Associations between perceived parenting, brain activity and connectivity, and depression symptoms in Brazilian adolescents.

In adolescence, parental care is associated with lower depression symptoms whereas parental overprotection is associated with greater depression symptoms, effects which may be mediated by adolescent brain activity and connectivity. The present study examined associations between perceived parenting, brain activity and connectivity, and depression symptoms in adolescents from Brazil, a middle-income country (MIC). Analyses included 100 adolescents who underwent functional magnetic resonance imaging scanning while completing a face matching task. Parental care and overprotection were associated with adolescent depression symptoms in expected directions. We also found that parental care and overprotection were associated with amygdala connectivity with several brain regions; however, amygdala activity was not associated with parenting and neither activity or connectivity mediated the association between parenting and depression symptoms. Results identify how parenting influences brain function and depression symptoms in youth from a MIC.

Inflammation and immune system pathways as biological signatures of adolescent depression-the IDEA-RiSCo study.

The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world's adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14-16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p < 0.001), interferon signaling (z-score = 2.464, p < 0.001), interferon alpha/beta signaling (z-score = 3.873, p < 0.001), and complement signaling (z-score = 2, p = 0.002) were upregulated in adolescents with MDD compared with adolescents without MDD independently from their level of risk. The up-regulation of such inflammation-related pathways was observed in females but not in males. Inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling were identified as key indicators of adolescent depression, and this effect was present only in females.

How much or how often? Examining the screening properties of the DSM cross-cutting symptom measure in a youth population-based sample.

BACKGROUND: The DSM Level 1 Cross-Cutting Symptom Measure (DSM-XC) allows for assessing multiple psychopathological domains. However, its capability to screen for mental disorders in a population-based sample and the impact of adverbial framings (intensity and frequency) on its performance are unknown. METHODS: The study was based on cross-sectional data from the 1993 Pelotas birth cohort in Brazil. Participants with completed DSM-XC and structured diagnostic interviews (n = 3578, aged 22, 53.6% females) were included. Sensitivity, specificity, positive (LR+), and negative (LR-) likelihood ratios for each of the 13 DSM-XC domains were estimated for detecting five internalizing disorders (bipolar, generalized anxiety, major depressive, post-traumatic stress, and social anxiety disorders) and three externalizing disorders (antisocial personality, attention-deficit/hyperactivity, and alcohol use disorders). Sensitivities and specificities >0.75, LR+ > 2 and LR- < 0.5 were considered meaningful. Values were calculated for the DSM-XC's original scoring and for adverbial framings. RESULTS: Several DSM-XC domains demonstrated meaningful screening properties. The anxiety domain exhibited acceptable sensitivity and LR- values for all internalizing disorders. The suicidal ideation, psychosis, memory, repetitive thoughts and behaviors, and dissociation domains displayed acceptable specificity for all disorders. Domains also yielded small but meaningful LR+ values for internalizing disorders. However, LR+ and LR- values were not generally meaningful for externalizing disorders. Frequency-framed questions improved screening properties. CONCLUSIONS: The DSM-XC domains showed transdiagnostic screening properties, providing small but meaningful changes in the likelihood of internalizing disorders in the community, which can be improved by asking frequency of symptoms compared to intensity. The DSM-XC is currently lacking meaningful domains for externalizing disorders.

Adolescent depression beyond DSM definition: a network analysis.

