Major Depressive Disorder In Children Research Articles

Dysregulations of amino acid metabolism and lipid metabolism in urine of children and adolescents with major depressive disorder: a case-control study.

The mechanisms underlying major depressive disorder (MDD) in children and adolescents are unclear. Metabolomics has been utilized to capture metabolic signatures of various psychiatric disorders; however, urinary metabolic profile of MDD in children and adolescents has not been studied. We analyzed urinary metabolites in children and adolescents with MDD to identify potential biomarkers and metabolic signatures. Here, liquid chromatography-mass spectrometry was used to profile metabolites in urine samples from 192 subjects, comprising 80 individuals with antidepressant-naïve MDD (AN-MDD), 37 with antidepressant-treated MDD (AT-MDD) and 75 healthy controls (HC). We performed orthogonal partial least squares discriminant analysis to identify differential metabolites and employed logistic regression and receiver operating characteristic analysis to establish a diagnostic panel. In total, 143 and 71 differential metabolites were identified in AN-MDD and AT-MDD, respectively. These were primarily linked to lipid metabolism, molecular transport, and small molecule biochemistry. AN-MDD additionally exhibited dysregulated amino acid metabolism. Compared to HC, a diagnostic panel of seven metabolites displayed area under the receiver operating characteristic curves of 0.792 for AN-MDD, 0.828 for AT-MDD, and 0.799 for all MDD. Furthermore, the urinary metabolic profiles of children and adolescents with MDD significantly differed from those of adult MDD. Our research suggests dysregulated amino acid metabolism and lipid metabolism in the urine of children and adolescents with MDD, similar to results in plasma metabolomics studies. This contributes to the comprehension of mechanisms underlying children and adolescents with MDD.

A narrative review and discussion of concepts and ongoing data regarding quantitative EEG as a childhood mood disorder biomarker

As the need for prompt identification and management of childhood mood. disorders continues to grow, increasing interest has shifted towards potential objective. biomarkers. One modality that has shown promise as a biomarker has been quantitative electroencephalography or qEEG. In this review, we expand on our previous investigation into qEEG biomarker research for child mood disorders and potential challenges faced in ongoing development. Ongoing research into qEEG: Since our last systematic review, qEEG biomarker research of childhood major depressive disorder remained sparse, with only one novel awake qEEG investigation in children despite ongoing adult depression qEEG research. For bipolar disorder, previously identified qEEG researchers have continued investigation into Bipolar II diagnosis identification, Bipolar I versus II diagnostic discrimination, and general bipolar biomarker utilization. Challenges faced by qEEG: While the nature of qEEG as a data-driven, easily performed, and easily analyzable biomarker is promising, challenges to clinical utilization remain, including direct anatomical correlation and generation of patientfacing clinically tested and usable tools. However, preliminary general utilization of qEEG in clinical settings with childhood mood disorder has shown excellent efficacy, and ongoing research to address these limitations is feasible and ongoing. Conclusions: While qEEG biomarker research in child mood disorders has remained slow, there is a clear need and strong ongoing potential for future investigations.

Multidimensional voiceprint feature assessment system for identifying the depression in children and adolescents: a diagnostic test.

We designed a diagnostic test to evaluate the effectiveness and accuracy of a multidimensional voiceprint feature diagnostic assessment (MVFDA) system vs. the 24-item Hamilton Rating Scale for Depression (HAMD-24) for adjunctive diagnosis of children and adolescents with major depressive disorder (MDD). This study included 55 children aged 6-16 years who were clinically diagnosed with MDD according to the DSM-5 and analyzed by professional physicians, and 55 healthy children (typically developing). Each subject completed a voice recording and was scored on the HAMD-24 scale by a trained rater. We calculated the validity indices, including sensitivity, specificity, Youden's index, likelihood ratio, and other indices including predictive value, diagnostic odds ratio, diagnostic accuracy, and area under the curve (AUC), to assess the effectiveness of the MVFDA system in addition to the HAMD-24. The sensitivity (92.73 vs. 76.36%) and the specificity (90.91 vs. 85.45%) of the MVFDA system are significantly higher than those of the HAMD-24. The AUC of the MVFDA system is also higher than that of the HAMD-24. There is a statistically significant difference between the groups (p < 0.05), and both of them have high diagnostic accuracy. In addition, the diagnostic efficacy of the MVFDA system is higher than that of HAMD-24 in terms of the Youden index, diagnostic accuracy, likelihood ratio, diagnostic odds ratio, and predictive value. The MVFDA has performed well in clinical diagnostic trials for the identification of MDD in children and adolescents by capturing objective sound features. Compared with the scale assessment method, the MVFDA system could be further promoted in clinical practice due to its advantages of simple operation, objective rating, and high diagnostic efficiency.

