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Background. Taxometric and behavioral genetic studies suggest that attention deficit hyperactivity disorder (ADHD) is best modeled as a dimension rather than a category. We extended these analyses by testing for the existence of putative ADHD-related deficits in basic information processing (BIP) and inhibitory-based executive function (IB-EF) in individuals in the subclinical and full clinical ranges. Consistent with the dimensional model, we predicted that ADHD-related deficits would be expressed across the full spectrum, with the degree of deficit linearly related to the severity of the clinical presentation. Method. A total of 1547 children (aged 6-12 years) participated in the study. The Development and Well-Being Assessment (DAWBA) was used to classify children into groups according to levels of inattention and hyperactivity independently: (1) asymptomatic, (2) subthreshold minimal, (3) subthreshold moderate and (4) clinical ADHD. Neurocognitive performance was evaluated using a two-choice reaction time task (2C-RT) and a conflict control task (CCT). BIP and IB-EF measures were derived using a diffusion model (DM) for decomposition of reaction time (RT) and error data. Results. Deficient BIP was found in subjects with minimal, moderate and full ADHD defined in terms of inattention (in both tasks) and hyperactivity/impulsivity dimensions (in the 2C-RT). The size of the deficit increased in a linear manner across increasingly severe presentations of ADHD. IB-EF was unrelated to ADHD. Conclusions. Deficits in BIP operate at subclinical and clinical levels of ADHD. The linear nature of this relationship provides support for a dimensional model of ADHD in which diagnostic thresholds are defined in terms of clinical and societal burden rather than representing discrete pathophysiological states.

Introduction: Digital psychiatry holds promise for expanding accessibility to mental health treatment, but concerns exist regarding its inclusivity and the potential for exacerbation of digital exclusion among vulnerable populations. This study aims to evaluate the inclusivity of digital psychiatry research and interventions, and to explore their potential to worsen digital exclusion., Methods: We conducted a cross-sectional analysis of sociodemographic data from two clinical trials that utilize psychiatric online treatment modalities in Brazil. Participants were recruited nationwide through digital media platforms., Results: The sample comprised 224 individuals, predominantly female (95.1%) and Caucasian (71.87%) participants, with an average of 15.12 years of schooling. It was observed that White individuals were overrepresented compared to national averages (42.8%). Additionally, participants had a higher average number of years of schooling compared to the national average (10.1 years). Our analysis revealed a clear profile among psychiatric patients with access to and interest in digital interventions, predominantly younger, White, educated, and female individuals., Discussion: As digital therapeutic solutions advance, ensuring their inclusivity and accessibility for vulnerable individuals is crucial. Initiatives to promote digital inclusion and reassess participant recruitment strategies are needed to effectively address digital exclusion. By adopting multifaceted approaches, digital mental health care can be made more effective and accessible to all., Competing Interests: No conflicts of interest declared concerning the publication of this article.

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Poor fetal growth affects eating behavior and the mesocorticolimbic system; however, its influence on the hippocampus has been less explored. Brain insulin sensitivity has been linked to developmental plasticity in response to fetal adversity and to cognitive performance following high-fat diet intake. We investigated whether poor fetal growth and exposure to chronic hyperpalatable food in adulthood could influence the recognition of environmental and food cues, eating behavior patterns, and hippocampal insulin signaling. At 60 days of life, we assigned male offspring from a prenatal animal model of 50% food restriction (FR) to receive either a high-fat and -sugar (HFS) diet or standard chow (CON) diet. Behavioral tests were conducted at 140 days, then tissues were collected. HFS groups showed a diminished hippocampal pAkt/Akt ratio. FR-CON and FR-HFS groups had higher levels of suppressor of cytokine signaling 3, compared to control groups. FR groups showed increased exploration of a novel hyperpalatable food, independent of their diet, and HFS groups exhibited overall lower entropy (less random, more predictable eating behavior) when the environment changed. Poor fetal growth and chronic HFS diet in adulthood altered hippocampal insulin signaling and eating patterns, diminishing the flexibility associated with eating behavior in response to extrinsic changes in food availability in the environment., (© 2024 The Authors. Developmental Psychobiology published by Wiley Periodicals LLC.)

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies ( n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13-83.76) when compared to placebo groups (71.21%, 67.00-75.09). Nausea was the most common adverse event (25.71%, CI 23.96-27.54), while weight change was the least common (3.56%, 1.68-7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.

Background: Intimate partner violence (IPV) increased extensively around the world during the pandemic, causing severe women's mental health damages. However, there are no studies showing these effects in Brazil., Purpose: To assess the perpetration of IPV and the presence of depression and suicidal ideation in women living in Brazil during the pandemic., Methods: Cross-sectional online survey including women living in Brazil from July 2020 to Jun 2021. Participants answered a 43-item self-applied questionnaire exploring their characteristics and life changes due to the pandemic (CoRonavIruS Health Impact Survey), IPV (World Health Organization Violence Against Women) and depressive symptoms or suicidal ideation (Patient Health Questionnaire-9). We used multiple Poisson regression analyses with robust variance to model associations between IPV and mental health outcomes, considering as covariates aspects of social vulnerability., Results: We found a high frequency of IPV (33.3%), depression (36.1%) and suicidal ideation (19.8%) among the participants. IPV was significantly associated with depression (PR=1.502, p=0.001 for one type of IPV; PR=2.702, p<0.001 for two or three types of IPV) and suicidal ideation (PR=2.264, p<0.001 for one type of VPI; PR=3.272, p<0.001 for two or three types of IPV). Food insecurity, being black, lower educational levels and being in a relationship with a person of the same gender were associated with one or both mental health outcomes., Conclusions: We demonstrated an association of IPV with higher frequencies of depression and suicidal ideation in women living in Brazil during the COVID-19 pandemic, highlighting the urgency of strengthening strategies to protect women during adversities., Competing Interests: Angelica Cerveira de Baumont received a Coordination for the Improvement of Higher Education Personnel (CAPES) postdoctoral scholarship, and Gisele Gus Manfro received a Brazilian National Council for Scientific and Technological Development CNPq senior scholarship (306249/2017-0). No other conflicts of interest declared concerning publication of this article.

