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This study evaluated whether Arnarson and Craighead's (2009, 2011) developmentally based behavioral and cognitive program that prevented the initial episode of depressive disorders among Icelandic adolescents could be adapted to prevent depressive disorders among "at-risk" Portuguese adolescents. One hundred sixty-eight Portuguese mid-adolescents (primarily 14 to 15 years old), who had subsyndromal symptoms of depression but who had never met criteria for a depressive disorder, were identified by classroom screening with the CDI and subsequent K-SADS-PL interview. All 168 adolescents were offered participation in the 14-week prevention program; 70 agreed to participate in the program, and 98 agreed to participate only in an assessment control group. Psychological disorders were evaluated at baseline, 6-, 12-, 18-, and 24-month assessments. During the 2-year follow-up period, 12 students in the assessment-only group experienced an initial depressive disorder versus 2 in the prevention group. Survival analyses indicated a significantly lower rate of initial episodes of depressive disorders, χ2(1) = 4.261, p = .039, among the prevention group participants compared to the assessment only comparison group. The hazard ratio was .207, and the NNT was 11. Survival analyses indicated no significant differences between the prevention condition and the assessment only condition in the occurrence of other psychiatric disorders, χ2(1) = 1.080, p =.299. The findings indicate the program can be successfully adapted for use in Portuguese schools, and they provide a preliminary indication that those "at-risk" adolescents who chose to participate in the program, compared to those who chose to participate only in the assessments, developed fewer initial episodes of depressive disorders over the course of 24 months. The program effects were similar to the outcomes of the prior study of this program in Iceland. As in the Icelandic version of the program, its effects appeared to be specific to the depressive disorders for which the program was designed. [ABSTRACT FROM AUTHOR]

The Association for Behavioral and Cognitive Therapies (ABCT) celebrates its 50 th year in 2016. Personal and historical anecdotes illustrating the growth of the organization, and the parallel evolution of its affiliated therapies, are presented. From the author’s perspective, the integration of behavioral and cognitive therapies marked the first few decades of ABCT; the incorporation of mindfulness represents the most significant change in cognitive and behavioral interventions in the last 20 years. Recent developments in therapy’s relationship with technology (including computer-based intervention, neuroimaging, and genetic analysis) are explored. Potential future impacts of these developments are discussed in regards to the dissemination of interventions and the prevention and diagnosis of disorders, the contributions of neuroscience findings and methodologies, and the personalization of treatment. [ABSTRACT FROM AUTHOR]

Understanding how persistent interpersonal difficulties distinctly affect the course of major depressive disorder (MDD) during emerging adulthood is critical, given that early experiences impact future coping resources and functioning. Research on stress and MDD has mostly concentrated on stressful life events, while chronic stress largely has not been explored. The present study examined interpersonal (intimate relationship, close friendships, social life, family relationships) and noninterpersonal (academic, work, financial, personal health, and family members' health) domains of chronic stress as time-varying predictors of depressive recurrence in emerging adults. Baseline assessments identified previously depressed emerging adults ( N = 119), who subsequently completed 6-month, 12-month and 18-month follow-up interviews to determine chronic stress experiences and onset of new major depressive episodes. Survival analyses indicated that time-varying total chronic stress and chronic interpersonal stress predicted higher risk for depression recurrence; however, chronic noninterpersonal stress was not associated with recurrence. Intimate relationship stress, close friendship stress, family relationship stress, personal health, and family members' health independently predicted MDD recurrence, over and above well-established depression risk factors of dysfunctional cognitions and personality disorder symptoms. Evidence that interpersonal stress could have substantial impact on course of depression is consistent with theories of emerging adulthood, a time when young people are individuating from the family and experiencing significant social transition. [ABSTRACT FROM AUTHOR]

Abstract: Behavioral activation (BA) is a psychosocial intervention that has shown promising treatment outcome results with depressed adults. The current pilot study evaluated a version of BA adapted for depressed adolescents. Six teens (3 male, 3 female, ages 14-17) who met criteria for major depressive disorder participated in the study. Participants were allowed to attend a maximum of 22 sessions (50 minutes each) over 18 weeks. Parents were systematically included in treatment for joint sessions at the beginning, middle, and end of treatment; therapists were also given the latitude to include parents idiographically as needed. Results showed that participants'' depression scores decreased significantly; in addition, scores on a measure of hope improved significantly. Implications of these findings, study limitations, and suggestions for future directions are discussed. [Copyright &y& Elsevier]

