State rumination predicts inhibitory control failures and dysregulation of default, salience, and cognitive control networks in youth at risk of depressive relapse: Findings from the RuMeChange trial.

Background: Trait rumination is a habitual response to negative experiences that can emerge during adolescence, increasing risk of depression. Trait rumination is correlated with poor inhibitory control (IC) and altered default mode network (DMN) and cognitive control network (CCN) engagement. Provoking state rumination in high ruminating youth permits investigation of rumination and IC at the neural level, highlighting potential treatment targets. Methods: Fifty-three high-ruminating youth were cued with an unresolved goal that provoked state rumination, then completed a modified Sustained Attention to Response Task (SART) that measures IC (commissions on no-go trials) in a functional MRI study. Thought probes measured state rumination about that unresolved goal and task-focused thoughts during the SART. Results: Greater state rumination during the SART was correlated with more IC failures. CCN engagement increased during rumination (relative to task-focus), including left dorsolateral prefrontal cortex and dorsalmedial prefrontal cortex. Relative to successful response suppression, DMN engagement increased during IC failures amongst individuals with higher state and trait rumination. Exploratory analyzes suggested more bothersome unresolved goals predicted higher left DLPFC activation during rumination. Limitations: The correlational research design did not permit a direct contrast of causal accounts of the relationship between rumination and IC. Conclusions: State rumination was associated with impaired IC and disrupted modulation of DMN and CCN. Increased CCN engagement during rumination suggested effortful suppression of negative thoughts, and this was greater for more bothersome unresolved goals. Relative task disengagement was observed during rumination-related errors. DMN-CCN dysregulation in high-ruminating youth may be an important treatment target.

Rumination-Focused Cognitive Behavioral Therapy Reduces Rumination and Targeted Cross-network Connectivity in Youth With a History of Depression: Replication in a Preregistered Randomized Clinical Trial.

Background: Rumination-focused cognitive behavioral therapy (RF-CBT) is designed to reduce depressive rumination or the habitual tendency to dwell on experiences in a repetitive, negative, passive, and global manner. RF-CBT uses functional analysis, experiential exercises, and repeated practice to identify and change the ruminative habit. This preregistered randomized clinical trial (NCT03859297, R61) is a preregistered replication of initial work. We hypothesized a concurrent reduction of both self-reported rumination and cross-network connectivity between the left posterior cingulate cortex and right inferior frontal and inferior temporal gyri. Methods: Seventy-six youths with a history of depression and elevated rumination were randomized to 10 to 14 sessions of RF-CBT (n = 39; 34 completers) or treatment as usual (n = 37; 28 completers). Intent-to-treat analyses assessed pre-post change in rumination response scale and in functional connectivity assessed using two 5 minute, 12 second runs of resting-state functional magnetic resonance imaging. Results: We replicated previous findings: a significant reduction in rumination response scale and a reduction in left posterior cingulate cortex to right inferior frontal gyrus/inferior temporal gyrus connectivity in participants who received RF-CBT compared with those who received treatment as usual. Reductions were large (z change = 0.84; 0.73, respectively [ps < .05]). Conclusions: This adolescent clinical trial further demonstrates that depressive rumination is a brain-based mechanism that is modifiable via RF-CBT. Here, we replicated that RF-CBT reduces cross-network connectivity, a possible mechanism by which rumination becomes less frequent, intense, and automatic. This National Institute of Mental Health-funded fast-fail study continues to the R33 phase during which treatment-specific effects of RF-CBT will be compared with relaxation therapy.

Negative association between non-suicidal self-injury in adolescents and default mode network activation during the distraction blocks of a rumination task.

INTRODUCTION: Rumination, or repetitive and habitual negative thinking, is associated with psychopathology and related behaviors in adolescents, including non-suicidal self-injury (NSSI). Despite the link between self-reported rumination and NSSI, there is limited understanding of how rumination is represented at the neurobiological level among youth with NSSI. METHOD: We collected neuroimaging and rumination data from 39 adolescents with current or past NSSI and remitted major depression. Participants completed a rumination induction fMRI task, consisting of both rumination and distraction blocks. We examined brain activation associated with total lifetime NSSI in the context of the rumination versus distraction contrast. RESULTS: Lifetime NSSI was associated with a greater discrepancy in activation during rumination relative to distraction conditions in clusters including the precuneus, posterior cingulate, superior, and middle frontal gyrus, and cerebellum. CONCLUSION: Difficulties associated with rumination in adolescents with NSSI may be related to requiring greater cognitive effort to distract from ruminative content in addition to increased attention in the context of ruminative content. Increasing knowledge of neurobiological circuits and nodes associated with rumination and their relationship with NSSI may enable us to better tailor interventions that can facilitate lasting well-being and neurobiological change.