Calls for refining the understanding of depression beyond diagnostic criteria have been growing in recent years. We examined the prevalence and relevance of DSM and non-DSM depressive symptoms in two Brazilian school-based adolescent samples with two commonly used scales, the Patient Health Questionnaire (PHQ-A) and the Mood and Feelings Questionnaire (MFQ). We analyzed cross-sectional data from two similarly recruited samples of adolescents aged 14-16 years, as part of the Identifying Depression Early in Adolescence (IDEA) study in Brazil. We assessed dimensional depressive symptomatology using the PHQ-A in the first sample (n = 7720) and the MFQ in the second sample (n = 1070). We conducted network analyses to study symptom structure and centrality estimates of the two scales. Additionally, we compared centrality of items included (e.g., low mood, anhedonia) and not included in the DSM (e.g., low self-esteem, loneliness) in the MFQ. Sad mood and worthlessness items were the most central items in the network structure of the PHQ-A. In the MFQ sample, self-hatred and loneliness, two non-DSM features, were the most central items and DSM and non-DSM items in this scale formed a highly interconnected network of symptoms. Furthermore, analysis of the MFQ sample revealed DSM items not to be more frequent, severe or interconnected than non-DSM items, but rather part of a larger network of symptoms. A focus on symptoms might advance research on adolescent depression by enhancing our understanding of the disorder.

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.

Physical activity and depressive symptoms among adolescents in a school-based sample

Objective: To explore associations between self-reported weekly physical activity and depressive symptomatology among adolescents in a school-based sample from Brazil. Methods: We surveyed 7,405 adolescents aged 14 to 16 years in 101 public schools in Porto Alegre, Brazil. We assessed physical activity using an adapted version of the Patient-Centered Assessment and Counseling for Exercise Plus Nutrition - Adolescent Physical Activity Measure (PACE+), and depressive symptoms using the Brazilian Portuguese version of the Patient Health Questionnaire - Adolescent Version. We compared the depressive symptom scores among adolescents with varying levels of physical activity. Results: Of the overall sample, 84.4% exercised less than the recommended frequency of 60 minutes/day, at least 5 days/week, of moderate to intense physical activity (PACE+ score ≥ 5). Adolescents whose physical activity levels fell below that threshold had higher median depression scores (8 [IQR = 10] vs. 7 [IQR = 9], W = 4060461, p < 0.001). A similar pattern was observed for depression scores in those with PACE+ < 1 (median of 10 [IQR = 11]) and ≥ 1 (7 [IQR = 9], W = 7457608, p < 0.001). Conclusion: In this large sample of Brazilian adolescents, those who exercised less frequently and vigorously than their peers reported more depressive symptoms.

Sleep disturbances, circadian activity, and nocturnal light exposure characterize high risk for and current depression in adolescence.

STUDY OBJECTIVES: Major depressive disorder (MDD) in adolescence is associated with irregularities in circadian rhythms and sleep. The characterization of such impairment may be critical to design effective interventions to prevent development of depression among adolescents. This study aimed to examine self-reported and actimetry-based circadian rhythms and sleep-wake behavior associated with current MDD and high risk (HR) for MDD among adolescents. METHODS: Ninety-six adolescents who took part in the IDEA-RiSCo study were recruited using an empirically developed depression-risk stratification method: 26 classified as low risk (LR), 31 as HR, and 39 as a current depressive episode (MDD). We collected self-report data on insomnia, chronotype, sleep schedule, sleep hygiene as well as objective data on sleep, rest-activity, and light exposure rhythms using actimetry for 10 days. RESULTS: Adolescents with MDD exhibited more severe insomnia, shorter sleep duration, higher social jetlag (SJL), lower relative amplitude (RA) of activity, and higher exposure to artificial light at night (ALAN) compared with the other groups. They also presented poorer sleep hygiene compared with the LR group. The HR group also showed higher insomnia, lower RA, higher exposure to ALAN, and higher SJL compared with the LR group. CONCLUSIONS: HR adolescents shared sleep and rhythm alterations with the MDD group, which may constitute early signs of depression, suggesting that preventive strategies targeting sleep should be examined in future studies. Furthermore, we highlight that actimetry-based parameters of motor activity (particularly RA) and light exposure are promising constructs to be explored as tools for assessment of depression in adolescence.

Youth depression and inflammation: Cross-sectional network analyses of C-Reactive protein, interleukin-6 and symptoms in a population-based sample.

