Major Depressive Disorder In Youth Research Articles

The clinical presentation of major depressive disorder in youth with co-occurring obsessive-compulsive disorder

BackgroundMajor depressive disorder (MDD) is common in youth and among the most frequent comorbid disorders in pediatric obsessive-compulsive disorder (OCD), but it is unclear whether the presence of OCD affects the symptom presentation of MDD in youth. MethodsA sample of youth with OCD and MDD (n = 124) and a sample of youth with MDD but no OCD (n = 673) completed the Patient Health Questionnaire for Adolescents (PHQ-A). The overall and symptom-level presentation of MDD were examined using group comparisons and network analysis. ResultsYouth with MDD and OCD, compared to those with MDD and no OCD, had more severe MDD (Cohen's d = 0.39) and more reported moderate to severe depression (75 % vs 61 %). When accounting for demographic variables and the overall severity of MDD, those with comorbid OCD reported lower levels of anhedonia and more severe difficulties with psychomotor retardation/agitation. No significant differences in the interconnections among symptoms emerged. LimitationsData were cross-sectional and self-reported, gold standard diagnostic tools were not used to assess OCD, and the sample size for the group with MDD and OCD was relatively small yielding low statistical power for network analysis. ConclusionsYouth with MDD and OCD have more severe MDD than those with MDD and no OCD and they experience more psychomotor issues and less anhedonia, which may relate to the behavioral activation characteristic of OCD.

459. A Meta-Analysis of Functional Neuroimaging Studies of Major Depressive Disorder in Youth

459. A Meta-Analysis of Functional Neuroimaging Studies of Major Depressive Disorder in Youth

Major Depressive Disorder in Youth: A Meta-Analysis of Functional Magnetic Resonance Imaging Studies

IntroductionMajor depressive disorder (MDD) is a highly prevalent mental illness that frequently originates in early development and is pervasive during adolescence. Despite its high prevalence and early age of onset, our understanding of the potentially unique neural basis of MDD in this age group is still not well understood, and the existing primary literature on the topic includes many new and divergent results. This limited understanding of MDD in youth presents a critical need to further investigate its neural basis in youth and presents an opportunity to also improve clinical treatments that target its neural abnormalities.ObjectivesThe present study aims to advance our understanding of the neural basis of MDD in youth by identifying abnormal functional activation in various brain regions compared with healthy controls.MethodsWe conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of MDD by using a well-established method, multilevel kernel density analysis (MKDA) with ensemble thresholding, to quantitatively combine all existing whole-brain fMRI studies of MDD in youth compared with healthy controls. This method involves a voxel-wise, whole-brain approach, that compares neural activation of patients with MDD to age-matched healthy controls across variations of task-based conditions, which we subcategorize into affective processing, executive functioning, positive valence, negative valence, and symptom provocation tasks.ResultsYouth with MDD exhibited statistically significant (p<0.05; FWE-corrected) hyperactivation and hypoactivation in multiple brain regions compared with age-matched healthy controls. These results include significant effects that are stable across various tasks as well as some that appear to depend on task conditions.ConclusionsThis study strengthens our understanding of the neural basis of MDD in youth and may also be used to help identify possible similarities and differences between youth and adults with depression. It may also help inform the development of new treatment interventions and tools for predicting unique treatment responses in youth with depression.Disclosure of InterestNone Declared

A Predictive Biomarker Model Using Quantitative Electroencephalography in Adolescent Major Depressive Disorder.

