Neutralizing Antibodies Induced by First-Generation gp41-Stabilized HIV-1 Envelope Trimers and Nanoparticles.

The immunogenicity of gp41-stabilized HIV-1 BG505 envelope (Env) trimers and nanoparticles (NPs) was recently assessed in mice and rabbits. Here, we combined Env-specific B-cell sorting and repertoire sequencing to identify neutralizing antibodies (NAbs) from immunized animals. A panel of mouse NAbs was isolated from mice immunized with a 60-meric I3-01 NP presenting 20 stabilized trimers. Three mouse NAbs potently neutralized BG505.T332N by recognizing a glycan epitope centered in the C3/V4 region on BG505 Env, as revealed by electron microscopy (EM), X-ray crystallography, and epitope mapping. A set of rabbit NAbs was isolated from rabbits immunized with a soluble trimer and a 24-meric ferritin NP presenting 8 trimers. Neutralization assays against BG505.T332N variants confirmed that potent rabbit NAbs targeted previously described glycan holes on BG505 Env and accounted for a significant portion of the autologous NAb response in both the trimer and ferritin NP groups. Last, we examined NAb responses that were induced by non-BG505 Env immunogens. We determined a 3.4-Å-resolution crystal structure for the clade C transmitted/founder (T/F) Du172.17 Env with a redesigned heptad repeat 1 (HR1) bend in gp41. This clade C Env, in a soluble trimer form and in a multivalent form with 8 trimers attached to ferritin NP, and the gp41-stabilized clade A Q482-d12 Env trimer elicited distinct NAb responses in rabbits, with notable differences in neutralization breadth. Although eliciting a broad NAb response remains a major challenge, our study provides valuable information on an HIV-1 vaccine design strategy that combines gp41 stabilization and NP display. IMPORTANCE Self-assembling protein nanoparticles (NPs) presenting BG505 envelope (Env) trimers can elicit tier 2 HIV-1-neutralizing antibody (NAb) responses more effectively than soluble trimers. In the present study, monoclonal NAbs were isolated from previously immunized mice and rabbits for structural and functional analyses, which revealed that potent mouse NAbs recognize the C3/V4 region and small NP-elicited rabbit NAbs primarily target known glycan holes on BG505 Env. This study validates the gp41 stabilization strategy for HIV-1 Env vaccine design and highlights the challenge in eliciting a broad NAb response.

Risk Factors for Depression in Adolescents With ADHD: The Impact of Cognitive Biases and Stress.

Objective: Youth diagnosed with ADHD are at heightened risk of depression. However, many do not develop depression. Individuals with specific cognitive biases are more likely to develop depression yet it remains untested whether these vulnerability-stress models apply to depression risk in youth with ADHD. Method: We examined whether interpretation and attention biases moderated the relation between stressful life events and depressive symptoms in a sample of adolescents (Mage = 14.42) with ADHD (n = 59) and without ADHD (n = 36). Results: Youth with ADHD experienced more stressful life events compared with those without ADHD. Interpretation biases moderated the association between stress and depressive symptoms in youth with and without ADHD. Attention biases moderated the association between stress and depressive symptoms in the non-ADHD youth only. Conclusion: These results enhance our understanding of vulnerability for depression in adolescence with ADHD and inform targeted prevention and treatment models during this critical developmental juncture.

A VH1-69 antibody lineage from an infected Chinese donor potently neutralizes HIV-1 by targeting the V3 glycan supersite.

An oligomannose patch around the V3 base of HIV-1 envelope glycoprotein (Env) is recognized by multiple classes of broadly neutralizing antibodies (bNAbs). Here, we investigated the bNAb response to the V3 glycan supersite in an HIV-1-infected Chinese donor by Env-specific single B cell sorting, structural and functional studies, and longitudinal analysis of antibody and virus repertoires. Monoclonal antibodies 438-B11 and 438-D5 were isolated that potently neutralize HIV-1 with moderate breadth, are encoded by the VH1-69 germline gene, and have a disulfide-linked long HCDR3 loop. Crystal structures of Env-bound and unbound antibodies revealed heavy chain-mediated recognition of the glycan supersite with a unique angle of approach and a critical role of the intra-HCDR3 disulfide. The mechanism of viral escape was examined via single-genome amplification/sequencing and glycan mutations around the N332 supersite. Our findings further emphasize the V3 glycan supersite as a prominent target for Env-based vaccine design.

