Positive Shifts in Emotion Evaluation Following Mindfulness-Based Cognitive Therapy (MBCT) in Remitted Depressed Participants

Objectives: A combination of negatively biased information processing and a reduced ability to experience positive emotions can persist into remission from major depression (rMDD). Studies have shown that mindfulness-based cognitive therapy (MBCT) can increase self-reported positive emotions in rMDD participants; similar changes using neuropsychological tasks have not been shown. In this study, we investigated neuropsychological change in emotional processing following MBCT in rMDD participants. Methods: Seventy-three rMDD participants, 40 of whom received MBCT and 33 of whom continued with treatment as usual (TAU), and 42 never depressed participants took part; neither the TAU nor never depressed participants received MBCT. All were assessed at baseline and immediately following MBCT or after an 8-week gap for those without active intervention. Participants completed emotion evaluation and face emotion recognition tasks with self-report measures (mood, mindfulness) at each session. Results: Results showed an MBCT-specific shift in ratings from less negative to more positive emotion evaluations, which correlated with mindfulness practice and self-report mindfulness change. Both the MBCT and TAU groups showed a small increase in overall face emotion recognition accuracy compared with no change in never depressed participants. Conclusions: These findings support a specific role for MBCT in encouraging more positive evaluations of life situations in those with previous depression rather than influencing lower-level processing of emotions. Results should be interpreted cautiously given that this was a non-randomised, preference choice trial. Trial Registration: NCT0222604

One session treatment for specific phobias in children: Comorbid anxiety disorders and treatment outcome.

BACKGROUND AND OBJECTIVES: One-Session Treatment (OST) for specific phobias has been shown to be effective in reducing phobia severity; however, the effect of different types of co-occurring anxiety disorders on OST outcomes is unknown. The present study examined (1) the effects of co-occurring generalized anxiety disorder (GAD), social anxiety disorder (SAD), or another non-targeted specific phobia (OSP) on the efficacy of OST for specific phobias, and (2) the effects of OST on these co-occurring disorders following treatment. METHODS: Three groups of 18 youth (7-15 years) with a specific phobia and comorbid GAD, SAD, or OSP were matched on age, gender, and phobia type. Outcome measures included diagnostic status and severity, and clinician rated improvement. RESULTS: All groups demonstrated an improvement in their specific phobia following treatment. Treatment was equally effective regardless of co-occurring anxiety disorder. In addition, comorbid anxiety disorders improved following OST; however, this effect was not equal across groups. The SAD group showed poorer improvement in their comorbid disorder than the GAD group post-treatment. However, the SAD group continued to improve and this differential effect was not evident six-months following treatment. LIMITATIONS: The current study sample was small, with insufficient power to detect small and medium effect sizes. Further, the sample only included a portion of individuals with primary GAD or SAD, which may have attenuated the findings. CONCLUSIONS: The current study demonstrated that co-occurring anxiety disorders did not interfere with phobia treatment. OST, despite targeting a single specific phobia type, significantly reduced comorbid symptomatology across multiple anxiety disorders

Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder.

Social anxiety disorder (SAD) involves abnormalities in social motivation, which may be independent of well-documented differences in fear and arousal systems. Yet, the neurobiology underlying motivational difficulties in SAD is not well understood. The aim of the current study was to spatiotemporally dissociate reward circuitry dysfunction from alterations in fear and arousal-related neural activity during anticipation and notification of social and non-social reward and punishment. During fMRI acquisition, non-depressed adults with social anxiety disorder (SAD; N = 21) and age-, sex- and IQ-matched control subjects (N = 22) completed eight runs of an incentive delay task, alternating between social and monetary outcomes and interleaved in alternating order between gain and loss outcomes. Adults with SAD demonstrated significantly reduced neural activity in ventral striatum during the anticipation of positive but not negative social outcomes. No differences between the SAD and control groups were observed during anticipation of monetary gain or loss outcomes or during anticipation of negative social images. However, consistent with previous work, the SAD group demonstrated amygdala hyper-activity upon notification of negative social outcomes. Degraded anticipatory processing in bilateral ventral striatum in SAD was constrained exclusively to anticipation of positive social information and dissociable from the effects of negative social outcomes previously observed in the amygdala. Alterations in anticipation-related neural signals may represent a promising target for treatment that is not addressed by available evidence-based interventions, which focus primarily on fear extinction and habituation processes

Sensitivity shift theory: A developmental model of positive affect and motivational deficits in social anxiety disorder.

