Daring to Feel: Emotion-Focused Psychotherapy Increases Amygdala Activation and Connectivity in Euthymic Bipolar Disorder-A Randomized Controlled Trial.

BACKGROUND: In bipolar disorder (BD), the alternation of extreme mood states indicates deficits in emotion processing, accompanied by aberrant neural function of the emotion network. The present study investigated the effects of an emotion-centered psychotherapeutic intervention on amygdala responsivity and connectivity during emotional face processing in BD. METHODS: In a randomized controlled trial within the multicentric BipoLife project, euthymic patients with BD received one of two interventions over 6 months: an unstructured, emotion-focused intervention (FEST), where patients were guided to adequately perceive and label their emotions (n = 28), or a specific, structured, cognitive behavioral intervention (SEKT) (n = 31). Before and after interventions, functional magnetic resonance imaging was conducted while patients completed an emotional face-matching paradigm (final functional magnetic resonance imaging sample of patients completing both measurements: SEKT, n = 17; FEST, n = 17). Healthy control subjects (n = 32) were scanned twice after the same interval without receiving any intervention. Given the focus of FEST on emotion processing, we expected FEST to strengthen amygdala activation and connectivity. RESULTS: Clinically, both interventions stabilized patients' euthymic states in terms of affective symptoms. At the neural level, FEST versus SEKT increased amygdala activation and amygdala-insula connectivity at postintervention relative to preintervention time point. In FEST, the increase in amygdala activation was associated with fewer depressive symptoms (r = 0.72) 6 months after intervention. CONCLUSIONS: Enhanced activation and functional connectivity of the amygdala after FEST versus SEKT may represent a neural marker of improved emotion processing, supporting the FEST intervention as an effective tool in relapse prevention in patients with BD.

Boosting the Theory of Mind Network: Specific Psychotherapy Increases Neural Correlates of Affective Theory of Mind in Euthymic Bipolar Disorder.

BACKGROUND: In bipolar disorder, impaired affective theory of mind (aToM) performance and aberrant neural activation in the ToM brain network partly explain social functioning impairments. However, it is not yet known whether psychotherapy of bipolar disorder influences neuroimaging markers of aToM. METHODS: In this study, conducted within the multicentric randomized controlled trial of the BipoLife consortium, patients with euthymic bipolar disorder underwent 2 group interventions over 6 months (mean = 28.45 weeks): 1) a specific, cognitive behavioral intervention (specific psychotherapeutic intervention [SEKT]) (n = 31) targeting impulse regulation, ToM, and social skills and 2) an emotion-focused intervention (FEST) (n = 28). To compare the effect of SEKT and FEST on neural correlates of aToM, patients performed an aToM task during functional magnetic resonance imaging before and after interventions (final functional magnetic resonance imaging sample of pre- and postcompleters, SEKT: n = 16; FEST: n = 17). Healthy control subjects (n = 32) were scanned twice with the same time interval. Because ToM was trained in SEKT, we expected an increased ToM network activation in SEKT relative to FEST postintervention. RESULTS: Both treatments effectively stabilized patients' euthymic state in terms of affective symptoms, life satisfaction, and global functioning. Confirming our expectations, SEKT patients showed increased neural activation within regions of the ToM network, bilateral temporoparietal junction, posterior cingulate cortex, and precuneus, whereas FEST patients did not. CONCLUSIONS: The stabilizing effect of SEKT on clinical outcomes went along with increased neural activation of the ToM network, while FEST possibly exerted its positive effect by other, yet unexplored routes.

Effectiveness of the First German-Language Group Psychotherapy Manual to Accompany Short-Term Treatment in Methamphetamine Dependence.

Background: Methamphetamine abuse is expanding in Europe, leading to a shortfall in medical care for related disorders in many regions. Research focusing on the effectiveness and feasibility of methamphetamine-specific treatment programs is scarce, especially in short-term settings. Methods: To this end, we treated 31 patients with methamphetamine dependence using a new group psychotherapy manual added to standard psychiatric care. Trained research assistants recorded demographic, illness and treatment variables using a standardized interview at baseline and a follow-up visit 3 months later. Outcome and process variables for this intervention encompassing 15 modules for qualified detoxification and motivation of patients with methamphetamine dependence are reported. Results: Retention and abstinence rates as well as acceptance and feasibility in daily routine were assessed positively. Patients with an unsuccessful outcome were characterized by longer regular methamphetamine use (t = -2.513, df = 29, p = 0.018) and a shorter abstinence period at baseline (U = 74.500, z = -1.808, p = 0.072). Among the demographic and clinical variables, the only predictor significantly increasing the odds of a successful outcome was a shorter period of regular methamphetamine use (OR = 1.318, CI 95% for OR = 1.021-1.700, b = 0.276, SE = 0.130, p = 0.034). Conclusions: This freely available therapy manual can help counter the shortfall in available psychotherapeutic interventions for patients with methamphetamine dependence in German-speaking countries. The routinely assessed parameters duration of regular methamphetamine use and abstinence before treatment were associated with outcome and may be used to personalize therapeutic strategies.