Mechanisms of rumination change in adolescent depression (RuMeChange): study protocol for a randomised controlled trial of rumination-focused cognitive behavioural therapy to reduce ruminative habit and risk of depressive relapse in high-ruminating adolescents.

BACKGROUND: Adolescent-onset depression often results in a chronic and recurrent course, and is associated with worse outcomes relative to adult-onset depression. Targeting habitual depressive rumination, a specific known risk factor for relapse, may improve clinical outcomes for adolescents who have experienced a depressive episode. Randomized controlled trials (RCTs) thus far have demonstrated that rumination-focused cognitive behavioral therapy (RFCBT) reduces depressive symptoms and relapse rates in patients with residual depression and adolescents and young adults with elevated rumination. This was also observed in a pilot RCT of adolescents at risk for depressive relapse. Rumination can be measured at the self-report, behavioral, and neural levels- using patterns of connectivity between the Default Mode Network (DMN) and Cognitive Control Network (CCN). Disrupted connectivity is a putative important mechanism for understanding reduced rumination via RFCBT. A feasibility trial in adolescents found that reductions in connectivity between DMN and CCN regions following RFCBT were correlated with change in rumination and depressive symptoms. METHOD: This is a phase III two-arm, two-stage, RCT of depression prevention. The trial tests whether RFCBT reduces identified risk factors for depressive relapse (rumination, patterns of neural connectivity, and depressive symptoms) in adolescents with partially or fully remitted depression and elevated rumination. In the first stage, RFCBT is compared to treatment as usual within the community. In the second stage, the comparator condition is relaxation therapy. Primary outcomes will be (a) reductions in depressive rumination, assessed using the Rumination Response Scale, and (b) reductions in resting state functional magnetic resonance imaging connectivity of DMN (posterior cingulate cortex) to CCN (inferior frontal gyrus), at 16 weeks post-randomization. Secondary outcomes include change in symptoms of depression following treatment, recurrence of depression over 12 months post-intervention period, and whether engagement with therapy homework (as a dose measure) is related to changes in the primary outcomes. DISCUSSION: RFCBT will be evaluated as a putative preventive therapy to reduce the risk of depressive relapse in adolescents, and influence the identified self-report, behavioral, and neural mechanisms of change. Understanding mechanisms that underlie change in rumination is necessary to improve and further disseminate preventive interventions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03859297 , registered 01 March 2019.

Malleability of rumination: An exploratory model of CBT-based plasticity and long-term reduced risk for depressive relapse among youth from a pilot randomized clinical trial.

CLINICAL TRIALS REGISTRATION: NCT01905267, https://clinicaltrials.gov/ct2/show/NCT01905267.

Rumination-focused cognitive behavioral therapy decreases anxiety and increases behavioral activation among remitted adolescents.

OBJECTIVES: Rumination involves a repetitive, passive focus on one's thoughts and feelings and has been hypothesized as a mechanism contributing to multiple psychopathologies. The current investigation explores secondary outcomes from a pilot study to examine whether rumination-focused cognitive behavior therapy (RFCBT) alleviates symptoms of anxiety, increases behavioral activation, or increases global functioning among adolescents with a history of Major Depressive Disorder (MDD). METHODS: Thirty-three adolescents were randomized to receive either RFCBT (n = 17) or assessment only (AO; n = 16) over the course of eight weeks. Mixed effects regression models were used to conduct intent-to-treat (ITT) analyses. RESULTS: The quadratic interaction for group-by-time-by-time was significant for anxiety. Adolescents in the RFCBT group experienced a significant decrease in anxiety across the first six weeks of intervention (F = 7.01, df = 108.49, p = .009). The group-by-time interaction was significant for the behavioral activation outcome (F = 4.28, df = 25.60, p = .049) with youth randomized to RFCBT demonstrating increasing activation compared to AO. Global functioning did not significantly differ between groups (F = .40, df = 1, p > .05). CONCLUSIONS: Preliminary evidence suggests that RFCBT may hold promise as an intervention that alleviates both depressive and anxiety symptoms when comorbid.

Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies.

BACKGROUND: Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks. METHOD: The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29 year olds) of typically developing (TD) individuals (n = 97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136). RESULTS: Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood. CONCLUSIONS: The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage.

Cognitive control neuroimaging measures differentiate between those with and without future recurrence of depression.

BACKGROUND: Major Depressive Disorder (MDD) is a prevalent, disruptive illness. A majority of those with MDD are at high risk for recurrence and increased risk for morbidity and mortality. This study examined whether multimodal baseline (and retest) Cognitive Control performance and neuroimaging markers (task activation and neural connectivity between key brain nodes) could differentiate between those with and without future recurrence of a major depressive (MD) episode within one year. We hypothesized that performance and neuroimaging measures of Cognitive Control would identify markers that differ between these two groups. METHODS: A prospective cohort study of young adults (ages 18-23) with history (h) of early-onset MDD (N = 60), now remitted, and healthy young adults (N = 49). Baseline Cognitive Control measures of performance, task fMRI and resting state connectivity (and reliability retest 4-12 weeks later) were used to compare those with future recurrence of MDD (N = 21) relative to those without future recurrence of MDD (N = 34 with resilience). The measures tested were (1) Parametric Go/No-Go (PGNG) performance, and task activation for (2) PGNG Correct Rejections, (3) PGNG Commission errors, and (4 & 5), resting state connectivity analyses of Cognitive Control Network to and from subgenual anterior cingulate. RESULTS: Relative to other groups at baseline, the group with MDD Recurrence had less bilateral middle frontal gyrus activation during commission errors. MDD Recurrence exhibited greater connectivity of right middle frontal gyrus to subgenual anterior cingulate (SGAC). SGAC connectivity was also elevated in this group to numerous regions in the Cognitive Control Network. Moderate to strong ICCs were present from test to retest, and highest for rs-fMRI markers. There were modest, significant correlations between task, connectivity and behavioral markers that distinguished between groups. CONCLUSION: Markers of Cognitive Control function could identify those with early course MD who are at risk for depression recurrence. Those at high risk for recurrence would benefit from maintenance or preventative treatments. Future studies could test and validate these markers as potential predictors, accounting for sample selection and bias in feature detection.

Reliability, Convergent Validity and Time Invariance of Default Mode Network Deviations in Early Adult Major Depressive Disorder.

There is substantial variability across studies of default mode network (DMN) connectivity in major depressive disorder, and reliability and time-invariance are not reported. This study evaluates whether DMN dysconnectivity in remitted depression (rMDD) is reliable over time and symptom-independent, and explores convergent relationships with cognitive features of depression. A longitudinal study was conducted with 82 young adults free of psychotropic medications (47 rMDD, 35 healthy controls) who completed clinical structured interviews, neuropsychological assessments, and 2 resting-state fMRI scans across 2 study sites. Functional connectivity analyses from bilateral posterior cingulate and anterior hippocampal formation seeds in DMN were conducted at both time points within a repeated-measures analysis of variance to compare groups and evaluate reliability of group-level connectivity findings. Eleven hyper- (from posterior cingulate) and 6 hypo- (from hippocampal formation) connectivity clusters in rMDD were obtained with moderate to adequate reliability in all but one cluster (ICC's range = 0.50 to 0.76 for 16 of 17). The significant clusters were reduced with a principle component analysis (5 components obtained) to explore these connectivity components, and were then correlated with cognitive features (rumination, cognitive control, learning and memory, and explicit emotion identification). At the exploratory level, for convergent validity, components consisting of posterior cingulate with cognitive control network hyperconnectivity in rMDD were related to cognitive control (inverse) and rumination (positive). Components consisting of anterior hippocampal formation with social emotional network and DMN hypoconnectivity were related to memory (inverse) and happy emotion identification (positive). Thus, time-invariant DMN connectivity differences exist early in the lifespan course of depression and are reliable. The nuanced results suggest a ventral within-network hypoconnectivity associated with poor memory and a dorsal cross-network hyperconnectivity linked to poorer cognitive control and elevated rumination. Study of early course remitted depression with attention to reliability and symptom independence could lead to more readily translatable clinical assessment tools for biomarkers.

Multivariate pattern analysis strategies in detection of remitted major depressive disorder using resting state functional connectivity.