The impact of childhood experiences on the development of psychopathology is well established in the literature. Few studies, however, have assessed parental bonding during childhood as a predictor of response to anxiety disorders treatment. The aim of the study was to examine whether emotional memories of childhood parenting could predict short-term and long-term outcome in three different interventions for patients with generalized anxiety disorder (GAD): mindfulness-based intervention (Body in Mind Training [BMT]), fluoxetine (FLX), and an active control group (quality of life [QoL]). A total of 124 participants from a randomized controlled trial for GAD treatment were evaluated pre- and post-treatment and after 18 months. Patients were assessed for the severity of GAD symptoms (GAD-7, PSWQ, and DERS), early memories of warmth and safeness (EMWSS), and recall of perceived threat and subordination/submission in childhood (ELES). Negative childhood memories predicted a greater reduction in anxiety symptoms on BMT treatment compared to FLX and QoL, whereas positive childhood memories predicted more symptomatic improvement in the QoL group. Our findings suggest that individuals with GAD who have early memories of subordination and threat appear to benefit more from interventions that focus on developing emotion-regulation strategies and enhancing self-compassion, such as mindfulness-based interventions., (© 2022 John Wiley & Sons Ltd.)

Background: Generalized anxiety disorder (GAD) is associated with the lowest treatment response rate among all anxiety disorders. Understanding mechanisms of improvement may help to develop more effective and personalized treatments., Aim: The objective of the study was to investigate different improvement mechanisms in the treatment of individuals diagnosed with GAD., Design: We reported data from a randomized controlled trial that evaluated three different GAD treatments (mindfulness-based intervention, BMT; fluoxetine, FLX; and an active comparison group, QoL) for 8 weeks., Method: Mediation analyses were performed evaluating the association between worry symptoms at baseline and anxiety scoring at the endpoint, considering self-compassion or mindfulness or its dimensions at mid-treatment as mediators for the whole sample (assessing GAD improvement mechanism) and the different interventions as moderators., Results: Contrary to mindfulness state scoring (C = .06; 95% CI = -.05 to .20), self-compassion (C = .11; 95% CI = .01 to .28) and non-judgement of inner experience (C = .10; 95% CI = .004 to .21) mediated the association between worry symptoms at baseline and anxiety at the endpoint. When comparing BMT to FLX, the intervention modality did not moderate these associations., Conclusion: Self-compassion and non-judgement of inner experience seem to be essential targets in GAD treatment, contrary to the mindfulness state itself. Although no difference was found considering the intervention modality, future research may assess how to boost these dimensions in specific treatments for GAD., (© 2022 British Psychological Society.)

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).)

Question: Randomised controlled trials assessing treatments for anxiety, obsessive-compulsive and stress-related disorders often present high placebo response rates in placebo groups. Understanding the placebo response is essential in accurately estimating the benefits of pharmacological agents; nevertheless, no studies have evaluated the placebo response across these disorders using a lifespan approach., Study Selection and Analysis: We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies and international registers from inception to 9 September 2022. The primary outcome was the aggregate measure of internalising symptoms of participants in the placebo arms of randomised controlled trials designed to assess the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in individuals diagnosed with anxiety, obsessive-compulsive or stress-related disorders. The secondary outcomes were placebo response and remission rates. Data were analysed through a three-level meta-analysis., Findings: We analysed 366 outcome measures from 135 studies (n=12 583). We found a large overall placebo response (standardised mean difference (SMD)=-1.11, 95% CI -1.22 to -1.00). The average response and remission rates in placebo groups were 37% and 24%, respectively. Larger placebo response was associated with a diagnosis of generalised anxiety disorder and post-traumatic stress disorder, when compared with panic, social anxiety and obsessive-compulsive disorder (SMD range, 0.40-0.49), and with absence of a placebo lead-in period (SMD=0.44, 95% CI 0.10 to 0.78). No significant differences were found in placebo response across age groups. We found substantial heterogeneity and moderate risk of bias., Conclusions: Placebo response is substantial in SSRI and SNRI trials for anxiety, obsessive-compulsive and stress-related disorders. Clinicians and researchers should accurately interpret the benefits of pharmacological agents in contrast to placebo response., Prospero Registration Number: CRD42017069090., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. Published by BMJ.)

