Children's Depression Rating Research Articles

Effect of Esketamine on Depressive Symptoms in Adolescents with Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study.

Effect of Esketamine on Depressive Symptoms in Adolescents with Major Depressive Disorder at Imminent Suicide Risk: A Randomized Psychoactive-Controlled Study.

Feasibility and effectiveness of a group therapy combining physical activity, surf therapy and cognitive behavioral therapy to treat adolescents with depressive disorders: a pilot study.

The high prevalence of depression among adolescents underlines the need for further research into effective treatment options. Previous research has demonstrated the effectiveness of physical activity in reducing depressive symptoms. Recently, studies on surf therapy, as an innovative approach of physical activity, have shown promising results regarding the reduction of depressive symptoms in adults and the improvement of general mental health problems in adolescents. However, research in this area is still limited. The aim of the current study was to investigate the feasibility and effectiveness of a group therapy program that combines physical activity, including surf therapy, with cognitive behavioral therapy for treating depression among adolescents. Thirty-two outpatients (28 female, four male) aged 13-18 years with a mean age of 15.58 years (SD = 1.52) and a primary diagnosis of depression were included. They participated in a 3-month group therapy program in groups of eight adolescents. The dropout rate was calculated as an aspect of feasibility. To evaluate effectiveness, depressive symptoms were assessed using the "Children's Depression Rating Scale-Revised" (CDRS-R) as the primary outcome measure at pre-program, post-program, and at 3-month follow-up. In addition, questionnaires assessing depressive symptoms ["Beck Depression Inventory II" (BDI-II)], emotion regulation strategies ["Fragebogen zur Erhebung der Emotionsregulation bei Kindern und Jugendlichen" (FEEL-KJ)] and self-esteem ["Selbstwertinventar für Kinder und Jugendliche" [SEKJ)] were administered as secondary outcome measures. Results showed a low dropout rate of 9.38% (n = 3). Depressive symptoms, assessed by the CDRS-R, were significantly reduced over time, with a large effect size. Symptom reductions were maintained at the 3-month follow-up. Study results suggest that the group therapy program is feasible and can reduce depressive symptoms. Further research that includes control groups is needed. As a clinical implication, novel treatment forms which integrate elements of physical activity, should be considered as a treatment option for depressed adolescents.

Electronically Monitored Antidepressant Adherence in Adolescents with Anxiety Disorders: A Pilot Study.

Background: Antidepressant medication adherence patterns are inconsistent in adolescents with anxiety and related disorders, and the clinical and demographic features predicting adherence are poorly understood. Methods: In an ongoing single-site prospective trial involving adolescents (aged 12-17) with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition anxiety disorders treated with escitalopram, adherence was measured for 12 weeks using electronic monitoring caps. Adherence patterns were examined using qualitative and unsupervised clustering approaches, and predictors of adherence were evaluated using logistic regression, with demographic (age, sex, and race) and clinical variables (e.g., anxiety severity [Pediatric Anxiety Rating Scale], irritability [Affective Reactivity Index], depressive symptoms [Children's Depression Rating Scale]). Results: Among adolescents (N = 33) aged 14.5 ± 1.8 years (64% female), four adherence patterns were identified: persistent adherence, intermittent adherence, early adherence-late nonadherence, and nonadherence. In a logistic model of a 5-day moving average measure of adherence, social anxiety disorder (β = -0.68 ± 0.19, p = 0.002) and separation anxiety disorder (β = -0.61 ± 0.18, p < 0.001) were associated with lower adherence. In contrast, panic disorder, attention-deficit/hyperactivity disorder, generalized anxiety disorder, and depressive symptoms were not associated with adherence. Baseline anxiety severity was linked to lower adherence (β = -0.199 ± 0.05, p < 0.001). Older age also reduced adherence (β = -0.342 ± 0.05, p < 0.001), with each additional year of age increasing time spent nonadherent by 5% (p < 0.001). Being female (β = 0.451 ± 0.17, p = 0.011) and expecting treatment to be efficacious (β = 0.092 ± 0.04, p = 0.011) increased adherence, while greater irritability was associated with nonadherence (β = -0.075 ± 0.03, p = 0.006). Conclusions: Antidepressant adherence is variable, with distinct patterns, and those with social and separation anxiety disorders were less likely to be adherent. Factors such as older age, severe anxiety, and greater irritability predicted lower adherence, while being female and expecting treatment efficacy were associated with better adherence. Interventions that address specific symptoms or enhance treatment expectations may improve adherence.

