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Extracellular vesicles (EVs) are present in numerous peripheral bodily fluids and function in critical biological processes, including cell-to-cell communication. Most relevant to the present study, EVs contain microRNAs (miRNAs), and initial evidence from the field indicates that miRNAs detected in circulating EVs have been previously associated with mental health disorders. Here, we conducted an exploratory longitudinal and cross-sectional analysis of miRNA expression in serum EVs from adolescent participants. We analyzed data from a larger ongoing cohort study, evaluating 116 adolescent participants at two time points (wave 1 and wave 2) separated by three years. Two separate data analyses were employed: A cross-sectional analysis compared individuals diagnosed with Major Depressive Disorder (MDD), Anxiety disorders (ANX) and Attention deficit/Hyperactivity disorder (ADHD) with individuals without psychiatric diagnosis at each time point. A longitudinal analysis assessed changes in miRNA expression over time between four groups showing different diagnostic trajectories (persistent diagnosis, first incidence, remitted and typically developing/control). Total EVs were isolated, characterized by size distribution and membrane proteins, and miRNAs were isolated and sequenced. We then selected differentially expressed miRNAs for target prediction and pathway enrichment analysis. In the longitudinal analysis, we did not observe any statistically significant results. In the cross-sectional analysis: in the ADHD group, we observed an upregulation of miR-328-3p at wave 1 only; in the MDD group, we observed a downregulation of miR-4433b-5p, miR-584-5p, miR-625-3p, miR-432-5p and miR-409-3p at wave 2 only; and in the ANX group, we observed a downregulation of miR-432-5p, miR-151a-5p and miR-584-5p in ANX cases at wave 2 only. Our results identified previously observed and novel differentially expressed miRNAs and their relationship with three mental health disorders. These data are consistent with the notion that these miRNAs might regulate the expression of genes associated with these traits in genome-wide association studies. The findings support the promise of continued identification of miRNAs contained within peripheral EVs as biomarkers for mental health disorders., (© 2023. The Author(s).)

Aim: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders which was published in 2002 and revised in 2008., Method: A consensus panel of 34 international experts representing 22 countries developed recommendations based on efficacy and acceptability of the treatments. In this version, not only medications but also psychotherapies and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medication treatments., Result: The present paper (Part II) contains recommendations based on published randomised controlled trials (RCTs) for the treatment of OCD ( n  = 291) and PTSD ( n  = 234) in children, adolescents, and adults. The accompanying paper (Part I) contains the recommendations for the treatment of anxiety disorders.For OCD, first-line treatments are selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioural therapy (CBT). Internet-CBT was also superior to active controls. Several second-line medications are available, including clomipramine. For treatment-resistant cases, several options are available, including augmentation of SSRI treatment with antipsychotics and other drugs.Other non-pharmacological treatments, including repetitive transcranial magnetic stimulation (rTMS), deep brain stimulation (DBS) and others were also evaluated.For PTSD, SSRIs and the SNRI venlafaxine are first-line treatments. CBT is the psychotherapy modality with the best body of evidence. For treatment-unresponsive patients, augmentation of SSRI treatment with antipsychotics may be an option., Conclusion: OCD and PTSD can be effectively treated with CBT and medications.

Aim: This is the third version of the guideline of the World Federation of Societies of Biological Psychiatry (WFSBP) Task Force for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Posttraumatic Stress Disorders (published in 2002, revised in 2008)., Method: A consensus panel of 33 international experts representing 22 countries developed recommendations based on efficacy and acceptability of available treatments. In total, 1007 RCTs for the treatment of these disorders in adults, adolescents, and children with medications, psychotherapy and other non-pharmacological interventions were evaluated, applying the same rigorous methods that are standard for the assessment of medications., Result: This paper, Part I, contains recommendations for the treatment of panic disorder/agoraphobia (PDA), generalised anxiety disorder (GAD), social anxiety disorder (SAD), specific phobias, mixed anxiety disorders in children and adolescents, separation anxiety and selective mutism. Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are first-line medications. Cognitive behavioural therapy (CBT) is the first-line psychotherapy for anxiety disorders. The expert panel also made recommendations for patients not responding to standard treatments and recommendations against interventions with insufficient evidence., Conclusion: It is the goal of this initiative to provide treatment guidance for these disorders that has validity throughout the world.

Generative Adversarial Networks (GANs) are promising analytical tools in machine learning applications. Characterizing atypical neurodevelopmental processes might be useful in establishing diagnostic and prognostic biomarkers of psychiatric disorders. In this article, we investigate the potential of GANs models combined with functional connectivity (FC) measures to build a predictive neurotypicality score 3-years after scanning. We used a ROI-to-ROI analysis of resting-state functional magnetic resonance imaging (fMRI) data from a community-based cohort of children and adolescents (377 neurotypical and 126 atypical participants). Models were trained on data from neurotypical participants, capturing their sample variability of FC. The discriminator subnetwork of each GAN model discriminated between the learned neurotypical functional connectivity pattern and atypical or unrelated patterns. Discriminator models were combined in ensembles, improving discrimination performance. Explanations for the model's predictions are provided using the LIME (Local Interpretable Model-Agnostic) algorithm and local hubs are identified in light of these explanations. Our findings suggest this approach is a promising strategy to build potential biomarkers based on functional connectivity., Competing Interests: LAR has received grant or research support from, served as a consultant to, and served on the speakers’ bureau of Abbott, Aché, Bial, Medice, Novartis/Sandoz, Pfizer/Upjohn, and Shire/Takeda in the last three years. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by LAR have received unrestricted educational and research support from the following pharmaceutical companies in the last three years: Novartis/Sandoz and Shire/Takeda. LAR has received authorship royalties from Oxford Press and ArtMed. All of these are outside of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with the author JS., (Copyright © 2023 Dos Santos, Mendes, Biazoli, Gadelha, Salum, Miguel, Rohde and Sato.)