Introduction: Metacognitive beliefs about worry may trigger anxiety. However, the effect of generalized anxiety disorder (GAD) treatment on metacognition has not yet been investigated., Objectives: To validate the Metacognitions Questionnaire (MCQ-30) in a Brazilian GAD sample and verify whether different interventions reduce metacognitive beliefs., Method: We recruited 180 GAD individuals and randomized them to Body in Mind Training (BMT), Fluoxetine (FLX), or an active control group (Quality of Life [QoL]) for 8 weeks. The MCQ-30 was assessed for internal consistency, was evaluated with confirmatory and exploratory factor analyses, and was tested for convergent validity with the Penn State Worry Questionnaire (PSWQ). Generalized estimating equations (GEE) were employed to analyze differences after the interventions., Results: The MCQ-30 demonstrated good internal consistency and acceptability; the original five-factor model was supported. There was a positive moderate correlation between MCQ-30 scores and worry. GEE showed a significant group x time interaction (p < 0.001). Both BMT (mean difference [MD] = -6.04, standard error [SE] = -2.39, p = 0.034) and FLX (MD = -5.78, SE = 1.91, p = 0.007) reduced MCQ-30 scores. FLX was superior to QoL, but not BMT, at weeks 5 and 8. There were no differences between BMT and QoL., Conclusion: The Brazilian-Portuguese version of MCQ-30 showed good psychometric properties. Furthermore, the positive effect of FLX and BMT on metacognition suggests it may represent a potential therapeutic target., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Introduction: Individuals diagnosed with generalized anxiety disorder (GAD) seek pleasurable foods to avoid their negative emotional experiences. Ineffective regulation of negative emotions may be a risk factor for emotional eating (EE), leading to suffering, dysfunctional behaviors, and weight gain., Objectives: The aim of this study is to understand the relationship between emotional dysregulation and EE, investigating potential mediators such as the intensity of the worry, avoidance of internal experiences, mindfulness, and self-compassion in female patients with anxiety., Methods: In this cross-sectional study, participants from a randomized clinical trial diagnosed with GAD answered the following instruments at baseline: the Difficulties in Emotion Regulation Scale (DERS), the Three Factor Eating Questionnaire (TFEQ-R21), the Penn State Worry Questionnaire (PSWQ), the Action and Acceptance Questionnaire (AAQ), the Five Facet Mindfulness Questionnaire (FFMQ), and the Self-Compassion Scale (SCS). We estimated Pearson correlation coefficients and performed mediation analyses., Results: We evaluated 51 female individuals, 34 of whom completed all the questionnaires. Our data showed that EE was positively correlated with emotional dysregulation (r = 0.593; p < 0.001), worry trait (r = 0.402; p = 0.018), and avoidance of internal experiences (r = 0.565; p < 0.001), whereas it was negatively correlated with self-compassion (r = -0.590; p < 0.001) and mindful state (r = -0.383; p = 0.026). Moreover, we demonstrated that self-compassion mediates the relationship between emotional dysregulation and EE (ab product estimate = 0.043, 95% confidence interval [95%CI] 0.003-0.084)., Conclusion: Our findings contribute to the literature by identifying psychological factors that could mediate the association between emotional dysregulation and EE, enabling identification of more effective eating behavior intervention targets for patients with GAD., Competing Interests: No conflicts of interest declared concerning the publication of this article.

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.)

Introduction: There is evidence that the coronavirus disease 2019 (COVID-19) pandemic impacted students on health care courses, including evidence of associations between anxiety or depression and inadequate coping mechanisms or unhealthy habits. However, little is known about possible predictors of mental health or psychiatric symptoms in Brazilian health care students during this period., Objective: To evaluate possible factors associated with anxiety and depressive symptoms, used to measure psychiatric outcomes, and quality of life, used as a parameter of overall functionality, in Brazilian students on health care courses during the COVID-19 pandemic., Methods: A cross-sectional study was conducted with Brazilian students on health care courses from May to December 2020. Participants were recruited through social media and answered a 71-item open online questionnaire exploring demographic characteristics and personal behavior during the pandemic, anxiety, depression, and quality of life. We searched for variables potentially associated with psychiatric symptoms and mental health in these individuals using Poisson regression models., Results: Multivariate models showed depression and anxiety were associated with poor quality of life and medication abuse was associated with greater anxiety and poor quality of life. Psychotherapy was an effective coping strategy for anxiety and meditation or mindfulness practice and physical activity improved the students' quality of life., Conclusions: Our study presents important information about the factors associated with psychological impacts of the COVID-19 pandemic and strategies for coping with them that should be helpful to reflect on and for designing appropriate interventions., Competing Interests: No conflicts of interest declared concerning the publication of this article.

Objective: Skin picking disorder (SPD) affects up to 5.4% of the population. Less than half of patients are correctly diagnosed and treated. Developing tools to recognize SPD can help professionals and patients alike. This trial aimed to validate the Skin Picking Scale-Revised (SPS-R) for the Brazilian population and assess the psychiatric and dermatological comorbidities of patients with SPD., Methods: Brazilians with a primary diagnosis of SPD, 18 years or older, were recruited from a community sample by media advertising and evaluated by a dermatologist and a psychiatrist. Self-report instruments were used: SPS-R, Dermatology Life Quality Index (DLQI), General Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Confirmatory factor analysis (CFA) was performed to evaluate the SPS-R, and Pearson correlation (r) was used to assess the relationship between instruments., Results: Overall, 124 patients were included. The SPS-R demonstrated good internal consistency (Cronbach's coefficient = 0.84). CFA found a good fit to the model according to all indices (?2 = 29.67; degrees of freedom [df] = 19; p = 0.056; root mean square error of approximation [RMSEA] = 0.067; comparative fit index [CFI] = 0.969; non-normed fit index [NNFI] = 0.954). SPS-R correlated with DLQI (r = 0.73), GAD-7 (r = 0.51), and PHQ-9 (r = 0.43). The sample had a high prevalence of psychiatric disorders, mainly generalized anxiety disorder (62.1%) and current (32.3%) and past (37.1%) depressive episodes., Conclusion: The Brazilian version of the SPS-R presents good psychometric properties. The severity of SPD is related to severity of depression, anxiety, and impairment in quality of life., Competing Interests: The authors report no conflicts of interest.

