Differences in estimates of the efficacy of CBT for depressed adolescents may stem from methodological differences between early and more recent investigations. Overall, results support the effectiveness of CBT for the treatment of adolescent depression.

We summarize and integrate research on cognitive vulnerability to depression among children and adolescents. We first review prospective longitudinal studies of the most researched cognitive vulnerability factors (attributional style, dysfunctional attitudes, and self-perception) and depression among youth. We next review research on information processing biases in youth. We propose that the integration of these two literatures will result in a more adequate test of cognitive vulnerability models. Last, we outline a program of research addressing methodological, statistical, and scientific limitations in the cognitive vulnerability literature.

Context Major Depressive Disorder (MDD) in adolescents is common and impairing. Efficacious treatments have been developed, but little is known about longer term outcomes, including recurrence. Objectives To determine whether adolescents who responded to acute treatments, or who received the most efficacious acute treatment, would have lower recurrence rates, and to identify predictors of recovery and recurrence. Design Naturalistic follow-up study. Setting Twelve academic sites in the United States. Participants One hundred ninety-six adolescents (86 males and 110 females) randomized to one of four acute interventions (fluoxetine (FLX), cognitive behavior therapy (CBT), their combination (COMB), or placebo (PBO)) in the Treatment for Adolescents with Depression Study (TADS) were followed for five years after study entry (44.6% of the original TADS sample). Main Outcome Measure Recovery was defined as absence of clinically significant MDD symptoms on the K-SADS-P/L interview for at least eight weeks, and recurrence as a new episode of MDD following recovery. Results Almost all participants (96.4%) recovered from their index episode of MDD during the follow-up period. Recovery by two years was significantly more likely for acute treatment responders (96.2%) than for partial or non-responders (79.1%) (p < .001), but was not associated with having received the most efficacious acute treatment (COMB). Of the 189 participants who recovered, 88 (46.6%) had a recurrence. Recurrence was not predicted by full acute treatment response or by original treatment. However, full or partial responders were less likely to have a recurrence (42.9%) than were non-responders (67.6%) (p = .03). Gender predicted recurrence (57.0% among females and 32.9% among males) (p = .024). Conclusions Almost all depressed adolescents recovered. However, recurrence occurs in almost half of recovered adolescents, with higher probability in females in this age range. Further research should identify and address the vulnerabilities to recurrence that are more common among young women.

Context:The Treatment for Adolescents With Depression Study evaluates the effectiveness of fluoxetine hydrochloride therapy, cognitive behavior therapy (CBT), and their combination in adolescents with major depressive disorder.Objective: To report effectiveness outcomes across 36 weeks of randomized treatment.Design and Setting: Randomized, controlled trial conducted in 13 academic and community sites in the United States. Cognitive behavior and combination therapies were not masked, whereas administration of placebo and fluoxetine was double-blind through 12 weeks, after which treatments were unblinded. Patients assigned to placebo were treated openly after week 12, and the placebo group is not included in these analyses by design.Participants: Three hundred twenty-seven patients aged 12 to 17 years with a primary DSM-IV diagnosis of major depressive disorder.Interventions: All treatments were administered per protocol. Main Outcome Measures:The primary dependent measures rated blind to treatment status by an independent evaluator were the Children's Depression Rating ScaleRevised total score and the response rate, defined as a Clinical Global Impressions-Improvement score of much or very much improved.Results: Intention-to-treat analyses on the Children's Depression Rating Scale-Revised identified a significant time ϫ treatment interaction (P Ͻ .001). Rates of response were 73% for combination therapy, 62% for fluoxetine therapy, and 48% for CBT at week 12; 85% for combination therapy, 69% for fluoxetine therapy, and 65% for CBT at week 18; and 86% for combination therapy, 81% for fluoxetine therapy, and 81% for CBT at week 36. Suicidal ideation decreased with treatment, but less so with fluoxetine therapy than with combination therapy or CBT. Suicidal events were more common in patients receiving fluoxetine therapy (14.7%) than combination therapy (8.4%) or CBT (6.3%). Conclusions:In adolescents with moderate to severe depression, treatment with fluoxetine alone or in combination with CBT accelerates the response. Adding CBT to medication enhances the safety of medication. Taking benefits and harms into account, combined treatment appears superior to either monotherapy as a treatment for major depression in adolescents.