Background: The obsession of turning into another person (transformation obsessions [TO]), and its related compulsions have been initially conceptualised as a form of mental contamination. Nevertheless, it has remained understudied in the current obsessive-compulsive disorder (OCD) literature. In parallel, disturbances of the self have been identified as markers of prodromal psychosis in patients with schizophrenia. Based on the later association, this study aimed to investigate the sociodemographic and clinical correlates of TO., Methods: In all, 1001 OCD outpatients from the Brazilian OCD Research Consortium were included in this study. Several semi-structured and structured instruments were used to compare 48 OCD patients with TO with 953 OCD patients without TO. A repression model investigated the relationships between the presence of current TO and statistically significant univariate test outcomes., Results: Participants with TO presented an overall younger age, a longer period of time between the onset of the OCD symptoms and an OCD diagnosis, greater severity of the sexual/religious dimension and increased suicidality symptoms., Conclusions: These results indicate that TO may be better conceptualised as a form of forbidden/taboo thoughts rather than contamination. While no significant associations with psychotic features (e.g. decreased insight) were observed, TO patients displayed increased suicidality, overall younger age and a significantly larger disparity between seeking treatment and OCD diagnosis. This demonstrates that further clinical awareness and research into TO as an OCD symptom is most needed.

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., (© 2022 John Wiley & Sons Ltd.)

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., (© 2022 Wiley Periodicals LLC.)

Background: The present study explored the influence of romantic love on the expression of several obsessive-compulsive disorder (OCD) characteristics, including symptom severity, symptom dimensions, age at onset, sensory phenomena (SP), and developmental course, as well as other related comorbid disorders. It was hypothesized that love-precipitated OCD would be associated with a set of distinct characteristics and exhibit greater rates of comorbid disorders., Methods: The analyses were performed using a large sample (n = 981) of clinical patients with a primary diagnosis of OCD (Females = 67.3%, M age = 35.31)., Results: Love-precipitated OCD was associated with greater severity of SP and later age at onset of obsessions. However, symptom severity, symptom dimension, developmental course, and psychiatric comorbidities were not associated with love-precipitated OCD., Conclusion: It was concluded that romantic love does shape the expression of OCD, especially with regard to SP and onset age. These findings encourage further exploration to determine its clinical significance as a phenotype.

Obsessive-compulsive disorder (OCD) commonly co-occurs with other psychiatric conditions. Though research is limited, there is preliminary evidence that OCD also co-occurs with compulsive sexual behavior (CSB). Yet, few studies have investigated the demographic, clinical, and psychiatric comorbidities associated with co-occurring OCD and CSB. To address this gap, the current study aimed to evaluate rates of co-occurring OCD and CSB, identify demographic and clinical factors associated with comorbid OCD and CSB, and assess associated psychiatric comorbidity. Participants (N = 950) were patients of a large multisite treatment for OCD. Standardized self-report measures were used to assess demographic and clinical characteristics such as anxiety, depression, and severity and dimensions of OCD. Semi-structured interviews including the SCID were used to assess psychiatric comorbidities. A total of 36 (3.8%) of participants met the criteria for CSB. Binary logistic regression analysis revealed that males were significantly more likely to present with CSB than females and CSB was associated with greater psychiatric comorbidity, particularly impulse control disorders. These findings suggest that individuals with co-occurring OCD and CSB may have more complex treatment needs, and more tailored interventions may be necessary., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Neuroimaging studies of obsessive-compulsive disorder (OCD) patients have highlighted the important role of deep gray matter structures. Less work has however focused on subcortical shape in OCD patients., Methods: Here we pooled brain MRI scans from 412 OCD patients and 368 controls to perform a meta-analysis utilizing the ENIGMA-Shape protocol. In addition, we investigated modulating effects of medication status, comorbid anxiety or depression, and disease duration on subcortical shape., Results: There was no significant difference in shape thickness or surface area between OCD patients and healthy controls. For the subgroup analyses, OCD patients with comorbid depression or anxiety had lower thickness of the hippocampus and caudate nucleus and higher thickness of the putamen and pallidum compared to controls. OCD patients with comorbid depression had lower shape surface area in the thalamus, caudate nucleus, putamen, hippocampus, and nucleus accumbens and higher shape surface area in the pallidum. OCD patients with comorbid anxiety had lower shape surface area in the putamen and the left caudate nucleus and higher shape surface area in the pallidum and the right caudate nucleus. Further, OCD patients on medication had lower shape thickness of the putamen, thalamus, and hippocampus and higher thickness of the pallidum and caudate nucleus, as well as lower shape surface area in the hippocampus and amygdala and higher surface area in the putamen, pallidum, and caudate nucleus compared to controls. There were no significant differences between OCD patients without co-morbid anxiety and/or depression and healthy controls on shape measures. In addition, there were also no significant differences between OCD patients not using medication and healthy controls., Conclusions: The findings here are partly consistent with prior work on brain volumes in OCD, insofar as they emphasize that alterations in subcortical brain morphology are associated with comorbidity and medication status. Further work is needed to understand the biological processes contributing to subcortical shape., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

The crosstalk between maternal stress exposure and fetal development may be mediated by epigenetic mechanisms, including DNA methylation (DNAm). To address this matter, we collect 32 cord blood samples from low-income Brazilian pregnant adolescents participants of a pilot randomized clinical intervention study (ClinicalTrials.gov, Identifier: NCT02807818). We hypothesized that the association between the intervention and infant neurodevelopmental outcomes at 12 months of age would be mediated by DNAm. First, we searched genome methylation differences between cases and controls using different approaches, as well as differences in age acceleration (AA), represented by the difference of methylation age and birth age. According to an adjusted p -value ≤ 0.05 we identified 3090 differentially methylated positions- CpG sites (DMPs), 21 differentially methylated regions (DMRs) and one comethylated module weakly preserved between groups. The intervention group presented a smaller AA compared to the control group ( p = 0.025). A logistic regression controlled by sex and with gestational age indicated a coefficient of -0.35 towards intervention group ( p = 0.016) considering AA. A higher cognitive domain score from Bayley III scale was observed in the intervention group at 12 months of age. Then, we performed a potential causal mediation analysis selecting only DMPs highly associated with the cognitive domain (adj. R 2 > 0.4), DMRs and CpGs of hub genes from the weakly preserved comethylated module and epigenetic clock as raw values. DMPs in STXBP6 , and PF4 DMR, mediated the association between the maternal intervention and the cognitive domain at 12 months of age. In conclusion, DNAm in different sites and regions mediated the association between intervention and cognitive outcome.