Abstract: This paper reports the 12-month follow-up results regarding a program designed to prevent the initial episode of depression and/or dysthymia among Icelandic adolescents. This indicated prevention program was implemented in school settings for 14–15 year-old students judged to be “at risk” for depression because of the presence of some depressive symptoms and/or a negative attributional style. We previously reported () that this program, when compared to treatment-as-usual, was effective in preventing the first episode of depression and/or dysthymia at 6-months following completion of the program. Survival analyses of the 12-month follow-up data indicated that the preventive effects were sustained at the end of 1 year following the completion of the prevention program with only 2 of the prevention program participants reporting an initial episode of MDD/DYS versus 13 of the TAU participants (χ 2 = 5.02, p = .025). Using logistic regression, we also found that initial level of depressive symptoms significantly (p = .0330) predicted the first episode of depression and/or dysthymia among TAU subjects. The limitations of the study were noted, and future directions of research regarding prevention of depression were discussed. [Copyright &y& Elsevier]

Abstract: Major depression and dysthymia are frequent, debilitating, and chronic disorders, whose highest rate of initial onset is during the late adolescent years. The effectiveness of a program designed to prevent an initial episode of major depression or dysthymia among adolescents was investigated. Participants were 171 fourteen-year-old “at risk” Icelandic adolescents who were randomly assigned to a prevention program or a treatment-as-usual assessment only control group. They were identified as “at risk” by reporting the presence of depressive symptoms or a negative attributional style. The program was based on a developmental psychosocial model of enhancement of resilience to factors associated with the occurrence of mood disorders. The results indicated that the prevention program resulted in a significantly lower rate of major depression and dysthymia than did the control group. The study demonstrated that school personnel in the school setting can implement such prevention programs. [Copyright &y& Elsevier]

Major Depressive Disorder (MDD) is a prevalent mental health condition that often begins in adolescence, with significant long-term implications. Indicated prevention programs targeting adolescents with mild symptoms have shown efficacy, yet the methods for identifying at-risk individuals need improvement. This study aims to evaluate the utility of Partial Least Squares Regression (PLSR) in predicting the onset of MDD among non-depressed adolescents, compared to traditional screening methods. The study recruited 1462 Portuguese adolescents aged 13–16, who were assessed using various self-report measures and followed for two years. Participants were randomly divided into training (70%, N = 1023) and testing (30%, N = 439) samples. PLSR models were developed to predict the occurrence of a major depressive episode (MDE) within two years, using 331 variables. The model's performance was compared to the Children's Depression Inventory (CDI) in predicting MDE onset. The best-fitting PLSR model with two components explained 19.1% and 16.9% of the variance in the training and testing samples, respectively, significantly outperforming the CDI, which explained 7.7% of the variance. The area under the ROC curve was 0.78 for PLSR, compared to 0.71 for CDI. An empirically derived cut-off point was used to create dichotomous risk categories, and it showed a significant difference in MDE rates between predicted high-risk and low-risk groups. The balanced accuracy of the PLSR model was 0.77, compared to 0.65 for the CDI method. The PLSR model effectively identified adolescents at risk for developing MDD, demonstrating superior predictive power over the CDI. This study supports the potential utility of ML techniques (e.g., PLSR) in enhancing early identification and prevention efforts for adolescent depression. • Novel method: Used Partial Least Squares Regression (PLSR) to predict MDD in teens. • Comparison: PLSR outperformed the Children's Depression Inventory (CDI). • Accuracy: PLSR explained more variance than the CDI in two year depression rate. • Risk categorization: PLSR effectively separated high-risk and low-risk groups. [ABSTRACT FROM AUTHOR]

