Major Depressive Disorder Adolescents Research Articles

Psychosocial factors affect the occurrence of nonsuicidal self-injury in adolescents with major depressive disorder through chain mediation.

In the adolescent group, about half of adolescents with major depressive disorder (MDD) have NSSI. Psychosocial factors are associated with the development of NSSI. Clarifying the relationship between psychosocial factors and NSSI in adolescents with MDD can help us achieve early prevent. Demographic data, Hamilton Depression Scale-24 (HAMA24), childhood trauma questionnaire, emotional intelligence scale and interpersonal reactivity index were collected from 187 adolescents with MDD. Use ANOVA, Chi-square test, Binary Logistic Regression, Pearson correlation analysis, Mediation effect analysis and the Structural Equation Model for data analysis. The results of ANOVA showed that there was significant difference between the two groups in HAMD24 total score, impulsiveness, emotional intelligence, and empathy (p < 0.05). In the regression analysis, women, depression degree, motor impulsiveness (MI), personal distress (PD) and appraisal of other's emotions empathy were the risk factors for MDD adolescents to produce NSSI behavior. Among the indicators that were significantly related to MDD and NSSI, MI and PD mediate the relationship between MDD and NSSI. The structural equation model showed that MDD, PD and MI had a direct impact on NSSI, but PD and MI had multiple intermediary effected in the relationship between MDD and NSSI. Emotional intelligence, emotional neglect and cognitive impulsiveness indirectly affected the occurrence of NSSI behavior. Impulsiveness, personal distress, emotional neglect, and emotional intelligence are important risk factors that affect NSSI behavior in adolescents with MDD, and they affect the occurrence of NSSI in adolescents with MDD through chain mediation.

The effects of childhood trauma on nonsuicidal self-injury and depressive severity among adolescents with major depressive disorder: The different mediating roles of positive and negative coping styles

ObjectiveWe aimed to examine whether positive and negative coping styles mediated the influences of childhood trauma on NSSI or depressive severity in adolescents with major depressive disorder (MDD). MethodsThe Children's Depression Inventory (CDI), the Ottawa Self-Injury Inventory Chinese Revised Edition (OSIC), the short-form Childhood Trauma Questionnaire (CTQ-SF), and the Simplified Coping Style Questionnaire (SCSQ) were evaluated in 313 adolescents with MDD. ResultsMDD adolescents with NSSI had higher CTQ-SF total score, emotional and sexual abuse subscale scores, but lower CDI total and subscale scores compared to the patients without NSSI. The multiple linear regression analysis revealed that emotional abuse (β = 0.075, 95 % CI: 0.042–0.107) and ineffectiveness (β = −0.084, 95 % CI: −0.160 ∼ −0.009) were significantly associated with the frequency of NSSI in adolescents with MDD, but emotional abuse (β = 0.884, 95 % CI: 0.570–1.197), sexual abuse (β = 0.825, 95 % CI: 0.527–1.124) and negative coping style (β = 0.370, 95 % CI: 0.036–0.704) were independently associated with the depressive severity in these adolescents. Furthermore, the mediation analysis demonstrated that positive coping style partially mediates the effect of childhood trauma on NSSI (Indirect effect = 0.002, 95 % bootCI: 0.001–0.004), while the negative coping style partially mediates the relationship between childhood trauma and depressive severity (Indirect effect = 0.024, 95 % bootCI: 0.005–0.051) in adolescents with MDD. LimitationsA cross-sectional design, the retrospective self-reported data, the small sample size. ConclusionOur findings suggest that coping styles may serve as mediators on the path from childhood trauma to NSSI or depressive severity in MDD adolescents.

The relationship between serum resolvin D1, NLRP3, cytokine levels, and adolescents with first-episode medication-naïve major depressive disorder

BackgroundInflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear.MethodsForty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6–8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1β, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment.ResultsSerum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1β, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1β, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents.ConclusionsOur study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.