Identification of Sex-Specific Plasma Biomarkers Using Metabolomics for Major Depressive Disorder in Children and Adolescents.

BackgroundChildren and adolescents are at a high risk of major depressive disorder (MDD) with known sex differences in epidemiology. However, there are currently no objective laboratory-based sex-specific biomarkers available to support the diagnoses of male and female patients with MDD.MethodsHere, a male set of 42 cases and 27 healthy controls (HCs) and a female set of 42 cases and 22 HCs were recruited. This study investigated the sex differences of plasma metabolite biomarkers in young patients with MDD by the application of ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry.ResultsThe metabolic profiles showed clear separations in both male and female sets. In total, this study identified 57 male-related and 53 female-related differential metabolites. Compared with HCs, both male and female subjects with MDD displayed four significantly altered pathways. Notably, biliverdin was selected as an independent diagnostic male-specific biomarker with an area under the receiver operating characteristic curve of 0.966, and phosphatidylcholine (10:0/14:1) was selected as a female-specific biomarker, achieving an area under the curve (AUC) of 0.957.ConclusionThis metabolomics study may aid in the development of a plasma-based test for the diagnosis of male and female children and adolescents with MDD, as well as give new insight into the pathophysiology of sex differences in children and adolescents with MDD.

Childhood depression and oxidative stress

BackgroundOxidative stress is a contributing factor in the etiopathogenesis of major depressive disorder (MDD). Pediatric studies regarding MDD-oxidative stress relationship are insufficient. In this study, we aimed to compare oxidative stress parameters of pediatric MDD patients with those of the control group and to examine factors affecting these parameters.ResultsTotal oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), malondialdehyde (MDA) and superoxide dismutase (SOD) activities of 42 patients with MDD and 38 healthy controls were evaluated. Children depression inventory (CDI) was applied to all participants. In the MDD group, serum levels of TOS, OSI and MDA were higher, while TAS and SOD levels were lower (p < 0.001). When all participants were examined, oxidative stress increased as the CDI score increased, but in the MDD group, SOD increased as the CDI score increased. Increase in body mass index (BMI) percentile increased the oxidative stress in the MDD group. When factors affecting the presence of MDD were analyzed by binary logistic regression analysis, a one-unit increase in SOD decreased depression by 0.190 times.ConclusionsThis study showed that oxidative stress increases in children and adolescents with MDD, and the increase in the severity of depression further increases oxidative stress, but when the depression becomes very severe, level of SOD increases compensatorily. It has been observed that high BMI in MDD patients creates an additional burden on oxidative stress. The role of oxidative stress in the etiopathogenesis of MDD in children and adolescents should be evaluated more comprehensively.

Polygenic scores for schizophrenia and major depression are associated with psychosocial risk factors in children: evidence of gene-environment correlation.

Whilst genetic and environmental risk factors for schizophrenia (SCZ) and major depressive disorder (MDD) have been established, it is unclear whether exposure to environmental risk factors is genetically confounded by passive, evocative or active gene-environment correlation (rGE). This study aims to investigate: (a) whether the genetic risk for SCZ/MDD in children is correlated with established environmental and psychosocial risk factors in two British community samples, the 1958 National Child Development Study (NCDS) and the Millennium Cohort Study (MCS), (b) whether these associations vary between both psychopathologies, and (c) whether findings differ across the two cohorts which were born 42 years apart. Polygenic risk scores (PRS) from existing large genome-wide associations studies (GWAS) were applied to test the correlation between the child genetic risk for SCZ/MDD and known environmental risk factors. In addition, parental and child genetic data from MCS were used to distinguish between passive and evocative rGE. The child polygenic risk for SCZ and MDD was correlated with single parenthood in MCS. Moreover, the lack of father's involvement in child care was associated with the genetic risk for SCZ in NCDS. However, we also found associations between several indicators of low socioeconomic status and heightened genetic risk for MDD in children in both cohorts. Further, the genetic risk for MDD was associated with parental lack of interest in the child's education in NCDS as well as more maternal smoking and less maternal alcohol consumption during childhood in MCS. According to sensitivity analyses in MCS (controlling for parental genotype), more than half of our significant correlations reflected passive rGE. Findings suggest that several established environmental and psychosocial risk factors for SCZ and MDD are at least partially associated with children's genetic risk for these psychiatric disorders.