The impact of published guidance on trends in the pharmacological management of depression in children and adolescents- a whole population e-cohort data linkage study in Wales, UK.

This study evaluated the impact of 2015/2016 prescribing guidance on antidepressant prescribing choices in children. A retrospective e-cohort study of whole population routine electronic healthcare records was conducted. Poisson regression was undertaken to explore trends over time for depression, antidepressant prescribing, indications and secondary care contacts. Time trend analysis was conducted to assess the impact of guidance. A total of 643 322 primary care patients in Wales UK, aged 6-17 years from 2010-2019 contributed 3 215 584 person-years of follow-up. Adjusted incidence of depression more than doubled (IRR for 2019 = 2.8 [2.5-3.2]) with similar trends seen for antidepressants. Fluoxetine was the most frequently prescribed first-line antidepressant. Citalopram comprised less than 5% of first prescriptions in younger children but 22.9% (95% CI 22.0-23.8; 95% CI 2533) in 16-17-year-olds. Approximately half of new antidepressant prescribing was associated with depression. Segmented regression analysis showed that prescriptions of 'all' antidepressants, Fluoxetine and Sertraline were increasing before the guidance. This upward trend flattened for both 'all' antidepressants and Fluoxetine and steepened for Sertraline. Citalopram prescribing was decreasing significantly pre guidance being issued with no significant change afterward. Targeted intervention is needed to address rising rates of depression in children. Practitioners are partially adhering to local and national guidance. The decision-making process behind prescribing choices is likely to be multi-factorial. Activities to support implementation of guidance should be adopted in relation to safety in prescribing of antidepressants in children including timely availability of talking therapies and specialist mental health services.

Agomelatine in pediatric patients with moderate to severe major depressive disorder: an open-label extension study.

Major depressive disorder (MDD) in young people is a common psychiatric disorder, but treatment options are limited. Agomelatine has demonstrated short-term efficacy and safety in pediatric patients. We report here the results of a 92-week open-label extension (OLE). The international, multicenter, double-blind, study randomized 400 patients (80 children, 320 adolescents) with moderate-to-severe MDD to one of four treatment groups: agomelatine 10mg (n = 102), agomelatine 25mg (n = 95), placebo (n = 103), and fluoxetine 10-20mg (n = 100). After 12weeks, patients who could benefit from treatment continuation were offered entry into an optional OLE during which they received agomelatine 10 or 25mg for a further 92weeks. A total of 339 patients (271 adolescents) entered the OLE. Treatment groups considered for the OLE analysis reflected those received in the double-blind and OLE periods: agomelatine (10 or 25mg) in both (ago/ago, n = 170); placebo then agomelatine 10-25mg (pcb/ago, n = 85); or fluoxetine then agomelatine 10-25mg (fluox/ago, n = 84). Mean age (± SD) at entry into the double-blind phase (Week 0) was 13.6 ± 2.7years and 61.9% were female. Mean changes in Children's Depression Rating Scale revised (CDRS-R) raw total score from Week 12 to last post-Week 12 value in the three groups were - 16.3 ± 12.2 (ago/ago), - 18.9 ± 16.1 (pcb/ago), and - 16.1 ± 15.5 (fluox/ago), reflecting the difference in efficacy between treatments during the double-blind period, and heterogeneity at W12 between the treatment groups. Adverse events considered related to treatment occurred in 14.5% of patients: 15.3% ago/ago, 16.5% pcb/ago, and 10.7% fluox/ago. Three patients (all adolescents) experienced treatment-related severe adverse events: two treated with ago/ago and one treated with pcb/ago. Among the adolescents, one treatment-related severe adverse event in a patient in the pcb/ago group led to study withdrawal. Agomelatine was associated with continuous improvement in depressive symptoms without unexpected safety signals. These findings support the safe use of agomelatine in a pediatric population with moderate-to-severe MDD for up to 104weeks.Trial registration No: EUDRACT No. 2015-002181-23.