Background: With evolving understanding of psychiatric diagnosis and treatment, demand for biomarkers for psychiatric disorders in children and adolescents has grown dramatically. This study utilized quantitative electroencephalography (qEEG) to develop a predictive model for adolescent major depressive disorder (MDD). We hypothesized that youth with MDD compared to healthy controls (HCs) could be differentiated using a singular logistic regression model that utilized qEEG data alone. Methods: qEEG data and psychometric measures were obtained in adolescents aged 14-17 years with MDD (n = 35) and age- and gender-matched HCs (n = 14). qEEG in four frequency bands (alpha, beta, theta, and delta) was collected and coherence, cross-correlation, and power data streams obtained. A two-stage analytical framework was then used to develop the final logistic regression model, which was then evaluated using a receiver-operating characteristic curve (ROC) analysis. Results: Within the initial analysis, six qEEG dyads (all coherence) had significant predictive values. Within the final biomarkers, just four predictors, including F3-C3 (R frontal) alpha coherence, P3-O1 (R parietal) theta coherence, CZ-PZ (central) beta coherence, and P8-O2 (L parietal occipital) theta power were used in the final model, which yielded an ROC area of 0.8226. Conclusions: We replicated our previous findings of qEEG differences between adolescents and HCs and successfully developed a single-value predictive model with a robust ROC area. Furthermore, the brain areas involved in behavioral disinhibition and resting state/default mode networks were again shown to be involved in the observed differences. Thus, qEEG appears to be a potential low-cost and effective intermediate biomarker for MDD in youth.

Clinical evaluation of Major Depressive Disorder (MDD) and Borderline Personality Disorder(BPD) in youth adolescents

IntroductionAccording to international studies, at least 70% of BPD in adolescence are comorbid with MDD.ObjectivesTo determine the clinical and psychopathological markers of MDD in BPD in adolescence.MethodsClinical psychopathological interview, SCID-II, Hamilton Depression Rating Scale (HDRS). Sample: N=73 male and female, age: 18-25 with MDD and BPD.ResultsMDD comorbid with BPD in adolescence is characterized by polymorphism of its’ psychopathological manifestations due to the structure of BPD and the input of the age factor. In the studied sample 31 (42,5%) with both MDD and BPD also revealed addictions; 24 patients (32,9%) - anxiety and obsessive-compulsive (OCD) disorders, 18 patients (24,7%) had overvalued ideas. The high contingency of MDD with autoaggressive actions confirmed their high suicidal risk (53 patients). Among them - 31 patients (58,5%) - had non-suicidal self-harm (NSSI), 7 patients – (13,2%) had suicidal attempt (SA), and 15 patients (28,3%) had NSSI and suicidal attempts (NSSI+SA). The highest incidence of NSSI and NSSI+SA was noted in MDD with addictive disorders: NSSI – N=20 (80,00%), NSSI+SA - N=5 (20,00%), SA – N=0. MDD with BPD and anxiety disorders: NSSI – N=9 (56,25%), NSSI+SA – N= 6 (37,50%), SA–N=1 (6,25%). MDD with BPD and overvalued ideas: NSSI – N=2 (16,67%), NSSI +SA – N= 4 (33,33%), SA N=6 (50,0%), (results p<0.01).ConclusionsPsychopathological relations between BPD and MDD in youth are different due to additional comorbid conditions, like addictions, anxiety and OCD, overvalued ideas and have clinical implications in terms of suicidal and NSSI risks, individualized interventions and prognosis.DisclosureNo significant relationships.

P289. Cortisol and Development of Depression in Adolescence and Young Adulthood - A Meta-Analysis

Previous evidence in adults suggests the involvement of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in the development of major depressive disorder (MDD). However, less is known in the context of depression in adolescence and young adulthood, in particular in low-and-middle-income countries. To address this, we conducted a meta-analysis of worldwide studies investigating the relationship between cortisol, as a measure of HPA axis activity, and MDD in youth.

Choline in Pediatric Depression

The prefrontal cortex has been previously implicated in the neuropathology of major depressive disorder (MDD). Hence, we used proton magnetic resonance spectroscopy (1H-MRS) to examine choline levels in the prefrontal cortex of youth with major depression. Twelve age- and sex-matched case-control pairs were examined (age range 10 to 18 years, 7 females and 5 males in each group). All subjects were treatment naive at the time of the scan. A long echo 1H-MRS scan was acquired from the right prefrontal cortex (4cc) in all subjects. Right prefrontal Choline/Creatine ratios were elevated in the youth with mood disorders (F1, 11=10.741, p=0.007) as compared with healthy controls. These findings suggest that prefrontal cytosolic choline may be increased in youth with MDD in comparison with healthy controls. This is consistent with reported findings in both adults and adolescents and suggests that MDD in youth is associated with alterations in choline metabolism in the prefrontal cortex.