BACKGROUND: Inflammation-related proteins constitute a promising avenue in studying biological correlates of major depressive disorder (MDD). However, MDD is a heterogeneous condition - a crucial aspect to be considered in association studies. We examined whether inflammatory proteins are associated with categorical diagnosis, a dimensional total sum-score, and specific depressive symptoms among youths. METHODS: We analyzed data from the 1993 Pelotas Birth Cohort, a population-based study in Brazil that followed individuals up to age 22 years. Categorical psychiatric diagnoses were derived using adapted modules of the Mini International Neuropsychiatric Interview (MINI). Dimensional symptomatology was assessed using the Brazilian Portuguese version of the Center for Epidemiological Studies-Depression Scale-Revised (CESD-R). We estimated network structures that included individual depressive symptoms as measured by CESD-R items, peripheral inflammatory markers (C-Reactive Protein [CRP] and Interleukin-6 [IL-6]), as well as relevant covariates. RESULTS: We evaluated 2586 participants (mean age = 22.5[SD = 0.33]) There were no associations between concentrations of inflammatory proteins and categorical diagnosis of MDD or with CESD-R total sum-scores. In symptom-specific analysis, CRP and IL-6 were positively connected to somatic and cognitive items. DISCUSSION: We found cross-sectional connections of two commonly studied inflammatory proteins and specific depressive symptoms. Conducting symptom-specific analyses in relation to biological markers might advance our understanding of the heterogeneity of MDD.

Physical activity and depressive symptoms among adolescents in a school-based sample.

OBJECTIVE: To explore associations between self-reported weekly physical activity and depressive symptomatology among adolescents in a school-based sample from Brazil. METHODS: We surveyed 7,405 adolescents aged 14 to 16 years in 101 public schools in Porto Alegre, Brazil. We assessed physical activity using an adapted version of the Patient-Centered Assessment and Counseling for Exercise Plus Nutrition - Adolescent Physical Activity Measure (PACE+), and depressive symptoms using the Brazilian Portuguese version of the Patient Health Questionnaire - Adolescent Version. We compared the depressive symptom scores among adolescents with varying levels of physical activity. RESULTS: Of the overall sample, 84.4% exercised less than the recommended frequency of 60 minutes/day, at least 5 days/week, of moderate to intense physical activity (PACE+ score ≥ 5). Adolescents whose physical activity levels fell below that threshold had higher median depression scores (8 [IQR = 10] vs. 7 [IQR = 9], W = 4060461, p < 0.001). A similar pattern was observed for depression scores in those with PACE+ < 1 (median of 10 [IQR = 11]) and ≥ 1 (7 [IQR = 9], W = 7457608, p < 0.001). CONCLUSION: In this large sample of Brazilian adolescents, those who exercised less frequently and vigorously than their peers reported more depressive symptoms.

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.

Depression in a youth population-based sample from Brazil: Prevalence and symptom structure.

BACKGROUND: We aimed to examine the occurrence of major depressive disorder (MDD) in a population-based youth sample, assessing both categorical and dimensional presentations of the disorder and its clinical and sociodemographic correlates. METHODS: We analyzed cross-sectional data from the latest assessment of the 1993 Pelotas Birth Cohort (n = 3,780), a population-based study from Brazil that followed individuals up to age 22 years. We estimated point-prevalence for categorical diagnosis of MDD and comorbid diagnoses using DSM criteria in a structured interview by trained psychologists. Dimensional symptomatology was assessed with the Brazilian Portuguese version of the Center for Epidemiological Studies-Depression Scale-Revised (CES-D-R). RESULTS: Point-prevalence of a current unipolar major depressive episode was 2.85% (95%CI 2.37-3.43%). The CES-D-R showed a mean of 9.20 (SD=9.72), with an area under the curve of 0.93 (95%CI 0.91 to 0.95) for the categorical diagnosis of MDD using a cutoff point of 16. Sad mood and somatic symptoms were the most frequent, and also had lower levels of latent values required for endorsement. Sad mood and anhedonia items were the most central items in the network structure. CONCLUSIONS: In a population-based sample of youths from a middle-income country, MDD prevalence estimates and comorbidity profile were consistent with previous global literature. A focus on symptoms might advance our understanding about MDD among youths by disentangling the heterogeneity of the disorder.