Although a number of neuroimaging biomarkers for response have been proposed, none have been tested prospectively for direct effects on treatment outcomes. To the best of our knowledge, this is the first prospective test of the clinical utility of the use of an imaging biomarker to select treatment for patients with major depressive disorder. Eligible participants (n = 60) had a primary diagnosis of major depressive disorder and were assigned to either escitalopram or cognitive behavioral therapy based on fluorodeoxyglucose positron emission tomography activity in the right anterior insula. The overall study remission rate after 12 weeks of treatment, based on the end point Hamilton Depression Rating Scale score, was then examined for futility and benefit of the strategy. Remission rates demonstrated lack of futility at the end of stage 1 (37%, 10/27), and the study proceeded to stage 2. After adjustment for the change in stage 2 sample size, the complete remission rate did not demonstrate evidence of benefit (37.7%, 95% confidence interval, 26.3%–51.4%, p =.38). However, total remission rates (complete and partial remission) did reach significance in post hoc analysis (49.1%, 95% confidence interval, 37.6%–60.7%, p =.020). The study shows some evidence for a role of the right anterior insula in the clinical choice of major depressive disorder monotherapy. The effect size, however, is insufficient for the use of insula activity as a sole predictive biomarker of remission. The study also demonstrates the logistical difficulties in establishing clinical utility of biomarkers. [ABSTRACT FROM AUTHOR]

Early life stress (ELS) is associated with an increased risk of depression and this association may be mediated by epigenetic mechanisms. A previous epigenome-wide DNA methylation (DNAm) study investigating human newborns and two animal models of ELS suggested that the epigenetic regulator MORC1 is differentially methylated following ELS. The ELS-induced DNAm alterations were long-lasting in the animal models. However, whether this finding is also transferable to humans experiencing ELS in childhood was not investigated. Further, MORC1 may provide a link between ELS and adult depression, as MORC1 DNAm and genetic variants were found to be associated with depressive symptoms in humans. In the present study, we investigated the validity of MORC1 DNAm as a biomarker of ELS in humans and its role in linking ELS to depression later in life by studying childhood maltreatment. We analyzed whole blood MORC1 DNAm in an adult cohort (N = 151) that was characterized for both the presence of depressive symptoms and childhood maltreatment. Further, we investigated the association between MORC1 DNAm, depressive symptoms and childhood maltreatment in two additional cohorts (N = 299, N = 310). Overall, our data do not indicate an association of MORC1 DNAm with childhood maltreatment. An association of MORC1 DNAm with depressive symptoms was present in all cohorts, but was inconsistent in the specific CpG sites associated and the direction of effect (Tuebingen cohort: standardized β = 0.16, unstandardized β = 0.01, 95% CI [-0.0004, −0.0179], p = 0.061, PReDICT cohort: standardized β = −0.12, unstandardized β = −0.01, 95% CI [-0.0258, −0.0003], p = 0.045), Grady cohort: standardized β = 0.16, unstandardized β = 0.008, 95% CI [0.0019, 0.0143], p = 0.01). Our study thus suggests that peripheral MORC1 DNAm cannot serve as biomarker of childhood maltreatment in adults, but does provide further indication for the association of MORC1 DNAm with depressive symptoms. [ABSTRACT FROM AUTHOR]

For patients with major depressive disorder (MDD), approaches to treatment differ for those with a single versus recurrent episodes. Based on studies of community samples, however, accuracy is low for identifying past episodes. Recall accuracy among clinical samples with a well-defined major depressive episode (MDE) has not been examined previously. We evaluated episode recall accuracy in 79 MDD patients in follow-up of the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study at 12- and 24-month time-points after starting treatment. Using the Structured Clinical Interview for DSM-IV, patients were asked to recall whether they had been experiencing the nine criterion symptoms of an MDE at the time of their intake assessment. Accuracy of recall for the index MDE was high, with 95% of patients at month 12 and 85% at month 24 recalling sufficient symptoms to meet the diagnostic criteria. Recall accuracy for specific symptoms varied considerably, from >90% for dysphoria and anhedonia, to 55% for psychomotor and weight/appetite changes. For the thoughts of death/suicide criterion, patients with erroneous recall were significantly more likely to recall having had the symptom at the intake evaluation (though they had denied it at the time) than vice versa (p <.007). Patients who have participated in a clinical trial are likely to recall accurately a past MDE up to two years prior. Optimal vigilance for suicidal ideation for treatment-naïve patients should include a combination of self-report and clinician assessments. • Participants in depression trials accurately recall their symptoms up to 2 years later. • Psychomotor and appetite changes are the least accurately recalled symptoms. • Suicidal thoughts may be under-reported by depressed patients entering treatment. [ABSTRACT FROM AUTHOR]