Depersonalization and derealization in embarrassing social interactions: an experience sampling study in social phobia, major depression and controls.

OBJECTIVE: The study explored the duration and frequency of depersonalization (DP) and derealization (DR) in embarrassing social interactions in the everyday life of individuals with social phobia (SP), major depressive disorder (MDD) and controls. METHODS: Experience sampling was used (seven days, five surveys per day). A total of N = 165 patients (n = 47 SP, n = 118 MDD) and n = 119 controls were included. DP/DR were assessed whenever an interaction has been indicated as embarrassing. RESULTS: Individuals with SP and MDD experienced more embarrassing social interactions than controls and, accordingly, more DP/DR. The frequency of DP in embarrassing social interactions was, compared to controls, only significantly higher in MDD (no difference between SP and MDD). Regarding DR, there were no between-group differences. The groups also did not differ regarding duration of DP/DR. CONCLUSIONS: The study is the first to demonstrate in an ecologically valid manner that DP/DR regularly occur in relation to feelings of embarrassment in controls and in individuals suffering from SP or MDD. DP and DR might be responses to strong emotions, like embarrassment, or might be attempts at coping. The higher emergence of embarrassment itself might be viewed as an indicator of maladaptation. Treatment interventions correcting for these misinterpretations might reduce DP/DR.

Post-Event Processing After Embarrassing Situations: Comparing Experience Sampling Data of Depressed and Socially Anxious Individuals.

Background: Post-event processing (PEP) after social interactions (SIs) contributes to the persistence of social phobia (SP). This study investigated whether PEP as a transdiagnostic process also occurs in major depressive disorder (MDD) and controls. We also tested to what extent PEP was explained by trait levels of social anxiety (SA) or depression. Method: For seven days, a total of n = 165 patients (n = 47 SP, n = 118 MDD) and n = 119 controls completed five surveys per day on their smartphones. Event-based experience sampling was used. PEP was assessed following subjective embarrassment in SIs with two reliable items from the Post-Event Processing Questionnaire. Data were analysed via multilevel regression analyses. Results: Individuals with SP or MDD experienced more embarrassing SIs than controls and, accordingly, more PEP. The relative frequency of PEP after embarrassing SIs was equally high in all groups (86-96%). The groups did not differ regarding the amount of time PEP was experienced. After controlling trait depression, embarrassment occurred more frequently only in SP compared to controls. When controlling trait SA, between-group differences in indications of embarrassment, and consequently in PEP, dissipated. Conclusions: PEP could be interpreted as a common coping strategy among all individuals, while more frequent embarrassment might be specific for clinical groups. Embarrassment was primarily driven by SA. The alleviation of SA could lead to the reduction of embarrassment and, further, of PEP. On this basis, a model describing PEP in MDD is proposed, while current models of PEP in SP are complemented.

Landscape context explains ecosystem multifunctionality in restored grasslands better than plant diversity.

There is strong evidence for a positive relationship between biodiversity and ecosystem functioning at local spatial scales. However, how different aspects of biodiversity relate to multiple ecosystem functions (multifunctionality) across heterogeneous landscapes, and how the magnitude of biodiversity, dominant species, and environmental effects on functioning compare, remain poorly understood. We compared relationships between plant phylogenetic, functional, and taxonomic diversity and ecosystem multifunctionality across 29 restored grasslands. Functional diversity was positively associated with multifunctionality, more strongly than other diversity measures; however, landscape composition explained nearly four times more variation in multifunctionality than did functional diversity, with plots within human-modified landscapes supporting lower multifunctionality. Individual functions were typically more strongly correlated with environmental variables than with diversity. We also found that abundance of the dominant species, Andropogon gerardii, was positively correlated with multifunctionality. Plant diversity, dominant species, and underlying environmental conditions underpin ecosystem multifunctionality in grasslands, but how biodiversity is measured matters for the strength and direction of biodiversity-ecosystem function relationships. Finally, in natural systems environmental variation unrelated to local biodiversity is important for determining ecosystem functioning.

Ecosystem multifunctionality increases with beta diversity in restored prairies.