Low-Dose Testosterone Augmentation for Antidepressant-Resistant Major Depressive Disorder in Women: An 8-Week Randomized Placebo-Controlled Study.

OBJECTIVE: Low-dose testosterone has been shown to improve depression symptom severity, fatigue, and sexual function in small studies in women not formally diagnosed with major depressive disorder. The authors sought to determine whether adjunctive low-dose transdermal testosterone improves depression symptom severity, fatigue, and sexual function in women with antidepressant-resistant major depression. A functional MRI (fMRI) substudy examined effects on activity in the anterior cingulate cortex (ACC), a brain region important in mood regulation. METHODS: The authors conducted an 8-week randomized double-blind placebo-controlled trial of adjunctive testosterone cream in 101 women, ages 21-70, with antidepressant-resistant major depression. The primary outcome measure was depression symptom severity as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary endpoints included fatigue, sexual function, and safety measures. The primary outcome of the fMRI substudy (N=20) was change in ACC activity. RESULTS: The participants' mean age was 47 years (SD=14) and their mean baseline MADRS score was 26.6 (SD=5.9). Eighty-seven (86%) participants completed 8 weeks of treatment. MADRS scores decreased in both study arms from baseline to week 8 (testosterone arm: from 26.8 [SD=6.3] to 15.3 [SD=9.6]; placebo arm: from 26.3 [SD=5.4] to 14.4 [SD=9.3]), with no significant difference between groups. Improvement in fatigue and sexual function did not differ between groups, nor did side effects. fMRI results showed a relationship between ACC activation and androgen levels before treatment but no difference in ACC activation with testosterone compared with placebo. CONCLUSIONS: Adjunctive transdermal testosterone, although well tolerated, was not more effective than placebo in improving symptoms of depression, fatigue, or sexual dysfunction. Imaging in a subset of participants demonstrated that testosterone did not result in greater activation of the ACC.

Effects of Open-Label, Adjunctive Ganaxolone on Persistent Depression Despite Adequate Antidepressant Treatment in Postmenopausal Women: A Pilot Study.

OBJECTIVE: The neuroactive steroid metabolite of progesterone, allopregnanolone, is a positive allosteric modulator of γ-aminobutyric acid-A (GABAA) receptors and a putative treatment for mood disorders. This pilot study was performed to determine whether an oral allopregnanolone analog (ganaxolone) may be effective adjunctive therapy for persistent depression despite adequate antidepressant treatment in postmenopausal women. METHOD: Ten postmenopausal women (mean ± SD age: 62.8 ± 6.3 years; range, 53-69 years) with persistent depression despite adequate antidepressant treatment (current DSM-IV-TR major depressive episode per the Structured Clinical Interview for DSM-IV-TR, Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 16, and treated with an adequately dosed antidepressant for ≥ 6 weeks) were studied from December 2016 to April 2018. Open-label ganaxolone (225 mg twice daily, increased to 450 mg twice daily if tolerated) was administered for 8 weeks, followed by a 2-week taper. RESULTS: Mean ± SEM total MADRS score (primary endpoint) decreased by 8 weeks (24.4 ± 1.6 to 12.8 ± 2.9, P = .015), and the decrease persisted over the 2-week taper (P = .019); of the 9 subjects who completed the full 8-week treatment period, 44% (4/9) experienced response (MADRS score decrease ≥ 50%) and remission (final MADRS score < 10), which persisted in 100% and 50% of subjects at 10 weeks, respectively. Secondary endpoints showed significant improvement, including Inventory of Depressive Symptomatology-Self-Report score (P = .003), MADRS reduced sleep subscale score (P < .001), total Symptoms of Depression Questionnaire (SDQ) score (P = .012), and scores on SDQ subscales for disruptions in sleep quality (P = .003) and changes in appetite and weight (P = .009) over 8 weeks. No significant effects were observed on quality of life or sexual function. All subjects experienced sleepiness and fatigue; 60% experienced dizziness. CONCLUSIONS: In this open-label, uncontrolled pilot study, adjunctive ganaxolone appears to exert antidepressant effects but produces sedation with twice-daily dosing. Ganaxolone may also improve sleep, which may be useful in patients with depression and insomnia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02900092.