Understanding abnormal resting-state functional connectivity of distributed brain networks may aid in probing and targeting mechanisms involved in major depressive disorder (MDD). To date, few studies have used resting state functional magnetic resonance imaging (rs-fMRI) to attempt to discriminate individuals with MDD from individuals without MDD, and to our knowledge no investigations have examined a remitted (r) population. In this study, we examined the efficiency of support vector machine (SVM) classifier to successfully discriminate rMDD individuals from healthy controls (HCs) in a narrow early-adult age range. We empirically evaluated four feature selection methods including multivariate Least Absolute Shrinkage and Selection Operator (LASSO) and Elastic Net feature selection algorithms. Our results showed that SVM classification with Elastic Net feature selection achieved the highest classification accuracy of 76.1% (sensitivity of 81.5% and specificity of 68.9%) by leave-one-out cross-validation across subjects from a dataset consisting of 38 rMDD individuals and 29 healthy controls. The highest discriminating functional connections were between the left amygdala, left posterior cingulate cortex, bilateral dorso-lateral prefrontal cortex, and right ventral striatum. These appear to be key nodes in the etiopathophysiology of MDD, within and between default mode, salience and cognitive control networks. This technique demonstrates early promise for using rs-fMRI connectivity as a putative neurobiological marker capable of distinguishing between individuals with and without rMDD. These methods may be extended to periods of risk prior to illness onset, thereby allowing for earlier diagnosis, prevention, and intervention.

Attenuated intrinsic connectivity within cognitive control network among individuals with remitted depression: Temporal stability and association with negative cognitive styles.

Many individuals with major depressive disorder (MDD) experience cognitive dysfunction including impaired cognitive control and negative cognitive styles. Functional connectivity magnetic resonance imaging 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 this 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 with the right dorsolateral prefrontal cortex and right inferior parietal lobule, results that were corroborated by supplemental independent component analysis. 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. Hum Brain Mapp 38:2939-2954, 2017. © 2017 Wiley Periodicals, Inc.

Effect of maternal rumination and disengagement during childhood on offspring neural response to reward in late adolescence.

Maternal rumination is a cognitive-affective trait that could influence offspring's ability to respond flexibly to positive and negative events, depending on the quality of maternal problem-solving behaviors with which rumination co-occurs. As reward circuitry is sensitive to stressors and related to risk for depression, reward circuitry is an appropriate candidate mechanism for how maternal characteristics influence offspring. We evaluated the independent and combined effect of maternal rumination and disengagement on adolescent neural response to reward win and loss. Participants were 122 boys and their mothers from low-income, urban backgrounds followed prospectively in a longitudinal study. The combination of high maternal rumination at child age 6 and high maternal disengagement during problem-solving at child age 10-12 was associated with lower anterior cingulate response to winning reward at age 20, but unrelated to neural response to losing reward. Lower anterior cingulate response to winning reward was associated with fewer anxiety symptoms during late adulthood. Findings suggest that maternal rumination occurring within the context of maternal disengagement during challenging experiences may be related to offspring blunted engagement during positive events. Helping highly ruminative mothers to restructure repetitive negative thoughts and to develop context-appropriate problem-solving behaviors may be important for promoting offspring affective development.

Domain-specific impairment in cognitive control among remitted youth with a history of major depression.

AIM: Impairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g. trait), scar, burden or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, set-shifting and cognitive control in a unique population of young, remitted, unmedicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD. METHODS: Youth aged 18-23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD: verbal fluency and processing speed, conceptual reasoning and set-shifting, processing speed with interference resolution, and cognitive control. RESULTS: rMDD youth performed comparably to HCs on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and set-shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants. CONCLUSION: MDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation.

Neural correlates of rumination in adolescents with remitted major depressive disorder and healthy controls.

The aim of the present 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 the patterns of neural activation during rumination versus a distraction condition among 26 adolescents in remission from major depressive disorder (rMDD) and in 15 healthy control adolescents. Self-report depression and rumination, as well as clinician-rated depression, were also assessed among all participants. All of the participants recruited regions in the default mode network (DMN), including the posterior cingulate cortex, medial prefrontal cortex, inferior parietal lobe, and medial temporal gyrus, 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 than did healthy peers. The present 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.