The impact of COVID-19 anxiety on mental health and its association with preventive measures is well-established. We aimed to study how COVID-19 anxiety and its dimensions vary over time (16 months) in a sample of individuals (N = 2717) suffering from mental distress in the pandemic context that participated in a randomized clinical trial testing psychosocial interventions in Brazil. Results showed that pandemic anxiety reduced over time. COVID-19 influences fear of others being infected and concerns about mental health being affected by COVID-19 were more significant than the fear of being infected or the physical health influenced by COVID-19. A similar temporal effect was not found for burnout, and this effect was not correlated with the number of COVID-related deaths. Habituation to pandemic anxiety or higher intolerance of uncertainty at the beginning of the pandemic is putative mechanisms for the patterns observed in the data. They might have implications for mental health interventions in the pandemic scenario and motivational strategies for prevention. TRIAL REGISTRATION NUMBER: Plataforma Basil (CAAE: 30608420.5.0000.5327), ClinicalTrials.gov (NCT04632082; November 17, 2020)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Prenatal growth impairment leads to higher preference for palatable foods in comparison to normal prenatal growth subjects, which can contribute to increased body fat mass and a higher risk for developing chronic diseases in small-for-gestational-age (SGA) individuals throughout life. This study aimed to investigate the effect of SGA on feeding behavior in children and adolescents, as well as resting-state connectivity between areas related to reward, self-control, and value determination, such as orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), amygdala and dorsal striatum (DS)., Methods: Caregivers and their offspring were recruited from two independent cohorts in Brazil (PROTAIA) and Canada (MAVAN). Both cohorts included anthropometric measurements, food choice tasks, and resting-state functional magnetic resonance imaging (fMRI) data., Results: In the Brazilian sample (17 ± 0.28 years, n=70), 21.4% of adolescents were classified as SGA. They exhibited lower monetary-related expenditure to buy a snack compared to controls in the food choice test. Decreased functional connectivity (n=40) between left OFC and left DL-PFC; and between right OFC and: left amygdala, right DS, and left DS were observed in the Brazilian SGA participants. Canadian SGA participants (14.9%) had non-significant differences in comparison with controls in a food choice task at 4 years old ( ± 0.01, n=315). At a follow-up brain scan visit (10.21 ± 0.140 years, n=49), SGA participants (28.6%) exhibited higher connectivity between the left OFC and left DL-PFC, also higher connectivity between the left OFC and right DL-PFC. We did not observe significant anthropometric neither nutrients' intake differences between groups in both samples., Conclusions: Resting-state fMRI results showed that SGA individuals had altered connectivity between areas involved in encoding the subjective value for available goods and decision-making in both samples, which can pose them in disadvantage when facing food options daily. Over the years, the cumulative exposure to particular food cues together with the altered behavior towards food, such as food purchasing, as seen in the adolescent cohort, can play a role in the long-term risk for developing chronic non-communicable diseases., Competing Interests: The 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., (Copyright © 2022 Dalle Molle, de Mendonça Filho, Minuzzi, Machado, Reis, Rodrigues, Mucellini, Franco, Buchweitz, Toazza, Bortoluzzi, Salum, Boscenco, Meaney, Levitan, Manfro and Silveira.)

While classically linked to memory, the hippocampus is also a feeding behavior modulator due to its multiple interconnected pathways with other brain regions and expression of receptors for metabolic hormones. Here we tested whether variations in insulin sensitivity would be correlated with differential brain activation following exposure to palatable food cues, as well as with variations in implicit food memory in a cohort of healthy adolescents, some of whom were born small for gestational age (SGA). Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) was positively correlated with activation in the cuneus, and negatively correlated with activation in the middle frontal lobe, superior frontal gyrus and precuneus when presented with palatable food images versus non-food images in healthy adolescents. Additionally, HOMA-IR and insulinemia were higher in participants with impaired food memory. SGA individuals had higher snack caloric density and greater chance for impaired food memory. There was also an interaction between the HOMA-IR and birth weight ratio influencing external eating behavior. We suggest that diminished insulin sensitivity correlates with activation in visual attention areas and inactivation in inhibitory control areas in healthy adolescents. Insulin resistance also associated with less consistency in implicit memory for a consumed meal, which may suggest lower ability to establish a dietary pattern, and can contribute to obesity. Differences in feeding behavior in SGA individuals were associated with insulin sensitivity and hippocampal alterations, suggesting that cognition and hormonal regulation are important components involved in their food intake modifications throughout life., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Mindfulness-based interventions (MBIs) are effective for some, but not all patients with anxiety disorders, but no clinical features have been consistently able to differentiate which patients are more likely to respond. In this study, we tested heart rate variability (HRV), a proposed correlate of regulated emotional response, as a moderator of treatment response to an MBI compared with pharmacotherapy., Methods: Seventy-seven patients with GAD had HRV data collected before randomization to pharmacological treatment with fluoxetine or Body-in-Mind Training (an MBI focused on bodily movement attention). HRV was used to predict treatment response measured by the Hamilton anxiety rating scale at 0 (baseline), 5, and 8 weeks (end of the intervention)., Results: The HF (nu) index of HRV was a strong moderator of treatment response between BMT and fluoxetine (estimate = 4.27 95%CI [1.19, 8.19]). Although fluoxetine was overall slightly superior to BMT in this study, no differences were found between groups in patients with high HF (nu) scores (estimate = -1.85 CI95% [-9.21, 5.52]). In contrast, patients with low HF (nu) achieved lower anxiety rating scores with fluoxetine treatment when compared with BMT (estimate = -10.29, 95% CI [-17.59, -2.99])., Limitations: A relatively small sample of patients was included., Conclusions: HRV was able to identify a subgroup for which MBI was less effective than pharmacotherapy and is a promising candidate as a selective biomarker for treatment response between an MBI and fluoxetine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders but the least successfully treated. The search for accessible clinical, psychological and biological markers is crucial for developing more effective and personalized interventions., Aims: To evaluate if changes in heart rate variability (HRV) between rest and stress conditions before interventions could predict improvement in emotional interference (EI) in a cognitive task after three different treatment modalities in patients with GAD., Method: This is a post-hoc analysis study reporting data from a larger randomized controlled trial (NCT03072264) assessing a mindfulness-based intervention (BMT), fluoxetine (FLX), and an active comparison group (QoL) in adult patients diagnosed with GAD. We assessed pulse plethysmography (PPG) data using a Shimmer3 GSR to measure HRV. Regression analyses were performed using the variation between baseline and endpoint EI scores as dependent variables and contrasts considering changing in HRV*group interaction in the baseline., Results: 106 individuals were included. The correlations between HRV changing from rest to task predicted improvement in IE only in the FLX versus control group contrast (estimated = -80.24; SE = 27.31; p = 0.005) and not in the BMT and control group contrast., Conclusion: More flexible HRV at baseline predicted EI improvement only in the FLX group. This finding is clinically relevant since it may help us develop more personalized interventions for GAD., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis., Methods and Findings: We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies' databases. No restriction was made regarding comorbidities with any other mental disorder, participants' age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration's risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD -0.56, 95% CI -0.62 to -0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials., Conclusions: In this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy., Competing Interests: The authors have declared that no competing interests exist.