Background: The symptoms of obsessive-compulsive disorder (OCD) are highly heterogeneous and it is unclear what is the optimal way to conceptualize this heterogeneity. This study aimed to establish a comprehensive symptom structure model of OCD across the lifespan using factor and network analytic techniques., Methods: A large multinational cohort of well-characterized children, adolescents, and adults diagnosed with OCD ( N = 1366) participated in the study. All completed the Dimensional Yale-Brown Obsessive-Compulsive Scale, which contains an expanded checklist of 87 distinct OCD symptoms. Exploratory and confirmatory factor analysis were used to outline empirically supported symptom dimensions, and interconnections among the resulting dimensions were established using network analysis. Associations between dimensions and sociodemographic and clinical variables were explored using structural equation modeling (SEM)., Results: Thirteen first-order symptom dimensions emerged that could be parsimoniously reduced to eight broad dimensions, which were valid across the lifespan: Disturbing Thoughts, Incompleteness, Contamination, Hoarding, Transformation, Body Focus, Superstition, and Loss/Separation. A general OCD factor could be included in the final factor model without a significant decline in model fit according to most fit indices. Network analysis showed that Incompleteness and Disturbing Thoughts were most central (i.e. had most unique interconnections with other dimensions). SEM showed that the eight broad dimensions were differentially related to sociodemographic and clinical variables., Conclusions: Future research will need to establish if this expanded hierarchical and multidimensional model can help improve our understanding of the etiology, neurobiology and treatment of OCD.

Individuals with obsessive-compulsive disorder (OCD) more often think about, attempt, and die by suicide than individuals from the general population. Sexual and religious obsessions (i.e., taboo obsessions) have been linked to increased risk of suicidality, but it is unclear if they explain additional risk over and above other risk factors. We refined the recently proposed multidimensional hierarchical model of OCD and explored how each symptom dimension in the model was associated with suicidality in a random half (n = 500) of a well-characterized cohort of patients with OCD. Symptom dimensions and other risk factors significantly associated with suicidality were included in a confirmatory multivariable model conducted with the other half of the sample (n = 501). The predictive confirmatory model accounted for 19% of the variance in suicidality. Taboo obsessions, the general OCD factor (i.e., having many different OCD symptoms at the same time), lifetime major depression, and lifetime substance use disorders significantly predicted suicidality in this model. Lifetime major depression explained most unique variance in suicidality (5.6%) followed by taboo obsessions and the general OCD factor (1.9% each). Taboo obsessions explain a small but significant proportion of variance in suicidality and should be considered an independent risk factor for suicidality in patients with OCD., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The high level of care needs for adolescents with mental health conditions represents a challenge to the public sector, especially in low and middle-income countries. We estimated the costs to the public purse of health, education, criminal justice and social care service use associated with psychiatric conditions among adolescents in Brazil; and examined whether the trajectory of psychopathology and its impact on daily life, and parental stigma towards mental illness, was associated with service utilisation and costs., Methods: Data on reported service use among adolescents from a prospective community cohort (n = 1,400) were combined with Brazilian unit costs. Logistic regression and generalised linear models were used to examine factors associated with service use and associated costs, respectively., Results: Twenty-two percent of those who presented with a psychiatric disorder used some type of service for their mental health in the previous twelve months. Higher odds of service use were associated with having a diagnosed mental disorder (either incident, [OR = 2.49, 95%CI = 1.44-4.30, p = 0.001], remittent [OR = 2.16, 95%CI = 1.27-3.69, p = 0.005] or persistent [OR = 3.01, 95%CI = 1.69-5.36, p<0.001]), higher impact of symptoms on adolescent's life (OR = 1.32, 95%CI = 1.19-1.47, p<0.001) and lower parental stigma toward mental illness (OR = 1.12, 95%CI = 1.05-1.20, p = 0.001). Average annual cost of service use was 527.14 USD (s.d. = 908.10). Higher cost was associated with higher disorder impact (β = 0.25, 95%CI = 0.12-0.39, p<0.001), lower parental stigma (β = 0.12, 95%CI = 0.02-0.23, p = 0.020) and white ethnicity (β = 0.55, 95%CI = 0.04-1.07, p = 0.036)., Conclusion: The impact of mental health problems on adolescents' daily lives and parental stigmatising attitudes toward mental illness were the main predictors of both service use and costs., Competing Interests: All authors report no conflict of interest associated with this publication. Luis Augusto Rohde has received grant or research support from, served as a consultant to, and served on the speakers’ bureau of Aché, Bial, Medice, Novartis/Sandoz, Pfizer/Upjohn, and Shire/Takeda in the last three years. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by Dr Rohde have received unrestricted educational and research support from the following pharmaceutical companies in the last three years: Novartis/Sandoz and Shire/Takeda. Dr Rohde has received authorship royalties from Oxford Press and ArtMed. None of these commercial relationships alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce., Methods: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment., Results: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities., Conclusions: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Objective: Maternal attention-deficit/hyperactivity disorder has not been investigated in relation to parenting skills in adolescent mothers. This study investigated whether maternal inattention and hyperactivity/impulsivity symptoms early in pregnancy predict poorer parenting skills and infant maltreatment during the first year of life in adolescent mothers living in adverse environmental conditions., Methods: The participants in this study were 80 adolescent mothers aged 14-19 years and their babies who were taking part in a randomized controlled trial on the effects of a home-visiting program on infant development. Symptoms of maternal attention-deficit/hyperactivity disorder were assessed in the first trimester of pregnancy. Parenting skills (maternal competence, attachment to the baby, home environment) and child maltreatment were assessed when the infants were aged 6 and 12 months. Multilevel linear regression models were constructed to test the extent to which prenatal maternal inattention and hyperactivity/impulsivity symptoms predicted these parenting variables during the first year of the infant's life., Results: Prenatal inattention symptoms significantly predicted lower maternal competence and attachment, a poorer home environment, and greater maltreatment during the first year of life. Hyperactivity did not significantly predict parenting skills or maltreatment., Conclusions: Our findings suggest that inattention symptoms may interfere with parenting abilities in adolescent mothers and should be considered in early intervention programs., Competing Interests: LAR has been a member of the speakers' bureau/advisory board and/or has acted as a consultant for Bial, Eli-Lilly, Janssen-Cilag, Medice, Novartis, Pfizer, and Shire in the last 3 years; receives authorship royalties from Oxford Press and ArtMed; and has received travel grants from Shire for attending the 2018 APA meetings. The ADHD and the Juvenile Bipolar Disorder Outpatient Programs LAR chairs have received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Eli-Lilly, Janssen-Cilag, Novartis, and Shire. GVP has acted as an advisor/consultant/speaker for Takeda, Medice, Aché, Novo Nordisk, and has received royalties from Editora Manole. The other authors report no conflicts of interest.

