RESUMEN

Engagement in nonsuicidal self-injury (NSSI) often begins in adolescence, and commonly occurs when a person is emotionally dysregulated. Parental emotion socialization (ES) plays a key role in shaping children's emotional expression, experience, and regulation. Longitudinal work is needed to understand how links between parental ES and adolescent clinical outcomes unfold over time. In this longitudinal study (N = 118; all assigned female at birth with a range of NSSI - from none to severe; age 12-17 years, Mage = 14.98 at the first assessment), for the Time 1 (T1) and Time 2 (T2) annual assessments; adolescents reported NSSI and adolescents and parents reported depressive symptoms. Parents (primarily mothers) reported on their supportive and unsupportive ES responses to youth expressions of sadness, anger, and happiness. We examined (1) concurrent relationships across time points, (2) longitudinal models (T1 to T2 change in parental ES and its associated T1 to T2 changes in adolescent clinical outcomes), and (3) prediction models (T1 parental ES predicting changes in adolescent clinical outcomes). Concurrent associations between parental supportive ES responses to sadness and anger were inversely related to adolescent's depressive symptoms and NSSI episodes. Longitudinal analyses showed that increases in unsupportive responses to sadness correspond with increases in depressive symptoms from T1 to T2. The findings underscore the importance of examining how parents respond to their children's emotions. Next steps are to investigate potential mechanisms of risk and consider interventions that enhance adaptive responses of parents to adolescents embroiled in negative emotional states.

RESUMEN

Background: Non-suicidal self-injury (NSSI) is a highly prevalent clinical concern in adolescents and is associated with impaired functioning and suicide risk. The BRIDGES (BRain Imaging Development of Girls' Emotion and Self) study was designed to collect longitudinal clinical and neurobiological data to advance our understanding of NSSI in adolescents. The purpose of this paper is to describe the clinical data collected as part of this study, including psychiatric diagnoses, depression symptoms, episodes of non-suicidal self-injury, suicidal thoughts and behaviors, childhood trauma, and personality domains. Methods: The baseline sample included 164 adolescents aged 12-16 assigned female at birth (Mean age = 14.97, SD = 1.20) with NSSI histories ranging from none to severe. Participants and their parent/guardian were invited to provide data at three time points spaced approximately one year apart. Descriptive analyses were conducted to provide estimates of rates and trajectories of clinical data. Results: Of the 164 study participants, 75.61% and 57.93% completed the second and third time points, respectively. Visual inspection of the data suggests an overall trend of decreasing severity of psychopathology over time, and adolescents with a history of NSSI appeared to have higher rates of psychopathology than those without. Conclusions: This paper describes longitudinal clinical trajectories in adolescents with a range of NSSI histories and presents readers with an overview of the rich, publicly available dataset that we hope will inspire future research to advance the understanding of the neurodevelopmental trajectories associated with NSSI, depression, and suicide risk.

RESUMEN

Precision medicine approaches hold tremendous promise to advance current clinical practice by providing information about which individuals will benefit from which treatments. This pilot study evaluated if baseline structure and function of the salience and emotion brain regions implicated in adolescent depression, specifically the amygdala and anterior cingulate cortex (ACC), predict response to Interpersonal Psychotherapy for Depressed Adolescents (IPT-A). Adolescents (n = 15; mean age = 14.5 (1.6); 80.0% female) diagnosed with a depressive disorder completed brain scans before the start of a 16 week trial of IPT-A. Clinical measures assessing depressive symptoms were completed before, during, and after a trial of therapy. Results show that at baseline, greater ACC activation in the context of an emotion-matching task and greater amygdala-ACC resting-state functional connectivity was related to greater improvement in depression symptoms. There was minimal evidence that brain structure predicted changes in depressive symptoms. The present study is the first to evaluate neural predictors of IPT-A response. While the results are preliminary, these findings suggest some avenues for future research to pursue in the hopes that more will benefit from treatment.