Objective: Vasomotor symptoms affect 60-80% of women during the menopausal transition. Anxiety, depression, and anxiety sensitivity can have an important role in the distressful experience of vasomotor symptoms. Our aim was to evaluate the prevalence and association of vasomotor and negative affect symptoms., Methods: A cross-sectional study was conducted with 89 perimenopausal women aged 45-55 years. Broad psychiatric and clinical evaluations were carried out. The primary outcome was the vasomotor symptom problem rating and the main study factor was anxiety sensitivity. Linear regression analyses were conducted to examine the associations between the study factors and the primary outcome, and a multiple regression model was created to assess which variables were independently associated with vasomotor symptom problem rating., Results: The prevalence of anxiety, depression, and vasomotor symptoms were 58, 62, and 73%, respectively. Negative affect symptoms were positively associated with vasomotor symptom problem rating. The association of anxiety sensitivity and vasomotor symptom problem rating remained significant after controlling for perimenopausal stage, thyrotropin, follicle-stimulating hormone levels, and psychotropic medication use (β = 0.314, p = 0.002)., Conclusion: A better understanding of the experience of vasomotor symptoms is needed, especially the role of negative affect symptoms and anxiety sensitivity. New strategies focusing on related thoughts and behaviors could improve the quality of life of perimenopausal women.

Evidence on the relationship between genetics and mental health are flourishing. However, few studies are evaluating early biomarkers that might link genes, environment, and psychopathology. We aimed to study telomere length (TL) and epigenetic age acceleration (AA) in a cohort of adolescents with and without anxiety disorders (N = 234). We evaluated a representative subsample of participants at baseline and after 5 years (n = 76) and categorized them according to their anxiety disorder diagnosis at both time points: (1) control group (no anxiety disorder, n = 18), (2) variable group (anxiety disorder in one evaluation, n = 38), and (3) persistent group (anxiety disorder at both time points, n = 20). We assessed relative mean TL by real-time quantitative PCR and DNA methylation by Infinium HumanMethylation450 BeadChip. We calculated AA using the Horvath age estimation algorithm and analyzed differences among groups using generalized linear mixed models. The persistent group of anxiety disorder did not change TL over time (p = 0.495). The variable group had higher baseline TL (p = 0.003) but no accelerated TL erosion in comparison to the non-anxiety control group (p = 0.053). Furthermore, there were no differences in AA among groups over time. Our findings suggest that adolescents with chronic anxiety did not change telomere length over time, which could be related to a delay in neuronal development in this period of life.

Anxiety sensitivity (AS) is a multidimensional construct associated with the etiology and maintenance of panic disorder (PD) symptoms. However, only a few studies have evaluated whether cognitive-behavioral group therapy (CBGT) can modify the condition. The objective of this study was to evaluate the impact of CBGT on AS in patients with PD and to analyze AS and its dimensions as predictors of response to CBGT. In the present clinical trial, an intervention group ( n  = 37) attended 12 CBGT sessions, while a control group ( n  = 52) did not receive any intervention. The severity of symptoms and of AS were evaluated before and after CBGT in the intervention group and once in the control group. Significant improvement occurred in all specific PD symptoms and in general anxiety and depressive symptoms. Furthermore, AS scores reduced significantly after intervention. This study confirmed that AS is higher in patients with more severe PD. The effectiveness of CBGT for reducing the physical, cognitive, and social dimensions of AS was also observed, supporting the hypothesis of a positive impact of therapy.

Introduction: Mindfulness-based interventions have been studied as an alternative treatment for anxiety disorders, but there are only a few studies comparing these with established treatments., Objective: To evaluate the efficacy of a Body in Mind Training (BMT) program for adults with generalized anxiety disorder (GAD), an active comparison protocol called Quality of Life and Psychoeducation (QoL), and treatment with fluoxetine (FLX)., Methods: This study comprises a 3-arm parallel-group, randomized clinical trial (ClinicalTrials.gov ID: NCT03072264). Adults with a primary diagnosis of GAD and no current treatment were recruited from the community and randomized in a ratio 1:1:1. The primary outcomes were assessed by means of the Hamilton Anxiety Rating Scale (HAM-A) and the Penn State Worry Questionnaire (PSWQ) at week 8. Data were analyzed using a superiority analysis (BMT vs. QoL) and a noninferiority analysis (BMT vs. FLX)., Results: A total of 249 participants were included and 223 were analyzed (76 BMT, 79 FLX, and 68 QoL). All groups improved after intervention. However, BMT was not superior to QoL at week 8 (mean difference = -1.36; p = 0.47), nor was it noninferior to FLX as assessed with theHAM-A (mean difference = 3.5; 95% CI -0.06 to 7.06; noninferiority margin = -2.43; p = 0.054). QoL (mean difference = 3.54; p = 0.04) and FLX (mean difference = -7.72; 95% CI -10.89 to -4.56; noninferiority margin = -2.09; p < 0.001) were superior to BMT in reducing PSWQ score., Conclusion: Our data suggest that BMT, in its current format, cannot be considered an effective mindfulness protocol to improve GAD., (© 2020 S. Karger AG, Basel.)