Item Response Analyses of the Children's Depression Rating Scale-Revised Using Data from Clinical Studies.

Objective: We aimed to identify which of the 17 items comprising the Children's Depression Rating Scale-Revised (CDRS-R) can sensitively capture changes in depression severity. Methods: We used data from four studies involving two antidepressants. For each of the 17 CDRS-R items, we conducted item response analyses to identify and evaluate those that reflect changes in depression severity. We created plots of the item characteristic curves (ICCs) estimated by the graded response model, and option characteristic curves and ICCs using nonparametric item response theory. The change from baseline in the CDRS-R subscale score with specified reflective items by item response analyses and the effect size between the treatment group and placebo group were calculated and compared with those of the CDRS-R total score. Results: CDRS-R items #2 (difficulty having fun), #3 (social withdrawal), #10 (low self-esteem), #11 (depressed feelings), and #15 (depressed facial expression) have favorable profiles that reflect disease severity. Changes from baseline in the CDRS-R total score (least square mean ± standard error) at week 8 were -22.3 ± 0.7 and -23.9 ± 0.7 in the placebo group and treatment group, respectively (difference, -1.5; estimated effect size, -0.113), changes from baseline in the CDRS-R5 (CDRS-R subscale consisting of the specified reflective items [#2, #3, #10, #11, and #15]) score at week 8 were -8.4 ± 0.3 and -9.6 ± 0.3 in each group, respectively (difference, -1.2; effect size, -0.202). Conclusions: The item response analyses clarified the properties of 17 items of the CDRS-R for major depressive disorder in children and adolescents. The CDRS-R5 might optimize the assessment of changes in overall depression severity and differentiation of treatment responses.

Evaluation of a Group of Scales That Can Be Used for the Diagnosis of Major Depressive Disorder in Children and Adolescents Using the Bayesian Method

Evaluation of a Group of Scales That Can Be Used for the Diagnosis of Major Depressive Disorder in Children and Adolescents Using the Bayesian Method

Neural Indicators of Anhedonia: Predictors and Mechanisms of Treatment Change in a Randomized Clinical Trial in Early Childhood Depression

BackgroundEarly childhood depression is associated with anhedonia and reduced event-related potential (ERP) responses to rewarding or pleasant stimuli. Whether these neural measures are indicators of target engagement or treatment outcome is not yet known. MethodsWe measured ERP responses to win and loss feedback in a guessing task and to pleasant versus neutral pictures in young (4.0–6.9 years of age) depressed children before and after randomization to either 18 weeks of Parent-Child Interaction Therapy–Emotion Development (PCIT-ED) or waitlist. ResultsAnalyses included reward positivity (RewP) data from 118 children randomly assigned to PCIT-ED (n = 60) or waitlist (n = 58) at baseline and late positive potential (LPP) data from 99 children (44 assigned to PCIT-ED vs. 55 assigned to waitlist) at baseline. Children undergoing PCIT-ED showed a greater reduction in anhedonia (F1,103 = 10.32, p = .002, partial η2 = .09). RewP reward responses increased more (F1,86 = 5.98, p = .02, partial η2 = .07) for PCIT-ED, but a greater change in RewP was not significantly associated with a greater reduction in major depressive disorder symptoms (r = −.12, p > .4). Baseline RewP did not predict treatment change. LPPs to positive pictures did not change across treatment, but greater baseline LPPs to positive pictures predicted a higher likelihood of remission from major depressive disorder in children undergoing PCIT-ED (B = 0.14; SE = 0.07; odds ratio = 1.15; p = .03). ConclusionsThe ERP reward response improved in young children with depression during a treatment designed to enhance emotion development, providing evidence of target engagement of the neural systems associated with reward. Further, greater baseline LPP responses to positive pictures was associated with a greater likelihood of depression remission, suggesting that this ERP measure can predict which children are most likely to respond to treatment.