Reward Functioning Abnormalities in Adolescents at High Familial Risk for Depressive Disorders

BackgroundA parental history of major depressive disorder (MDD) is an established risk factor for MDD in youth, and clarifying the mechanisms related to familial risk transmission is critical. Aberrant reward processing is a promising biomarker of MDD risk; accordingly, the aim of this study was to test behavioral measures of reward responsiveness and underlying frontostriatal resting activity in healthy adolescents both with (high-risk) and without (low-risk) a maternal history of MDD. MethodsLow-risk and high-risk 12- to 14-year-old adolescents completed a probabilistic reward task (n = 74 low-risk, n = 27 high-risk) and a resting-state functional magnetic resonance imaging scan (n = 61 low-risk, n = 25 high-risk). Group differences in response bias toward reward and resting ventral striatal and medial prefrontal cortex (mPFC) fractional amplitude of low-frequency fluctuations (fALFFs) were examined. Computational modeling was applied to dissociate reward sensitivity from learning rate. ResultsHigh-risk adolescents showed a blunted response bias compared with low-risk adolescents. Computational modeling analyses revealed that relative to low-risk adolescents, high-risk adolescents exhibited reduced reward sensitivity but similar learning rate. Although there were no group differences in ventral striatal and mPFC fALFFs, groups differed in their relationships between mPFC fALFFs and response bias. Specifically, among high-risk adolescents, higher mPFC fALFFs correlated with a blunted response bias, whereas there was no fALFFs–response bias relationship among low-risk youths. ConclusionsHigh-risk adolescents exhibit reward functioning impairments, which are associated with mPFC fALFFs. The blunted response bias–mPFC fALFFs association may reflect an excessive mPFC-mediated suppression of reward-driven behavior, which may potentiate MDD risk.

Short- and Long-Term Antidepressant Clinical Trials for Major Depressive Disorder in Youth: Findings and Concerns.

The diagnosis of major depressive disorder (MDD) in U.S. youth is increasing as is the rate of antidepressant medication (ADM) treatment for the disorder. Fluoxetine and escitalopram are FDA approved for the short term and maintenance treatment of MDD in youth. Placebo-controlled short-term ADM trials represent the basis for Food and Drug Administration (FDA) approval. Meta-analyses in 2007 and 2016 revealed that short-term ADM treatment of youth diagnosed with MDD resulted in no meaningful benefit for children and only marginal benefit for adolescents. Placebo substitution trials of ADM short-term responders represent the basis for FDA approval of ADM maintenance treatment. These ADM placebo substitution maintenance trials for youth with MDD are characterized by high dropout rates, a rapid withdrawal that often can follow the switch to placebo, and relapse rates that are not dissimilar from those in the natural course of the disorder. Without the evidence from problematic ADM placebo substitution trials, there is no acceptable support for the inclusion of ADM in maintenance treatment for MDD in youth.

2.55 Inflammatory and Neurotrophic Markers and the Pathogenesis of Major Depressive Disorder in Youth: A Preliminary Analysis

2.55 Inflammatory and Neurotrophic Markers and the Pathogenesis of Major Depressive Disorder in Youth: A Preliminary Analysis

Reconsidering Animal Models of Major Depressive Disorder in the Elderly.

