Neural Correlates of Trait Impulsivity among Adult Healthy Individuals.

Objective: : Impulsivity can be observed in individuals with or without mental illness. The discovery of neural correlates responsible for trait impulsivity can therefore help to understand the severity of psychiatric symptoms, personality characteristics and social adjustment. In this study, we aimed to identify the gray matter substrates of trait impulsivity in healthy individuals. Methods: : Seventy-five healthy individuals were enrolled. At baseline, trait impulsivity was assessed using the Barratt Impulsiveness Scale (BIS) and all participants underwent T1-weighted magnetic resonance imaging scan. Beck Anxiety Inventory (BAI), World Health Organization Quality of Life (WHOQOL-BREF) and Connor-Davidson Resilience Scale (CD-RISC) were also assessed. Mean cortical thickness (CT) and the local gyrification index (LGI) were calculated to perform whole-brain vertex-wise correlation analysis, which were performed to investigate the relationship between BIS scores and CT or LGI in each brain region. We also revealed the relationship between brain regions and psychological measurements. Results: : Total BIS scores were significantly and negatively correlated with mean CT values in the left lateral occipital cortex (OC) and LGIs in the inferior frontal gyrus (IFG). Correlation analyses revealed that the lateral OC's mean CT values were negatively correlated with BAI scores and positively correlated with WHOQOL-BREF scores, while LGI in the IFG was positively correlated with CD-RISC scores. Conclusion: : Our study showed that trait impulsivity might be associated with the lateral OC and IFG in healthy individuals. Understanding the neural correlates of trait impulsivity could provide ways to expect high impulsivity, anxiety, and poor resilience in healthy adults.

Identification of inulin-responsive bacteria in the gut microbiota via multi-modal activity-based sorting.

Prebiotics are defined as non-digestible dietary components that promote the growth of beneficial gut microorganisms. In many cases, however, this capability is not systematically evaluated. Here, we develop a methodology for determining prebiotic-responsive bacteria using the popular dietary supplement inulin. We first identify microbes with a capacity to bind inulin using mesoporous silica nanoparticles functionalized with inulin. 16S rRNA gene amplicon sequencing of sorted cells revealed that the ability to bind inulin was widespread in the microbiota. We further evaluate which taxa are metabolically stimulated by inulin and find that diverse taxa from the phyla Firmicutes and Actinobacteria respond to inulin, and several isolates of these taxa can degrade inulin. Incubation with another prebiotic, xylooligosaccharides (XOS), in contrast, shows a more robust bifidogenic effect. Interestingly, the Coriobacteriia Eggerthella lenta and Gordonibacter urolithinfaciens are indirectly stimulated by the inulin degradation process, expanding our knowledge of inulin-responsive bacteria.

Impact of Intolerance of Uncertainty on Brain Structural Changes in Panic Disorder.

OBJECTIVE: This study investigated the impact of intolerance of uncertainty (IU) on structural changes in the brain and symptom severity in patients with panic disorder. METHODS: This study included 90 participants diagnosed with panic disorder. The IU Scale, Panic Disorder Severity Scale (PDSS), Beck Depression Inventory-II (BDI-II), Penn State Worry Questionnaire (PSWQ), Self-Forgiveness Scale (SFS), and Short Form 36 Health Survey (SF) were used. A voxel-wise correlation analysis was conducted to investigate the structural differences in the gray matter. RESULTS: As IU increased, the cortical thickness of the right lingual gyrus decreased significantly, while the gray matter volume of the right pars triangularis increased. The cortical thickness of the right lingual gyrus showed a significant negative correlation with the BDI-II score and a positive correlation with the SFS. Additionally, the gray matter volume of the right pars triangularis was positively correlated with the PDSS, PSWQ, and BDI-II scores and negatively correlated with the mental health domain of the SF. CONCLUSION: According to our findings, elevated IU in participants with panic disorder was associated with cortical thinning in the lingual gyrus and increased gray matter volume in the pars triangularis. These structural alterations may also have an impact on perceived quality of life, as well as high levels of depression and anxiety.

Long-term benefits of mindfulness on white matter tracts underlying the cortical midline structures in panic disorder: A 2-year longitudinal study.