Investigating thyroid function and iodine status in adolescents with and without paediatric major depressive disorder.

Depression has been associated with subclinical hypothyroidism and altered hypothalamic-pituitary-thyroid axis functioning. Adequate iodine nutrition is essential for healthy thyroid functioning. We therefore determined associations of iodine and thyroid status with paediatric major depressive disorder (pMDD) among Swiss adolescents and explored whether associations are sex-specific and mediated by stress. We conducted a matched case-control study in 95 adolescents with diagnosed pMDD and 95 healthy controls. We assessed depression severity using the Children's Depression Rating Scale-Revised and stress using the perceived stress scale (PSS) and measuring hair cortisol levels. We determined iodine status by measuring urinary iodine concentrations (UIC) and thyroid status by thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in serum. Median (IQR) UIC did not differ between cases (121 (87, 174) µg/l) and controls (114 (66, 183) μg/l, P = 0·3). Median TSH and FT4 were lower in cases than controls (TSH: 1·36 (0·91, 2·00) mlU/l v. 1·50 (1·18, 2·06) mlU/l, P = 0·039; FT4: 14·7 (12·9, 16·9) pmol/l v. 15·7 (14·3, 17·2) pmol/l, P = 0·004). The prevalence of hypothyroxinaemia (normal TSH; low FT4) was higher among female cases than controls (21 % v. 4%, P = 0·006). PSS scores were higher while hair cortisol was lower in cases than controls (PSS: 25 (20, 28) v. 11 (7, 15), P < 0·001; cortisol: 2·50 (1·34, 3·57) pg/mg v. 3·23 (1·79, 4·43) pg/mg, P = 0·044). After adjusting for confounders, the associations of TSH and hair cortisol with pMDD were no longer significant. Furthermore, TSH and FT4 were not associated with PSS scores and hair cortisol levels. Summarising, iodine nutrition was adequate for adolescents with and without pMDD. However, FT4 concentrations were lower in those with pMDD, and 1 in 5 female adolescents with pMDD were hypothyroxinaemic.

Depression severity and verbal comprehension in children and adolescents with a major depressive episode.

Severe depression is a prevalent psychiatric illness in children and adolescents associated with high levels of morbidity, disability, and a high risk of suicidal behavior. Cognitive factors associated with depression severity in juveniles have been poorly reported. We investigated the relationship between depression severity and intelligence quotient (IQ)with its subscales in 65 juveniles (aged 10-17 years) with a current major depressive episode evaluated at the Mood Disorder Program of Bambino Gesù Children's Hospital in Rome. Pearson's correlation analyses were followed by a Benjamini-Hochberg correction and linear multivariable regression model. Depression severity measured with the total score of the Children's Depression Rating Scale-Revised (CDRS-R) was positively associated with the Verbal Comprehension Index (VCI; Pearson's r = 0.309 [0.042-0.534]; p = 0.024). The CDRS-R subscales positively associated with VCI by Pearson's correlation were depressed feelings, suicidal ideation, excessive weeping, and reduced facial expressions. Suicidal ideation was the only factor independently and significantly associated with higher VCI in the multivariable linear regression model. Suicidal ideation was significantly and independently associated with higher verbal comprehension, indicating that depressed juveniles with better verbal ability may be at a greater risk of showing suicidal ideation.

A Dose-Finding, Biomarker Validation, and Effectiveness Study of Transcranial Magnetic Stimulation for Adolescents With Depression