Multivariate association between psychosocial environment, behaviors, and brain functional networks in adolescent depression

BackgroundAdolescent depression shows high clinical heterogeneity. Brain functional networks serve as a powerful tool for investigating neural mechanisms underlying depression profiles. A key challenge is to characterize how variation in brain functional organization links to behavioral features and psychosocial environmental influences. MethodsWe recruited 80 adolescents with major depressive disorder (MDD) and 42 healthy controls (HCs). First, we estimated the differences in functional connectivity of resting-state networks (RSN) between the two groups. Then, we used sparse canonical correlation analysis to characterize patterns of associations between RSN connectivity and symptoms, cognition, and psychosocial environmental factors in MDD adolescents. Clustering analysis was applied to stratify patients into homogenous subtypes according to these brain-behavior-environment associations. ResultsMDD adolescents showed significantly hyperconnectivity between the ventral attention and cingulo-opercular networks compared with HCs. We identified one reliable pattern of covariation between RSN connectivity and clinical/environmental features in MDD adolescents. In this pattern, psychosocial factors, especially the interpersonal and family relationships, were major contributors to variation in connectivity of salience, cingulo-opercular, ventral attention, subcortical and somatosensory-motor networks. Based on this association, we categorized patients into two subgroups which showed different environment and symptoms characteristics, and distinct connectivity alterations. These differences were covered up when the patients were taken as a whole group. ConclusionThis study identified the environmental exposures associated with specific functional networks in MDD youths. Our findings emphasize the importance of the psychosocial context in assessing brain function alterations in adolescent depression and have the potential to promote targeted treatment and precise prevention.

Effect of Acute Ketamine Treatment on Sympathetic Regulation Indexed by Electrodermal Activity in Adolescent Major Depression.

Ketamine is a potential rapid-onset antidepressant characterized by sympathomimetic effects. However, the question of ketamine's use in treating adolescents' major depressive disorder (MDD) is still discussed. Thus, we aimed to study the acute effect of ketamine infusion treatment on sympathetic regulation using electrodermal activity (EDA) in addition to an assessment of depressive symptomatology in MDD adolescents. Twenty hospitalized adolescent girls with MDD (average age: 15.0 ± 1.46 yrs.) were examined before and two hours after a single intravenous infusion of ketamine. EDA was continuously recorded for 6 min, and depressive symptoms were assessed before and two hours after ketamine administration. The evaluated parameters included skin conductance level (SCL), nonspecific electrodermal responses (NS-SCRs), MADRS (questions no. 1-10, total score), and CDI (items A-E, total score). EDA parameters showed no significant changes after the ketamine treatment, and depressive symptoms were significantly reduced after the ketamine infusion. The analysis revealed a significant negative correlation between index SCL and CDI-A, CDI-E, and the total CDI score and between index NS-SCRs and MADRS no. 4 before the ketamine treatment. In conclusion, ketamine improved depressive symptomatology without a significant effect on EDA, indicating its potential safety and efficiency as an acute antidepressant intervention in adolescent MDD.

The Neuroimaging Role of Modified Electroconvulsive Therapy in the Major Depressive Disorder: Effectiveness in First-Episode Antipsychotic-Naive Major Depressive Disorder Patients

Objectives. It is a high risk for adolescents with first-episode major depressive disorder (MDD) to commit suicide. However, few studies reported the effect of modified electroconvulsive therapy (MECT) in first-episode antipsychotic-naive MDD adolescents. Methods. The study explores the alternations of regional homogeneity of modified electroconvulsive therapy to treat the first-episode antipsychotic-naive major depressive disorder. 72 first-episode MDD patients were recruited from Tianyou Hospital Affiliated to Wuhan University of Science and Technology from October 2017 to May 2020, and 65 of 72 completed the trial. Results. Before MECT treatment, ReHo values of the bilateral cerebellum and left cuneus were higher, and ReHo value of left postcentral and supramarginal gyrus was lower in MDD patients compared to healthy subjects (HS). After treatment, the MDD patients have higher ReHo values of the right insula and postcentral gyrus, while left fusiform gyrus were lower than the pretreatment. Compared to the HS, the ReHo values of left lingual gyrus, right calcarine cortex, and right mid occipital thalamus were higher in the posttreatment. In the posttreatment, left calcarine cortex and right cerebrum were lower than in healthy subjects. Conclusions. The study confirmed that MECT improves psychotic symptoms in patients with first-episode antipsychotic-naive MDD. These results further contributed to a more tailored treatment approach to MDD from the pathophysiological and neuroimaging views.