AIMS: We aimed to examine the long-term benefits of mindfulness-based cognitive therapy (MBCT) on white matter plasticity in the cortical midline structures (CMS) for a period of 2 years in patients with panic disorder and the relationships between white matter changes in the CMS and severity of state and trait symptoms. METHODS: Seventy-one participants were enrolled and underwent diffusion tensor imaging at baseline and after 2 years (26 who received MBCT as an adjunct to pharmacotherapy [MBCT+PT], 20 treated with pharmacotherapy alone [PT-alone], and 25 healthy controls [HCs]). The severity of symptoms and fractional anisotropy (FA) in white matter regions underlying the CMS were assessed at baseline and 2-year follow-up. RESULTS: The MBCT+PT group showed better outcomes after 2 years than the PT-alone group. The groups showed different FA changes: the MBCT+PT group showed decreased FA in the left anterior cingulate cortex (ACC); the PT-alone group showed increased FA in the bilateral dorsomedial prefrontal cortex, posterior cingulate cortex (PCC), and precuneus. Decreased white matter FA in the ACC, PCC, and precuneus was associated with improvements in the severity of state and trait symptoms in patients with panic disorder. CONCLUSION: Alleviation of excessive white matter connectivity in the CMS after MBCT leads to improvements in clinical symptoms and trait vulnerability in patients with panic disorder. Our study provides new evidence for the long-term benefits of MBCT on white matter plasticity and its clinical applicability as a robust treatment for panic disorder.

Multiple roads lead to Rome: unique morphology and chemistry of endospores, exospores, myxospores, cysts and akinetes in bacteria.

The production of specialized resting cells is a remarkable survival strategy developed by many organisms to withstand unfavourable environmental factors such as nutrient depletion or other changes in abiotic and/or biotic conditions. Five bacterial taxa are recognized to form specialized resting cells: Firmicutes, forming endospores; Actinobacteria, forming exospores; Cyanobacteria, forming akinetes; the δ-Proteobacterial order Myxococcales, forming myxospores; and Azotobacteraceae, forming cysts. All these specialized resting cells are characterized by low-to-absent metabolic activity and higher resistance to environmental stress (desiccation, heat, starvation, etc.) when compared to vegetative cells. Given their similarity in function, we tested the potential existence of a universal morpho-chemical marker for identifying these specialized resting cells. After the production of endospores, exospores, akinetes and cysts in model organisms, we performed the first cross-species morphological and chemical comparison of bacterial sporulation. Cryo-electron microscopy of vitreous sections (CEMOVIS) was used to describe near-native morphology of the resting cells in comparison to the morphology of their respective vegetative cells. Resting cells shared a thicker cell envelope as their only common morphological feature. The chemical composition of the different specialized resting cells at the single-cell level was investigated using confocal Raman microspectroscopy. Our results show that the different specialized cells do not share a common chemical signature, but rather each group has a unique signature with a variable conservation of the signature of the vegetative cells. Additionally, we present the validation of Raman signatures associated with calcium dipicolinic acid (CaDPA) and their variation across individual cells to develop specific sorting thresholds for the isolation of endospores. This provides a proof of concept of the feasibility of isolating bacterial spores using a Raman-activated cell-sorting platform. This cross-species comparison and the current knowledge of genetic pathways inducing the formation of the resting cells highlights the complexity of this convergent evolutionary strategy promoting bacterial survival.

Safety and Effectiveness of Desvenlafaxine in Korean Patients with Major Depressive Disorder: A 6-month Postmarketing Surveillance Study.

Objective: Although the safety and efficacy of desvenlafaxine have been demonstrated, long-term evidence in Asians is lacking. We examined the safety and effectiveness of desvenlafaxine for up to 6 months in routine clinical practice in Korea. Methods: This multicenter, open-label, prospective observational study was conducted from February 2014 to February 2020 as a postmarketing surveillance study of desvenlafaxine (ClinicalTrials.gov identifier: NCT02548949). Adult patients with major depressive disorder (MDD) were observed from the initiation of treatment for 8 weeks (acute treatment phase) and then up to 6 months (continuation treatment phase) in a subsample. Safety was evaluated by incidence of adverse events (AE) and adverse drug reactions. Treatment response was assessed using the Clinical Global Impression- Improvement (CGI-I) scale. Results: We included 700 and 236 study subjects in the analysis of acute and continuation treatment phase, respectively. In acute treatment phase, AE incidence was 9.86%, with nausea being most common (2.00%). In continuation treatment phase, AE incidence was 2.97%, with tremor occurring most frequently. After acute treatment (n = 464), the treatment response rate according to the CGI-I score at week 8 was 28.9%. In long-term users (n = 213), the response rate at month 6 was 45.5%. During the study period, no clinically relevant changes in BP were found regardless of concomitant use of antihypertensive drugs. Conclusion: This study provides evidence on the safety and effectiveness of desvenlafaxine in adults with MDD, with a low incidence of AE, consistent AE profile with previous studies, and improved response after long-term treatment.