Major depressive disorder (MDD) is a common psychiatric illness with high morbidity that poses a huge burden to healthcare systems worldwide. According to the World Health Organization, the lifetime prevalence of MDD is approximately 3–17% globally (Richards, 2011). However, after major, but limited, success with selective serotonin reuptake inhibitors (SSRIs) or serotonin–noradrenaline reuptake inhibitors, few promising therapeutic approaches have been developed from preclinical studies using current animal models of MDD, despite intensive research involving laborious methods and substantial costs. Traditionally, most research using rodent models of MDD has been conducted using relatively young adult animals, aged approximately 8 weeks, to avoid any involvement of aging-related biological factors. The major rationale of this strategy is based on epidemiological findings that the occurrence of MDD displays a robust peak in young adults rather than in the elderly (Jorm, 2000; Copeland et al., 2004; Blazer and Hybels, 2005). Further, the elderly may have aging-related factors rendering this group an inappropriate model of “genuine” MDD. A critical question is whether this strategy is indeed appropriate. Despite the consistent findings of a lower lifetime prevalence rate of MDD in the elderly than in young adults, there remain persistent doubts regarding the underdiagnosis of MDD in the elderly (Hoertel et al., 2013). It has been heavily argued that patients diagnosed with MDD in youth will often be rediagnosed with a bipolar disorder (Lish et al., 1994; Leonpacher et al., 2015). Thus, a considerable number of cases of MDD in young adults may be misdiagnosed. In addition, MDD in the elderly has distinct biological/environmental backgrounds and consequences compared with that in young adults. In this opinion article, we primarily shed light on the significance of MDD in the elderly (known as geriatric MDD or late-onset depression) and problems associated with the methodology of preclinical studies undertaken to investigate the characteristics and treatment of this disorder.

Meta-analysis of Functional Neuroimaging of Major Depressive Disorder in Youth.

Despite its high prevalence and morbidity, the underlying neural basis of major depressive disorder (MDD) in youth is not well understood. To identify in youth diagnosed as having MDD the most reliable neural abnormalities reported in existing functional neuroimaging studies and characterize their relations with specific psychological dysfunctions. Searches were conducted in PubMed and Web of Science to identify relevant studies published from November 2006 through February 2015. The current analysis took place from August 21, 2014, to March 28, 2015. We retained articles that conducted a comparison of youth aged 4 to 24 years diagnosed as having MDD and age-matched healthy controls using task-based functional magnetic resonance imaging and a voxelwise whole-brain approach. We extracted coordinates of brain regions exhibiting differential activity in youth with MDD compared with healthy control participants. Multilevel kernel density analysis was used to examine voxelwise between-group differences throughout the whole brain. Correction for multiple comparisons was performed by computing null hypothesis distributions from 10 000 Monte Carlo simulations and calculating the cluster size necessary to obtain the familywise error rate control at P < .05. Abnormal levels of activation in youth diagnosed as having MDD compared with control participants during a variety of affective processing and executive functioning tasks. Compared with age-matched healthy control participants (n = 274), youth with MDD (n = 246) showed reliable patterns of abnormal activation, including the following task-general and task-specific effects: hyperactivation in subgenual anterior cingulate cortex (P < .05) and ventrolateral prefrontal cortex (P < .05) and hypoactivation in caudate (P < .01) across aggregated tasks; hyperactivation in thalamus (P < .03) and parahippocampal gyrus (P < .003) during affective processing tasks; hypoactivation in cuneus (P < .001), dorsal cingulate cortex (P < .05), and dorsal anterior insula (P < .05) during executive functioning tasks; hypoactivity in posterior insula (P < .005) during positive valence tasks; and hyperactivity in dorsolateral prefrontal cortex (P < .001) and superior temporal cortex (P < .003) during negative valence tasks. Altered activations in several distributed brain networks may help explain the following seemingly disparate symptoms of MDD in youth: hypervigilance toward emotional stimuli from the overactivation of central hubs in the subgenual anterior cingulate cortex and thalamus that lead to a cascade of other symptoms; ineffective emotion regulation despite increased activation of the dorsolateral prefrontal cortex and ventrolateral prefrontal cortex during affective processing, which may reverse across development or the clinical course; maladaptive rumination and poor executive control from difficulties shifting from default mode network activity to task-positive network activity during cognitively demanding tasks; and anhedonia from hypoactivation of the cuneus and posterior insula during reward processing.

