as a mediator or moderator. We studied a probabilistic school-based sample of 2016 children from 6 to 12 years. Mental disorders were assessed using the Development and Well-Being Assessment with parents and children. Children answered questions about exposure to child maltreatment and were evaluated with a set of cognitive tasks addressing inhibitory control, working memory, cognitive flexibility and planning. Childhood maltreatment was strongly associated with DBD (OR = 7.7, CI 95% 4.5-12.9). No association was found between childhood maltreatment and EF performance. Children with DBD showed worse performance in cognitive flexibility, which was not identified as a mediator or moderator of the association between childhood maltreatment and DBD. Results indicate that the association between maltreatment and disruptive behavior occurs regardless of performance in executive function in a community sample. Future studies are essential to confirm these findings and elucidate the cognitive mechanisms involved in this association.

Associations between children's family environment, spontaneous brain oscillations, and emotional and behavioral problems.

The family environment in childhood has a strong effect on mental health outcomes throughout life. This effect is thought to depend at least in part on modifications of neurodevelopment trajectories. In this exploratory study, we sought to investigate whether a feasible resting-state fMRI metric of local spontaneous oscillatory neural activity, the fractional amplitude of low-frequency fluctuations (fALFF), is associated with the levels of children's family coherence and conflict. Moreover, we sought to further explore whether spontaneous activity in the brain areas influenced by family environment would also be associated with a mental health outcome, namely the incidence of behavioral and emotional problems. Resting-state fMRI data from 655 children and adolescents (6-15 years old) were examined. The quality of the family environment was found to be positively correlated with fALFF in the left temporal pole and negatively correlated with fALFF in the right orbitofrontal cortex. Remarkably, increased fALFF in the temporal pole was associated with a lower incidence of behavioral and emotional problems, whereas increased fALFF in the orbitofrontal cortex was correlated with a higher incidence.

Cross-Sectional and Longitudinal Associations of Temperament and Mental Disorders in Youth.

Here we evaluate the cross-sectional and longitudinal associations between temperament and mental disorders in adolescents. Temperament was assessed in a cohort of 1540 youths by the revised self-report Early Adolescence Temperament Questionnaire (EATQ-R) at baseline and confirmatory factor analyses were used to test the best empirical model. Mental disorders were assessed by parental interview using the Development and Well-Being Behavior Assessment at baseline and at 3-year follow-up. Participants were grouped into Typically Developing Comparisons, Phobias, Distress, Attention-Deficit/Hyperactivity Disorder (ADHD) and Disruptive Behavior Disorders (DBD). Logistic regression models tested the effects of temperament on incidence and remission of mental disorders. The bifactor model of EATQ-R presented the best fit. Distress, ADHD and DBD have lower levels of effortful control in baseline. Adjusted longitudinal analysis showed that effortful control predicted lower incidence of Phobias (OR 0.74; p = 0.018), distress (OR 0.74; p = 0.014) and DBD (OR 0.68; p = 0.037). Temperament factors did not predicted remission rates.

The association between psychotic experiences and traumatic life events: the role of the intention to harm.

BACKGROUND: Previous work showed traumatic life events (TLE) with intention to harm, like bullying and abuse, to be more strongly associated with psychotic experiences (PE) than other types of trauma, like accidents. However, this association is subject to reporting bias and can be confounded by demographic characteristics and by differences in dose of exposure across different trauma categories. We studied the association between TLE with and without intention to harm and PE, taking into account potential confounders and biases. METHODS: A total of 2245 children and adolescents aged 6-14 years were interviewed by psychologists. The interview included the presence of 20 PE (both self-report and psychologist evaluation). In addition, parents provided information on child exposure to trauma, mental health and PE. RESULTS: Results showed no significant association between TLE without intention to harm only and PE for the three methods of assessment of PE (self-report, parent report and psychologist rating). On the other hand, there was a positive association between PE and TLE in groups exposed to traumatic experiences with intention to harm (with intention to harm only and with and without intention to harm). Results remained significant after controlling for demographic and clinical confounders, but this positive association was no longer significant after adjusting for the number of TLE. CONCLUSIONS: TLE with intention to harm display a stronger association with PE than TLE without intention to harm, and this difference is likely reducible to a greater level of traumatic exposure associated with TLE with intention to harm.

The economic impact of subthreshold and clinical childhood mental disorders.