Objective: Eating behavior is affected by psychological and neurocognitive factors. However, little is known about this relationship in anxious patients. Our aim was to investigate the associations between impulsivity, inhibitory control, energy-dense food consumption, and body mass index (BMI) in women with generalized anxiety disorder (GAD)., Methods: In this cross-sectional study, 51 adult females with GAD answered the Barratt Impulsiveness Scale (BIS-11) and participated in a go/no-go task using food images. Anthropometric measurements were evaluated. A food frequency questionnaire and a snack test were used to study eating behavior. Pearson correlation and multiple linear regression were performed to analyze the variables of interest, adjusted by age., Results: Impulsivity predicted intake of sugar (p = 0.016, 95%CI 0.67-6.05), total fat (p = 0.007, 95%CI 0.62-3.71), and saturated fat (p = 0.004, 95%CI 0.30-1.48). The snack test showed a positive correlation between presence of impulsivity and intake of biscuits (R = 0.296; p = 0.051). Response inhibition to food images in the go/no-go task paradigm did not predict BMI or food intake., Conclusion: Impulsivity was predictive of higher sugar and saturated fat intake in women diagnosed with GAD. Our findings add to the literature regarding the association between neuropsychological factors and food consumption in this specific population.

Introduction Children with anxiety disorders have been suggested to possess deficits in verbal fluency, shifting and attention, with inconsistent results regarding working memory and its subcomponents. This study extends previous findings by analyzing the performance of children with anxiety disorders in a wide range of neuropsychological functions. Methods We evaluated 54 children with a primary diagnosis of an anxiety disorder according to diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) using subtests of a neuropsychological battery. The severity of anxiety disorders was assessed using the Pediatric Anxiety Rating Scale (PARS). We calculated the frequency of neuropsychological impairments (-1.5 standard deviation of the normative sample). Comparisons between groups were performed based on the severity of anxiety symptoms, as well as in the presence of one vs. more diagnoses of anxiety disorder. Results We found higher impairment in visuospatial working memory (23.1%), semantic memory (27.8%), oral language (35.4%) and word writing (44.4%) in anxious children. Moreover, children with higher anxiety severity presented lower performance in visuospatial working memory, inferential processing, word reading, writing comprehension, copied writing, and semantic verbal fluency (d = 0.49 to 0.96 [Cohen's d]). The higher the number of anxiety diagnoses, the lower the performance in episodic memory and oral and written language (d = 0.56 to 0.77). Conclusion Our data suggested the presence of memory (visuospatial working memory and semantic memory) and language deficits (oral and writing) in some children with an anxiety disorder. Severity and number of anxiety diagnoses were associated with lower performance in memory and language domains in childhood.

Objective: Anxiety and depression are prevalent among medical students. Brazilian medical students have higher levels of depression and lower quality of life than their U.S. counterparts, and no preventive intervention exists for this risk group in Brazil. The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP), a cognitive-behavioral treatment protocol for neuroticism, was recently adapted into a single-session, preventive intervention. This study tested the impact of this protocol on psychiatric symptoms and quality of life in Brazilian medical students., Methods: In this open trial, the intervention protocol was translated and adapted to Brazilian Portuguese. Medical students over 18 years of age without psychotic symptoms, severe depressive episodes, or acute psychiatric risk were included, undergoing a psychiatric clinical interview (Mini-International Neuropsychiatric Interview [MINI]) and evaluation at baseline and at 7 and 30 days after a single-session UP that included experimental avoidance, quality of life, self-esteem, empathy, and anxiety symptom scales. A new evaluation was performed 90 days after the intervention., Results: Sixty-two students participated. Ninety days after the intervention, there were significant reductions in the number of students who met the criteria for social anxiety disorder (p = 0.013) or panic disorder (p = 0.001). There were also significant improvements in depressive symptoms (Beck Depression Inventory, p < 0.001) and quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire, p < 0.001)., Conclusion: UP improved anxiety and depressive symptoms in medical students. The single-session group format could reduce costs and facilitate application. Future placebo-controlled studies are necessary to confirm these findings.

Purpose: Psychotic experiences in childhood (such as hearing voices or being suspicious) represent an important phenotype for early intervention. However, these experiences can be defined in several ways: self-reported psychotic experiences (SRPE) rely exclusively on the child's report, clinically validated psychotic experiences (CRPE) are based on clinical assessment, and attenuated psychotic symptoms (APS) represents a categorization to do with clinical relevance in relation to severity. Very few studies have investigated how these distinctions impact clinical and other domains. The present study aims to compare SRPE, CRPE, and APS among children and adolescents. Methods: This study is part of the Brazilian High-Risk Cohort Study for Psychiatric Disorders, in which 2,241 individuals aged 6-14 years provided self-ratings of 20 psychotic experiences using the Community Assessment of Psychic Experiences (CAPE). A trained psychologist conducted an interview to validate or reject reported experiences and to rate the presence of APS and affective flattening. In parallel, parents provided information about child mental health to an independent interviewer. We tested the association of mutually exclusive categories of non-validated SRPE (nSRPE), clinically validated PE below the threshold for APS (nCRPE), and APS (nSRPE = 33%, nCRPE = 11%, APS = 6%), with parents' information about the child's positive attributes and levels of psychopathology and psychologist assessment of blunted affect. Results: Most associations were qualitatively similar, and there was a dose-response in the strength of associations across categories, such that APS > nCRPE > nSRPE. Experiences in all three categories were associated with female sex. nSRPE were associated with overall levels of psychopathology, but to a lesser degree than nCRPE and APS. APS and nCRPE were associated with less positive attributes, with APS more so than nCRPE. Only APS was associated with affective flattening. Conclusions: In children and adolescents, SRPE, CRPE, and APS all index liability for psychopathology, but as clinician rated relevance increases, associations get stronger and become evident across more domains., (Copyright © 2019 Moriyama, van Os, Gadelha, Pan, Salum, Manfro, Mari, Miguel, Rohde, Polanczyk, McGuire, Bressan and Drukker.)