Rational-emotive and cognitive-behavior therapy (REBT/CBT) versus pharmacotherapy versus REBT/CBT plus pharmacotherapy in the treatment of major depressive disorder in youth; A randomized clinical trial

Major depressive disorder is a highly prevalent and debilitating condition in youth, so developing efficient treatments is a priority for mental health professionals. Psychotherapy (i.e., cognitive behavioral therapy/CBT), pharmacotherapy (i.e., SSRI medication), and their combination have been shown to be effective in treating youth depression; however, the results are still mixed and there are few studies engaging multi-level analyses (i.e., subjective, cognitive, and biological). Therefore, the aims of this randomized control study (RCT) were both theoretical - integrating psychological and biological markers of depression in a multi-level outcome analysis - and practical – testing the generalizability of previous results on depressed Romanian youth population. Eighty-eight (N=88) depressed Romanian youths were randomly allocated to one of the three treatment arms: group Rational Emotive Behavior Therapy (REBT)/CBT (i.e., a form of CBT), pharmacotherapy (i.e., sertraline), and group REBT/CBT plus pharmacotherapy. The results showed that all outcomes (i.e., subjective, cognitive, and biological) significantly change from pre to post-treatment under all treatment conditions at a similar rate and there were no significant differences among conditions at post-test. In case of categorical analysis of the clinical response rate, we found a non-significant trend favoring group REBT/CBT therapy. Results of analyses concerning outcome interrelations are discussed.

12-weeks supervised exercise training is a feasible and efficacious treatment for reducing depression in youth with major depressive disorder

Introduction: Major Depressive Disorder (MDD) has high prevalence among adolescents and young adults. Evidence of any effective treatments is limited. Exercise as an effective treatment for adults has some support but studies in younger populations are lacking. Therefore the aim of this study was to investigate the feasibility and preliminary efficacy of brief motivational interviewing (MI) plus 12-weeks exercise training as a treatment for MDD in youth.

Re-examining the risk for switch from unipolar to bipolar major depressive disorder in youth with ADHD: A long term prospective longitudinal controlled study

BackgroundRecent studies have identified subthreshold forms of bipolar (BP)-I disorder and deficits in emotional regulation as risk factors for bipolar disorder in youth. The primary aim of this study was to investigate whether emotional dysregulation and subthreshold forms of BP-I disorder increase the risk for BP switches in ADHD youth with non-bipolar MDD. MethodsWe used data from two large controlled longitudinal family studies of boys and girls with and without ADHD. Subjects (N=522) were followed prospectively and blindly over an average follow up period of 11.4 years. Comparisons were made between ADHD youth with unipolar major depression (MDD) who did (N=24) and did not (N=79) switch to BP-I disorder at follow-up. ResultsThe rate of conversion to BP-I disorder at follow up was higher in MDD subjects with subthreshold BP-I disorder at baseline compared to those without (57% vs. 21%; OR=9.57, 95% CI=1.62−56.56, p=0.013) and in MDD subjects with deficient emotional self-regulation (OR=3.54, 95% CI=1.08−11.60, p=0.037). LimitationsThe sample was largely Caucasian, so these results may not generalize to minority groups. The sample of youth with SED was small, which limited the statistical power for some analyses. ConclusionsSwitches from unipolar MDD to BP-I disorder in children with ADHD and MDD were predicted by baseline subthreshold BP-I disorder symptoms and baseline deficits in emotional regulation. More work is needed to assess whether these risk factors are operant outside the context of ADHD.

Developmentally Informed Pharmacotherapy for Child and Adolescent Depressive Disorders

This article reviews evidence-based pharmacotherapy for children and adolescents with depression. Several randomized controlled trials (RCTs) support the use of fluoxetine for the treatment of childhood and adolescent depression as well as escitalopram in the treatment of adolescent depression. To date, one RCT has demonstrated the effectiveness of sertraline or citalopram for the treatment of major depressive disorder in youth. Only a small number of RCTs for depression have included children, and none of these trials were adequately powered to detect differences in the efficacy of medication between children and adolescents.