BACKGROUND: Mental disorders are common health problems associated with serious impairment and economic impact. AIMS: To estimate the costs of clinical and subthreshold mental disorders in a sample of Brazilian children. METHOD: The High Risk Cohort Study is a community study conducted in two major Brazilian cities. Subjects were 6-14 years old children being registered at school. From an initial pool of 9937 children, two subgroups were further investigated using a random-selection (n = 958) and high-risk group selection procedure (n = 1554), resulting in a sample of 2512 subjects. Mental disorder assessment was made using the Development and Well-Being Assessment. Costs for each child were estimated from the following components: mental health and social services use, school problems and parental loss of productivity. RESULTS: Child subthreshold and clinical mental disorders showed lifetime mean total cost of $1750.9 and $3141.2, respectively. National lifetime cost estimate was $9.9 billion for subthreshold mental disorders and $11.6 billion for clinical mental disorders (values in US$ purchasing power parity). CONCLUSIONS: This study provides evidence that child mental disorders have a great economic impact on society. There is an urgent need to plan an effective system of care with cost-effective programs of treatment and prevention to reduce economic burden.

The Social Aptitudes Scale: looking at both "ends" of the social functioning dimension.

PURPOSE: Dimensional approaches are likely to advance understanding of human behaviors and emotions. Nevertheless, it is unclear whether instruments in psychiatry capture variability at the full spectrum of these dimensions. We aimed to investigate this issue for two scales assessing distinct aspects of social functioning: the Social Aptitudes Scale (SAS), a "bidirectional" scale constructed to investigate both "ends" of social functioning; and the social Child Behavior Checklist (CBCL-social), a "unidirectional" scale constructed to assess social problems. METHODS: We investigated 2512 children and adolescents aged 6-14. Item response theory was used to investigate on which range of the trait each scale captures information. We performed quantile regressions to investigate if correlations between SAS and CBCL-social vary within different levels of social aptitudes dimension and multiple logistic regressions to investigate associations with negative and positive clinical outcomes. RESULTS: SAS was able to provide information on the full range of social aptitudes, whereas CBCL-social provided information on subjects with high levels of social problems. Quantile regressions showed SAS and CBCL-social have higher correlations for subjects with low social aptitudes and non-significant correlations for subjects with high social aptitudes. Multiple logistic regressions showed that SAS was able to provide independent clinical predictions even after adjusting for CBCL-social scores. CONCLUSIONS: Our results provide further validity to SAS and exemplify the potential of "bidirectional" scales to dimensional assessment, allowing a better understanding of variations that occur in the population and providing information for children with typical and atypical development.

Epigenetic evidence for involvement of the oxytocin receptor gene in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic neurodevelopmental disorder that affects up to 3% of the general population. Although epigenetic mechanisms play a role in neurodevelopment disorders, epigenetic pathways associated with OCD have rarely been investigated. Oxytocin is a neuropeptide involved in neurobehavioral functions. Oxytocin has been shown to be associated with the regulation of complex socio-cognitive processes such as attachment, social exploration, and social recognition, as well as anxiety and other stress-related behaviors. Oxytocin has also been linked to the pathophysiology of OCD, albeit inconsistently. The aim of this study was to investigate methylation in two targets sequences located in the exon III of the oxytocin receptor gene (OXTR), in OCD patients and healthy controls. We used bisulfite sequencing to quantify DNA methylation in peripheral blood samples collected from 42 OCD patients and 31 healthy controls. RESULTS: We found that the level of methylation of the cytosine-phosphate-guanine sites in two targets sequences analyzed was greater in the OCD patients than in the controls. The higher methylation in the OCD patients correlated with OCD severity. We measured DNA methylation in the peripheral blood, which prevented us from drawing any conclusions about processes in the central nervous system. CONCLUSION: To our knowledge, this is the first study investigating DNA methylation of the OXTR in OCD. Further studies are needed to evaluate the roles that DNA methylation and oxytocin play in OCD.

Default mode network maturation and psychopathology in children and adolescents.

BACKGROUND: The human default mode (DMN) is involved in a wide array of mental disorders. Current knowledge suggests that mental health disorders may reflect deviant trajectories of brain maturation. METHOD: We studied 654 children using functional magnetic resonance imaging (fMRI) scans under a resting-state protocol. A machine-learning method was used to obtain age predictions of children based on the average coefficient of fractional amplitude of low frequency fluctuations (fALFFs) of the DMN, a measure of spontaneous local activity. The chronological ages of the children and fALFF measures from regions of this network, the response and predictor variables were considered respectively in a Gaussian Process Regression. Subsequently, we computed a network maturation status index for each subject (actual age minus predicted). We then evaluated the association between this maturation index and psychopathology scores on the Child Behavior Checklist (CBCL). RESULTS: Our hypothesis was that the maturation status of the DMN would be negatively associated with psychopathology. Consistent with previous studies, fALFF significantly predicted the age of participants (p < .001). Furthermore, as expected, we found an association between the DMN maturation status (precocious vs. delayed) and general psychopathology scores (p = .011). CONCLUSIONS: Our findings suggest that child psychopathology seems to be associated with delayed maturation of the DMN. This delay in the neurodevelopmental trajectory may offer interesting insights into the pathophysiology of mental health disorders.