A magnetic resonance imaging-based morphometric and structural covariance network study of Brazilian adolescents stratified by depression risk

Objectives: To explore differences in regional cortical morphometric structure between adolescents at risk for depression or with current depression. Methods: We analyzed cross-sectional structural neuroimaging data from a sample of 150 Brazilian adolescents classified as low-risk (LR) (n=50) or high-risk (HR) for depression (n=50) or with current depression (n=50) through a vertex-based approach with measurements of cortical volume (CV), surface area (SA), and cortical thickness (CT). Differences between groups in subcortical volume and in the organization of networks of structural covariance were also explored. Results: No significant differences in brain structure between groups were observed in whole-brain vertex-wise CV, SA, or CT. Also, no significant differences in subcortical volume were observed between risk groups. In relation to the structural covariance network, there was an indication of an increase in the hippocampus betweenness centrality index in the HR group network compared to the LR and current depression group networks. However, this result was only statistically significant when applying false discovery rate correction for nodes within the affective network. Conclusion: In an adolescent sample recruited using an empirically based composite risk score, no major differences in brain structure were detected according to the risk and presence of depression.

An MRI-based morphometric and structural covariance network study of Brazilian adolescents stratified by depression risk.

OBJECTIVE: To explore differences in regional cortical morphometric structure between adolescents at risk for depression or with current depression. METHODS: We analyzed cross-sectional structural neuroimaging data from a sample of 150 Brazilian adolescents classified as low-risk (n=50) or high-risk for depression (n=50) or with current depression (n=50) through a vertex-based approach with measurements of cortical volume, surface area and thickness. Differences between groups in subcortical volumes and in the organization of networks of structural covariance were also explored. RESULTS: No significant differences in brain structure between groups were observed in whole-brain vertex-wise cortical volume, surface area or thickness. Also, no significant differences in subcortical volume were observed between risk groups. In relation to the structural covariance network, there was an indication of an increase in the hippocampus betweenness centrality index in the high-risk group network compared to the low-risk and current depression group networks. However, this result was only statistically significant when applying false discovery rate correction for nodes within the affective network. CONCLUSION: In an adolescent sample recruited using an empirically based composite risk score, no major differences in brain structure were detected according to the risk and presence of depression.

Frontolimbic Network Topology Associated With Risk and Presence of Depression in Adolescents: A Study Using a Composite Risk Score in Brazil.

BACKGROUND: There have been significant challenges in understanding functional brain connectivity associated with adolescent depression, including the need for a more comprehensive approach to defining risk, the lack of representation of participants from low- and middle-income countries, and the need for network-based approaches to model connectivity. The current study aimed to address these challenges by examining resting-state functional connectivity of frontolimbic circuitry associated with the risk and presence of depression in adolescents in Brazil. METHODS: Adolescents in Brazil ages 14 to 16 years were classified into low-risk, high-risk, and depressed groups using a clinical assessment and composite risk score that integrates 11 sociodemographic risk variables. After excluding participants with excessive head movement, resting-state functional magnetic resonance imaging data of 126 adolescents were analyzed. We compared group differences in frontolimbic network connectivity using region of interest-to-region of interest, graph theory, and seed-based connectivity analyses. Associations between self-reported depressive symptoms and brain connectivity were also explored. RESULTS: Adolescents with depression showed greater dorsal anterior cingulate cortex (ACC) connectivity with the orbitofrontal cortex compared with the 2 risk groups and greater dorsal ACC global efficiency than the low-risk group. Adolescents with depression also showed reduced local efficiency and a lower clustering coefficient of the subgenual ACC compared with the 2 risk groups. The high-risk group also showed a lower subgenual ACC clustering coefficient relative to the low-risk group. CONCLUSIONS: These findings highlight altered connectivity and topology of the ACC within frontolimbic circuitry as potential neural correlates and risk factors of developing depression in adolescents in Brazil. This study broadens our understanding of the neural connectivity associated with adolescent depression in a global context.

Reward- and threat-related neural function associated with risk and presence of depression in adolescents: a study using a composite risk score in Brazil.

