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

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Recently, several studies have investigated the neurodevelopment of psychiatric disorders using brain data acquired via structural magnetic resonance imaging (sMRI). These analyses have shown the potential of sMRI data to provide a relatively precise characterization of brain structural biomarkers. Despite these advances, a relatively unexplored question is how reliable and consistent a model is when assessing subjects from other independent datasets. In this study, we investigate the performance and generalizability of the same model architecture trained from distinct datasets comprising youths in diverse stages of neurodevelopment and with different mental health conditions. We employed models with the same 3D convolutional neural network (CNN) architecture to assess autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), brain age, and a measure of dimensional psychopathology, the Child Behavior Checklist (CBCL) total score. The investigated datasets include the Autism Brain Imaging Data Exchange II (ABIDE-II, N = 580), Attention Deficit Hyperactivity Disorder (ADHD-200, N = 922), Brazilian High-Risk Cohort Study (BHRCS, N = 737), and Adolescent Brain Cognitive Development (ABCD, N = 11,031). Models' performance and interpretability were assessed within each dataset (for diagnosis tasks) and inter-datasets (for age estimation). Despite the demographic and phenotypic differences of the subjects, all models presented significant estimations for age (p value < 0.001) within and between datasets. In addition, most models showed a moderate to high correlation in age estimation. The results, including the models' brain regions of interest (ROI), were analyzed and discussed in light of the youth neurodevelopmental structural changes. Among other interesting discoveries, we found that less confounded training datasets produce models with higher generalization capacity.

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Objectives: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. Methods: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. Results: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. Conclusion: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.

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Neuroimaging studies suggest that brain development mechanisms might explain at least some behavioural and cognitive attention-deficit/hyperactivity disorder (ADHD) symptoms. However, the putative mechanisms by which genetic susceptibility factors influence clinical features via alterations of brain development remain largely unknown. Here, we set out to integrate genomics and connectomics tools by investigating the associations between an ADHD polygenic risk score (ADHD-PRS) and functional segregation of large-scale brain networks. With this aim, ADHD symptoms score, genetic and rs-fMRI (resting-state functional magnetic resonance image) data obtained in a longitudinal community-based cohort of 227 children and adolescents were analysed. A follow-up was conducted approximately 3 years after the baseline, with rs-fMRI scanning and ADHD likelihood assessment in both stages. We hypothesised a negative correlation between probable ADHD and the segregation of networks involved in executive functions, and a positive correlation with the default-mode network (DMN). Our findings suggest that ADHD-PRS is correlated with ADHD at baseline, but not at follow-up. Despite not surviving for multiple comparison correction, we found significant correlations between ADHD-PRS and segregation of cingulo-opercular networks and DMN at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation. These directions of associations corroborate the proposed counter-balanced role of attentional networks and DMN in attentional processes. However, the association between ADHD-PRS and brain networks functional segregation was not found at follow-up. Our results provide evidence for specific influences of genetic factors on development of attentional networks and DMN. We found significant correlations between polygenic risk score for ADHD (ADHD-PRS) and segregation of cingulo-opercular networks and default-mode network (DMN) at baseline. ADHD-PRS was negatively correlated with the segregation level of cingulo-opercular networks but positively correlated with the DMN segregation.

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BACKGROUND: Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement. METHODS: Children and adolescents aged 6-17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline (n = 677) and at 3-year follow-up (n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions (n = 216). Deviations from this model were constructed for the remaining individuals (n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses. RESULTS: Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control. CONCLUSIONS: Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.

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OBJECTIVES: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. METHODS: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. RESULTS: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. CONCLUSIONS: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.

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INTRODUCTION: The administration of multiple esketamine doses has shown efficacy for unipolar and bipolar treatment-resistant depression (TRD). Nevertheless, the probability of responding or not after each dose in the real-world remains unknown. This study aimed to estimate it throughout four doses of esketamine, administrated via subcutaneous (SC). MATERIAL AND METHODS: We conducted a retrospective analysis of a case series of 70 patients with TRD who received treatment from the esketamine assistance program at Federal University of Sao Paulo, between April 2017 and December 2018. The SC injections were administrated weekly at a dose of 0.5-1.0mg/kg, in conjunction with patients' psychotropic drugs. Response was defined as a decrease of at least 50% in the Montgomery-Åsberg Depression Rating Scale between baseline and 24h after dose. We used hidden Markov modeling in order to estimate de probability of response after each esketamine injection. RESULTS: The probability of a patient that was a "non-responder" to become a "responder" following a SC injection of esketamine was 17.30% and the probability that this patient remains a "non-responder" was 82.70%. The probability of a patient that was a "responder" to remain as a "responder" was 95%. CONCLUSIONS: Patients with TRD who had not responded after the first dose of esketamine, still had a chance of responding after the subsequent dose administrated via SC.

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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.

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Background: Thalamic volume measures have been linked to obsessive-compulsive disorder (OCD) in children and adolescents. However, it is unclear if alterations in thalamic volumes occur before or after symptom onset and if there is a relation to the presence of sub-clinical obsessive-compulsive symptoms (OCS). Here, we explore the relationship between OCS and the rate of thalamic volume change in a cohort of children and youth at high risk to develop a mental disorder. A secondary aim was to determine if there is a relationship between OCS and the individual's OCD polygenic risk score (OCD-PRS) and between the rate of thalamic volume change and the OCD-PRS. Methods: The sample included 378 children enrolled in the longitudinal Brazilian High-Risk Cohort for Mental Conditions. Participants were assessed for OCS and the symmetrized percent change (SPC) of thalamic volume across two time-points separated by 3 years, along with the OCD-PRS. Zero-altered negative binomial models were used to analyze the relationship between OCS and thalamic SPC. Multiple linear regressions were used to examine the relationship between thalamic SPC and OCD-PRS. Results: A significant relationship between OCS and the right thalamus SPC (p = 0.042) was found. There was no significant relationship between changes in thalamic volume SPC and OCD-PRS. Conclusions: The findings suggest that changes in the right thalamic volume over the course of 3 years in children may be associated to OCS. Future studies are needed to confirm these results and further characterize the specific nature of OCS symptoms associated with thalamic volumes.