Background: The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented challenge for public health and has caused the loss of millions of lives worldwide. Hospital workers play a key role in averting the collapse of the health system, but the mental health of many has deteriorated during the pandemic. Few studies have been devoted to identifying the needs of workers on frontline duty., Aim: To investigate dimensions of common emotional symptoms and associated predictors among Brazilian workers in a COVID-19 reference hospital., Methods: This is an observational study of the mental health of professionals in a COVID-19 hospital in the city of São Paulo. We invited all hospital employees to respond to an online survey between July and August 2020, during the first peak of the pandemic. Data of 1000 participants who completed the survey were analyzed (83.9% were women and 34.3% were aged 30 to 40). Hospital workers self-reported the presence of symptoms of depression, anxiety, trauma-related stress, and burnout through the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Impact of Event Scale-Revised and the Mini-Z Burnout Assessment respectively. Responses were assembled and subjected to exploratory factor analysis to reveal workers' core emotional distress. Multiple linear regression models were subsequently carried out to estimate the likelihood of dimensions of distress using questions on personal motivation, threatening events, and institutional support., Results: Around one in three participants in our sample scored above the threshold of depression, anxiety, post-traumatic stress disorder, and burnout. The factor analysis revealed a three-factor structure that explained 58% of the total data variance. Core distressing emotional domains were avoidance and re-experience, depression-anxiety, and sleep changes. Regression analysis revealed that institutional support was a significant protective factor for each of these dimensions (β range = -0.41 to -0.20, P < 0.001). However, participants' personal motivation to work in healthcare service was not associated with these emotional domains. Moreover, the likelihood of presenting the avoidance and re-experience dimension was associated with having a family member or close friend be hospitalized or die due to COVID-19 and having faced an ethical conflict., Conclusion: Distressing emotional domains among hospital workers were avoidance and re-experience, depression and anxiety, and sleep changes. Improving working conditions through institutional support could protect hospital workers' mental health during devastating public health crises., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest in this work., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Young people can receive mental health care from many sources, from formal and informal sectors. Caregiver characteristics/experiences/beliefs may influence whether young people get help and the type of care or support used by their child. We investigate facilitators/barriers to receiving formal and/or informal care, particularly those related to the caregiver's profile., Methods: We interviewed 1,400 Brazilian primary caregivers of young people (aged 10-19), participants of a high-risk cohort. Caregivers reported on young people's formal/informal mental health care utilization, and associated barriers and facilitators to care. Data were also collected on youth mental health and its impact on everyday life; and caregiver characteristics-education, socioeconomics, ethnicity, mental health, and stigma. Logistic regression models were used to examine the relationship between caregiver and young people characteristics with formal/informal care utilization., Results: Persistence and greater impact of youth mental health conditions were associated with a higher likelihood of care, more clearly for formal care. Caregiver characteristics, however, also played a key role in whether young people received any care: lower parental stigma was associated with greater formal service use, and lower socioeconomic class showed higher odds of informal care (mainly from religious leaders)., Conclusions: This study highlights the key role of the caregivers as gatekeepers to child treatment access, particularly parental stigma influencing whether young people received any mental health care, even in a low resource setting. These results help to map barriers for treatment access and delivery for young people, aiming to improve intervention efforts and mental health support.

This study aimed to identify the factors associated with a delay in treatment-seeking among patients with obsessive-compulsive disorder (OCD), a disabling neuropsychiatric disorder. To achieve this purpose, we conducted a cross-sectional study examining latency to treatment (LTT) and its associated correlates in 863 patients with OCD. We defined LTT as the time lag between the awareness of discomfort and/or impairment caused by symptoms and the beginning of OCD-specific treatment. To determine the socio-demographic and clinical characteristics associated with LTT, we built an interval-censored survival model to simultaneously assess the relationship between all variables, representing the best fit to our data format. The results of our study showed that approximately one-third of OCD patients sought treatment within two years of symptom awareness, one-third between two and nine years, and one-third after ten or more years. Median LTT was 4.0 years (mean = 7.96, SD = 9.54). Longer LTT was associated with older age, early onset of OCD symptoms, presence of contamination/cleaning symptoms and full-time employment. Shorter LTT was associated with the presence of aggression symptoms and comorbidity with hypochondriasis. The results of our study confirm the understanding that LTT in OCD is influenced by several interdependent variables - some of which are modifiable. Strategies for reducing LTT should focus on older patients, who work in a full-time job, and on individuals with early onset of OCD and contamination/cleaning symptoms., (Copyright © 2022. Published by Elsevier B.V.)

Background: Most early children's experiences will occur in a family context; therefore, the quality of this environment is critical for development outcomes. Not many studies have assessed the correlations between brain functional connectivity (FC) in important areas such as the default mode network (DMN) and the quality of parent-child relationships in school-age children and early adolescence. The quality of family relationships and maternal behavior have been suggested to modulate DMN FC once they act as external regulators of children's affect and behavior. Objective: We aimed to test the associations between the quality of family environment/maternal behavior and FC within the DMN of school-age children. Method: Resting-state, functional magnetic resonance imaging data, were collected from 615 children (6-12 age range) enrolled in the Brazilian High-Risk Cohort (HRC) study. We assessed DMN intra-connectivity between the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), and inferior parietal lobule (IPL-bilateral) regions. The family functioning was assessed by levels of family cohesiveness and conflict and by maternal behavior styles such as maternal responsiveness, maternal stimulus to the child's autonomy, and maternal overprotection. The family environment was assessed with the Family Environment Scale (FES), and maternal behavior was assessed by the mother's self-report. Results: We found that the quality of the family environment was correlated with intra-DMN FC. The more conflicting the family environment was, the greater the FC between the mPFC-left IPL (lIPL), while a more cohesive family functioning was negatively correlated with FC between the PCC-lIPL. On the other hand, when moderated by a positive maternal behavior, cohesive family functioning was associated with increased FC in both regions of the DMN (mPFC-lIPL and PCC-lIPL). Conclusions: Our results highlight that the quality of the family environment might be associated with differences in the intrinsic DMN FC.