Fluoxetine in the Management of Major Depressive Disorder in Children and Adolescents: A Meta-Analysis of Randomized Controlled Trials.

Fluoxetine is a serotonin-specific reuptake inhibitor antidepressant and is the only approved pharmacological treatment for major depressive disorder (MDD) in children and adolescent. We searched the published randomized controlled-trials to review fluoxetine efficacy and tolerability using the databases PubMed, EudraCT, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for fluoxetine role in managing MDD in children and adolescents. A meta-analysis was conducted using the identified 7 clinical trials to assess efficacy using the outcomes: Children's Depression Rating Scale-Revised (CDRS-R), Clinical Global Impressions-Severity of Illness (CGI-S) and Clinical Global Impressions-Improvement (CGI-I) response rate. The risk of discontinuation due to adverse effects and common side effects were examined. The mean difference in change from baseline for CDRS-R was -2.72 (95% confidence interval [CI], -3.96, -1.48) favoring fluoxetine treatment (P < .001). Similarly, mean difference for CGI-S was -0.21 (95% CI, -0.36, -0.06). The risk ratio (RR) of discontinuing due to adverse events was 0.98 (95% CI, 0.54, 1.83), with RR for headache side effects 1.34 (95% CI, 1.03, 1.74) and rash 2.6 (95% CI, 1.32, 5.14). Fluoxetine demonstrates significant improvements in symptom intensity control in young patients suffering from MDD and is considered well tolerated with similar rates of trials discontinuation; however, fluoxetine was associated with a higher risk of headache and rash side effects. These findings will guide psychiatrists and pharmacists in their clinical role for supporting the care of young mental health patients.

A narrative review of major depressive disorder in children and adolescents

Major depressive disorder is a substantial health problem that affects people of all ages. Researchers have estimated that 2-6% of children and adolescents in the community suffer from depression. Major depressive disorder in children and adolescents is a chronic and relapsing condition, which does not remits spontaneously. A major proportion of depression in children and adolescents remains underdiagnosed and undertreated. Children with depression cannot just snap out of it on their own. If left untreated, depression in children and adolescents canin lead to school failure, conduct disorder, anorexia and bulimia, school phobia, panic attacks, substance abuse, or even suicide. Depression in adolescents substantially heightens the risk of suicide. Hence, there is a need to identify and treat the same at the earliest to reduce its long-term negative consequences.

Assessment of Transcultural Psychotherapy in Child Major Depressive Disorder

Assessment of Transcultural Psychotherapy in Child Major Depressive Disorder

The Impact of Placebo Response Rates on Clinical Trial Outcome: A Systematic Review and Meta-Analysis of Antidepressants in Children and Adolescents with Major Depressive Disorder.

Objective: The high placebo response rate may hamper the discovery of antidepressants in children and adolescents with major depressive disorder (MDD). The aim of the study was to clarify the relationship between the placebo response rate and clinical trial outcomes of the use of antidepressants in children and adolescents, and distinguish main factors responsible to placebo response rate. Methods: The PubMed and Cochrane Library databases were searched for double-blind randomized placebo-controlled trials of the new-generation antidepressants for the acute treatment of MDD in children and adolescents. The response rate differences (RDs) between placebo group and treatment group under different level of placebo response rate were pooled by random-effects meta-analysis. The classification thresholds for low, medium, and high placebo response rate were set at <40%, 40%-50%, and ≥50%, respectively. Predictors of placebo response rate were explored using meta-regression. Results: The analysis included 18 trials with 4365 participants. This study found that the lower the placebo response rate, the greater the efficacy differences between antidepressants and placebo. In the high, moderate, and low placebo response rate subgroups, the response RDs (95% CI) between antidepressants and placebo were 8 (1-14)%, 10 (2-17)%, and 21 (9-32)%, respectively. The meta-regression showed that the number of study sites was the factor most associated with placebo response rate, and that response rate increased 3% with every additional 10 study sites. Conclusions: The clinical outcome was related to the placebo response rates in the clinical trials of antidepressants in children and adolescents with MDD. The efficacy differences between antidepressants and placebo will be maximized when placebo response rates are reduced. The number of study sites was the factor most associated with the placebo response rates.