The loss of biodiversity at local and larger scales has potentially dramatic effects on ecosystem functioning. Many studies have shown that ecosystem functioning depends on biodiversity, but the role of beta diversity, spatial variation in community composition, is less clear than that of local-scale (alpha) diversity. To test the hypothesis that beta diversity would increase ecosystem multifunctionality through variation in species functional traits, we gathered data on plant community composition, plant functional traits, and seven ecosystem functions across 29 restored prairies. We found that averaged multifunctionality (mean of seven ecosystem functions) increased with both taxonomic beta diversity and functional beta diversity. The abundance of the dominant species, big bluestem, played a more minor role, suggesting a limited role for the selection effect. Neither taxonomic nor functional alpha richness was associated with multifunctionality, though this finding may be sensitive to the identity of the functions included because alpha diversity was associated with some individual functions in opposing directions. These findings suggest that in systems structured largely by natural processes, beta diversity (a patchwork of functionally different plant communities) and dominant species abundance may be more important than alpha diversity in fostering ecosystem multifunctionality. These findings suggest the need for an increased focus on community heterogeneity to reestablish functional ecosystems during restoration.

Effects of methylmercury on the secretion of pro-inflammatory cytokines from primary microglial cells and astrocytes.

Glial cells, including oligodendrocytes, astrocytes and microglia are important to proper central nervous system (CNS) function. Deregulation or changes to CNS populations of astrocytes and microglia in particular are expected to play a role in many neurodegenerative diseases, including Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). Previous studies have reported methylmercury (MeHg) induced changes in glial cell function; however, the effects of MeHg on these cells remains poorly understood. This study aims to examine the effect of MeHg on the secretion of pro-inflammatory cytokines from microglia and astrocytes. The impact of the microglia/astrocyte ratio on cytokine secretion was also examined. Microglia and astrocytes were cultured from the brains of neo-natal BALB/C mice and dosed with MeHg (0-1 µM) and stimulated with PAM(3)CSK(4) (PAM(3)), a toll-like receptor (TLR) ligand. After this, the secretion of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and interleukin-1-beta (IL-1ß) was measured by ELISA. MeHg reduced the secretion of IL-6 in a dose dependant manner but did not effect the secretion of TNF-α. No change in IL-1ß was observed in any treatments, indicating that PAM(3) cannot induce the secretion of this cytokine from glial cells. Additionally, the ratio of microglia/astrocyte had an effect on the secretion of IL-6 but not TNF-α. These results indicate that MeHg can modify the response of glial cells and the interactions with astrocytes can affect the response of the microglia cells in culture. These results are significant in understanding the potential relationship with MeHg and neurodegenerative diseases and for the interpretation of results of future in vitro studies using monoculture.

Effective stimulation of growth in MCF-7 human breast cancer cells by inhibition of syntaxin18 by external guide sequence and ribonuclease P.

Syntaxin18 (Stx18) is an endoplasmic reticulum (ER)-membrane bound SNARE protein involved in membrane trafficking between the ER and Golgi as well as in phagocytosis. Stx18 has also been shown to physically interact with proteins involved in the cell cycle and apoptosis. These findings suggest the possible role of Stx18 in regulating cell growth. In this study, we used theoretically designed external guide sequence molecule which utilizes RNase P to cleave Stx18 mRNA and down-regulate Stx18 levels in MCF-7 human breast cancer cells. We showed that down-regulation of Stx18 leads to significant enhancement of growth in MCF-7 cells. Consistent with this finding was the observation that over-expression of Stx18 using the CMV promoter led to suppression of cell growth. Over-expressing Stx18 had no effect on c-myc mRNA expression and half-life, suggesting that the mechanism does not involve control at the transcriptional and post-transcriptional level of the c-myc gene. Finally, we showed that Stx18 is over-expressed in clinical human breast cancer. Overall, this study showed that Stx18 plays a role in the growth of human breast cancer cells and provided the basis for further investigation in determining whether it can be used as a prognostic marker and as a molecular target in the treatment of breast cancer.

Destroying RNA as a therapeutic approach.

The ability to target RNA, mRNA and viral RNA in particular, for degradation is a powerful approach in molecular biology and pharmacology. Such approaches can be used in the study of gene function as in functional genomics, in the identification of disease-associated genes, and for the treatment of human diseases. This review provides a comprehensive up-to-date look at all the current available technologies used for the destruction of RNA, with a focus on their therapeutic potential. This includes approaches that utilize the activity of protein ribonucleases such as antisense oligonucleotide, small interfering RNA, RNase P-associated external guide sequence, onconase and bovine seminal RNase. Sequence-specific approaches that do not utilize activity of protein ribonucleases, such as ribozyme and DNazyme, are also reviewed and discussed. This review should provide a useful starting framework for researchers interested in using the RNA-destruction methodologies on the bench and in the clinic, and serves as a stimulus for further development of novel and more potent RNA degradation technologies. This is particularly critical, given the anticipation of discoveries of new cellular RNA degradation machineries and human diseases that are associated with dysfunctional RNA molecules.