Objective: A lack of universal definitions for response and remission in pediatric obsessive-compulsive disorder (OCD) has hampered the comparability of results across trials. To address this problem, we conducted an individual participant data diagnostic test accuracy meta-analysis to evaluate the discriminative ability of the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in determining response and remission. We also aimed to generate empirically derived cutoffs on the CY-BOCS for these outcomes., Method: A systematic review of PubMed, PsycINFO, Embase and CENTRAL identified 5,401 references; 42 randomized controlled clinical trials were considered eligible, and 21 provided data for inclusion (N = 1,234). Scores of ≤2 in the Clinical Global Impressions Improvement and Severity scales were chosen to define response and remission, respectively. A 2-stage, random-effects meta-analysis model was established. The area under the curve (AUC) and the Youden Index were computed to indicate the discriminative ability of the CY-BOCS and to guide for the optimal cutoff, respectively., Results: The CY-BOCS had sufficient discriminative ability to determine response (AUC = 0.89) and remission (AUC = 0.92). The optimal cutoff for response was a ≥35% reduction from baseline to posttreatment (sensitivity = 83.9, 95% CI = 83.7-84.1; specificity = 81.7, 95% CI = 81.5-81.9). The optimal cutoff for remission was a posttreatment raw score of ≤12 (sensitivity = 82.0, 95% CI = 81.8-82.2; specificity = 84.6, 95% CI = 84.4-84.8)., Conclusion: Meta-analysis identified empirically optimal cutoffs on the CY-BOCS to determine response and remission in pediatric OCD randomized controlled clinical trials. Systematic adoption of standardized operational definitions for response and remission will improve comparability across trials for pediatric OCD., (Copyright © 2021 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to assess mental health in Latin American pediatric rheumatologists (LAPRs) during the COVID-19 pandemic., Methods: A cross-sectional study was performed with 318 LAPRs based on an online, self-rated survey about clinical practice/mental health impacts during the COVID-19 pandemic. Validated self-reported scales for anxiety (Generalized Anxiety Disorder [GAD-7]) and depression (Patient Health Questionnaire [PHQ-9]) were evaluated., Results: The response rate was 126 of 318 (40%), including 13 of 20 (65%) Latin American countries. Working on the COVID-19 frontline was reported by 27% of LAPRs. Anxiety and moderate/severe depression were observed in 49% and 25%, respectively. No LAPRs reported previous mental health disorders. Deaths of childhood-onset systemic lupus erythematosus and juvenile idiopathic arthritis patients with confirmed/suspected COVID-19 were reported by 8% and 2% of LAPRs, respectively. Further analysis of LAPRs revealed that the median current age was significantly lower in LAPRs with anxiety than in those without anxiety (39 [29-43] vs 45 [30-70] years, p = 0.029). Working on the frontline of COVID-19 (37% vs 17%, p = 0.015), feeling helpless (39% vs 17%, p = 0.009), and experiencing burnout (39% vs 11%, p = 0.0001) were factors significantly higher in LAPRs with anxiety. Median nighttime sleep abnormalities measured by the visual analog scale (VAS) (8 [0-10] vs 4 [0-10], p = 0.009) were significantly higher in the anxiety group, whereas the physical activity VAS was lower (0.5 [0-10] vs 3 [0-10], p = 0.005). A positive Spearman correlation was shown between the GAD-7 score and nighttime sleep abnormality VAS score (r = +0.348, p < 0.001), and a negative correlation was shown between the GAD-7score and physical activity VAS score (r = -0.192, p = 0.031)., Conclusions: Anxiety and depression were relevant to the experience of LAPRs during the COVID-19 pandemic, impacting their mental health. Reporting information about mental health is essential to planning future preventive and health promotion strategies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Obsessive-compulsive disorder (OCD) is a common psychiatric condition classically characterized by obsessions (recurrent, intrusive and unwanted thoughts) and compulsions (excessive, repetitive and ritualistic behaviors or mental acts). OCD is heterogeneous in its clinical presentation and not all patients respond to first-line treatments. Several neurocircuit models of OCD have been proposed with the aim of providing a better understanding of the neural and cognitive mechanisms involved in the disorder. These models use advances in neuroscience and findings from neuropsychological and neuroimaging studies to suggest links between clinical profiles that reflect the symptoms and experiences of patients and dysfunctions in specific neurocircuits. Several models propose that treatments for OCD could be improved if directed to specific neurocircuit dysfunctions, thereby restoring efficient neurocognitive function and ameliorating the symptomatology of each associated clinical profile. Yet, there are several important limitations to neurocircuit models of OCD. The purpose of the current review is to highlight some of these limitations, including issues related to the complexity of brain and cognitive function, the clinical presentation and course of OCD, etiological factors, and treatment methods proposed by the models. We also provide suggestions for future research to advance neurocircuit models of OCD and facilitate translation to clinical application.

Introduction: First-line treatment for obsessive-compulsive disorder (OCD) includes exposure and response prevention behavioral therapy and serotonin reuptake inhibitors, particularly in combination. New and more effective treatments are needed, give that recent studies suggest that glutamatergic neurotransmission contributes to the pathophysiology of the disorder. In these circumstances, ketamine, as a potent N-methyl-D-aspartate receptor antagonist and glutamate modulator, offers alternative possibilities for OCD treatment., Methods: This systematic review aims to investigate the effects of ketamine in OCD, following the Preferred Reporting Items for Systematic Review and Meta-analyses Protocols (PRISMA-P). Searches were carried out using the PubMed/MEDLINE, Embase, and PsycINFO databases., Results: Nine articles were included, of which three were randomized controlled trials, three case reports, two open-label trials, and one a retrospective chart review. Reported data have shown a potential for fast onset of action and good tolerability of ketamine for OCD, even though the principal studies used only single-session racemic ketamine treatments, administered intravenously, and the results have been erratic. In addition, none of the available evidence demonstrates whether racemic ketamine, S-ketamine, or R-ketamine has the best efficacy in controlling OCD symptoms, and only sparse evidence suggests that a combination of ketamine and psychotherapy could benefit patients with OCD., Conclusion: In order to advance clinical practice regarding the use of ketamine in treating OCD, future randomized, double-blind, placebo-controlled trials are required. These trials need to use larger samples to explore ketamine and its enantiomers, with different methods of administration, multiple sessions, and appropriate washout periods., (Copyright © 2022 President and Fellows of Harvard College.)