Targeting Ruminative Thinking in Adolescents at Risk for Depressive Relapse: Rumination-Focused Cognitive Behavior Therapy in a Pilot Randomized Controlled Trial with Resting State fMRI.

This pilot randomized control trial was designed to examine whether Rumination-Focused Cognitive Behavior Therapy (RFCBT) reduces rumination and residual depressive symptoms among adolescents with a history of Major Depressive Disorder (MDD) who are at risk for relapse. We also examined whether these changes in symptoms were associated with changes in functional connectivity of the posterior cingulate cortex (PCC), a key node in the default mode network (DMN). Thirty-three adolescents (ages 12-18) were randomized to eight weeks of RFCBT or an assessment only (AO) control. Twenty two adolescents successfully completed fMRI scans pre- and post-intervention. Adolescents were recruited from the clinic and community and met criteria for at least one previous episode of MDD and were currently in full or partial remission. An Independent Evaluator interviewed parent and child before and after the eight-week intervention. The left PCC (-5, -50, 36) seed was used to probe resting state functional connectivity of the DMN. Adolescents who received RFCBT demonstrated reduced rumination (F = -2.76, df = 112, p < .01, 95% CI [-4.72,-0.80]) and self-report depression across eight weeks (F = -2.58, df = 113, p < .01, 95% CI [-4.21, -0.94]). Youth who received RFCBT also demonstrated significant decreases in connectivity between the left PCC and the right inferior frontal gyrus (IFG) and bilateral inferior temporal gyri (ITG). Degree of change in connectivity was correlated with changes in self-report depression and rumination. These data suggest that rumination can be reduced over eight weeks and that this reduction is associated with parallel decreases in residual depressive symptoms and decreased functional connectivity of the left PCC with cognitive control nodes. These changes may enhance the ability of vulnerable youth to stay well during the transition to adulthood. TRIAL REGISTRATION: ClinicalTrials.gov NCT01905267.

Aberrant resting-state functional connectivity in limbic and cognitive control networks relates to depressive rumination and mindfulness: A pilot study among adolescents with a history of depression.

BACKGROUND: Resting state functional connectivity (RSFC) research among adults indicates abnormalities within and between neural networks during acute depressive episodes, some of which are likely to remain into remission. The examination of RSFC among adolescents within the remitted state of MDD may implicate markers of illness course during a critical developmental window wherein secondary prevention can be implemented. METHODS: RSFC data were collected on a 3.0T GE scanner from adolescents (12-18, M=15.61, SD=1.90; 57% female) in full or partial remission from MDD (rMDD; n=23) and age- and gender-matched healthy controls (HC; n=10). RSFC data were examined using seed-based connectivity of the left amygdala, left dorsolateral prefrontal cortex (dlPFC), and left posterior cingulate cortex (PCC). These seeds were chosen to probe the emotional salience, cognitive control, and default mode networks, respectively. RESULTS: rMDD adolescents demonstrated relative hyperconnectivity from the left amygdala to the right PCC, as well as from the left dlPFC to the right middle frontal and left inferior frontal gyri (MFG, IFG). Amygdala to PCC connectivity was correlated with greater rumination, dlPFC to MFG connectivity was positively associated with depression severity, and dlPFC to IFG connectivity was inversely associated with mindfulness. CONCLUSIONS: Aberrant functional connectivity within and between neural networks responsible for salience attribution, introspective thought, and executive control can be observed among adolescents in the remitted phase of MDD and is associated with residual clinical symptoms. These patterns may confer risk for future relapse or alternatively, support wellness.

Sex-specific neural activity when resolving cognitive interference in individuals with or without prior internalizing disorders.

The processing of cognitive interference is a self-regulatory capacity that is impaired in persons with internalizing disorders. This investigation was to assess sex differences in the neural correlates of cognitive interference in individuals with and without an illness history of an internalizing disorder. We compared functional magnetic resonance imaging blood-oxygenation-level-dependent responses in both males (n=63) and females (n=80) with and without this illness history during performance of the Simon task. Females deactivated superior frontal gyrus, inferior parietal lobe, and posterior cingulate cortex to a greater extent than males. Females with a prior history of internalizing disorder also deactivated these regions more compared to males with that history, and they additionally demonstrated greater activation of right inferior frontal gyrus. These group differences were represented in a significant sex-by-illness interaction in these regions. These deactivated regions compose a task-negative or default mode network, whereas the inferior frontal gyrus usually activates when performing an attention-demanding task and is a key component of a task-positive network. Our findings suggest that a prior history of internalizing disorders disproportionately influences functioning of the default mode network and is associated with an accompanying activation of the task-positive network in females during the resolution of cognitive interference.