RESUMEN

Problems in parent-adolescent relationships are a significant risk factor for the development of depression in adolescents. This paper describes the development of a novel and innovative intervention for parents of depressed adolescents that targets attachment-related parenting behaviors, including parent responses to adolescents' emotions (Healthy Emotions and Relationships with Teens-A Guide for Parents [HEART-P]; Reigstad, 2017) and provides results of an open pilot study that was conducted to assess the feasibility and acceptability of the intervention. 15 parents/parent dyads of adolescents (age 12-18) with a depression diagnosis (14 mothers, and one father) participated in a 10-week open trial of HEART-P. Data regarding acceptability and feasibility were collected. Self-report measures of parenting, stress, family relationships, and adolescent depression were also completed by parents at baseline, week 10, and 2 months post-intervention. Parents completed the intervention with 100% adherence to the protocol and expressed high levels of satisfaction. Parents reported reductions in parenting stress, improvement in the quality of their relationship with their adolescent, and improvement in the perception of their parenting skills, with effect sizes in the medium to large range. Adolescents reported reductions in depression, with effect sizes in the small to medium range. Outcomes appear positive and promising, and the intervention was feasible to implement and acceptable to families. Conducting a full-scale randomized control trial to evaluate the efficacy of this newly developed intervention is warranted and timely given the public health need for improved depression treatment outcomes.

Asunto(s)

RESUMEN

The neurobiology of adolescent depression remains poorly understood. Initial studies suggested impaired white matter microstructure in adults and adolescents, but findings have not been consistent. Challenges in this literature have included small samples, medication confounds and inconsistent correction for type I error. This study addressed these issues in a new examination of fractional anisotropy (FA) in adolescents with major depressive disorder (MDD) using diffusion tensor imaging. We examined FA in 81 adolescents aged 12-19 (44 MDD [all unmedicated], 37 controls). We conducted logistic regression analyses to examine the odds of MDD versus control based on FA within standard white matter tracts that were delineated by probabilistic tractography. We also examined relationships between FA and disease severity (overall depression and dimensions of illness). Finally, we conducted a voxel-wise group comparison of FA. All analyses covaried for age, sex and socioeconomic status, and applied rigorous corrections for multiple testing. Logistic regression did not reveal significant associations between diagnosis and FA within white matter tracts defined by probabilistic tractography. Dimensional analyses revealed that greater lassitude was associated with higher FA in right cingulum bundle and bilateral corticospinal tracts, but with lower FA in right anterior thalamic radiation. Voxel-wise group comparisons of FA did not reveal significant group differences. The current findings do not support low FA as a neurobiological marker of adolescent depression. Dimensional results suggest that FA relates to lassitude but not overall depression. Given the clinical and neurobiological heterogeneity of depression, future work utilizing dimensional approaches may help elucidate the role of white matter microstructure in adolescent depression neurobiology.

Asunto(s)

RESUMEN

A personalized approach to treatment with patients being matched to the best-fit treatment has been proposed as one possible solution to the currently modest treatment response rates for adolescent depression. Personalized treatment involves identifying and characterizing subgroups likely to respond differently to different treatments. We investigated the feasibility of this approach, by focusing on two key risk factors that are the purported treatment targets of cognitive behavioral therapy (CBT) and interpersonal psychotherapy for depressed adolescents (IPT-A): negative unrealistic cognitions and interpersonal relationship difficulties, respectively. We sought to learn whether subgroups high and low on the two risk factors, respectively, might be identified in a large sample of depressed, treatment-seeking adolescents. Latent class analysis (LCA) was conducted on measures of the two risk factors among 431 adolescents (age 12-17) in the Treatment for Adolescents with Depression Study. LCA identified three classes: (1) adolescents with high levels of problems in both family relationships and cognitions (21.6% of sample), (2) adolescents with moderate levels of problems in both domains (52.4%), and (3) adolescents with low levels of problems in both domains (26.0%). These subgroups did not predict treatment outcome with CBT or CBT + fluoxetine (COMB). The results challenge a current assumption about how treatments could be personalized, and they support a multi-causal model of depression rather than a risk-factor-specific model. Strategies other than risk factor-based personalizing for case assignment to CBT vs. IPT-A are discussed.

Asunto(s)

RESUMEN

OBJECTIVE: Practice parameters recommend systematic assessment of depression symptoms over the course of treatment to inform treatment planning; however, there are currently no guidelines regarding how to use symptom monitoring to guide treatment decisions for psychotherapy. The current study compared two time points (week 4 and week 8) for assessing symptoms during interpersonal psychotherapy for depressed adolescents (IPT-A) and explored four algorithms that use the symptom assessments to select the subsequent treatment. METHOD: Forty adolescents (aged 12-17 years) with a depression diagnosis began IPT-A with an initial treatment plan of 12 sessions delivered over 16 weeks. Adolescents were randomized to a week 4 or week 8 decision point for considering a change in treatment. Insufficient responders at either time point were randomized a second time to increased frequency of IPT-A (twice per week) or addition of fluoxetine. Measures were administered at baseline and weeks 4, 8, 12, and 16. RESULTS: The week 4 decision point for assessing response and implementing treatment augmentation for insufficient responders was more efficacious for reducing depression symptoms than the week 8 decision point. There were significant differences between algorithms in depression and psychosocial functioning outcomes. CONCLUSION: Therapists implementing IPT-A should routinely monitor depression symptoms and consider augmenting treatment for insufficient responders as early as week 4 of treatment. CLINICAL TRIAL REGISTRATION INFORMATION: An Adaptive Treatment Strategy for Adolescent Depression. https://clinicaltrials.gov; NCT02017535.