Maladaptive emotion regulation strategies, such as rumination and catastrophizing, are transdiagnostic risk factors for psychopathology. FK506-binding protein 51 ( FKBP5 ) has been found to moderate the relationship between stressful life events and various psychiatric disorders. Given the cross-disorder moderation effect of FKBP5 at the diagnostic level, the aim of the current study was to examine whether the relationship between exposure to childhood trauma and transdiagnostic maladaptive emotion regulation processes would also be moderated by genetic FKBP5 variation in a community sample of adolescents. We hypothesized that adolescent carriers of the FKBP5 CATT haplotype composed of rs9296158, rs3800373, rs1360780, and rs9470080, that has been associated with increased risk for psychiatric disorders in adulthood, would also show higher levels of rumination and catastrophizing. Participants included 1345 genotyped adolescents (M age = 13.95, 64.2% female; 100% European Caucasians of Portuguese descent) who completed self-report measures on exposure to childhood trauma and emotion regulation strategies. Genotypes of rs9296158, rs3800373, rs1360780, and rs9470080 were used to estimate the CATT haplotype (carriers versus non-carriers). Consistent with our hypotheses and previous findings, adolescent CATT haplotype carriers with higher levels of childhood trauma endorsed higher levels of both rumination and catastrophizing compared to non-carriers. Given the association of these maladaptive emotion regulation processes and psychiatric disorders, the findings suggest possible psychological mechanisms why FKBP5 haplotype carriers exposed to childhood trauma are more vulnerable to developing a psychiatric disorder later in life. [ABSTRACT FROM AUTHOR]

Glucocorticoid challenge tests such as the dexamethasone suppression test (DST) and the combined dexamethasone/corticotropin-releasing hormone (dex-CRH) test are considered to be able to sensitively measure hypothalamic-pituitary-adrenal (HPA) axis activity in stress-related psychiatric and endocrine disorders. We used mass-spectrometry to assess the relationship of plasma dexamethasone concentrations and the outcome of these tests in two independent cohorts. Dexamethasone concentrations were measured after oral ingestion of 1.5 mg dexamethasone in two cohorts that underwent a standard (dexamethasone at 23:00 h) as well as modified (18:00 h) DST and dex-CRH test. The first study population was a case/control cohort of 105 depressed patients and 133 controls in which peripheral blood mRNA expression was also measured. The second was a cohort of 261 depressed patients that underwent a standard dex-CRH test at baseline and after 12 weeks’ treatment with cognitive-behavioral therapy or antidepressants. Dexamethasone concentrations explained significant proportions of the variance in the DST in both the first (24.6%) and the second (5.2%) cohort. Dexamethasone concentrations explained a higher proportion of the variance in the dex-CRH test readouts, with 41.9% of the cortisol area under the curve (AUC) in the first sample and 24.7% in the second sample. In contrast to these strong effects at later time points, dexamethasone concentrations did not impact cortisol or ACTH concentrations or mRNA expression 3 hours after ingestion. In the second sample, dexamethasone concentrations at baseline and week 12 were highly correlated, independent of treatment type and response status. Importantly, a case/control effect in the Dex-CRH test was only apparent when controlling for dexamethasone concentrations. Our results suggest that the incorporation of plasma dexamethasone concentration or measures of earlier endocrine read-outs may help to improve the assessment of endocrine dysfunction in depression. [ABSTRACT FROM AUTHOR]