Suicide risk within 1 year of dementia diagnosis in older adults: a nationwide retrospective cohort study.

BACKGROUND: Although severe dementia could protect against suicide death by decreasing a person's capacity to implement a suicide plan, patients with early dementia may have better cognition, giving them more sustained insight into their disease and better enabling them to carry out a suicide plan. This study investigated suicide risk in older adults within 1 year of receiving a diagnosis of dementia. METHODS: This study used National Health Insurance Service Senior Cohort data and included 36 541 older adults with newly diagnosed dementia (a Mini-Mental State Examination score ≤ 26 and a Clinical Dementia Rating score ≥ 1 or a Global Deterioration Scale score ≥ 3), including Alzheimer disease, vascular dementia and other/unspecified dementia, from 2004 to 2012. We selected older adults without dementia through 1:1 propensity-score matching using sex, age, comorbidities and index year, with follow-up throughout 2013. We estimated adjusted hazard ratios (AHRs) of suicide deaths within 1 year after diagnosis using a time-dependent Cox proportional hazards model. RESULTS: We verified 46 suicide deaths during the first year after a dementia diagnosis. Older adults with dementia had an increased risk of suicide death compared to those without dementia (AHR 2.57; 95% confidence interval [CI] 1.49-4.44). Older adults with Alzheimer disease (AHR 2.50; 95% CI 1.41-4.44) or other/unspecified dementia (AHR 4.32; 95% CI 2.04-9.15) had an increased risk of suicide death compared to those without dementia. Patients with dementia but without other mental disorders (AHR 1.96; 95% CI 1.02-3.77) and patients with dementia and other mental disorders (AHR 3.22; 95% CI 1.78-5.83) had an increased risk of suicide death compared to patients without dementia. Patients with dementia and schizophrenia (AHR 8.73; 95% CI 2.57-29.71), mood disorders (AHR 2.84; 95% CI 1.23-6.53) or anxiety or somatoform disorders (AHR 3.53; 95% CI 1.73-7.21), respectively, had an increased risk of suicide death compared to patients with those conditions but without dementia. LIMITATIONS: This study examined only elderly patients in South Korea, a population with a substantially higher suicide rate than the global population. Caution must be exercised when generalizing the results to populations with dissimilar backgrounds. CONCLUSION: Patients with dementia had an increased risk of suicide death within 1 year after diagnosis compared to those without dementia.

Optofluidic Raman-activated cell sorting for targeted genome retrieval or cultivation of microbial cells with specific functions.

Stable isotope labeling of microbial taxa of interest and their sorting provide an efficient and direct way to answer the question "who does what?" in complex microbial communities when coupled with fluorescence in situ hybridization or downstream 'omics' analyses. We have developed a platform for automated Raman-based sorting in which optical tweezers and microfluidics are used to sort individual cells of interest from microbial communities on the basis of their Raman spectra. This sorting of cells and their downstream DNA analysis, such as by mini-metagenomics or single-cell genomics, or cultivation permits a direct link to be made between the metabolic roles and the genomes of microbial cells within complex microbial communities, as well as targeted isolation of novel microbes with a specific physiology of interest. We describe a protocol from sample preparation through Raman-activated live cell sorting. Subsequent cultivation of sorted cells is described, whereas downstream DNA analysis involves well-established approaches with abundant methods available in the literature. Compared with manual sorting, this technique provides a substantially higher throughput (up to 500 cells per h). Furthermore, the platform has very high sorting accuracy (98.3 ± 1.7%) and is fully automated, thus avoiding user biases that might accompany manual sorting. We anticipate that this protocol will empower in particular environmental and host-associated microbiome research with a versatile tool to elucidate the metabolic contributions of microbial taxa within their complex communities. After a 1-d preparation of cells, sorting takes on the order of 4 h, depending on the number of cells required.

Effects of BDNF Val66Met Polymorphism on White Matter Microalterations of the Corpus Callosum in Patients with Panic Disorder in Korean Populations.

OBJECTIVE: The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with BDNF Val66Met polymorphism in PD. METHODS: Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics. RESULTS: The GG genotype in BDNF Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II. CONCLUSION: Our findings demonstrate that the BDNF Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.

Rational design of a microbial consortium of mucosal sugar utilizers reduces Clostridiodes difficile colonization.