Prevalence and factors associated with major depressive disorder in children and adolescents at the Uganda Cancer Institute

BackgroundThe prevalence and factors associated with major depressive disorder (MDD) among adults with cancer have been documented in the scientific literature. However, this data is limited among children and adolescents with cancer; especially in low resource settings such as Uganda. We assessed the prevalence and factors associated with MDD in children and adolescents attending the Uganda cancer institute out-patient clinic.MethodsThis was a cross-sectional study in which three hundred and fifty-two children and adolescents with any cancer diagnosis were screened for depression using the Child Depression Inventory (CDI) and evaluated with the mini neuropsychiatric interview for children and adolescents (MINI-KID). Associated factors were assessed using a standardized questionnaire that assessed child and caregiver demographic and psychosocial characteristics. Multiple logistic regression models were used to assess factors independently associated with MDD.ResultsOf the 352 children and adolescents recruited in the study 134(38%) scored above a cut-off point of 13 on the CDI indicating significant depression symptoms. However, 91(26%) met criteria for MDD. The majority of those with MDD (n = 59 64.8%) had CDI scores of 13–19 indicating mild depression, 30(33%) had scores of 20–25 indicating moderate depression and 2(2.2%) had scores of 25 and above indicating severe depression. Protective factors against MDD were having a special person in the respondent’s life (p = 0.002) and using self-distraction as a coping method (p = < 0.001). Risk factors were being an adolescent(p = < 0.001).ConclusionThe prevalence of MDD is substantial in children and adolescents with cancer in Uganda. Given that the majority had a mild-moderate depression, there is an urgent need to integrate psychotherapy-the first-line treatment for depression into the routine care of children and adolescents with cancer.

Effectiveness of Providing Cognitive-behavioral Group Therapy for Both Children and their Parents Separately in the Treatment of Childhood Major Depressive Disorder: A Pilot Study

Background: Three social learning mechanisms were hypothesized to influence the development of depressogenic cognitive styles: modeling of parents’ negative cognitive styles; direct learning from negative parental inferential feedback regarding the stressful events in the child’s life; and indirect learning from negative parenting practices. In this study, I proposed an approach addressing psychopathology in parents as well as their children through providing cognitive behavioral therapy for both, separately, in treatment of childhood Major depressive disorder. This study’s objective is to evaluate the effectiveness of this approach. Method: Cognitive behavioral group therapy was provided separately to seven children diagnosed with Major depressive disorder, and their parents in 12 weekly 1-hour sessions. Parents’ sessions were parallel to children sessions, focused on learning the same skills and techniques taught in the children’s groups, targeting modifying negative cognitive styles of parents as well as children. Psychiatric clinical interview by specialized child psychiatrists and Parent-rated Mood and Feelings Questionnaire (PMFQ) were used pre- and post-treatment to evaluate depressive symptoms. Results: At the end of the treatment, all children no longer met criteria for major depressive disorder. There were statistically significant reductions in scores of parent-rated Mood and Feelings Questionnaire, which also demonstrated that none of the children no longer had a score indicative of depressive disorder. Conclusion: This study suggested that providing cognitive behavioral group therapy for both children and their parents, separately, is an effective approach for childhood major depressive disorder treatment.

Major depressive disorder in children and adolescents.

Major depressive disorder (MDD) is one of the most common psychiatric disorders of childhood and adolescence, but because of symptom variation from the adult criteria, it is often unrecognized and untreated. Symptom severity predicts the initial mode of treatment ranging from psychotherapy to medications to combination treatment. Several studies have assessed the efficacy of treatment in children and adolescents, and others have evaluated the risk of developing adverse effects and/or new or worsening suicidal thoughts and behaviors. Optimal treatment often includes a combination of therapy and antidepressant medication. The most studied combination includes fluoxetine with cognitive behavioral therapy. Once symptom remission is obtained, treatment should be continued for 6 to 12 months before a slow taper is initiated. Although most children and adolescents recover from their first depressive episode, a large number will continue to present with MDD in adulthood. Untreated depression in children and adolescents may increase the risk of substance abuse; poor work, academic, and social functioning; and risk of suicidal behaviors.