The research output on child and adolescent suicide in Brazil: a systematic review of the literature

Objective: Suicide is the third leading cause of death among Brazilians aged 10 to 24 years. We aimed to review and describe the research output on suicide in children and adolescents in Brazil and to identify strengths and gaps in this literature. Methods: PubMed/MEDLINE was searched for studies on suicide of children and adolescents (aged 0-19 years) in Brazil, published from inception to December 31, 2017. Results: Our search identified 1,061 records, of which 146 were included. A large proportion (134 studies; 90.4%) were original articles classified as observational epidemiological studies. Fifty-two articles (35.6%) used primary data. Of those, 18 (12.3%) evaluated prevalence of suicidal behaviors in population-based samples. Seventy studies (47.9%) addressed death by suicide, and the remainder reported other phenomena, such as ideation, planning, or suicide attempt. Only 37 publications (25.3%) studied children and/or adolescents exclusively. Most of the studies (53.5%) were conducted with samples from the South and Southeast regions of Brazil. Conclusion: Our findings indicate that the body of evidence on suicide among children and adolescents in Brazil is limited. The scientific output is of low quality, and there is a complete lack of interventional studies specifically designed for the youth population.

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.

The research output on child and adolescent suicide in Brazil: a systematic review of the literature.

OBJECTIVE: Suicide is the third leading cause of death among Brazilians aged 10 to 24 years. We aimed to review and describe the research output on suicide in children and adolescents in Brazil and to identify strengths and gaps in this literature. METHODS: PubMed/MEDLINE was searched for studies on suicide of children and adolescents (aged 0-19 years) in Brazil, published from inception to December 31, 2017. RESULTS: Our search identified 1,061 records, of which 146 were included. A large proportion (134 studies; 90.4%) were original articles classified as observational epidemiological studies. Fifty-two articles (35.6%) used primary data. Of those, 18 (12.3%) evaluated prevalence of suicidal behaviors in population-based samples. Seventy studies (47.9%) addressed death by suicide, and the remainder reported other phenomena, such as ideation, planning, or suicide attempt. Only 37 publications (25.3%) studied children and/or adolescents exclusively. Most of the studies (53.5%) were conducted with samples from the South and Southeast regions of Brazil. CONCLUSION: Our findings indicate that the body of evidence on suicide among children and adolescents in Brazil is limited. The scientific output is of low quality, and there is a complete lack of interventional studies specifically designed for the youth population.

What doesn't kill you makes you stronger and weaker: how childhood trauma relates to temperament traits.

Childhood trauma arises from damaging experiences and the absence of a secure and reliable environment for child development. Despite many studies on the risk for developing psychiatric disorders, much less is known on the relationship between traumatic experiences and personality traits. A total of 10,800 participants (mean age 27.7 ± 7.8 years old, 69.8% women) anonymously answered the Childhood Trauma Questionnaire (CTQ) and the Affective and Emotional Composite Temperament Scale (AFECTS) in the Brazilian Internet Study on Temperament and Psychopathology (BRAINSTEP). The results showed that total trauma score was associated with lower levels of positive traits (volition, control, coping, and stability), higher scores of negative traits (sensitivity, anger, anxiety) and a higher frequency of depressive and cyclothymic temperaments. Linear regression analysis showed similar findings for emotional abuse and neglect, whereas physical abuse and neglect were positively associated with more volition and coping as well as less fear, sensitivity and anxiety traits, especially in men. This study has a cross-sectional design and the sole use of self-reporting as the main limitations. In conclusion, dysfunctional temperament profiles were associated mainly with emotional trauma and sexual abuse. Some adaptive traits were associated with physical abuse and neglect, especially in men. These results reinforce the negative impact of emotional trauma and people's resilience to physical trauma, which may even translate into adaptive trait expression in males particularly. We propose that the "context-dependent nature" of stress should be further studied to break down the influence of specific types and contexts of adversity on psychological and psychiatric outcomes.