Escitalopram for the treatment of major depressive disorder in youth

Introduction:Major depressive disorder (MDD) is a serious public problem, affecting 4 – 6% of adolescents at any one time. Although adolescent MDD needs early and appropriate intervention, concerns regarding the risk of suicidality associated with antidepressant treatment and efficacy of pharmacotherapy have led to decreased use of antidepressants in children and adolescents. After the approval of fluoxetine in 2003, escitalopram received FDA approval in 2009 for the acute and maintenance treatment of MDD in adolescent patients.Areas covered:The paper addressed the following questions: Is escitalopram effective for adolescent MDD? How large is the magnitude of effectiveness? Does escitalopram treatment have any benefit in adolescents compared with the risk of suicidal behavior and treatment-emergent adverse events?Expert opinion:The efficacy of escitalopram in adolescent MDD was demonstrated in a double-blind, randomized, controlled trial and extrapolated from a similar citalopram trial. The optimal dose is 10 mg/day and the magnitude of the antidepressant effect is modest. Escitalopram treatment is generally well tolerated by adolescents, but treatment-emergent agitation, suicidal behavior and manic symptoms should be closely monitored. Escitalopram can be used as one of the first-line treatment options for moderate to severe MDD in adolescents.

Psychopharmacologic treatment of pediatric major depressive disorder

The role of pharmacotherapy in the treatment of major depressive disorder (MDD) in youth has received much attention in recent years due to concerns of efficacy and safety of the antidepressants for the treatment of MDD in youth. This review describes the existing published and unpublished literature regarding the efficacy and short-term safety of the antidepressants and decision-making process required for the use of these medications for youth with MDD. In addition, current continuation and maintenance treatments are discussed. In general, nine depressed youth must be treated with an antidepressant to obtain one clinical response above that achieved with placebo. To date, fluoxetine has showed the most consistent positive treatment effects. Depressed youth had also acutely responded to other antidepressants, but the response to placebo has also been high. Overall, the antidepressants are well tolerated, but 1-3 children and adolescents of 100 taking antidepressants showed onset or worsening of suicidal ideation and, more rarely, suicide attempts. There is a positive risk-benefit ratio for the use of antidepressants in the acute treatment of depressed youth. First-line antidepressant treatment with-or without-specific types of psychotherapy is indicated for youth with MDD of at least moderate severity. All youth taking antidepressants must be closely monitored for suicidality and medication side effects. Many youth will likely require psychotherapy or additional medication treatments to address comorbid disorders. Treatments to prevent relapses and recurrences require further study.

Methodological complexities in the diagnosis of major depression in youth: an analysis of mother and youth self-reports.

Considering the well-documented low level of agreement between youth and parent reports on the diagnosis of major depressive disorder (MDD), uncertainties remain as to the informativeness of discrepant youth and parent reports in clinical studies. To this end we evaluated whether morbidity and functional correlates on the diagnosis of MDD in youth vary by informant source. The sample consisted of 186 pairs of independently assessed mother and youth self-reports on the diagnosis of MDD using structured diagnostic interviews ascertained in a large study of youth with and without attention deficit hyperactivity disorder of both genders. Subjects were also assessed on measures of interpersonal, school, and family functioning as well as prior treatment history. The diagnosis of MDD endorsed by youth self-report only when compared with that reported by the mother was characterized by significantly: shorter duration episode, later age at onset, milder depression-associated impairment, less impairment in interpersonal functioning, lower rates of comorbid disorders, and decreased likelihood to receive any course of treatment for depression. The morbidity and dysfunction associated with MDD varied significantly by informant source, and followed a dose-response association with the highest morbidity associated with the concurrent reports of the youth and the mothers, followed by mother report alone, with the least morbidity and dysfunction when endorsed by youth alone. These findings suggest that exclusive reliance on youth self-reports may identify a mild form of depression associated with limited morbidity and disability compared with that identified by parental reports.

Emotional Problems During Youth as Predictors of Stature During Early Adulthood: Results From a Prospective Epidemiologic Study

Adults with emotional disorders exhibit abnormalities in growth hormone secretion. If these abnormalities were to occur during childhood, they could affect growth. The purpose of this study was to examine the relationship between youth emotional disorders and stature in early adulthood. Using data from a prospective epidemiologic study of youth psychopathologic status, we used linear regression to examine the prospective relationship between anxiety disorders (separation anxiety and over-anxious disorders) or major depressive disorder in youth and stature in early adulthood. Anxiety disorders during childhood prospectively predicted relatively short stature in early adulthood among females, accounting for more than 5% of the variance in adult height. However, these associations were not found among males. There may be an association between abnormalities in growth and emotional problems in youth. Further research should examine biological measures related to growth among youth with emotional disorders.