Cardiac Autonomic Balance Is Altered during the Acute Stress Response in Adolescent Major Depression-Effect of Sex.

Autonomic nervous system (ANS) abnormalities are associated with major depressive disorder (MDD) already at adolescent age. The majority of studies so far evaluated parasympathetic and sympathetic branches of ANS individually, although composite indices including cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR) seem to measure ANS functioning more comprehensively and thus could provide better psychopathologies' predictors. We aimed to study CAB and CAR derived from high-frequency bands of heart rate variability and left ventricular ejection time during complex stress response (rest-Go/NoGo task-recovery) in MDD adolescents with respect to sex. We examined 85 MDD adolescents (52 girls, age: 15.7 ± 0.14 yrs.) and 80 age- and sex-matched controls. The MDD group showed significantly reduced CAB compared to controls at rest, in response to the Go/NoGo task, and in the recovery phase. Moreover, while depressed boys showed significantly lower CAB at rest and in response to the Go/NoGo task compared to control boys, depressed girls showed no significant differences in evaluated parameters compared to control girls. This study for the first time evaluated CAB and CAR indices in drug-naïve first-episode diagnosed MDD adolescents during complex stress responses, indicating an altered cardiac autonomic pattern (i.e., reciprocal sympathetic dominance associated with parasympathetic underactivity), which was predominant for depressed boys.

Automatic Positive and Negative Emotion Regulation in Adolescents with Major Depressive Disorder

Introduction: Adolescents with major depressive disorder (MDD) exhibit hypoactivity to positive stimuli and hyperactivity to negative stimuli in terms of neural responses. Automatic emotion regulation (AER) activates triple networks (i.e., the central control network, default mode network, and salience network). Based on previous studies, we hypothesized that adolescents with MDD exhibit dissociable spatiotemporal deficits during positive and negative AER. Methods: We first collected EEG data from 32 adolescents with MDD and 35 healthy adolescents while they performed an implicit emotional Go/NoGo task. Then, we characterized the spatiotemporal dynamics of cortical activity during AER. Results: In Go trials, MDD adolescents exhibited reduced N2 amplitudes, enhanced theta power for positive pictures, and stronger bottom-up information flow from the left orbitofrontal cortex (OFC) to the right superior frontal gyrus compared to top-down information flow than the controls. In contrast, in NoGo trials, MDD adolescents exhibited elevated P3 amplitudes, enhanced theta power, and stronger top-down information flows from the right middle frontal gyrus to the right OFC and the left insula than the controls. Conclusion: Overall, adolescents with MDD exhibited impaired automatic attention to positive emotions and impaired automatic response inhibition. These findings have potential implications for the clinical treatment of adolescents with MDD.

Abnormal brain spontaneous activity in major depressive disorder adolescents with non-suicidal self injury and its changes after sertraline therapy.