Many intestinal pathogens, including Clostridioides difficile, use mucus-derived sugars as crucial nutrients in the gut. Commensals that compete with pathogens for such nutrients are therefore ecological gatekeepers in healthy guts, and are attractive candidates for therapeutic interventions. Nevertheless, there is a poor understanding of which commensals use mucin-derived sugars in situ as well as their potential to impede pathogen colonization. Here, we identify mouse gut commensals that utilize mucus-derived monosaccharides within complex communities using single-cell stable isotope probing, Raman-activated cell sorting and mini-metagenomics. Sequencing of cell-sorted fractions reveals members of the underexplored family Muribaculaceae as major mucin monosaccharide foragers, followed by members of Lachnospiraceae, Rikenellaceae, and Bacteroidaceae families. Using this information, we assembled a five-member consortium of sialic acid and N-acetylglucosamine utilizers that impedes C. difficile's access to these mucosal sugars and impairs pathogen colonization in antibiotic-treated mice. Our findings underscore the value of targeted approaches to identify organisms utilizing key nutrients and to rationally design effective probiotic mixtures.

PhenoChip: A single-cell phenomic platform for high-throughput photophysiological analyses of microalgae.

Photosynthetic microorganisms are key players in aquatic ecosystems with strong potential for bioenergy production, yet their systematic selection at the single-cell level for improved productivity or stress resilience ("phenotyping") has remained largely inaccessible. To facilitate the phenotyping of microalgae and cyanobacteria, we developed "PhenoChip," a platform for the multiparametric photophysiological characterization and selection of unicellular phenotypes under user-controlled physicochemical conditions. We used PhenoChip to expose single cells of the coral symbiont Symbiodinium to thermal and chemical treatments and monitor single-cell photophysiology via chlorophyll fluorometry. This revealed strain-specific thermal sensitivity thresholds and distinct pH optima for photosynthetic performance, and permitted the identification of single cells with elevated resilience toward rising temperature. Optical expulsion technology was used to collect single cells from PhenoChip, and their propagation revealed indications of transgenerational preservation of photosynthetic phenotypes. PhenoChip represents a versatile platform for the phenotyping of photosynthetic unicells relevant to biotechnology, ecotoxicology, and assisted evolution.

Single-cell bacterial transcription measurements reveal the importance of dimethylsulfoniopropionate (DMSP) hotspots in ocean sulfur cycling.

Dimethylsulfoniopropionate (DMSP) is a pivotal compound in marine biogeochemical cycles and a key chemical currency in microbial interactions. Marine bacteria transform DMSP via two competing pathways with considerably different biogeochemical implications: demethylation channels sulfur into the microbial food web, whereas cleavage releases sulfur into the atmosphere. Here, we present single-cell measurements of the expression of these two pathways using engineered fluorescent reporter strains of Ruegeria pomeroyi DSS-3, and find that external DMSP concentration dictates the relative expression of the two pathways. DMSP induces an upregulation of both pathways, but only at high concentrations (>1 µM for demethylation; >35 nM for cleavage), characteristic of microscale hotspots such as the vicinity of phytoplankton cells. Co-incubations between DMSP-producing microalgae and bacteria revealed an increase in cleavage pathway expression close to the microalgae's surface. These results indicate that bacterial utilization of microscale DMSP hotspots is an important determinant of the fate of sulfur in the ocean.

Raman-based sorting of microbial cells to link functions to their genes.

In our recent work, we developed an optofluidic platform that allows a direct link to be made between the phenotypes (functions) and the genotypes (genes) of microbial cells within natural communities. By combining stable isotope probing, optical tweezers, Raman microspectroscopy, and microfluidics, the platform performs automated Raman-based sorting of taxa from within a complex community in terms of their functional properties. In comparison with manual sorting approaches, our method provides high throughput (up to 500 cells per hour) and very high sorting accuracy (98.3 ± 1.7%), and significantly reduces the human labour required. The system provides an efficient manner to untangle the contributions of individual members within environmental and host-associated microbiomes. In this News and Thoughts, we provide an overview of our platform, describe potential applications, suggest ways in which the system could be improved, and discuss future directions in which Raman-based analysis of microbial populations might be developed.

Generating Controlled, Dynamic Chemical Landscapes to Study Microbial Behavior.