Proof of concept for rational design of hepatitis C virus E2 core nanoparticle vaccines.

Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are responsible for cell entry, with E2 being the major target of neutralizing antibodies (NAbs). Here, we present a comprehensive strategy for B cell-based HCV vaccine development through E2 optimization and nanoparticle display. We redesigned variable region 2 in a truncated form (tVR2) on E2 cores derived from genotypes 1a and 6a, resulting in improved stability and antigenicity. Crystal structures of three optimized E2 cores with human cross-genotype NAbs (AR3s) revealed how the modified tVR2 stabilizes E2 without altering key neutralizing epitopes. We then displayed these E2 cores on 24- and 60-meric nanoparticles and achieved substantial yield and purity, as well as enhanced antigenicity. In mice, these nanoparticles elicited more effective NAb responses than soluble E2 cores. Next-generation sequencing (NGS) defined distinct B cell patterns associated with nanoparticle-induced antibody responses, which target the conserved neutralizing epitopes on E2 and cross-neutralize HCV genotypes.

Evaluating the combination of a Brief Motivational Intervention plus Cognitive Behavioral Therapy for Depression and heavy episodic drinking in college students.

[Correction Notice: An Erratum for this article was reported in Vol 34(2) of Psychology of Addictive Behaviors (see record 2020-16883-001). In the original article the order of authorship was incorrect. The correct second and third authors should appear instead as Brian Borsari and Jennifer E. Merrill.] Heavy episodic drinking (HED) and depressive symptoms often co-occur among college students and are associated with significant impairment. However, evidence-based treatments for these common co-occurring conditions are not available for college students. The current study compared the effectiveness of a treatment combining Cognitive-Behavioral Therapy for Depression and Brief Motivational Interviewing (CBT-D + BMI) versus Cognitive-Behavioral Therapy for Depression (CBT-D) alone among 94 college students with HED and depressive symptoms. Both treatment programs were associated with significant reductions of similar magnitude in HED, alcohol-related problems (ARP), and depressive symptoms at the end of treatment and at the 1-month follow-up assessment. Moderation analyses indicated that, among college students with fewer depressive symptoms at baseline, CBT-D was associated with greater sustained reduction in heavy drinking relative to CBT-D + BMI at the 1-month follow-up. Although the study did not include a no-treatment condition, the magnitude of improvement during treatment in both groups was greater than what is expected with passage of time. Although clinicians in college counseling centers may lack specialty training for co-occurring conditions, CBT-D is widely implemented in college settings. Our findings suggest that CBT-D may reduce both depressive symptoms and HED in college students and may be used to address a significant public health problem. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

The interactive association of proximal life stress and cumulative HPA axis functioning with depressive symptoms.

BACKGROUND: Stress is consistently implicated in depression. Using a vulnerability-stress framework, the hypothalamic-pituitary-adrenal (HPA) axis may be one factor affecting the stress-depression association. However, the interactive influence of recent life stress and HPA axis functioning on depressive symptoms remains unclear. It is particularly important to understand the synergistic association during adolescence, as this is a developmental period associated with a high risk for depression. METHODS: A community sample of 58 adolescents (67% female, 59% Caucasian; mean age, 15.07 years) participated. Adolescents completed a well-validated measure of depressive symptoms and a structured life events interview to assess recent life stress. Hair cortisol concentration was obtained to measure cumulative exposure to HPA axis functioning. RESULTS: Recent life stress and cumulative HPA axis exposure measured through hair cortisol were directly associated with higher depressive symptoms. Further, cumulative HPA axis exposure moderated the relationship between recent life stress and depressive symptoms. The recent life stress-depression association occurred for adolescents who experienced average and high, but not low, levels of cumulative HPA axis exposure. CONCLUSIONS: The current study builds on prior work and finds both a direct and interactive association of recent life stress and cumulative HPA axis functioning with depressive symptoms during adolescence. Identifying youth who experience high levels of HPA axis exposure is important to prevent the onset of depression.

Intrinsic Functional Brain Connectivity Predicts Onset of Major Depression Disorder in Adolescence: A Pilot Study.