Social anxiety disorder (SAD) is a common and impairing condition that emerges in early adolescence, confers significant interpersonal disability and often persists into adulthood. Prevailing interventions for socially anxious youth are largely based on cognitive-behavioral models originally developed in adult samples, but produce only modest rates of remission in adolescents. The purposes of this review are to examine plausible explanations for these modest rates of treatment response and to critically evaluate the relevance of developmental mechanisms related to reward circuitry function. In doing so, we propose Sensitivity Shift Theory (SST), an integrated theoretical model addressing the development of social anhedonia in a meaningful subset of adolescents and adults with SAD. The central prediction of SST involves a shift, or developmental transition from social sensitivity during the late childhood/early adolescent period into later-emerging social anhedonia that includes reductions in positive affect, infrequent social approach behaviors and social skills deficits. We further provide a complementary mechanistic account by which these newly identified processes may be addressed using available evidence-based treatments that influence positive affect, including mindfulness-based interventions (MBIs). Collectively, SST provides a mechanisms-focused framework for explaining relatively modest rates of response to current front-line treatments in socially anxious youth, as well as discrepant observations in SAD samples of both high- and low- levels of social motivation depending on developmental factors and learning history

Attention Bias Modification Treatment for Adolescents With Social Anxiety Disorder.

Social anxiety disorder (SAD) tends to emerge during the early teenage years and is particularly refractory to change even when standard evidence-based CBT treatments are delivered. Efforts have been made to develop novel, mechanistic-driven interventions for this disorder. In the present study, we examined Attention Bias Modification Treatment (ABMT) for youth with SAD. Participants were 58 adolescents (mean age = 14.29 years) who met diagnostic criteria for SAD and who were randomized to ABMT or a placebo control condition, Attention Control Training (ACT). We predicted that ABMT would result in greater changes in both threat biases and social anxiety symptoms. We also explored potential moderators of change including the severity of social anxiety symptoms, the level of threat bias at pretreatment, and the degree of temperament-defined attention control. Contrary to our hypotheses, changes in attention bias were not observed in either condition, changes in social anxiety symptoms and diagnosis were small, and significant differences were not observed between the ABMT and ACT conditions. Little support for the proposed moderators was obtained. Reasons for our failure to find support for ABMT and its potential moderators are explored and recommendations for changes in the ABMT paradigm are suggested

Identification of Leptospira interrogans Phospholipase C as a Novel Virulence Factor Responsible for Intracellular Free Calcium Ion Elevation during Macrophage Death

BACKGROUND: Leptospira-induced macrophage death has been confirmed to play a crucial role in pathogenesis of leptospirosis, a worldwide zoonotic infectious disease. Intracellular free Ca(2+) concentration ([Ca(2+)]i) elevation induced by infection can cause cell death, but [Ca(2+)]i changes and high [Ca(2+)]i-induced death of macrophages due to infection of Leptospira have not been previously reported. METHODOLOGY/PRINCIPAL FINDINGS: We first used a Ca(2+)-specific fluorescence probe to confirm that the infection of L. interrogans strain Lai triggered a significant increase of [Ca(2+)]i in mouse J774A.1 or human THP-1 macrophages. Laser confocal microscopic examination showed that the [Ca(2+)]i elevation was caused by both extracellular Ca(2+) influx through the purinergic receptor, P(2)X(7), and Ca(2+) release from the endoplasmic reticulum, as seen by suppression of [Ca(2+)]i elevation when receptor-gated calcium channels were blocked or P(2)X(7) was depleted. The LB361 gene product of the spirochete exhibited phosphatidylinositol phospholipase C (L-PI-PLC) activity to hydrolyze phosphatidylinositol-4,5-bisphosphate (PIP(2)) into inositol-1,4,5-trisphosphate (IP(3)), which in turn induces intracellular Ca(2+) release from endoplasmic reticulum, with the Km of 199 µM and Kcat of 8.566E-5 S(-1). Secretion of L-PI-PLC from the spirochete into supernatants of leptospire-macrophage co-cultures and cytosol of infected macrophages was also observed by Western Blot assay. Lower [Ca(2+)]i elevation was induced by infection with a LB361-deficient leptospiral mutant, whereas transfection of the LB361 gene caused a mild increase in [Ca(2+)]i. Moreover, PI-PLCs (PI-PLC-β3 and PI-PLC-γ1) of the two macrophages were activated by phosphorylation during infection. Flow cytometric detection demonstrated that high [Ca(2+)]i increases induced apoptosis and necrosis of macrophages, while mild [Ca(2+)]i elevation only caused apoptosis. CONCLUSIONS/SIGNIFICANCE: This study demonstrated that L. interrogans infection induced [Ca(2+)]i elevation through extracellular Ca(2+) influx and intracellular Ca(2+) release cause macrophage apoptosis and necrosis, and the LB361 gene product was shown to be a novel PI-PLC of L. interrogans responsible for the [Ca(2+)]i elevation