Background: Subjects with panic disorder are nearly 4 times as likely to attempt suicide as compared to subjects without this condition., Methods: We searched the literature from Jan 1, 1960 to May, 4, 2019. Articles that reported a dichotomous sample of patients with panic disorder with and without suicidal behavior were included., Outcomes: Twelve studies with 1958 participants were included. Comorbid depression (k = 3, ES = 4.47 [2.63; 7.60]), depressive symptoms (k = 2, ES = 1.98 [1.26; 3.11]), older age (k = 3, ES = 1.66 [1.32; 2.10]), younger age of panic disorder onset (k = 2, ES = 0.65 [0.45; 0.94]), and history of alcohol dependence (k = 2, ES = 8.70 [1.20; 63.04]) were associated with suicide attempt in panic disorder. Depressive symptoms (k = 2, ES = 2.29 (1.60; 3.37]), anxiety symptoms (k = 2, ES = 1.90 [1.33; 2.69]), longer illness duration (k = 2, ES = 3.31 [1.90; 5.74]), comorbid depressive disorder (k = 4, ES = 3.88 [2.03; 7.41]), agoraphobia (k = 2, ES = 4.60 [1.47; 14.42]) and younger age of onset (k = 2, ES = 0.60 [0.38; 0.96]) were associated with suicidal ideation in panic disorder., Interpretation: Our findings provide a framework for the development of suicide prevention strategies in this population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Although resilience and coping are important factors associated with mental health, they are rarely investigated in the treatment of patients with panic disorder (PD)., Objective: To evaluate the response to four resilience and coping strategy sessions added to the standard cognitive behavioral group therapy (CBGT) protocol for PD., Design: Controlled clinical trial., Methods: The control group (n = 50) attended 12 CBGT sessions, while the intervention group (n = 50) received four additional resilience and coping strategy sessions, i.e., 16 in total. Symptom severity, resilience, coping strategies, and quality of life were assessed at baseline and post-CBGT., Results: Symptom severity and maladaptive coping strategies decreased significantly in both groups. However, the intervention group had increased resilience and improvement in the environment domain of quality of life., Conclusions: Additional sessions have potential benefits for coping skills and resilience in PD patients, but these benefits should be evaluated in further long-term studies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Anxiety disorders (ADs) are chronic conditions that often have their onset in childhood and adolescence. Inflammation and oxidative stress markers have been associated with the vulnerability to ADs, however it is not known if ADs in childhood can influence these biomarkers levels longitudinally. This study aims to investigate a possible association between ADs and serum levels of IL-10, IL-6, IL-1β, TNF-α, BDNF, and protein carbonyl content, assessed after 5 years of follow-up. Moreover, we studied possible mediators for these associations, including physical activity, metabolic markers and childhood trauma. From 240 individuals evaluated at baseline, 73 were re-evaluated in the follow-up. Psychiatric diagnoses were assessed with the K-SADS or the MINI and child trauma questionnaire (CTQ) to evaluate presence of trauma. We searched serum levels of IL-10, IL-6, IL-1β and TNF-α (flow cytometry), BDNF (sandwich-ELISA) and carbonyl content in proteins (PCC method). We found a significant direct association between ADs at baseline and log IL-6 (B = 0.34, S.E. = 0.11, p = 0.002) and between AD and log BDNF (B = -0.10, S.E. = 0.05, p = 0.033) five years later. Searching for possible mediators of these association, we found that levels of HDL-cholesterol (ΔB = -0.148) partially mediated the association between ADs and IL-6. No significant mediators were found in the association between ADs and BDNF. Moreover, this association is no longer significant after controlling for the presence of depression. Our results demonstrated that previous AD diagnosis was associated with higher levels of IL-6 in the follow-up evaluation, suggesting that the presence of anxiety in childhood could influence altered inflammatory markers., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

Introduction: Early life adversity, including the perception of poor quality of maternal care, is associated with long-term metabolic and psychosocial consequences. The negative quality of mother/child relationship is associated with emotional overeating in young children, which is defined by eating in response to emotional arousal states such as fear, anger or anxiety. However, it is not known if this association persists through adolescence. Therefore, we aimed at verifying if maternal care during infancy can influence emotional eating in young adults., Methods: Seventy-five adolescents, residents of Porto Alegre, who participated in the PROTAIA Program (anxiety disorder in childhood and adolescence program), answered the Parental Bonding Instrument (PBI - assessment of perceived maternal care), and the Dutch Eating Behavior Questionnaire (DEBQ). Regression analysis models were built to predict Emotional Eating, a domain of the DEBQ, using maternal care, gender, and anxiety as independent variables., Results: The model was statistically significant when adjusted for potential confounders (r 2  = 0.272; p < 0.0001). Emotional eating was significantly predicted by levels of maternal care, anxiety and gender (beta = -0.316; p = 0.006)., Conclusion: The results demonstrated a negative association between the quality of maternal care and emotional eating in young adults, suggesting that the early environment could be involved on the development of eating disorders or on the differential eating behavior in adolescents with emotional disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background Emotional disorders are risk factors for atherosclerosis and consequent cardiovascular disease. However, it is not clear whether emotional symptoms (ESs) have direct effects on cardiovascular disease. The aim of the present study is to investigate the effects of early ESs on carotid atherosclerosis in young adults. Methods and Results We tested the association between expression of ESs at 11 and 15 years of age and carotid intima-media thickness at 18 years of age in the 1993 Pelotas Birth Cohort (N=5249, n=4336 with complete mental health data). ES s were assessed using the Strengths and Difficulties Questionnaire. Propensity score weighting procedure was run using generalized boosted regression model to adjust for potential confounding between exposure and outcome. We also tested whether traditional cardiovascular risk factors could mediate this relationship. Adjusted high expression of ESs , both at 11 and 15 years of age, led to mean increases in carotid intima-media thickness of 1.84 and 2.58 μm, respectively, at 18 years of age (both P<0.001). Longitudinal effects of ESs on atherosclerosis were direct and not significantly mediated by traditional cardiovascular risk factors. Male sex at age 15 years significantly enhanced the effects of ESs on carotid intima-media thickness at age 18 years ( P<0.001 for interaction): although high expression of ESs led to mean increases of 1.14 μm in females ( P<0.05), it led to mean increases of 5.83 μm in males ( P<0.001). Conclusions In this large birth cohort, expression of ESs in adolescence was longitudinally associated with a higher carotid intima-media thickness in young adults. The association is direct and not mediated by traditional cardiovascular risk factors. Interactions by sex might have important implications for designing future interventions.