ObjectiveFunctional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD.MethodfcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18–23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain.ResultsCompared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely.ConclusionsFindings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.

The aim of the current study was to use fMRI to examine the neural correlates of engaging in rumination among a sample of remitted depressed adolescents, a population at high risk for future depressive relapse. A rumination induction task was used to assess differences in patterns of neural activation during rumination as compared with a distraction condition among 26 adolescents in remission from major depressive disorder (rMDD) and 15 healthy control adolescents. Self-report depression and rumination as well as clinician-rated depression were also assessed among all participants. All participants recruited regions in the default mode network (DMN), including the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), inferior parietal lobe (IPL), and medial temporal gyrus (MTG) during rumination. Increased activation in these regions during rumination was correlated with increased self-report rumination and symptoms of depression across all participants. Adolescents with rMDD also exhibited greater activation in regions involved in visual, somatosensory, and emotion processing when compared to healthy peers. The current findings suggest that during ruminative thought, adolescents with rMDD are characterized by increased recruitment of regions within the DMN and in areas involved in visual, somatosensory, and emotion processing.

Many individuals with major depressive disorder (MDD) experience cognitive dysfunction including impaired cognitive control and negative cognitive styles. Functional connectivity MRI studies of individuals with current MDD have documented altered resting-state connectivity within the default-mode network and across networks. However, no studies to date have evaluated the extent to which impaired connectivity within the cognitive control network (CCN) may be present in remitted MDD (rMDD), nor have studies examined the temporal stability of such attenuation over time. This represents a major gap in understanding stable, trait-like depression risk phenotypes. In the present study, resting-state functional connectivity data were collected from 52 unmedicated young adults with rMDD and 47 demographically-matched healthy controls, using three bilateral seeds in the CCN (dorsolateral prefrontal cortex, inferior parietal lobule, and dorsal anterior cingulate cortex). Mean connectivity within the entire CCN was attenuated among individuals with rMDD, was stable and reliable over time, and was most pronounced from the right dorsolateral prefrontal cortex and right inferior parietal lobule to the three bilateral CCN seeds. Attenuated connectivity in rMDD appeared to be specific to the CCN as opposed to representing attenuated within-network coherence in other networks (e.g., default-mode, salience). In addition, attenuated connectivity within the CCN mediated relationships between rMDD status and cognitive risk factors for depression, including ruminative brooding, pessimistic attributional style, and negative automatic thoughts. Given that these cognitive markers are known predictors of relapse, these results suggest that attenuated connectivity within the CCN could represent a biomarker for trait phenotypes of depression risk.

Background Recent meta-analyses of resting-state networks in major depressive disorder (MDD) implicate network disruptions underlying cognitive and affective features of illness. Heterogeneity of findings to date may stem from the relative lack of data parsing clinical features of MDD such as phase of illness and the burden of multiple episodes. Method Resting-state functional magnetic resonance imaging data were collected from 17 active MDD and 34 remitted MDD patients, and 26 healthy controls (HCs) across two sites. Participants were medication-free and further subdivided into those with single v. multiple episodes to examine disease burden. Seed-based connectivity using the posterior cingulate cortex (PCC) seed to probe the default mode network as well as the amygdala and subgenual anterior cingulate cortex (sgACC) seeds to probe the salience network (SN) were conducted. Results Young adults with remitted MDD demonstrated hyperconnectivity of the left PCC to the left inferior frontal gyrus and of the left sgACC to the right ventromedial prefrontal cortex (PFC) and left hippocampus compared with HCs. Episode-independent effects were observed between the left PCC and the right dorsolateral PFC, as well as between the left amygdala and right insula and caudate, whereas the burden of multiple episodes was associated with hypoconnectivity of the left PCC to multiple cognitive control regions as well as hypoconnectivity of the amygdala to large portions of the SN. Conclusions This is the first study of a homogeneous sample of unmedicated young adults with a history of adolescent-onset MDD illustrating brain-based episodic features of illness.