Prevalence of major depressive disorder in children and adolescents in China: A systematic review and meta-analysis

BackgroundPrevalence figures of major depressive disorder (MDD) in children and adolescents across various epidemiological studies have been inconclusive. This is a systematic review and meta-analysis of the pooled prevalence of MDD and its associated factors in children and adolescents in China. MethodA systematic review and literature search were conducted covering PubMed, PsycINFO, EMBASE and Chinese databases (China National Knowledge Internet, WANFANG Data and SinoMed) to identify studies reporting the prevalence of MDD in children and adolescents in China. The pooled prevalence estimates and associated factors were examined using the Comprehensive Meta-Analysis program, Version 2. ResultsFourteen studies involving 82,592 subjects were included in this meta-analysis. The pooled point prevalence of MDD in Chinese children and adolescents was 1.3% (95% CI: 0.8%–2.0%). Subgroup and meta-regression analyses revealed that diagnostic criteria, age, year of survey and study quality were significantly associated with the prevalence of MDD. ConclusionsThe point prevalence of MDD in children and adolescents in China is similar to worldwide figures. Further national epidemiological studies with the view of developing effective intervention strategies should be considered.

Subsyndromal Manifestations of Depression in Children Predict the Development of Major Depression

To evaluate the utility of assessing subsyndromal symptoms of major depressive disorder in childhood, indexed through the Child Behavior Checklist (CBCL) anxiety/depression scale, in predicting risk of developing major depressive disorder in adolescent and young adult years. The sample consisted of 537 children, 6-17 years of age, originally ascertained for a longitudinal family genetic study of youth with and without attention-deficit hyperactivity disorder and their first-degree relatives who were followed prospectively and blindly for 10 years from childhood into young adult years. Children with full diagnosis major depressive disorder at baseline were excluded. For analysis, the sample was stratified into 4 groups based on the presence or absence of parental mood disorders and by the presence or absence of subsyndromal scores on the CBCL anxiety/depression scale at baseline assessment in childhood. Children of parents with mood disorders plus subsyndromal scores on the CBCL anxiety/depression scale at baseline (n = 22) had the highest risk for developing major depressive disorder and anxiety disorders at the 10-year follow-up when compared with the other groups. Children with either subsyndromal scores on the CBCL anxiety/depression scale at baseline alone (n = 22) or parental mood disorders alone (n = 172) had intermediate outcomes. The CBCL anxiety/depression scale was useful in identifying children at high risk for the development of major depressive disorder and anxiety disorders at the 10-year prospective follow-up. Furthermore, our results emphasized the importance of familial psychiatric history in youth with subthreshold symptoms of depression. Parental mood disorder and subthreshold anxiety/depressive symptoms were predictive of developing depression.

Polyunsaturated fatty acids metabolism, purine metabolism and inosine as potential independent diagnostic biomarkers for major depressive disorder in children and adolescents

Major depressive disorder (MDD) in children and adolescents is a recurrent and disabling condition globally but its pathophysiology remains poorly elucidated and there are limited effective treatments available. We performed metabolic profiling of plasma samples based on ultra-high-performance liquid chromatography equipped with quadrupole time-offlight mass spectrometry to explore the potential biomarkers of depression in children and adolescents with MDD. We identified several perturbed pathways, including fatty acid metabolism—particularly the polyunsaturated fatty acids metabolism, and purine metabolism—that were associated with MDD in these young patients. In addition, inosine was shown as a potential independent diagnostic biomarker for MDD, achieving an area under the ROC curve of 0.999 in discriminating drug-naive MDD patients and 0.866 in discriminating drug-treated MDD from healthy controls. Moreover, we found evidence for differences in the pathophysiology of MDD in children and adolescents to that of adult MDD, specifically with tryptophan metabolism. Through metabolomic analysis, we have identified links between a framework of metabolic perturbations and the pathophysiology and diagnostic biomarker of child and adolescent MDD.

Comparative efficacy and tolerability of new-generation antidepressants for major depressive disorder in children and adolescents: protocol of an individual patient data meta-analysis

IntroductionAlthough previous conventional meta-analyses and network meta-analyses have provided some important findings about pharmacological treatments for children and adolescents with depressive disorders in the past decades, several questions still remain...