BACKGROUND: Neuroimaging studies on adolescents at risk for depression have relied on a single risk factor and focused on adolescents in high-income countries. Using a composite risk score, this study aims to examine neural activity and connectivity associated with risk and presence of depression in adolescents in Brazil. METHODS: Depression risk was defined with the Identifying Depression Early in Adolescence Risk Score (IDEA-RS), calculated using a prognostic model that included 11 socio-demographic risk factors. Adolescents recruited from schools in Porto Alegre were classified into a low-risk (i.e., low IDEA-RS and no lifetime depression), high-risk (i.e., high IDEA-RS and no lifetime depression), or clinically depressed group (i.e., high IDEA-RS and depression diagnosis). One hundred fifty adolescents underwent a functional MRI scan while completing a reward-related gambling and a threat-related face-matching task. We compared group differences in activity and connectivity of the ventral striatum (VS) and amygdala during the gambling and face-matching tasks, respectively, and group differences in whole-brain neural activity. RESULTS: Although there was no group difference in reward-related VS or threat-related amygdala activity, the depressed group showed elevated VS activity to punishment relative to high-risk adolescents. The whole-brain analysis found reduced reward-related activity in the lateral prefrontal cortex of patients and high-risk adolescents compared with low-risk adolescents. Compared with low-risk adolescents, high-risk and depressed adolescents showed reduced threat-related left amygdala connectivity with thalamus, superior temporal gyrus, inferior parietal gyrus, precentral gyrus, and supplementary motor area. CONCLUSIONS: We identified neural correlates associated with risk and presence of depression in a well-characterized sample of adolescents. These findings enhance knowledge of the neurobiological underpinnings of risk and presence of depression in Brazil. Future longitudinal studies are needed to examine whether the observed neural patterns of high-risk adolescents predict the development of depression.

The Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo): Rationale, Methods, and Baseline Characteristics.

Background: The characterization of adolescents at high risk for developing depression has traditionally relied on the presence or absence of single risk factors. More recently, the use of composite risk scores combining information from multiple variables has gained attention in prognostic research in the field of mental health. We previously developed a sociodemographic composite score to estimate the individual level probability of depression occurrence in adolescence, the Identifying Depression Early in Adolescence Risk Score (IDEA-RS). Objectives: In this report, we present the rationale, methods, and baseline characteristics of the Identifying Depression Early in Adolescence Risk Stratified Cohort (IDEA-RiSCo), a study designed for in-depth examination of multiple neurobiological, psychological, and environmental measures associated with the risk of developing and with the presence of depression in adolescence, with a focus on immune/inflammatory and neuroimaging markers. Methods: Using the IDEA-RS as a tool for risk stratification, we recruited a new sample of adolescents enriched for low (LR) and high (HR) depression risk, as well as a group of adolescents with a currently untreated major depressive episode (MDD). Methods for phenotypic, peripheral biological samples, and neuroimaging assessments are described, as well as baseline clinical characteristics of the IDEA-RiSCo sample. Results: A total of 7,720 adolescents aged 14-16 years were screened in public state schools in Porto Alegre, Brazil. We were able to identify individuals at low and high risk for developing depression in adolescence: in each group, 50 participants (25 boys, 25 girls) were included and successfully completed the detailed phenotypic assessment with ascertainment of risk/MDD status, blood and saliva collections, and magnetic resonance imaging (MRI) scans. Across a variety of measures of psychopathology and exposure to negative events, there was a clear pattern in which either the MDD group or both the HR and the MDD groups exhibited worse indicators in comparison to the LR group. Conclusion: The use of an empirically-derived composite score to stratify risk for developing depression represents a promising strategy to establish a risk-enriched cohort that will contribute to the understanding of the neurobiological correlates of risk and onset of depression in adolescence.

Mind the brain gap: The worldwide distribution of neuroimaging research on adolescent depression.

Adolescents comprise one fourth of the world's population, with about 90% of them living in low- and middle-income countries (LMICs). The incidence of depression markedly increases during adolescence, making the disorder a leading cause of disease-related disability in this age group. However, most research on adolescent depression has been performed in high-income countries (HICs). To ascertain the extent to which this disparity operates in neuroimaging research, a systematic review of the literature was performed. A total of 148 studies were identified, with neuroimaging data available for 4,729 adolescents with depression. When stratified by income group, 122 (82%) studies originated from HICs, while 26 (18%) were conducted in LMICs, for a total of 3,705 and 1,024 adolescents with depression respectively. A positive Spearman rank correlation was observed between country per capita income and sample size (rs=0.673, p = 0.023). Our results support the previous reports showing a large disparity between the number of studies and the adolescent population per world region. Future research comparing neuroimaging findings across populations from HICs and LMICs may provide unique insights to enhance our understanding of the neurobiological processes underlying the development of depression.

New Insights into Mechanisms of Immune Checkpoint Inhibitor-Induced Cardiovascular Toxicity.