Asunto(s)

RESUMEN

OBJECTIVE(S): This study examined changes in depressed adolescents' reports of attachment anxiety and avoidance with interpersonal psychotherapy (IPT-A), and the relationship between attachment style and change in depression with IPT-A. METHOD: Forty adolescents (aged 12-17) participated in a 16-week randomized clinical trial of 4 adaptive treatment strategies for adolescent depression that began with IPT-A and augmented treatment for insufficient responders (n = 22) by adding additional IPT-A sessions (n = 11) or the antidepressant medication, fluoxetine (n = 11). Adolescents were 77.5% female and 22.5% male (mean age = 14.8, SD = 1.8). Ten percent of adolescents were Latino. Racial composition was 7.5% Asian, 7.5% American Indian/Alaska Native, 80.0% white, and 5.0% biracial. Measures of attachment style (Experience in Close Relationships Scale-Revised [ECR-R]) and depression (Children's Depression Rating Scale-Revised [CDRS-R]) were administered at baseline and Weeks 8 and 16. RESULTS: Attachment Anxiety and Avoidance (ECR-R) decreased significantly from baseline to Week 16. Baseline Avoidance positively predicted greater reductions in depression (CDRS-R), controlling for fluoxetine. Reductions in Anxiety and Avoidance were also significantly associated with reductions in CDRS-R, controlling for fluoxetine. CONCLUSIONS: Adolescents' reports of attachment anxiety and avoidance are amenable to intervention with IPT-A. IPT-A may be particularly beneficial for adolescents who report a high level of avoidant attachment. Clinical or methodological significance of this article Our findings suggest that attachment anxiety and avoidance are constructs that are amenable to intervention during adolescence, and therefore viable targets of treatment. IPT-A was found to be an effective intervention for addressing problems in attachment style, and decreases in attachment anxiety and avoidance were associated with reductions in depression. This provides support for selecting IPT-A as a treatment option for adolescents who are depressed and describe difficulty with attachment security. IPT-A appears to be particularly effective for adolescents with an avoidant attachment style, who experience discomfort with and have a tendency to avoid intimacy.

Asunto(s)

RESUMEN

BACKGROUND: Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed. Ketamine has been studied in adults with TRD, but little information is available for adolescents. This study investigated efficacy and tolerability of intravenous ketamine in adolescents with TRD, and explored clinical response predictors. METHODS: Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0.5 mg/kg) infusions over 2 weeks. Clinical response was defined as a 50% decrease in Children's Depression Rating Scale-Revised (CDRS-R); remission was CDRS-R score ≤28. Tolerability assessment included monitoring vital signs and dissociative symptoms using the Clinician-Administered Dissociative States Scale (CADSS). RESULTS: Thirteen participants (mean age 16.9 years, range 14.5-18.8 years, eight biologically male) completed the protocol. Average decrease in CDRS-R was 42.5% (p = 0.0004). Five (38%) adolescents met criteria for clinical response. Three responders showed sustained remission at 6-week follow-up; relapse occurred within 2 weeks for the other two responders. Ketamine infusions were generally well tolerated; dissociative symptoms and hemodynamic symptoms were transient. Higher dose was a significant predictor of treatment response. CONCLUSIONS: These results demonstrate the potential role for ketamine in treating adolescents with TRD. Limitations include the open-label design and small sample; future research addressing these issues are needed to confirm these results. Additionally, evidence suggested a dose-response relationship; future studies are needed to optimize dose. Finally, questions remain regarding the long-term safety of ketamine as a depression treatment; more information is needed before broader clinical use.