Research and clinical application of transcranial magnetic stimulation (TMS) for adolescents with major depressive disorder (MDD) has advanced slowly. Significant gaps persist in our understanding of optimized, age-specific protocols and dosing strategies. This study aimed to compare the clinical effects of 1 Hz versus 10 Hz TMS regimens and examine a biomarker-informed treatment approach with glutamatergic intracortical facilitation (ICF). Participants with moderate-to-severe symptoms of MDD were randomized to 30 sessions of left prefrontal 1 Hz or 10 Hz TMS, stratified by baseline ICF measures. The primary clinical outcome measure was the Children's Depression Rating Scale, Revised (CDRS-R). The CDRS-R and ICF biomarker were collected weekly. Forty-one participants received either 1 Hz (n = 22) or 10 Hz (n = 19) TMS treatments. CDRS-R scores improved compared to baseline in both 1 Hz and 10 Hz groups. For participants with low ICF at baseline, the overall least squares means of CDRS-R scores over the 6-week trial showed that depressive symptom severity was lower for the group treated with 1 Hz TMS than for those who received 10 Hz TMS. There were no significant changes in weekly ICF measurements across the 6 weeks of TMS treatment. Low ICF may reflect optimal glutamatergic N-methyl-d-aspartate (NMDA) receptor activity that facilitates the therapeutic effect of 1 Hz TMS through long-term depression-like mechanisms on synaptic plasticity. The stability of ICF suggests that it is a tonic, trait-like measure of NMDA receptor-mediated neurotransmission, with potential utility to inform parameter selection for therapeutic TMS in adolescents with MDD.

Safety and Efficacy of Levomilnacipran Extended Release in Pediatric Patients Aged 7-17 Years with Major Depressive Disorder: Results of Two Phase 3, Randomized, Double-Blind Studies.

Objective: Major depressive disorder (MDD) presents a significant psychosocial burden, and there is an unmet need for additional treatment options in pediatric patients. Here, we report the results of two phase 3 multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group studies evaluating the efficacy and safety of levomilnacipran extended release in children and adolescents with MDD. Methods: In the first study, LVM-MD-11, patients aged 12-17 years received daily doses of levomilnacipran 40 mg (n = 134), levomilnacipran 80 mg (n = 138), fluoxetine 20 mg (n = 134), or placebo (n = 141). In the second study, LVM-MD-14, patients aged 7-17 years received levomilnacipran 40 to 80 mg (n = 166), fluoxetine 20 mg (n = 166), or placebo (n = 160) daily. Primary and secondary efficacy endpoints were changes in Children's Depression Rating Scale-Revised (CDRS-R) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively. Results: In LVM-MD-11, there were no significant differences in change in CDRS-R total score between patients treated daily with placebo (least squares mean [LSM] change in CDRS-R total score -22.9) versus levomilnacipran 40 mg (-23.3; p = 0.8035) or 80 mg (-22.6; p = 0.8681). Similarly, in LVM-MD-14, there were no significant differences in LSM change in CDRS-R total score with placebo (-21.3) versus levomilnacipran 40 to 80 mg daily (-23.0; p = 0.2215). There were also no significant differences between the fluoxetine and placebo groups in either study for changes in CDRS-R total score. Changes in CGI-S score were not significant between placebo and levomilnacipran 40 to 80 mg daily or between placebo and fluoxetine. Levomilnacipran was generally well tolerated. Conclusions: The high placebo response in this study prevented the detection of an effect of levomilnacipran in children and adolescents. Clinical Trial Registration numbers: NCT02431806 and NCT03569475.

Prevalence and Correlates of Eating Disorder Symptoms in Adolescents with Bipolar I Disorder.

Objective: To investigate the prevalence and correlates of eating disorder symptoms in adolescents with bipolar I disorder (BP I). Methods: We retrospectively collected a DSM-IV-TR-based diagnostic assessment of 179 adolescents with BP I and evaluated clinical variables in those with and without eating disorder symptoms. For comparison, we retrospectively evaluated eating disorder symptoms in adolescents with generalized anxiety disorder (GAD). Results: Thirty-six percent of adolescents with BP I experienced lifetime eating disorder symptoms; among comorbid adolescents, 74% reported eating disorder cognitions and 40% reported symptoms related to bingeing, 25% purging, and 17% restricting. BP I adolescents with (vs. without) eating disorder symptoms had higher Children's Depression Rating Scale-Revised scores (40.5 vs. 34.5; p < 0.001; effect size = 0.59) and were more likely to be female (75% vs. 45%; p < 0.001; odds ratio = 3.8). There were no differences in Young Mania Rating Scale scores (p = 0.70); lifetime presence of attention-deficit/hyperactivity disorder (p = 0.86) and alcohol (p = 0.59) or substance (p = 0.89) abuse/dependence symptoms; age of BP I onset (p = 0.14); inpatient hospitalization status at baseline (p = 0.53); presence of lifetime inpatient hospitalization (p = 0.64) or suicide attempt (p = 0.35); seriousness of suicidality (p = 0.86); body mass index (p = 0.48); and second-generation antipsychotic (SGA; p = 0.32) or non-SGA mood stabilizer (p = 0.09) use. Eating disorder cognitions (rather than behaviors) were higher in the GAD group (58%) compared with the BP I group (27%; p = 0.004). Limitations: A retrospective study is subject to recall bias and limits our understanding of the temporal relationship between eating disorder and mood symptoms. Conclusions: Eating disorder symptoms are frequently comorbid in adolescents with BP I. The comorbidity is associated with more severe depression but does not confer a more severe illness course.