Objective: The present study aims to investigate the occurrence of psychiatric and cognitive impairments in a cohort of survivors of moderate or severe forms of COVID-19., Method: 425 adults were assessed 6 to 9 months after hospital discharge with a structured psychiatric interview, psychometric tests and a cognitive battery. A large, multidisciplinary, set of clinical data depicting the acute phase of the disease, along with relevant psychosocial variables, were used to predict psychiatric and cognitive outcomes using the 'Least Absolute Shrinkage and Selection Operator' (LASSO) method., Results: Diagnoses of 'depression', 'generalized anxiety disorder' and 'post-traumatic stress disorder' were established respectively in 8%, 15.5% and 13.6% of the sample. After pandemic onset (i.e., within the previous year), the prevalence of 'depression' and 'generalized anxiety disorder' were 2.56% and 8.14%, respectively. Memory decline was subjectively reported by 51.1% of the patients. Psychiatric or cognitive outcomes were not associated with any clinical variables related to the severity of acute-phase disease, nor by disease-related psychosocial stressors., Conclusions: This is the first study to access rates of psychiatric and cognitive morbidity in the long-term outcome after moderate or severe forms of COVID-19 using standardized measures. As a key finding, there was no significant association between clinical severity in the acute-phase of SARS-CoV-2 infection and the neuropsychiatric impairment 6 to 9 months thereafter., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Lesbian, Gay, Bisexual, Transgender, Queer, and Asexual (LGBTQA+) youth have a greater chance of experiencing stressful life events when compared to cisgender heterosexual peers, which can lead to mental health problems. We aimed to estimate the prevalence of mental disorders among LGBTQA+ youths from two large cities in Brazil., Methods: Participants were 13-22 years old youths from the 3rd wave of the Brazilian High-Risk Cohort for Psychiatric Disorders (n = 1475). Mental disorders were assessed using the Development and Well-Being Behavior Assessment. Sexual orientation and gender identity were assessed using a self-report confidential questionnaire. Data were analyzed through logistic regressions (adjusting for sociodemographic) using sampling weights to account for attrition and our oversampling high-risk design., Results: 15.18% of the sample described themselves as LGBTQA+. The LGBTQA+ group presented higher rates of anxiety disorders (30.14% vs. 13.37%; OR = 3.37; 95%CI:2.51-4.50), depressive disorders (27.75% vs. 15.34%; OR = 2.17; 95%CI:1.60-2.93) and post-traumatic stress disorder (4.98% vs. 2.25%; OR = 4.20; 95%CI:2.24-7.82), if compared with the cisgender heterosexual group. No difference was found for conduct disorders (2.97% vs. 5.21%; OR = 0.82; 95%CI:0.35-1.65) or attention deficit hyperactivity disorder (5.92% vs. 3.28%; OR = 1.56; 95%CI:0.83-2.79)., Limitations: Although recruitment was performed at 57 schools in the two cities, sampling was non-probabilistic and included only urban areas, which might bias prevalence estimates and group comparisons., Conclusions: Our results elucidate the mental health disparities between LGBTQA+ people and cisgender heterosexuals in Brazil. It highlights the need to promote the inclusion of this population in policy formulation and support actions to mitigate the suffering related to sexual orientation and gender identity., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: Although the Dimensional Yale-Brown Obsessive-Compulsive Scale (DY-BOCS) is a widely used instrument for assessing different obsessive-compulsive symptom dimensions, its factor structure has never been studied in a Brazilian population. Thus, we aimed to assess the goodness-of-fit indexes and factor loadings of two higher-order models of the DY-BOCS using confirmatory factor analysis (CFA) in a large obsessive-compulsive disorder (OCD) sample., Methods: We tested two CFA models in a sample of 955 adults with OCD who had been assessed with the DY-BOCS in a cross-sectional multi-site study. The first model encompassed the symptom checklist (present or absent), whereas the second focused on items related to severity scores., Results: Both models presented adequate goodness-of-fit indexes. The comparative fit index, Tucker-Lewis index, and omega were > 0.9, while the root mean square error of approximation was ≤ 0.06 for both models. Factor loadings for each item of each dimension are presented and discussed., Conclusion: Higher-order factor models showed adequate goodness-of-fit indexes, indicating that they appropriately measured OCD dimensions in this Brazilian population.

Objective: It is unclear if pediatric executive dysfunction assessed only with cognitive tasks predicts clinically relevant outcomes independently of psychiatric diagnoses. This study tested the stability and validity of a task-based classification of executive function., Method: A total of 2,207 individuals (6-17 years old) from the Brazilian High-Risk Cohort Study participated in this study (1,930 at baseline, 1,532 at follow-up). Executive function was measured using tests of working memory and inhibitory control. Dichotomized age- and sex-standardized performances were used as input in latent class analysis and receiver operating curves to create an executive dysfunction classification (EDC). The study tested EDC's stability over time, association with symptoms, functional impairment, a polymorphism in the CADM2 gene, polygenic risk scores (PRS), and brain structure. Analyses covaried for age, sex, social class, IQ, and psychiatric diagnoses., Results: EDC at baseline predicted itself at follow-up (odds ratio [OR] = 5.11; 95% CI 3.41-7.64). Participants in the EDC reported symptoms spanning several domains of psychopathology and exhibited impairment in multiple settings, including more adverse school events (OR = 2.530; 95% CI 1.838-3.483). Children in the EDC presented higher attention-deficit/hyperactivity disorder and lower educational attainment PRS at baseline; higher schizophrenia PRS at follow-up; and lower chances of presenting a polymorphism in a gene previously linked to high performance in executive function (CADM2 gene). They also exhibited smaller intracranial volumes and smaller bilateral cortical surface areas in several brain regions., Conclusion: Task-based executive dysfunction is associated with several validators, independently of psychiatric diagnoses and intelligence. Further refinement of task-based assessments might generate clinically useful tools., (Copyright © 2020 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Objective: In 2020, the COVID-19 pandemic brought a work and stress overload to healthcare workers, increasing their vulnerability to mental health impairments. In response, the authors created the COMVC-19 program. The program offered preventive actions and mental health treatment for the 22,000 workers of The Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). This paper aims to describe its implementation and share what we have learned from this experience., Methods: Workers were able to easily access the program through a 24/7 hotline. Additionally, a mobile phone app that screened for signs and symptoms of emotional distress and offered psychoeducation and/or referral to treatment was made available. Data from both these sources as well as any subsequent psychiatric evaluations were collected., Results: The first 20 weeks of our project revealed that most participants were female, and part of the nursing staff working directly with COVID-19 patients. The most frequently reported symptoms were: anxiety, depression and sleep disturbances. The most common diagnoses were Adjustment, Anxiety, and Mood disorders., Conclusions: Implementing a mental health program in a multimodal intervention was feasible in a major quaternary public hospital. Our data also suggests that preventive actions should primarily be aimed at anxiety and depression symptoms, with a particular focus on the nursing staff.