PURPOSE OF REVIEW: The review aims to summarize the present knowledge about cardiovascular toxicities associated with immune checkpoint inhibitors (ICI) and dissect underlying mechanism associated with individual cardiovascular toxicity. RECENT FINDINGS: Widespread use of ICI therapy has allowed for increasing recognition of a wide spectrum of immune-related adverse events that leave all organ systems vulnerable. Immune-mediated cardiovascular toxicities, initially thought to be rare, are more often being reported and present considerable challenges due to their non-specific clinical presentation, potential to have a fulminant progression, and overlap with other cardiovascular and general medical illnesses. Myocarditis is the most common manifestation of ICI-associated cardiovascular toxicity. Pericardial diseases, vasculitis, Takotsubo syndrome, conduction abnormalities, and destabilization of atherosclerotic lesions constitute other significant adverse events. At this stage, mechanisms underlying fundamental biology of cardiac toxicity have not been studied comprehensively and there remain gaps of knowledge in the current literature concerning the underlying pathomechanisms. It is hypothesized that immune-mediated myocarditis is a result of an exaggerated adaptive immune response against shared epitopes in the myocardium and tumor cells. Further, underlying mechanism of other cardiovascular toxicities is still unclear, further compounded by sparsity of epidemiological data. It is paramount to understand the mechanisms behind ICI-induced cardiovascular toxicities to develop appropriate treatment and prevention strategies and minimize the morbidity and mortality of cancer patients undergoing ICI therapy.

Neuroimaging adolescents with depression in a middle-income country: feasibility of an fMRI protocol and preliminary results

Objective: To test the feasibility and to present preliminary results of a neuroimaging protocol to evaluate adolescent depression in a middle-income setting. Methods: We assessed psychotropic medication-free adolescents (age range 14-16 years) with a diagnosis of major depressive disorder (MDD). Participants underwent a comprehensive clinical evaluation and both structural and functional magnetic resonance imaging (fMRI). In this pilot study, a preliminary single-group analysis of resting-state fMRI (rs-fMRI) data was performed, with a focus on the default mode network (DMN), cognitive control network (CCN), and salience network (SN). Results: The sample included 29 adolescents with MDD (mean age 16.01, SD 0.78) who completed the protocol. Only two participants were excluded due to MRI quality issues (head movement), and were not included in the analyses. The scans showed significant connectivity between the medial prefrontal cortex and posterior cingulate cortex (DMN), the ACC and anterior insula (SN), and the lateral prefrontal cortex and dorsal parietal cortex (CCN). Conclusion: We demonstrated the feasibility of implementing a complex neuroimaging protocol in a middle-income country. Further, our preliminary rs-fMRI data revealed patterns of resting-state connectivity consistent with prior research performed in adolescents from high-income countries.

Neuroimaging adolescents with depression in a middle-income country: feasibility of an fMRI protocol and preliminary results.

OBJECTIVE: To test the feasibility and to present preliminary results of a neuroimaging protocol to evaluate adolescent depression in a middle-income setting. METHODS: We assessed psychotropic medication-free adolescents (age range 14-16 years) with a diagnosis of major depressive disorder (MDD). Participants underwent a comprehensive clinical evaluation and both structural and functional magnetic resonance imaging (fMRI). In this pilot study, a preliminary single-group analysis of resting-state fMRI (rs-fMRI) data was performed, with a focus on the default mode network (DMN), cognitive control network (CCN), and salience network (SN). RESULTS: The sample included 29 adolescents with MDD (mean age 16.01, SD 0.78) who completed the protocol. Only two participants were excluded due to MRI quality issues (head movement), and were not included in the analyses. The scans showed significant connectivity between the medial prefrontal cortex and posterior cingulate cortex (DMN), the ACC and anterior insula (SN), and the lateral prefrontal cortex and dorsal parietal cortex (CCN). CONCLUSION: We demonstrated the feasibility of implementing a complex neuroimaging protocol in a middle-income country. Further, our preliminary rs-fMRI data revealed patterns of resting-state connectivity consistent with prior research performed in adolescents from high-income countries.

Intrinsic Brain Connectivity Following Long-Term Treatment with Methylphenidate in Children with Attention-Deficit/Hyperactivity Disorder.

INTRODUCTION: Although widely used for the treatment of attention-deficit/hyperactivity disorder (ADHD) across the life span, the effects of methylphenidate (MPH) on the brain are not completely understood. Functional neuroimaging techniques may help increase knowledge about the mechanisms of MPH action. OBJECTIVE: To evaluate changes in functional connectivity patterns of the default mode network (DMN) in children with ADHD following long-term treatment with MPH. METHODS: Twenty-three right-handed treatment-naïve boys with ADHD underwent a protocol of intrinsic functional connectivity before and after 6 months of treatment with MPH. Functional connectivity was analyzed using a region of interest (ROI) approach and independent component analysis (ICA). RESULTS: ROI analyses showed no significant changes in connectivity between regions of the DMN following treatment, with a relatively small increase in the anterior-posterior connectivity of the network. ICA revealed a significant increase in connectivity between the left putamen and the DMN (p < 0.001, corrected). There was a correlation between the reduction of symptoms and the increased connectivity between the putamen and the DMN after treatment (rho = -0.65, p = 0.017). CONCLUSION: Dysfunctions in cortical-subcortical circuits have often been associated with the pathophysiology of ADHD. Our findings suggest that effective treatment with MPH in children with ADHD may affect brain functioning by increasing connectivity between the DMN and subcortical nuclei.