Background Treatment approaches for major depressive disorder (MDD) result in approximately one third of patients achieving remission after a first treatment. Added treatment generally improves remission rates, but approximately one third of all patients fail to respond after several treatments (sequential monotherapies or combined treatment). A pretreatment biomarker could help identify these patients. Overactivity of the subcallosal cingulate has been associated with failure of response to treatment in MDD, and it is a potential candidate for such a biomarker. Methods Investigators enrolled 82 patients with MDD currently not receiving treatment in a two-phase treatment study. Patients underwent a fluorodeoxyglucose positron emission tomography scan. After scanning, patients were randomly assigned to 12 weeks of treatment with either escitalopram or cognitive-behavioral therapy (CBT). Patients not achieving remission after 12 weeks of initial treatment were treated with an additional 12 weeks of escitalopram plus CBT. Subcallosal cingulate metabolism was compared between patients who failed to achieve a response and patients who achieved remission as a result of either phase one or phase two treatment. This analysis was followed by a whole-brain analysis making the same comparison. Results After two phases of treatment (24 weeks), 36 patients were identified as remitters, 6 patients were responders, and 9 patients were nonresponders. Subcallosal cingulate metabolism was significantly higher in nonresponders than remitters. In the follow-up whole-brain analysis, increased superior temporal sulcus activity was also associated with nonresponse to two treatments. Conclusions Patients with MDD who fail to achieve remission as a result of CBT or escitalopram, either alone or in combination, have a distinct brain metabolic pattern compared with patients who achieve remission as a result of CBT, escitalopram, or their combination. [ABSTRACT FROM AUTHOR]

Abstract: Previous studies suggest that individual preferences for medication- or psychotherapy-based treatments for depression may affect outcomes in clinical trials that compare these two forms of treatment. We assessed patients’ beliefs about the causes of their depression, their preferred treatment, and strength of that preference in 80 patients participating in a 12-week clinical trial evaluating neuroimaging predictors of response to cognitive behavior therapy (CBT) or escitalopram. Forty-five patients expressed a preference for one of the 2 treatments, but being matched to preference did not influence remission or completion rates. Medication-preferring patients were more likely to terminate the trial early, regardless of treatment received. CBT-preferring patients rarely endorsed unknown causes for their depression, and medication-preferring patients were highly unlikely to identify pessimistic attitudes as a source of their depression. Among patients willing to be randomized to treatment, preference does not appear to strongly influence outcome. Specific preferences for CBT or medication may reflect differing conceptualizations about depressive illness, knowledge of which may enhance treatment retention and efficacy. [Copyright &y& Elsevier]

Abstract: Background: The dexamethasone–corticotropin releasing hormone (Dex–CRH) test may differentially predict which depressed patients will respond to antidepressant medication. However, a comprehensive analysis of the safety of this test in psychiatric patients has not previously been performed. Methods: We conducted a pooled analysis of depressed patients in four clinical studies. Observed and subjectively reported side-effects in 454 patients were collected for 90minutes following CRH administration. Pre-test electrocardiograms were available in 250 patients to assess cardiac safety. Descriptive statistics were performed to evaluate these safety data. Results: Eight-six (18.9%) subjects experienced no side-effects from the procedure. The mean number of side-effects per subject was 1.4±1.0. The most frequent adverse events were: flushing (n =216, 47.6%), feeling of warmth (144, 31.7%), hyperpnea/tachypnea (108, 23.8%), palpitations (37, 8.1%), and tachycardia (28, 6.2%). Side-effects were consistently mild and brief in duration. There were no serious adverse events. Conclusion: The Dex–CRH test produces a mild, predictable side-effect profile, characterized by flushing, feelings of warmth, hyperpnea/tachypnea, palpitations, and tachycardia. These results provide reassurance that the Dex–CRH test is well tolerated in psychiatric patients. [ABSTRACT FROM AUTHOR]

Objectives: To develop a cognitive-behavioral treatment for depressed, substance-abusing adolescents, determine its feasibility, and test its association with symptomatic improvement. Method: Based on the efficacy of cognitive-behavioral interventions for either adolescent depression or substance abuse, an integrated group and family therapy intervention was developed for adolescents with both problems. The developers treated a group of six adolescents and families, and then trained experienced therapists to deliver the treatment to a second group of seven. Adolescents were 14 to 18 years of age. Measures of depression and substance abuse were collected before, during, and after treatment. Results: High retention in treatment and attendance at sessions supported feasibility. Parent interviews demonstrated significant improvement in adolescent substance abuse, and adolescent measures demonstrated significant improvement in both domains. Conclusions: Integrated outpatient cognitive-behavioral intervention is feasible and associated with improvement for depressed, substance-abusing adolescents. Controlled efficacy studies are needed. Additional treatment modalities will be required for a proportion of these adolescents. [ABSTRACT FROM AUTHOR]