Children with familial risk for major depressive disorder (MDD) have elevated risk for developing depression as adolescents. Here, we investigated longitudinally whether resting-state functional connectivity (RSFC) could predict the onset of MDD. In this pilot study, we followed a group of never-depressed children with familial risk for MDD and a group of age-matched controls without familial risk who had undergone an MRI study at 8-14 years of age. Participants were reassessed 3-4 years later with diagnostic interviews. We first investigated group differences in RSFC from regions in the emotion regulation, cognitive control, and default mode networks in the children who later developed MDD (converted), the children who did not develop MDD (nonconverted), and the control group. We then built a prediction model based on baseline RSFC that was independent of the group differences to classify the individuals who later developed MDD. Compared with the nonconverted group, the converted group exhibited hypoconnectivity between subgenual anterior cingulate cortex (sgACC) and inferior parietal lobule (IPL) and between left and right dorsolateral prefrontal cortices. The nonconverted group exhibited higher sgACC-IPL connectivity than did both the converted and control groups, suggesting a possible resilience factor to MDD. Classification between converted and nonconverted individuals based on baseline RSFC yielded high predictive accuracy with high sensitivity and specificity that was superior to classification based on baseline clinical rating scales. Intrinsic brain connectivity measured in healthy children with familial risk for depression has the potential to predict MDD onset, and it can be a useful neuromarker in early identification of children for preventive treatment.

Neural markers of depression risk predict the onset of depression.

Although research highlights neural correlates of Major Depressive Disorder (MDD), it is unclear whether these correlates reflect the state of depression or a pre-existing risk factor. The current study examined whether baseline differences in brain activations, resting-state connectivity, and brain structural differences between non-symptomatic children at high- and low-risk for MDD based on familial depression prospectively predict the onset of a depressive episode or increases in depressive symptomatology. We re-assessed 44 participants (28 high-risk; 16 low-risk) who had undergone neuroimaging in a previous study 3-4 years earlier (Mean age at follow-up = 14.3 years, SD = 1.9 years; 45% females; 70% Caucasian). We investigated whether baseline brain imaging data (including an emotional face match task fMRI, resting-state fMRI and structural MRI) that differentiated the risk groups also predicted the onset of depression. Resting-state functional connectivity abnormalities in the default mode and cognitive control network that differentiated high-risk from low-risk youth at baseline predicted the onset of MDD during adolescence, after taking risk status into account. Increased functional activation to both happy and fearful faces was associated with greater decreases in self-reported depression symptoms at follow-up. This preliminary evidence could be used to identify youth at-risk for depression and inform early intervention strategies.

Cognitive reappraisal attenuates the association between depressive symptoms and emotional response to stress during adolescence.

Depression is associated with increased emotional response to stress. This is especially the case during the developmental period of adolescence. Cognitive reappraisal is an effective emotion regulation strategy that has been shown to reduce the impact of emotional response on psychopathology. However, less is known about whether cognitive reappraisal impacts the relationship between depressive symptoms and emotional responses, and whether its effects are specific to emotional reactivity or emotional recovery. The current study examined whether cognitive reappraisal moderated the relationship between depressive symptoms and trait or state measures of emotional reactivity and recovery. A community sample of 127 adolescents (M-age = 15.28; 49% female, 47% Caucasian), at an age of risk for depression, completed self-report measures of trait emotional responding and depressive symptoms. In addition, they completed an in vivo social stress task and were assessed on state emotional reactivity and recovery from the stressor. Findings suggested that cognitive reappraisal was associated with an attenuated impact of depressive symptoms on trait and state emotional recovery. These results provide evidence that cognitive reappraisal may be an effective strategy for improving some aspects of emotional responding in relation to depressive symptoms among adolescents.

Rationale, Methods, Feasibility, and Preliminary Outcomes of a Transdiagnostic Prevention Program for At-Risk College Students.