Deep transcranial magnetic stimulation for adolescents with treatment-resistant depression: A preliminary dose-finding study exploring safety and clinical effectiveness

Deep transcranial magnetic stimulation for adolescents with treatment-resistant depression: A preliminary dose-finding study exploring safety and clinical effectiveness

Iron status in Swiss adolescents with paediatric major depressive disorder and healthy controls: a matched case–control study

PurposeDepression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status.MethodsThis is a matched case–control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13–17 years. We assessed depression severity using the Children’s Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire.ResultsSF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) μg/L) and controls (32.5 (22.6, 48.3) μg/L, p = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls (p = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls.ConclusionCases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain.

Personality traits predict treatment outcome of an antidepressant in untreated adolescents with depression: An 8-week, open-label, flexible-dose study

Personality traits predict treatment outcome of an antidepressant in untreated adolescents with depression: An 8-week, open-label, flexible-dose study

Abnormal Serum BDNF and p-mTOR in MDD in Adolescents with Childhood Trauma.

Adolescents with major depressive (MDD) episodes associated with childhood trauma have a poorer response to treatment and a higher risk of suicide. The underlying etiology is unclear. Brain-derived neurotrophic factor (BDNF) could improve depressive symptoms by down-regulating mammalian target of rapamycin (mTOR) signaling pathways, which was involved in adverse environmental stimuli during neurodevelopment. BDNF and mTOR have not been reported simultaneously in adolescents with major depressive episodes associated with childhood trauma. Childhood Trauma Questionnaire-Short Form (CTQ-SF), Children's Depression Inventory (CDI) and Children's Depression Rating Scale-Revised (CDRS-R) were used to evaluate the recruited adolescents with major depression episodes. Serum BDNF and p-mTOR levels were measured by ELISA in 31 adolescents with major depression episodes with childhood trauma and 18 matched healthy control. The serum levels of BDNF were significantly lower (p<0.001); and the serum levels of p-mTOR were high (p=0.003) in the adolescents with the first episode of major depressive episode accompanied by childhood trauma. Of the 31 adolescents with major depressive episodes, 17 had suicide or self-injury. Compared with the healthy control group, the serum levels of BDNF in patients with suicide or self-injury were lower than those without suicide or self-injury(p<0.001); the serum levels of p-mTOR were higher than those without suicide or self-injury (p=0.01). While in patients without suicide or self-injury, only serum p-mTOR was significantly higher than that in healthy group (p=0.028).BDNF was negatively correlated with CDRS-R (r=-0.427, p=0.006), p-mTOR was positively correlated with CDI (r=0.364, p=0.048). According to Receiver Operating Characteristic Curve (ROC), the combination of serum BDNF and p-mTOR levels have better diagnostic value. Neurotrophic and signaling pathways, involving BDNF and p-mTOR, may play a role in adolescent MDD with a history of childhood trauma, especially patients with suicide and self-injury tendencies.

Treatment guesses in the Treatment for Adolescents with Depression Study: Accuracy, unblinding and influence on outcomes.