Background: The objective of this study is to assess group differences in symptom reduction between individuals receiving group cognitive behavioral therapy (G-CBT) and attention bias modification (ABM) compared to their respective control interventions, control therapy (CT), and attention control training (ACT), in a 2 × 2 factorial design., Methods: A total of 310 treatment-naive children (7-11 years of age) were assessed for eligibility and 79 children with generalized, separation or social anxiety disorder were randomized and received G-CBT (n = 42) or CT (n = 37). Within each psychotherapy group, participants were again randomized to ABM (n = 38) or ACT (n = 41) in a 2 × 2 factorial design resulting in four groups: G-CBT + ABM (n = 21), G-CBT + ACT (n = 21), CT + ABM (n = 17), and CT + ACT (n = 20). Primary outcomes were responder designation as defined by Clinical Global Impression-Improvement (CGI-I) scale (≤2) and change on the Pediatric Anxiety Rating Scale (PARS)., Results: There were significant improvements of symptoms in all groups. No differences in response rates or mean differences in PARS scores were found among groups: G-CBT + ABM group (23.8% response; 3.9 points, 95% confidence interval [CI] -0.3 to 8.1), G-CBT + ACT (42.9% response; 5.6 points, 95% CI 2.2-9.0), CT + ABM (47.1% response; 4.8 points 95% CI 1.08-8.57), and CT + ACT (30% response; 0.8 points, 95% CI -3.0 to 4.7). No evidence or synergic or antagonistic effects were found, but the combination of G-CBT and ABM was found to increase dropout rate., Conclusions: We found no effect of G-CBT or ABM beyond the effects of comparison groups. Results reveal no benefit from combining G-CBT and ABM for anxiety disorders in children and suggest potential deleterious effects of the combination on treatment acceptability.

Poor fetal growth is associated with long-term behavioral, metabolic and psychiatric alterations, including impulsivity, insulin resistance, and mood disorders. However, the consumption of omega-3 polyunsaturated fatty acid (n-3 PUFA) seems to be protective for this population, improving inhibitory control and behavioral reactivity. We investigated whether the presence of the A allele of rs8887 SNP (PLIN4 gene), known to be associated with increased sensitivity to the consumption of n-3 PUFAs, interacts with fetal growth influencing inhibitory control. 152 five-year-old children were genotyped and performed the Stop Signal Task (SSRT). There was a significant interaction between birth weight and the presence of the A allele on SSRT performance, in which lower birth weight associated with poorer inhibitory control only in non-carriers. These results suggest that a higher responsiveness to n-3 PUFAS protects small for gestational age children from developing poor response inhibition, highlighting that optimizing n-3 PUFA intake may benefit this population., (Copyright © 2018. Published by Elsevier Ltd.)

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.

Anxiety disorders (AD) typically manifest in children and adolescents and might persist into adulthood. However, there are still few data concerning epigenetic mechanisms associated with onset, persistence or remission of AD over time. We investigated a cohort of adolescents and young adults at baseline (age; 13.19 ± 2.38) and after 5 years and classified them according to the AD diagnosis and their longitudinal trajectories into 4 groups: (1) Typically Developing Comparisons (TDC; control group, n = 14); (2) Incident (AD in the second evaluation only, n = 11); (3) Persistent (AD in both evaluations, n = 14) and (4) Remittent (AD in the first evaluation only, n = 8). DNA methylation was evaluated with the Infinium HumanMethylation450 BeadChip from saliva samples collected at both evaluations. Gene set enrichment analysis was applied to consider biological pathways. We found decreased DNA methylation in TDC group while the chronic cases of AD presented hypermethylation in central nervous system development pathways. Moreover, we showed that this persistent group also presented hypermethylation while the other three groups were associated with hypomethylation in nervous system development pathway. Incidence and remission groups were associated with increased and decreased methylation in neuron development pathways, respectively. Larger studies are likely to detect specific genes relevant to AD.

Objective: Panic disorder (PD) respiratory subtype (RS) was described in order to cluster patients according to their symptoms. These patients are characterized by experiencing a relatively high number of noticeable respiratory symptoms during a panic attack (PA) and a higher reactivity to CO 2 . In this study, we aimed to evaluate the clinical relevance of this diagnostic category, evaluating if there are different responses to cognitive-behavioral therapy in patients with panic disorder RS as compared to those with the non-respiratory subtype (NRS), using serum phosphate as a biological marker., Methods: Patients were assessed by a clinical interview followed by a structured diagnostic interview (M.I.N.I) and classified as RS or NRS based on symptoms. The severity of PD was evaluated throughout the PDSS, CGI, HAM-A, STAI and the BDI rating scales. All patients underwent 12 structured sessions of group-CBT for PD and had their blood collected at baseline and after treatment to assess phosphate levels., Results: One hundred and thirty-eight patients have been assessed, and 102 were included in this trial. Sixty-nine patients completed the treatment protocol, 42 were classified as RS and 27 as NRS. Both RS and NRS patients improved in all clinical scales (p < 0.001). The mean phosphate levels increased from 2.44 mg/dl ± 0.49 at baseline to 3.38 mg/dl ± 0.52 (p < 0.01) in the RS group as well as from 2.46 mg/dl ± 0.64 at baseline to 3.46 mg/dl ± 0.61 (p < 0.01) in the NSR group., Limitations: Small sample size and the lack of assessment of other clinical and physiological parameters, such as respiratory variables., Conclusion: Our findings suggest that both RS and NRS benefit from group CBT and that there was a change in phosphate levels after effective treatment in both groups. Our data support the idea that there is a reversal of the conditions that promote hypophosphatemia as chronic hyperventilation after CBT treatment, whereas it is in disagreement to the presence of two different PD subtypes based on phosphate levels once their rates did not differ at baseline and had a similar increase after effective treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)