Non-suicidal self-injury (NSSI) commonly occurs among adolescents with major depressive disorder (MDD), causing adverse effects on the physical and mental health of the patients. However, the underlying neurobiological mechanism of NSSI in adolescents with MDD (nsMDDs) remains unclear, and there are still challenges in the treatment. Studies have suggested that sertraline administration could be an effective way for treatment. To verify the effectiveness and to explore the neurobiological processes, we treated a group of adolescents with nsMDDs with sertraline in this study. The brain spontaneous activity alteration was then investigated in fifteen unmedicated first-episode adolescent nsMDDs versus twenty-two healthy controls through the resting-state functional magnetic resonance imaging. Besides the baseline scanning for all participants, the nsMDDs group was scanned again after eight weeks of sertraline therapy to examine the changes after treatment. At pre-treatment, whole brain analysis of mean amplitude of low-frequency fluctuation (mALFF) was performed to examine the neuronal spontaneous activity alteration, and increased mALFF was found in the superior occipital extending to lingual gyrus in adolescent nsMDDs compared with controls. Meanwhile, decreased mALFF was found in the medial superior frontal in adolescent nsMDDs compared with controls. Compared with the pre-treatment, the nsMDDs group was found to have a trend of, respectively, decreased and increased functional neuronal activity at the two brain areas after treatment through the region of interest analysis. Further, whole brain comparison of mALFF at pre-treatment and post-treatment showed significantly decreased spontaneous activity in the orbital middle frontal and lingual gyrus in adolescent nsMDDs after treatment. Also, depression severity was significantly decreased after treatment. The abnormal functional neuronal activity found at frontal and occipital cortex implied cognitive and affective disturbances in adolescent nsMDDs. The trend of upregulation of frontal neuronal activity and downregulation of occipital neuronal activity after sertraline treatment indicated that the therapy could be effective in regulating the abnormality. Notably, the significantly decreased neuronal activity in the decision related orbital middle frontal and anxiety-depression related lingual gyrus could be suggestive of reduced NSSI in adolescent MDD after therapy.

Changes in microstates of first-episode untreated nonsuicidal self-injury adolescents exposed to negative emotional stimuli and after receiving rTMS intervention.

Nonsuicidal self-injury (NSSI) is a common mental health threat in adolescents, peaking in adolescence with a lifetime prevalence of ~17%-60%, making it a high-risk risk factor for suicide. In this study, we compared changes in microstate parameters in depressed adolescents with NSSI, depressed adolescents, and healthy adolescents during exposure to negative emotional stimuli, and further explored the improvement of clinical symptoms and the effect of microstate parameters of repetitive transcranial magnetic stimulation (rTMS) in depressed adolescents with NSSI, and more evidence was provided for potential mechanisms and treatment optimization for the occurrence of NSSI behaviors in adolescents. Sixty-six patients with major depressive disorder (MDD) exhibiting NSSI behavior (MDD + NSSI group), 52 patients with MDD (MDD group), and 20 healthy subjects (HC group) were recruited to perform neutral and negative emotional stimulation task. The age range of all subjects was 12-17 years. All participants completed the Hamilton Depression Scale, the Patient Health Questionnaire-9, the Ottawa Self-Injury Scale and a self-administered questionnaire to collect demographic information. We provided two different treatments to 66 MDD adolescents with NSSI; 31 patients received medication and completed post-treatment scale assessments and EEG acquisitions, and 21 patients received medication combined with rTMS and completed post-treatment scale assessments and EEG acquisitions. Multichannel EEG was recorded continuously from 64 scalp electrodes using the Curry 8 system. EEG signal preprocessing and analysis was performed offline, using the EEGLAB toolbox in MATLAB. Use the Microstate Analysis Toolbox in EEGLAB for segmentation and computation of microstates, and calculate a topographic map of the microstate segmentation of the EEG signal for a single subject in each dataset, and four parameters were obtained for each microstate classification: global explained variance (GEV), mean duration (Duration), average number of occurrences per second (Occurrence), and average percentage of total analysis time occupied (Coverage), which were then statistically analyzed. Our results indicate that MDD adolescents with NSSI exhibit abnormalities in MS 3, MS 4, and MS 6 parameters when exposed to negative emotional stimuli compared to MDD adolescents and healthy adolescents. The results also showed that medication combined with rTMS treatment improved depressive symptoms and NSSI performance more significantly in MDD adolescents with NSSI compared to medication treatment, and affected MS 1, MS 2, and MS 4 parameters in MDD adolescents with NSSI, providing microstate evidence for the moderating effect of rTMS. MDD adolescents with NSSI showed abnormal changes in several microstate parameters when receiving negative emotional stimuli, and compared to those not receiving rTMS treatment, MDD adolescents with NSSI treated with rTMS showed more significant improvements in depressive symptoms and NSSI performance, as well as improvements in EEG microstate abnormalities.