Asunto(s)

RESUMEN

OBJECTIVE: Typically, about 30 to 50% of adolescents with depression fail to respond to evidence-based treatments, including antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs). Efforts for identifying predictors and moderators of treatment response are needed to begin to address critical questions relevant to personalized care in adolescent depression. In this pilot study, we aim to identify biological predictors of response to antidepressant treatment. METHOD: We used a multiple levels of analysis approach to evaluate threat system functioning (fronto-limbic system and the associated hormonal cascade) to determine if key biological indexes at baseline could predict improvement in depressive symptoms after eight weeks of antidepressant treatment in adolescents with depression. RESULTS: Neural predictors of favorable treatment response included lower amygdala connectivity with left supplementary motor area and with right precentral gyrus, and greater amygdala connectivity with right central opercular cortex and Heschl's gyrus connectivity during rest. During an emotion task, neural predictors of treatment response were greater activation of the bilateral anterior cingulate cortex and left medial frontal gyrus. Additionally, different patterns of salivary cortisol obtained in the context of a modified Trier Social Stress Test were associated with those whose depressive symptoms remitted as compared to those whose symptoms persisted. CONCLUSIONS: This approach shows significant promise for identifying predictors of treatment response in adolescents with depression. Future work is needed that incorporates sufficiently powered, randomized control trials to provide the basis by which both predictors and moderators of treatment response are identified. The hope is that this work will inform the development of methods that can guide clinician decision-making in assigning beneficial treatments for adolescents who are suffering from depression.

Asunto(s)

RESUMEN

BACKGROUND: Nonsuicidal self-injury (NSSI) is common in adolescents and young adults, and few evidence-based treatments are available for this significant problem. N-acetylcysteine (NAC) is a widely available nutritional supplement that has been studied in some psychiatric disorders relevant to NSSI including mood and addictive disorders. This pilot study tested the use of NAC as a potential treatment for NSSI in youth. METHODS: Thirty-five female adolescents and young adults with NSSI aged 13-21 years were enrolled in this study that had an open-label, single-arm study design. All participants were given oral NAC as follows: 600 mg twice daily (weeks 1-2), 1200 mg twice daily (weeks 3-4), and 1800 mg twice daily (weeks 5-8). Patients were seen every 2 weeks throughout the trial, at which time youth reported the frequency of NSSI episodes. Levels of depression, impulsivity, and global psychopathology were measured at baseline and at the end of the trial using the Beck Depression Inventory-II (BDI-II), Barratt Impulsivity Scale, and Symptoms Checklist-90 (SCL-90). RESULTS: About two-thirds of the enrolled female youth completed the trial (24/35). NAC was generally well tolerated in this sample. NAC treatment was associated with a significant decrease in NSSI frequency at visit 6 and visit 8 compared to baseline. We also found that depression scores and global psychopathology scores (but not impulsivity scores) decreased after NAC treatment. Decrease in NSSI was not correlated with decrease in BDI-II or SCL-90 scores, suggesting these might be independent effects. CONCLUSION: We provide preliminary evidence that NAC may have promise as a potential treatment option for adolescents with NSSI. The current results require follow-up with a randomized, placebo-controlled trial to confirm efficacy.

Asunto(s)

RESUMEN

BACKGROUND: Non-suicidal self-injury (NSSI) is a significant mental health problem among adolescents. Research is needed to clarify the neurobiology of NSSI and identify candidate neurobiological targets for interventions. Based on prior research implicating heightened negative affect and amygdala hyperactivity in NSSI, we pursued a systems approach to characterize amygdala functional connectivity networks during rest (resting-state functional connectivity [RSFC)]) and a task (task functional connectivity [TFC]) in adolescents with NSSI. METHOD: We examined amygdala networks in female adolescents with NSSI and healthy controls (n = 45) using resting-state fMRI and a negative emotion face-matching fMRI task designed to activate the amygdala. Connectivity analyses included amygdala RSFC, amygdala TFC, and psychophysiological interactions (PPI) between amygdala connectivity and task conditions. RESULTS: Compared to healthy controls, adolescents with NSSI showed atypical amygdala-frontal connectivity during rest and task; greater amygdala RSFC in supplementary motor area (SMA) and dorsal anterior cingulate; and differential amygdala-occipital connectivity between rest and task. After correcting for depression symptoms, amygdala-SMA RSFC abnormalities, among others, remained significant. LIMITATIONS: This study's limitations include its cross-sectional design and its absence of a psychiatric control group. CONCLUSIONS: Using a multi-modal approach, we identified widespread amygdala circuitry anomalies in adolescents with NSSI. While deficits in amygdala-frontal connectivity (driven by depression symptoms) replicates prior work in depression, hyperconnectivity between amygdala and SMA (independent of depression symptoms) has not been previously reported. This circuit may represent an important mechanism underlying the link between negative affect and habitual behaviors. These abnormalities may represent intervention targets for adolescents with NSSI.

Asunto(s)