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., (© 2021 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Objective: To review the most common mental health strategies aimed at alleviating and/or preventing mental health problems in individuals during the coronavirus disease 2019 (COVID-19) and other coronavirus pandemics., Methods: We conducted a systematic review of the literature assessing three databases (PubMed, SCOPUS, and PsycINFO). A meta-analysis was performed with data from randomized controlled trials (RCTs). For non-RCT studies, a critical description of recommendations was performed., Results: From a total of 2,825 articles, 125 were included. Of those, three RCTs were included in the meta-analysis. The meta-analysis revealed that the interventions promoted better overall mental health outcomes as compared to control groups (standardized mean difference [SMD] = 0.87 [95%CI 0.33-1.41], p < 0.001, I2 = 69.2%), but did not specifically improve anxiety (SMD = 0.98 [95%CI -0.17 to 2.13], p > 0.05; I2 = 36.8%). Concerning the systematic review, we found a large body of scientific literature proposing recommendations involving psychological/psychiatric interventions, self-care, education, governmental programs, and the use of technology and media., Conclusions: We found a large body of expert recommendations that may help health practitioners, institutional and governmental leaders, and the general population cope with mental health issues during a pandemic or a crisis period. However, most articles had a low level of evidence, stressing the need for more studies with better design (especially RCTs) investigating potential mental health interventions during COVID-19., Prospero Registration: CRD42020190212.

Background: Daily routine and situations may worsen, stabilise, or improve symptoms of obsessive-compulsive disorder (OCD). We investigated which factors OCD patients perceived to be related to the worsening of their OCD symptoms and their relationship to patients' OCD symptom severity., Methods: Seven-hundred and forty-two OCD patients completed the Yale-Brown Obsessive-Compulsive Scale as a measure of OCD symptom severity and the Yale OCD Natural History Questionnaire assessing perception of impact of environmental and routine factors on symptoms. We conducted univariate exploratory analyses and a multivariate regression., Results: Reporting of worsening OCD symptoms when having a meal (B = 0.093, p = 0.008), during hot weather (B = 0.153, p < 0.001) and while watching television (B = 0.080, p = 0.039) was associated with more severe OCD symptoms., Conclusion: People with more severe OCD report symptom worsening while having a meal, when exposed to higher temperatures, and whilst watching television. While our study may be limited by its cross-sectional design (limiting inferences of causality) and analysis of broad (rather than specific) OCD symptoms, our findings point to a potential common biological abnormality that is disturbed by certain events in OCD. We present clinical implications of our findings and areas for further exploration., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls., Results: There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences., Conclusions: DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD., (© 2021. The Author(s).)

Aims: Mental health problems early in life can negatively impact educational attainment, which in turn have negative long-term effects on health, social and economic opportunities. Our aims were to: (i) estimate the impacts of different types of psychiatric conditions on educational outcomes and (ii) to estimate the proportion of adverse educational outcomes which can be attributed to psychiatric conditions., Methods: Participants ( N = 2511) were from a school-based community cohort of Brazilian children and adolescents aged 6-14 years enriched for high family risk of psychiatric conditions. We examined the impact of fear- (panic, separation and social anxiety disorder, specific phobia, agoraphobia and anxiety conditions not otherwise specified), distress- (generalised anxiety disorder, major depressive disorder and depressive disorder not otherwise specified, bipolar, obsessive-compulsive, tic, eating and post-traumatic stress disorder) and externalising-related conditions (attention deficit and hyperactivity disorder, conduct and oppositional-defiant conditions) on grade repetition, dropout, age-grade distortion, literacy performance and bullying perpetration, 3 years later. Psychiatric conditions were ascertained by psychiatrists, using the Development and Well-Being Behaviour Assessment. Propensity score and inverse probability weighting were used to adjust for potential confounders, including comorbidity, and sample attrition. We calculated the population attributable risk percentages to estimate the proportion of adverse educational outcomes in the population which could be attributed to psychiatric conditions. Analyses were conducted separately for males and females., Results: Fear and distress conditions in males were associated with school dropout (odds ratio (OR) = 2.76; 95% confidence interval (CI) = 1.06, 7.22; p < 0.05) and grade repetition (OR = 2.76; 95% CI = 1.32, 5.78; p < 0.01), respectively. Externalising conditions were associated with grade repetition in males (OR = 1.66; 95% CI = 1.05, 2.64; p < 0.05) and females (OR = 2.03; 95% CI = 1.15, 3.58; p < 0.05), as well as age-grade distortion in males (OR = 1.66; 95% CI = 1.05, 2.62; p < 0.05) and females (OR = 2.88; 95% CI = 1.61, 5.14; p < 0.001). Externalising conditions were also associated with lower literacy levels ( β = -0.23; 95% CI = -0.34, -0.12; p < 0.001) and bullying perpetration (OR = 3.12; 95% CI = 1.50, 6.51; p < 0.001) in females. If all externalising conditions were prevented or treated, we estimate that 5.0 and 4.8% of grade repetition would not have occurred in females and males, respectively, as well as 10.2 (females) and 5.3% (males) of age-grade distortion cases and 11.4% of female bullying perpetration., Conclusions: The study provides evidence of the negative impact of psychiatric conditions on educational outcomes in a large Brazilian cohort. Externalising conditions had the broadest and most robust negative impacts on education and these were particularly harmful to females which are likely to limit future socio-economic opportunities.