PURPOSE: Early adulthood represents one period of increased risk for the emergence of a serious mental illness. The college campus provides a unique opportunity to assess and monitor individuals in this at-risk age group. However, there are no validated early detection programs that are widely implemented on college campuses. In an effort to address this gap, we designed and tested an early detection and prevention program tailored to college students. A transdiagnostic approach was employed because of evidence for shared risk factors across major mental illnesses. DESIGN: Single arm, prospective study evaluating outcomes following a 4-week intervention. METHOD: Three in-person mental health screenings were conducted on the campus of one university. Undergraduate students with at least mildly elevated, self-reported levels of depressive or subclinical psychotic symptoms, who were not receiving treatment for these symptoms, were invited to participate in a 4-session workshop focused on increasing self- and other- awareness and emotion regulation using established mindfulness, self-compassion, and mentalization principles and experiential exercises. Symptoms, resilience-promoting capacities, and aspects of social functioning were assessed pre- and post- intervention. RESULTS: 416 students were screened and a total of 63 students participated in the workshop. 91% attended at least 3 of the 4 sessions. The majority of participants found the workshop interesting and useful and would recommend it to a friend. Significant pre-to-post reductions in symptoms (depression, anxiety, and subclinical psychotic symptoms, ps < 0.004) and improvements in resilience-promoting capacities (self-compassion and self-efficacy, ps < 0.006) and indices of social functioning (social motivation, activity, and a measure of comfort with the physical presence of others, ps < 0.04) were observed. Moreover, the significant increases in resilience-promoting capacities correlated with the reductions in affective symptoms (ps < 0.03). CONCLUSIONS: These findings suggest that an on-campus mental health screening and early intervention program is feasible, acceptable, and may be associated with improvements in resilience-related capacities and symptom reductions in young adults with non-impairing, subclinical symptoms of psychopathology. Follow-up work will determine whether this program can improve both shorter and longer-term mental health and functional outcomes in this at-risk population.

Understanding the effects of emotional reactivity on depression and suicidal thoughts and behaviors: Moderating effects of childhood adversity and resilience.

BACKGROUND: Early adulthood is a period of increased risk for depression and suicide. Emotional reactivity (a tendency to react to stress with increases in negative affect and maladaptive interpretations of events) is an important risk factor for these outcomes that has been under-studied. We hypothesized that elevated emotional reactivity would be associated with higher levels of depressive symptoms and suicidal thoughts and behaviors. Further, we hypothesized that experiences of childhood maltreatment would amplify this relationship, whereas the presence of resilience would act as a buffer. METHODS: 1703 young adults (Mean Age = 19.56 years), 71% female) completed well-validated self-report questionnaires at a single time point. RESULTS: Higher emotional reactivity was directly associated with higher levels of depressive symptoms and suicidal thoughts and behaviors. Further, resilience levels significantly moderated the relationships between emotional reactivity and depressive symptoms and suicidal thoughts and behaviors. Finally, childhood trauma significantly moderated the relationship between emotional reactivity and suicidal thoughts and behaviors only. LIMITATIONS: This study was cross-sectional in design and relied upon self-report measures only. CONCLUSIONS: The current study demonstrates an association between emotional reactivity, depressive symptoms, and suicidal thoughts and behaviors during emerging adulthood. Whereas a history of childhood maltreatment may amplify the relationship between emotional reactivity, depression, and suicidal thoughts and behaviors, certain qualities associated with resilience may buffer against the effects of emotional reactivity. Future studies can identify the resilience-promoting factors that are most protective and develop and test interventions that can potentially augment those factors.

Sex Differences in the Association between Heavy Drinking and Behavioral Distress Tolerance and Emotional Reactivity Among Non-Depressed College Students.

BACKGROUND: Heavy episodic drinking (HED) is a common behavior among college students that is associated with severe negative consequences. Negative reinforcement processes have been applied to elucidate mechanisms underlying relationships between consumption of alcohol and the desire to alleviate negative feelings. Distress tolerance (DT) and emotional reactivity are two mechanisms that are consistent with the self-medication model that may contribute to HED. The current study investigated relationships between DT, emotional reactivity, defined as frustration reactivity and irritability reactivity, and HED in a non-depressed college population. Given differential patterns of consumption and motivation for drinking between males and females, sex differences were also examined. SHORT SUMMARY: The study examined two constructs consistent with negative reinforcement processes, behavioral distress tolerance (DT) and emotional reactivity (frustration reactivity and irritability reactivity), to explain heavy episodic drinking (HED) among non-depressed college students. Behavioral DT and frustration reactivity independently predicted HED. Higher HED was associated with higher frustration reactivity and lower behavioral DT in women, but nor in men. METHODS: One-hundred-ten college students without depressive symptoms completed alcohol use measures and the Paced Auditory Serial Attention Task (PASAT-C) to assess behavioral DT and emotional reactivity. RESULTS: DT and frustration reactivity independently predicted HED. The association between DT and HED was moderated by sex such that higher levels of DT predicted higher HED among females, but not among males. Higher frustration reactivity scores were associated with a greater number of HED. CONCLUSIONS: Results provide supporting evidence that DT and emotional reactivity are distinct factors, and that they predict HED independently. Results underscore the importance of examining sex differences when evaluating the association between HED and negative reinforcement processes in this population.