Aberrant single-subject morphological brain networks in first-episode, treatment-naive adolescents with major depressive disorder.

Neuroimaging-based connectome studies have indicated that major depressive disorder (MDD) is associated with disrupted topological organization of large-scale brain networks. However, the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD. To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD. Twenty-five first-episode, treatment-naive adolescents with MDD and 19 healthy controls (HCs) underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests. Single-subject morphological brain networks were constructed separately based on cortical thickness, fractal dimension, gyrification index, and sulcus depth, and topologically characterized by graph-based approaches. Between-group differences were inferred by permutation testing. For significant alterations, partial correlations were used to examine their associations with clinical and neuropsychological variables in the patients. Finally, a support vector machine was used to classify the patients from controls. Compared with the HCs, the patients exhibited topological alterations only in cortical thickness-based networks characterized by higher nodal centralities in parietal (left primary sensory cortex) but lower nodal centralities in temporal (left parabelt complex, right perirhinal ectorhinal cortex, right area PHT and right ventral visual complex) regions. Moreover, decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients. These results were largely reproducible for binary and weighted network analyses. Finally, topological properties of the cortical thickness-based networks were able to distinguish the MDD adolescents from HCs with 87.6% accuracy. Adolescent MDD is associated with disrupted topological organization of morphological brain networks, and the disruptions provide potential biomarkers for diagnosing and monitoring the disease.

Resting-state functional magnetic resonance imaging-based identification of altered brain the fractional amplitude of low frequency fluctuation in adolescent major depressive disorder patients undergoing electroconvulsive therapy.

PurposeWhile electroconvulsive therapy (ECT) has been repeatedly been shown to effectively and efficiently treat the major depressive disorder (MDD), the mechanistic basis for such therapeutic efficacy remains to be firmly established. As such, further research exploring the ECT-based treatment of MDD in an adolescent population is warranted.MethodsThis study included 30 treatment-naïve first-episode MDD patients and 30 healthy control (HC) individuals (aged 12–17 years). All participants were scanned using rs-fMRI, and the 30 MDD patients were scanned again after 2 weeks of the ECT treatment period. Intrinsic local activity in each voxel was assessed based on the fractional amplitude of low frequency fluctuation (fALFF) parameter, with all fALFF analyses being completed using the REST application. Correlations between ECT-related changes in fALFF and clinical parameters were additionally examined.ResultsRelative to HCs, MDD patients exhibited increased fALFF values in the right inferior frontal gyrus (ORBinf), inferior occipital gyrus (IOG), and the left middle frontal gyrus (MFG) at baseline. Following ECT, these patients exhibited significant increases in fALFF values in the right medial superior frontal gyrus (SFGmed), dorsolateral superior frontal gyrus (SFGdor), anterior cingulate, and paracingulate gyrus (ACG), median cingulate and paracingulate gyrus (DCG), and left MFG. MDD patient HAMD scores were negatively correlated with fALFF values when analyzing pre-ECT vs. post-HCT ΔHAMD and fALFF values in the right SFGmed, SFGdor, and the left MFG.ConclusionThese data suggest that ECT induced altered fALFF in some regions of the brain, suggesting that these alterations may serve as a neurobiological indicator of ECT effectiveness in MDD adolescents.

Longitudinal effects of antidepressant treatment on resting state functional connectivity in adolescents with major depressive disorder