We evaluated the presence and impact of unblinding during the influential Treatment for Adolescents with Depression Study (ClinicalTrials.gov Identifier: NCT00006286). Our analysis was part of a Restoring Invisible and Abandoned Trials reanalysis. Treatment for Adolescents with Depression Study trialled fluoxetine, placebo, cognitive behaviour therapy or their combination, in treating adolescents with major depressive disorder. We analysed the accuracy of guesses of fluoxetine or placebo allocation, and their effects on change in Children's Depression Rating Scale-Revised at 12 weeks. Of 221 participants allocated to fluoxetine or placebo, 151 adolescents (68%) had their guess about pill-treatment-arm allocation recorded at week 6, and guesses were recorded for 154 independent evaluators, 159 parents and 164 pharmacotherapists. All of these groups guessed treatment allocation more accurately than would be expected by chance (60-66% accuracy; all p-values ⩽ 0.004). Guesses did not become more accurate between 6 and 12 weeks and were not predicted by adverse events, though event documentation was poor. Treatment guess had a substantial and statistically significant effect on outcome (Children's Depression Rating Scale-Revised change mean difference 9.12 [4.69; 13.55], β = 0.334, p < 0.001), but actual treatment arm did not (1.53 [-2.83; 5.89], β = 0.056, p = 0.489). Removing guess from the analysis increased the apparent effect of treatment arm, making it almost statistically significant at the conventional alpha-level of 0.05 (p = 0.06). For Treatment for Adolescents with Depression Study, treatment guesses strongly predicted outcomes and may have led to the exaggeration of drug effectiveness in the absence of actual effects. The integrity of double-blinding in trials should be routinely assessed and reported.

Evidence for Altered Electroencephalography Coherence in Depressed Adolescents with Suicidal Ideation and Behaviors.

Introduction: Major depressive disorder (MDD) is a primary risk factor for suicide, which is one of the leading causes of death among adolescents worldwide. Understanding the heterogeneity of suicidality in adolescents with MDD is critical for suicide prevention and intervention discovery. Quantitative electroencephalography (EEG) is a promising tool to address the knowledge gaps related to the neurophysiological characteristics of depression and suicidality. This study sought to examine resting-state EEG coherence differences in adolescents with MDD and suicidal ideation (SI)/behaviors (SB) and healthy controls (HC) to assess the utility of coherence as a biomarker of suicide. Methods: Twenty-six adolescents with MDD who were hospitalized for suicidality and 30 HC were recruited. The clinical sample was divided into SI (n = 9) and SB (n = 19) subgroups. Eyes closed resting-state EEG were recorded, and coherence was calculated. Depression severity and suicidality were assessed with the Children's Depression Rating Scale Revised and the Columbia Suicide Severity Rating Scale, respectively. Results: There were intrahemispheric differences in the right hemisphere across multiple electrode pairs. Delta, alpha, and beta coherence were higher in the SB group over the right prefrontofrontal and left parietooccipital electrode pairs, while alpha coherence was higher in the HC group over the right centroparietal electrode pair. There were no significant differences between HC and SI groups in any electrode pair. Conclusions: Patients with recent SB showed increased coherence in right frontal regions compared with patients with SI, suggesting altered cognitive states between those with SB and SI. These findings may have implications for suicide prevention in adolescents and could serve as useful biomarkers in clinical settings, but larger studies are needed to confirm the results.

Clinical implication of children's depression rating scale-revised score: Linking the children's depression rating scale-revised score and clinical global impression using patients data from clinical trials.

The Children's Depression Rating Scale-Revised (CDRS-R) score has been widely used to assess the severity of major depression in children and adolescents; however, the clinical implications of changes in the CDRS-R score remain unclear. We evaluated these clinical implications by assessing the relationship between changes in the CDRS-R score and changes in the Clinical Global Impression of Improvement (CGI-I), in clinical research on major depression. We used data from four clinical trials involving two antidepressants and evaluated the relationship between CDRS-R score changes and the CGI-I score using the equipercentile linking method. CDRS-R score changes corresponding to a minimally improved (score of 3) CGI-I score was approximately 14 points. Our findings from the linking analyses are useful for interpreting the clinical implications of changes in the CDRS-R score.

Measures of Connectivity and Dorsolateral Prefrontal Cortex Volumes and Depressive Symptoms Following Treatment With Selective Serotonin Reuptake Inhibitors in Adolescents

Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression. To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control. This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022. Depressive symptoms were assessed using the Children's Depression Rating Scale-Revised. The outcome measure was defined as the change in Children's Depression Rating Scale-Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not. Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment. The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD.

