Abnormal emotional reactivity in depression: Contrasting theoretical models using neurophysiological data.

Several theoretical models of aberrant emotional experiences in depression have been suggested. These models include potentiated reactivity to negatively-valenced stimuli, attenuated reactivity to positively-valenced stimuli, and attenuated emotional reactivity across contexts (termed emotion-context insensitivity). It is unclear if these models apply uniquely to depression or if they can explain other closely related symptoms, such as anxiety or general negative affect. The current study (N = 122) is the first to utilize structural equation modeling (SEM) techniques on neurophysiological data (event-related potentials, or ERPs) to empirically compare these theoretical models, thereby integrating perspectives from clinical psychology with affective neuroscience and advanced statistical techniques. We recorded ERPs during a passive viewing emotional task. Correlational analyses revealed several small, non-significant negative relationships between depression symptoms and emotional reactivity to both pleasant and unpleasant stimuli. However, SEM analyses revealed significantly attenuated emotional reactivity, to both pleasant and unpleasant stimuli, for depressive symptomatology. These relationships were specific to depression and did not apply to anxiety or internalizing symptoms broadly. Model comparisons revealed support for the emotional-context insensitivity hypothesis. Findings from this study are evidence in support of marrying novel techniques (here, SEM and ERPs) to test important theoretical questions regarding internalizing symptomatology.

Differential effects of state and trait mindfulness on the late positive potential.

Mindfulness is an effective emotion regulation strategy, and its principles have formed the basis for several psychotherapies. Of interest is how a mindful perspective changes not only the subjective experience of emotion, but also neural activity involved in emotional processing. In a previous event-related potential (ERP) study, trait mindfulness was linked with reduced neural activity in response to affective stimuli, as measured by the late positive potential (LPP). Building on this result, we investigated how both state (i.e., task-induced) and trait mindfulness would jointly affect the LPP in a large adult sample (N = 118). First, participants passively viewed affective images while ERP data were recorded. Participants were then instructed to adopt a mindful perspective and viewed a second, equivalent set of images. We hypothesized that the LPP would be reduced from the passive viewing to the mindful viewing condition. Contrary to our hypothesis, task-induced mindfulness increased LPP amplitude relative to passive viewing across all image types, suggesting that state mindfulness increases motivated attention to stimuli, regardless of affective valence and arousal. Trait mindfulness did not correlate with LPP amplitude in either the passive or mindful viewing conditions. As an unexpected finding, gender moderated the association between trait mindfulness and LPP amplitude to emotional images during mindful viewing. We propose that state and trait mindfulness impact emotional processing through different neural mechanisms and discuss implications for mindfulness as an emotion regulation strategy. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PD-1 suppresses protective immunity to Streptococcus pneumoniae through a B cell-intrinsic mechanism.

Despite the emergence of the programmed cell death 1 (PD-1):PD-1 ligand (PD-L) regulatory axis as a promising target for treating multiple human diseases, remarkably little is known about how this pathway regulates responses to extracellular bacterial infections. We found that PD-1(-/-) mice, as well as wild-type mice treated with a PD-1 blocking Ab, exhibited significantly increased survival against lethal Streptococcus pneumoniae infection following either priming with low-dose pneumococcal respiratory infection or S. pneumoniae-capsular polysaccharide immunization. Enhanced survival in mice with disrupted PD-1:PD-L interactions was explained by significantly increased proliferation, isotype switching, and IgG production by pneumococcal capsule-specific B cells. Both PD-L, B7-H1 and B7-DC, contributed to PD-1-mediated suppression of protective capsule-specific IgG. Importantly, PD-1 was induced on capsule-specific B cells and suppressed IgG production and protection against pneumococcal infection in a B cell-intrinsic manner. To our knowledge, these results provide the first demonstration of a physiologic role for B cell-intrinsic PD-1 expression in vivo. In summary, our study reveals that B cell-expressed PD-1 plays a central role in regulating protection against S. pneumoniae, and thereby represents a promising target for bolstering immunity to encapsulated bacteria.

Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice.

Complement receptor 2-deficient (Cr2(-/-)) mice are resistant to mesenteric ischemia/reperfusion (I/R) injury because they lack a component of the natural Ab repertoire. Neither the nature of the Abs that are involved in I/R injury nor the composition of the target Ag, to which recognition is lacking in Cr2(-/-) mice, is known. Because anti-phospholipid Abs have been shown to mediate fetal growth retardation and loss when injected into pregnant mice, we performed experiments to determine whether anti-phospholipid Abs can also reconstitute I/R injury and, therefore, represent members of the injury-inducing repertoire that is missing in Cr2(-/-) mice. We demonstrate that both murine and human monoclonal and polyclonal Abs against negatively charged phospholipids can reconstitute mesenteric I/R-induced intestinal and lung tissue damage in Cr2(-/-) mice. In addition, Abs against beta2 glycoprotein I restore local and remote tissue damage in the Cr2(-/-) mice. Unlike Cr2(-/-) mice, reconstitution of I/R tissue damage in the injury-resistant Rag-1(-/-) mouse required the infusion of both anti-beta2-glycoprotein I and anti-phospholipid Ab. We conclude that anti-phospholipid Abs can bind to tissues subjected to I/R insult and mediate tissue damage.