IntroductionAdolescents with major depressive disorder (MDD) often show reduced prefrontal functional connectivity with the subcortical regions than healthy controls (HC) (Tang et al., 2018). However, relatively little is known about longitudinal effects of antidepressant (AD) treatment on resting state functional connectivity (RSFC) in the prefrontal cortex (PFC).ObjectivesThis study aimed to investigate abnormal PFC RSFC in MDD adolescents compared to HC and longitudinal effects of AD on PFC RSFC.Methods This study included 59 adolescents with MDD and 43 HC. MDD adolescents were treated with escitalopram in an 8 week, open-label trial. The treatment outcome was assessed by Children’s Depression Rating Scale (CDRS-R) and patients showing at least a 40% improvement in CDRS-R scores from baseline to week 8 were defined as “responders”. Functional and T1 images collected before and after treatment were processed using AFNI and Freesurfer. Our seed was the lateral PFC (LPFC, BA46). T-tests and repeated measures ANCOVAs, controlling for age and IQ, were conducted to examine abnormal PFC RSFC and longitudinal effects of AD on LPFC RSFC.ResultsRelative to HC, MDD showed increased LPFC RSFC with the posterior middle temporal gyrus (pMTG) and superior frontal cortex (SFG) involved in attentional networks. Responders showed greater changes in LPFC RSFC with the MTG and SFG after AD treatment compared to non-responders and HC (Figure 1).ConclusionsOur finding suggests that reduced LPFC RSFC with the pMTG and SFG reflecting decreased attentional network connectivity may serve as a biomarker to predict AD treatment outcome in adolescents with MDD.DisclosureNo significant relationships.

Abnormalities in Electroencephalographic Microstates Among Adolescents With First Episode Major Depressive Disorder.

Background: Recent studies have reported changes in the electroencephalograms (EEG) of patients with major depressive disorder (MDD). However, little research has explored EEG differences between adolescents with MDD and healthy controls, particularly EEG microstates differences. The aim of the current study was to characterize EEG microstate activity in adolescents with MDD and healthy controls (HCs).Methods: A total of 35 adolescents with MDD and 35 HCs were recruited in this study. The depressive symptoms were assessed by Hamilton Depression Scale (HAMD) and Children's Depression Inventory (CDI), and the anxiety symptoms were assessed by Chinese version of DSM-5 Level 2-Anxiety-Child scale. A 64-channel EEG was recorded for 5 min (eye closed, resting-state) and analyzed using microstate analysis. Microstate properties were compared between groups and correlated with patients' depression scores.Results: We found increased occurrence and contribution of microstate B in MDD patients compared to HCs, and decreased occurrence and contribution of microstate D in MDD patients compared to HCs. While no significant correlation between depression severity (HAMD score) and the microstate metrics (occurrence and contribution of microstate B and D) differing between MDD adolescents and HCs was found.Conclusions: Adolescents with MDD showed microstate B and microstate D changes. The obtained results may deepen our understanding of dynamic EEG changes among adolescents with MDD and provide some evidence of changes in brain development in adolescents with MDD.

Hippocampal Subfield Volumes in Major Depressive Disorder Adolescents with a History of Suicide Attempt.

Suicidal behavior is a leading cause of death and often commences during adolescence/young adulthood (15~29 years old). The hippocampus, which consists of multiple functionally specialized subfields, may contribute to the pathophysiology of depression and suicidal behavior. We aimed to investigate the differences of hippocampal subfield volume between major depressive disorder (MDD) patients with and without suicide attempts and healthy controls in adolescents and young adults. A total of 40 MDD suicide attempters (MDD+SA), 27 MDD patients without suicide attempt (MDD-SA), and 37 healthy controls (HC) were recruited. High-resolution T1 MRI images were analyzed with the automated hippocampal substructure module in FreeSurfer 6.0. Volume differences among the groups were analyzed by a generalized linear model controlling for intracranial cavity volume (ICV). The relationship between hippocampal subfield volumes and clinical characteristics (HAM-D and SSI scores) was assessed using two-tailed partial correlation controlling for ICV in MDD+SA and MDD-SA. We found that MDD-SA had significantly smaller bilateral hippocampal fissure volume than HC and MDD+SA. No significant correlation was observed between hippocampal subfield volume and clinical characteristics (HAM-D and SSI scores) in MDD+SA and MDD-SA. Adolescent/young adult suicide attempters with MDD suicide attempters have larger bilateral hippocampal fissures than depressed patients without suicide attempts, independently from clinical characteristics. Within the heterogeneous syndrome of major depressive disorder that holds a risk for suicidality for subgroups, hippocampal morphology may help to explain or possibly predict such risk, yet longitudinal and functional studies are needed for understanding the biological mechanisms underlying.