Trajectories of Functioning Into Emerging Adulthood Following Treatment for Adolescent Depression.

PURPOSE: It is well established that empirically supported treatments reduce depressive symptoms for most adolescents; however, it is not yet known whether these interventions lead to sustained improvements in global functioning. The goal of this study is to assess the clinical characteristics and trajectories of long-term psychosocial functioning among emerging adults who have experienced adolescent-onset major depressive disorder. METHODS: Global functioning was assessed using the Clinical Global Assessment Scale for children (participants ≤18 years), the Global Assessment of Functioning (participants ≥ 19 years) and the Health of the Nation Outcome Scales for Adolescents among 196 adolescents who elected to complete 3.5 years of naturalistic follow-up subsequent to their participation in the Treatment for Adolescents with Depression Study. The Treatment for Adolescents with Depression Study examined the efficacy of cognitive behavior therapy, fluoxetine, and the combination of cognitive behavior therapy and fluoxetine (combination treatment) over the course of 36 weeks. Mixed-effects regression models were used to identify trajectories and clinical predictors of functioning over the naturalistic follow-up. RESULTS: Global functioning and achievement of developmental milestones (college, employment) improved over the course of follow-up for most adolescents. Depressive relapse, initial randomization to the placebo group, and the presence of multiple psychiatric comorbidities conferred risk for relatively poorer functioning. CONCLUSIONS: Functioning generally improves among most adolescents who have received empirically supported treatments. However, the presence of recurrent major depressive disorder and multiple psychiatric comorbidities is associated with poorer functioning trajectories, offering targets for maintenance treatment or secondary prevention.

Amygdala and dorsomedial hyperactivity to emotional faces in youth with remitted Major Depression.

We present neuroimaging markers of the remitted state of major depressive disorder (rMDD) during facial emotion perception in 84 individuals during fMRI. Participants comprised 47 individuals (aged 18-23) diagnosed with rMDD and 37 healthy controls (HCs). Participants classified emotional faces or animals (control condition) in the Facial Emotion Perception Test (FEPT) during fMRI. Behavioural performance on the FEPT did not differ significantly between groups. During fMRI, both groups demonstrated significant blood oxygen level-dependent (BOLD) activity in bilateral inferior frontal gyri for the faces minus animals (F-A) contrast. The rMDD group additionally showed BOLD activity during F-A in numerous regions, including the bilateral paracingulate gyri, middle temporal gyri and right amygdala. The rMDD group exhibited significantly greater activity than the HC group in regions including the bilateral middle temporal gyri and left superior frontal gyrus. Although the rMDD group did not manifest the behavioural performance deficits on facial emotion recognition tasks that have been observed in actively depressed individuals, the rMDD group nevertheless showed increased BOLD activity compared with never-depressed controls during F-A in multiple posterior brain regions, suggesting that persistent effects of illness or possible trait vulnerabilities may distinguish individuals with rMDD from never-depressed controls.

Stress Response to the Functional Magnetic Resonance Imaging Environment in Healthy Adults Relates to the Degree of Limbic Reactivity during Emotion Processing.

BACKGROUND: Imaging techniques are increasingly being used to examine the neural correlates of stress and emotion processing; however, relations between the primary stress hormone cortisol, the functional magnetic resonance imaging (fMRI) environment, and individual differences in response to emotional challenges are not yet well studied. The present study investigated whether cortisol activity prior to, and during, an fMRI scan may be related to neural processing of emotional information. METHODS: Twenty-six healthy individuals (10 female) completed a facial emotion perception test during 3-tesla fMRI. RESULTS: Prescan cortisol was significantly correlated with enhanced amygdala, hippocampal, and subgenual cingulate reactivity for facial recognition. Cortisol change from pre- to postscanning predicted a greater activation in the precuneus for both fearful and angry faces. A negative relationship between overall face accuracy and activation in limbic regions was observed. CONCLUSION: Individual differences in response to the fMRI environment might lead to a greater heterogeneity of brain activation in control samples, decreasing the power to detect differences between clinical and comparison groups. © 2015 S. Karger AG, Basel.