Psychotic experiences (PE) are forms of hallucinations and delusions neither reaching the intensity and functional impairment required to be regarded as full psychotic symptoms nor a psychotic disorder. Here we investigated the ability to predict PE using multiple models (regressions, mediation and moderation) using polygenic risk score for psychotic experiences (PE-PRS), polygenic risk score for schizophrenia (SCZ-PRS), and polyenvironmental risk score (PERS) in youth from a Brazilian sample. The scores were not able to predict outcome, either when both scores were combined (PERS + PE-PRS and PERS + SCZ-PRS) or separately. Our results show that there is no association between PE and PRS or PERS among adolescents in our Brazilian sample. The lack of association may be a result of the absence of better representativeness regarding genetic and environmental factors of our population., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: While previous studies have implicated white matter (WM) as a core pathology of obsessive-compulsive disorder (OCD), the underlying neurobiological processes remain elusive. This study used free-water (FW) imaging derived from diffusion magnetic resonance imaging to identify cellular and extracellular WM abnormalities in patients with OCD compared with control subjects. Next, we investigated the association between diffusion measures and clinical variables in patients., Methods: We collected diffusion-weighted magnetic resonance imaging and clinical data from 83 patients with OCD (56 women/27 men, age 37.7 ± 10.6 years) and 52 control subjects (27 women/25 men, age 32.8 ± 11.5 years). Fractional anisotropy (FA), FA of cellular tissue, and extracellular FW maps were extracted and compared between patients and control subjects using tract-based spatial statistics and voxelwise comparison in FSL Randomise. Next, we correlated these WM measures with clinical variables (age of onset and symptom severity) and compared them between patients with and without comorbidities and patients with and without psychiatric medication., Results: Patients with OCD demonstrated lower FA (43.4% of the WM skeleton), lower FA of cellular tissue (31% of the WM skeleton), and higher FW (22.5% of the WM skeleton) compared with control subjects. We did not observe significant correlations between diffusion measures and clinical variables. Comorbidities and medication status did not influence diffusion measures., Conclusions: Our findings of widespread FA, FA of cellular tissue, and FW abnormalities suggest that OCD is associated with microstructural cellular and extracellular abnormalities beyond the corticostriatothalamocortical circuits. Future multimodal longitudinal studies are needed to understand better the influence of essential clinical variables across the illness trajectory., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Nile tilapia (Oreochromis niloticus) skin is a well-known biomaterial used as an occlusive dressing for burn treatment. It is also an inexpensive and important source of collagen. This study aims to describe the ultrastructural aspects of Nile tilapia skin, assess its collagen amount and organization, and compare quantitative methods of histochemical and immunohistochemical analysis (in all sterilization steps for use in burn dressings). One sample (0.5 × 0.5 cm) of ten different fish skins was divided in four groups: in natura skin (IN), chemical sterilization (CH), additional irradiation (30 kGy) (IR), and skins used in burn treatment (BT) to compare histochemical and immunohistochemical findings of collagen amount and describe ultrastructural aspects through scanning electron microscopy. The amount of type I collagen decreased during sterilization and clinical use owing to gradual reduction of immunostaining (anti-collagen-I) and decreasing fiber thickness of the collagen, when compared to type III (Picrosirius-red-polarized light). The collagen fibers were rearranged at each sterilization step, with a low collagen percentage and large structural disorganization in BT. The amount of type-I collagen was further reduced after BT (p < 0.05). Both the methods did not exhibit a quantified value difference (p = 0.247), and a positive correlation (r = 0.927; 95 % CI = 0.720-0.983) was observed between them, with concordance for collagen quantification in similar samples, presenting a low systematic error rate (Dalberg coefficient: 6.70). A significant amount of type-I collagen is still observed despite sterilization, although clinical application further reduces type I collagen. Its quantification can be performed both by immunohistochemistry and/or Picrosirius Red reliably., (Copyright © 2021 Elsevier GmbH. All rights reserved.)

An important challenge in mental health research is to translate findings from cognitive neuroscience and neuroimaging research into effective treatments that target the neurobiological alterations involved in psychiatric symptoms. To address this challenge, in this review we propose a heuristic neurocircuit-based taxonomy to guide the treatment of obsessive-compulsive disorder (OCD). We do this by integrating information from several sources. First, we provide case vignettes in which patients with OCD describe their symptoms and discuss different clinical profiles in the phenotypic expression of the condition. Second, we link variations in these clinical profiles to underlying neurocircuit dysfunctions, drawing on findings from neuropsychological and neuroimaging studies in OCD. Third, we consider behavioral, pharmacological, and neuromodulatory treatments that could target those specific neurocircuit dysfunctions. Finally, we suggest methods of testing this neurocircuit-based taxonomy as well as important limitations to this approach that should be considered in future research., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

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., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Cold plasma is an innovative strategy to strengthen the polysaccharide-based films characteristics. This study evaluated the effects of dielectric barrier discharge (DBD) plasma on the hydrophilic character, water vapor permeability (WVP), and tensile properties of corn starch-based films. Starch films were exposed to plasma processing operating at an excitation frequency of 200 Hz for 10, 15, and 20 min. DBD plasma resulted in further enhanced tensile strength and stiffness, and lower hydrophilicity and water solubility; however, it did not present significant effects on the WVP of the resulting films within the ranges studied. Higher hydrophobicity, strength, and stiffness were verified after 20 min. The results presented in this work suggest that the DBD plasma has the potential to make starch-based films a more suitable packaging material., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nonsuicidal self-injury (NSSI) is prevalent and affects mainly the youth population. It is prospectively associated with suicide attempts, making it a target for suicide prevention. Recently, several studies have investigated neural pathways of NSSI using neuroimaging. However, there is a lack of systematized appraisal of these findings. This systematic review aims to identify and summarize the main neuroimaging findings of NSSI in youth. We followed PRISMA statement guidelines and searched MEDLINE, APA PsycInfo, and Google Scholar databases for neuroimaging studies, irrespective of imaging modality, specifically investigating NSSI in samples with a mean age of up to 25 years old. Quality assessment was made using the Newcastle-Ottawa and Joanna Briggs Institute scales. The initial search retrieved 3030 articles; 21 met inclusion criteria, with a total of 938 subjects. Eighteen studies employed functional neuroimaging techniques such as resting-state and task-based fMRI (emotional, interpersonal exposure/social exclusion, pain, reward, and cognitive processing paradigms). Three studies reported on structural MRI. An association of NSSI behavior and altered emotional processing in cortico-limbic neurocircuitry was commonly reported. Additionally, alterations in potential circuits involving pain, reward, interpersonal, self-processing, and executive function control processes were identified. NSSI has complex and diverse neural underpinnings. Future longitudinal studies are needed to understand its developmental aspects better.