Effects of Antidepressant Treatment on Symptom Measures of Attention in Adolescents with Depression: A Preliminary Open-Label Study.

Objective: The effects of selective serotonin reuptake inhibitor (SSRI) on deficits in attention and executive function in adolescents with major depressive disorder (MDD) are relatively unknown. We aimed to investigate changes in symptom measures of attention in adolescents with MDD treated with escitalopram. Methods: The study included 82 MDD adolescents and 54 healthy controls aged from 12 to 17 years. Symptom measures of attention were assessed using the Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) and Child Behavior Checklist attention problems scale at baseline and during week 8. Adolescents who showed at least 40% improvement in the Children's Depression Rating Scale-Revised (CDRS-R) scores from baseline to week 8 were referred to as "responders." Results: No baseline differences were found between the responders (n = 47) and nonresponders (n = 35) in their age, sex, intelligence quotient, CDRS-R score, and attention measures. Linear mixed models showed significant group-by-time interaction effect in the ADHD-RS inattention subscale score, but not in the other attention measures. Conclusion: Our results suggest that treating depressive symptoms with SSRI may lead to improvements in attention in MDD adolescents. Monitoring changes in symptom measures of attention can be useful when treating adolescents with MDD. ClinicalTrials.gov identifier: NCT03547219.

Attention-Deficit/Hyperactivity Disorder and Suicidal Risk in Major Depression: Analysis of 141,530 Adolescent Hospitalizations.

ObjectivesWe conducted a cross-sectional study to understand the differences in demographics and psychiatric comorbidities in adolescents with major depressive disorder (MDD) and assess the risk of suicidality due to comorbid attention-deficit/hyperactivity disorder (ADHD).MethodsWe included 141,530 adolescents (age, 12 to 18 years) with a primary diagnosis of MDD from the nationwide inpatient sample (NIS, 2012-2014), and grouped by a comorbid diagnosis of ADHD (N = 22,665, 16%). Logistic regression analysis was used to measure the demographic predictors for ADHD in adolescents with MDD, and to measure the suicidal risk in ADHD versus non-ADHD.ResultsComorbid ADHD was prevalent in whites (71.9%), and males had two times higher odds (95% CI 2.25-2.41) compared to females. The most prevalent comorbidities seen in ADHD-cohort were anxiety disorders (46.3%) and substance abuse (20.1%) with 1.3 times higher odds of substance abuse (95% CI 1.41-1.65) compared to non-ADHD. Suicidal behaviors were seen in a higher proportion of the ADHD cohort compared to the non-ADHD cohort (54.3% vs. 52.7%). ADHD and suicidal behaviors relationship was statistically significant but had a very small positive association (OR 1.04, 95% CI 1.01-1.08) after controlling for demographic confounders and comorbidities. There was a significant increase in the number of MDD hospitalization with ADHD for suicidal behaviors from 51.1% (N = 3,360) in 2012 to 58.2% (N = 5,115) in 2014.ConclusionThere exists a significant but small positive association between suicidal behaviors and comorbid ADHD in MDD adolescents. The suicide rate has increased by 52.2% during the study period in depressed adolescents with ADHD. This calls for early diagnosis and management of ADHD and early-onset depression in adolescents to prevent suicide risk.

Emotional Contexts Modulate Anticipatory Late Positive Component and Reward Feedback Negativity in Adolescents With Major Depressive Disorder.