Mindfulness-Based Interventions in Psychiatry.

Mindfulness meditation has a longstanding history in eastern practices that has received considerable public interest in recent decades. Indeed, the science, practice, and implementation of Mindfulness Based Interventions (MBIs) have dramatically increased in recent years. At its base, mindfulness is a natural human state in which an individual experiences and attends to the present moment. Interventions have been developed to train individuals how to incorporate this practice into daily life. The current article will discuss the concept of mindfulness and describe its implementation in the treatment of psychiatric disorders. We further identify for whom MBIs have been shown to be efficacious and provide an up-to-date summary of how these interventions work. This includes research support for the cognitive, psychological, and neural mechanisms that lead to psychiatric improvements. This review provides a basis for incorporating these interventions into treatment.

Ketamine-Associated Brain Changes: A Review of the Neuroimaging Literature.

Major depressive disorder (MDD) is one of the most prevalent conditions in psychiatry. Patients who do not respond to traditional monoaminergic antidepressant treatments have an especially difficult-to-treat type of MDD termed treatment-resistant depression. Subanesthetic doses of ketamine-a glutamatergic modulator-have shown great promise for rapidly treating patients with the most severe forms of depression. As such, ketamine represents a promising probe for understanding the pathophysiology of depression and treatment response. Through neuroimaging, ketamine's mechanism may be elucidated in humans. Here, we review 47 articles of ketamine's effects as revealed by neuroimaging studies. Some important brain areas emerge, especially the subgenual anterior cingulate cortex. Furthermore, ketamine may decrease the ability to self-monitor, may increase emotional blunting, and may increase activity in reward processing. Further studies are needed, however, to elucidate ketamine's mechanism of antidepressant action.

Compassionate Hearts Protect Against Wandering Minds: Self-compassion Moderates the Effect of Mind-Wandering on Depression.

Depression is associated with high levels of mind-wandering and low levels of self-compassion. However, little is known about whether and how these two factors interact with one another to influence depressive symptoms. The current study examined the interaction between mind-wandering, self-compassion and depressive symptoms in a depressed sample and tested the effects of an eight-week Mindfulness Based Cognitive Therapy (MBCT) program on these constructs. At baseline, mind-wandering was associated with higher depressive symptoms only among individuals with low self-compassion. Self-compassion additionally predicted depressive improvement. As expected, MBCT increased self-compassion and reduced mind-wandering compared to a treatment-as-usual control group. Overall, longitudinal changes in self-compassion produced a moderation effect similar to the one at baseline so that increases in mind-wandering were associated with increases in depressive symptoms only among those who decreased in self-compassion. Results provide the first evidence that self-compassion can protect against the deleterious effects of mind-wandering among depressed participants, both at baseline and longitudinally. Findings also suggest that self-compassion is an effective predictor of depressive improvement. Finally, MBCT is effective not only at reducing depressive symptoms, but also at targeting protective and risk factors associated with depression.

Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors.

Interaction of Biological Stress Recovery and Cognitive Vulnerability for Depression in Adolescence.

Major Depressive Disorder is a common mental illness with rates increasing during adolescence. This has led researchers to examine developmental antecedents of depression. This study examined the association between depressive symptoms and the interaction between two empirically supported risk factors for depression: poor recovery of the biological stress system as measured through heart rate and cortisol, and cognitive vulnerabilities as indexed by rumination and a negative cognitive style. Adolescents (n = 127; 49 % female) completed questionnaires and a social stress task to elicit a stress response measured with neuroendocrine (cortisol) and autonomic nervous system (heart rate) endpoints. The findings indicated that higher depressive symptoms were associated with the combination of higher cognitive vulnerabilities and lower cortisol and heart rate recovery. These findings can enhance our understanding of stress responses, lead to personalized treatment, and provide a nuanced understanding of depression in adolescence.

Mindfulness-based cognitive therapy for depressed individuals improves suppression of irrelevant mental-sets.

An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.