Associations of n-3 polyunsaturated fatty acid status and intake with paediatric major depressive disorder in Swiss adolescents: A case-control study

BackgroundObservational studies suggest a link between n-3 polyunsaturated fatty acid (PUFA) intake, n-3 PUFA status, and depression in adults, but studies in adolescents are scarce. This study aimed to determine associations of n-3 PUFA status and intake with paediatric major depressive disorder (pMDD) in Swiss adolescents. MethodsWe conducted a matched case-control study in 95 adolescents diagnosed with pMDD and 95 healthy controls aged 13 to <18 years. We analysed red blood cell (RBC) fatty acid (FA) composition (% of total FA). n-3 PUFA intake was assessed using a focused food frequency questionnaire and depression severity was assessed by the Children's Depression Rating Scale-Revised (CDRS-R). ResultsMean RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower in cases than controls (EPA: 0.41 ± 0.11 vs 0.46 ± 0.12, p < 0.001; DHA: 4.07 ± 1.04 vs 4.73 ± 1.04, p < 0.001). Subsequently, the mean RBC n-3 index was lower (4.51 ± 1.10 vs 5.20 ± 1.11, p < 0.001) and the n-6/n-3 PUFA ratio higher (5.51 ± 1.25 vs 4.96 ± 1.08, p < 0.001) in cases than controls. Adolescents with a higher n-3 index had lower odds for depression (OR = 0.49 [95% CI: 0.32–0.71]). In contrast, the n-6/n-3 PUFA ratio was associated with higher odds for depression (OR = 1.58 [95% CI: 1.14–2.25]). Intake of alpha-linolenic acid, EPA and DHA did not differ between cases and controls. ConclusionOur results suggest that a higher RBC n-3 PUFA status during adolescence is associated with a lower risk for pMDD, whereas a higher n-6/n-3 PUFA ratio is associated with a higher risk for pMDD. Differences in n-3 PUFA intake did not explain the observed differences in n-3 PUFA status.

Prediction of Diagnosis and Treatment Response in Adolescents With Depression by Using a Smartphone App and Deep Learning Approaches: Usability Study.

Lack of quantifiable biomarkers is a major obstacle in diagnosing and treating depression. In adolescents, increasing suicidality during antidepressant treatment further complicates the problem. We sought to evaluate digital biomarkers for the diagnosis and treatment response of depression in adolescents through a newly developed smartphone app. We developed the Smart Healthcare System for Teens At Risk for Depression and Suicide app for Android-based smartphones. This app passively collected data reflecting the social and behavioral activities of adolescents, such as their smartphone usage time, physical movement distance, and the number of phone calls and text messages during the study period. Our study consisted of 24 adolescents (mean age 15.4 [SD 1.4] years, 17 girls) with major depressive disorder (MDD) diagnosed with Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version and 10 healthy controls (mean age 13.8 [SD 0.6] years, 5 girls). After 1 week's baseline data collection, adolescents with MDD were treated with escitalopram in an 8-week, open-label trial. Participants were monitored for 5 weeks, including the baseline data collection period. Their psychiatric status was measured every week. Depression severity was measured using the Children's Depression Rating Scale-Revised and Clinical Global Impressions-Severity. The Columbia Suicide Severity Rating Scale was administered in order to assess suicide severity. We applied the deep learning approach for the analysis of the data. Deep neural network was employed for diagnosis classification, and neural network with weighted fuzzy membership functions was used for feature selection. We could predict the diagnosis of depression with training accuracy of 96.3% and 3-fold validation accuracy of 77%. Of the 24 adolescents with MDD, 10 responded to antidepressant treatments. We predicted the treatment response of adolescents with MDD with training accuracy of 94.2% and 3-fold validation accuracy of 76%. Adolescents with MDD tended to move longer distances and use smartphones for longer periods of time compared to controls. The deep learning analysis showed that smartphone usage time was the most important feature in distinguishing adolescents with MDD from controls. Prominent differences were not observed in the pattern of each feature between the treatment responders and nonresponders. The deep learning analysis revealed that the total length of calls received as the most important feature predicting antidepressant response in adolescents with MDD. Our smartphone app demonstrated preliminary evidence of predicting diagnosis and treatment response in depressed adolescents. This is the first study to predict the treatment response of adolescents with MDD by examining smartphone-based objective data with deep learning approaches.