BackgroundNeuroimaging research has determined deficits in the dopaminergic circuit of major depressive disorder (MDD) during adolescence. This study investigated how emotional contexts modulate the temporal dynamics of reward anticipation and feedback in adolescents.MethodsEEG data from 35 MDD and 37 healthy adolescents were recorded when they conducted a gambling task after being presented with emotional pictures.ResultsThe results demonstrated that both MDD and healthy adolescents exhibited the largest late positive component (LPC) in positive contexts at the frontal sites and the largest LPC in negative contexts at the central sites; however, MDD adolescents exhibited anticipatory LPC hypoactivation than healthy adolescents. However, MDD adolescents exhibited smaller gain feedback negativity (FN) than healthy adolescents independent of emotional contexts, positively correlating with the trait anhedonia according to the consummatory aspect of the Temporal Experience of Pleasure Scale. In contrast, MDD adolescents exhibited greater FN loss in positive and neutral contexts than healthy adolescents while no difference in FN loss was found between the two groups in negative contexts. Moreover, the FN loss amplitudes negatively correlated with hedonic tone according to the Snaith-Hamilton Pleasure Scale over the past week.ConclusionsThese findings suggest that MDD adolescents exhibited dissociable deficits in reward anticipation and gain or loss feedback that are distinctly modulated by emotional contexts, and they deepen our understanding of the modulation of emotional contexts on the temporal dynamic reorganization of the reward circuit in MDD adolescents.

Abnormal Functional and Structural Connectivity of Amygdala-Prefrontal Circuit in First-Episode Adolescent Depression: A Combined fMRI and DTI Study.

BackgroundAbnormalities of functional and structural connectivity in the amygdala-prefrontal circuit which involved with emotion processing have been implicated in adults with major depressive disorder (MDD). Adolescent MDD may have severer dysfunction of emotion processing than adult MDD. In this study, we used resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) to examine the potential functional and structural connectivity abnormalities within amygdala-prefrontal circuit in first-episode medication-naïve adolescents with MDD.MethodsRs-fMRI and DTI data were acquired from 36 first-episode medication-naïve MDD adolescents and 37 healthy controls (HC). Functional connectivity between amygdala and the prefrontal cortex (PFC) and fractional anisotropy (FA) values of the uncinate fasciculus (UF) which connecting amygdala and PFC were compared between the MDD and HC groups. The correlation between the FA value of UF and the strength of the functional connectivity in the PFC showing significant differences between the two groups was identified.ResultsCompared with the HC group, decreased functional connectivity between left amygdala and left ventral PFC was detected in the adolescent MDD group. FA values were significant lower in the left UF within the adolescent MDD group compared to the HC group. There was no significant correlation between the UF and FA, and the strength of functional connectivity within the adolescent MDD group.ConclusionsFirst-episode medication-naïve adolescent MDD showed decreased functional and structural connectivity in the amygdala-prefrontal circuit. These findings suggest that both functional and structural abnormalities of the amygdala-prefrontal circuit may present in the early onset of adolescent MDD and play an important role in the neuropathophysiology of adolescent MDD.

Early changes of serum BDNF and SSRI response in adolescents with major depressive disorder

BackgroundRecent evidence suggests that brain-derived neurotrophic factor (BDNF) levels and their early changes may predict antidepressant response in adults with major depressive disorder (MDD). However, in adolescents, BDNF levels in depression and their changes during antidepressant treatment are relatively unknown. We aimed to investigate whether pre-treatment BDNF levels and their early changes predict antidepressant response in depressed adolescents. MethodsThe study included 83 MDD adolescents and 52 healthy controls aged 12 to 17 years. All depressed adolescents were treated with escitalopram in an 8 week, open-label trial. Depression severity and serum BDNF level at baseline, and weeks 2 and 8 were measured with the Children's Depression Rating Scale-Revised (CDRS-R) and ELISA, respectively. ResultsResponders showed a significant decrease in BDNF levels at week 2 but non-responders and healthy controls had no changes in BDNF levels at week 2. The early decrease (baseline – week 2) of BDNF levels predicted SSRI response with moderate sensitivity and specificity. Logistic regression analysis revealed that early BDNF decrease predicted SSRI response at week 8 after controlling for other demographic and clinical variables. LimitationsThe follow-up duration of the study was limited in 8 weeks. It remains possible that serum BDNF levels would have changed with longer treatment. ConclusionsThis is the first longitudinal study to investigate the effect of antidepressants on BDNF levels in adolescents with MDD. Our findings suggest that a decrease of serum BDNF levels in early phase of SSRI treatment may be associated later SSRI response in adolescents with MDD.