We demonstrate a method for the generation of controlled, dynamic chemical pulses-where localized chemoattractant becomes suddenly available at the microscale-to create micro-environments for microbial chemotaxis experiments. To create chemical pulses, we developed a system to introduce amino acid sources near-instantaneously by photolysis of caged amino acids within a polydimethylsiloxane (PDMS) microfluidic chamber containing a bacterial suspension. We applied this method to the chemotactic bacterium, Vibrio ordalii, which can actively climb these dynamic chemical gradients while being tracked by video microscopy. Amino acids, rendered biologically inert ('caged') by chemical modification with a photoremovable protecting group, are uniformly present in the suspension but not available for consumption until their sudden release, which occurs at user-defined points in time and space by means of a near-UV-A focused LED beam. The number of molecules released in the pulse can be determined by a calibration relationship between exposure time and uncaging fraction, where the absorption spectrum after photolysis is characterized by using UV-Vis spectroscopy. A nanoporous polycarbonate (PCTE) membrane can be integrated into the microfluidic device to allow the continuous removal by flow of the uncaged compounds and the spent media. A strong, irreversible bond between the PCTE membrane and the PDMS microfluidic structure is achieved by coating the membrane with a solution of 3-aminopropyltriethoxysilane (APTES) followed by plasma activation of the surfaces to be bonded. A computer-controlled system can generate user-defined sequences of pulses at different locations and with different intensities, so as to create resource landscapes with prescribed spatial and temporal variability. In each chemical landscape, the dynamics of bacterial movement at the individual scale and their accumulation at the population level can be obtained, thereby allowing the quantification of chemotactic performance and its effects on bacterial aggregations in ecologically relevant environments.

White Matter-Based Structural Brain Network of Anxiety.

Anxiety disorders are characterized by excessive fear and anxiety and related behavioral disturbances. Because diffusion tensor imaging is sensitive to detect subtle pathology of the brain, it has been used to characterize differences in white matter microstructure for a broad spectrum of psychiatric disorders. The neurobiological underpinnings of a trait anxiety seem to be associated with the uncinate fasciculus, a major pathway between the amygdala and orbitofrontal cortex. Apparent WM micro-alterations in patients with panic disorder are present in diverse and widespread regions, although alterations vary in terms of clinical symptom severity and comorbidities. Social anxiety disorder is associated with structural dysconnectivity in a fronto-limbic network consistent with reduced fractional anisotropy values in uncinate fasciculus and inferior longitudinal fasciculus. The pathogenesis of obsessive-compulsive disorder may include abnormal findings in not only the fronto-striato-thalamic circuit but also the posterior and temporal regions of forceps major and cingulum bundle. Studies of white matter status in anxiety revealed overlapping patterns of front-cortical and fronto-limbic changes with uncinate fasciculus and cingulum alterations a frequent component.

A 12-week multidomain intervention for late-life depression: a community-based randomized controlled trial.

BACKGROUND: Given that current unimodal strategies for treating late-life depression are insufficient, the awareness of the necessity and importance of multidomain intervention has increased. We assessed the efficacy of multidomain intervention in reducing symptoms of late-life depression. METHODS: This was a 12-week community-based randomized controlled trial in 78 older adults diagnosed with major depressive disorder. Participants were randomly assigned to the multidomain intervention or supportive therapy group. We provided four home visits and 12 telephone calls over 12 weeks. Four therapeutic approaches (physical activity, healthy diet, social activity, and brief cognitive restructuring) were incorporated into the multidomain intervention. The primary outcome was the change in depressive symptoms, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Secondarily, we investigated changes in resting-state functional connectivity. RESULTS: The MADRS total score was reduced more in the multidomain intervention group than in the supportive therapy group during the 12 weeks (intervention × time interaction, P = =0.007). After correction for multiple comparisons, the multidomain intervention group exhibited a lower MADRS total score at week 12 (score difference 5.117; P = =0.029). At follow-up, the multidomain intervention group also exhibited less functional connectivity between the posterior cingulate cortex and left inferior parietal lobule within the default mode network (FDR < 0.1). LIMITATIONS: Caution is needed in the interpretation of the results, considering the small sample size and high percentage of female participants. CONCLUSIONS: A 12-week multidomain intervention resulted in a greater reduction of depressive symptoms among the elderly with major depressive disorder than their counterparts who received supportive therapy.

Psychiatric disorders and suicide risk among adults with disabilities: A nationwide retrospective cohort study.

BACKGROUND: Adults with disabilities demonstrate a higher suicide risk than the general population; however, the association between mental illness and death by suicide among disabled adults remains relatively unknown. We aimed to explore the relationship between psychiatric disorders and suicide risk in adults with disabilities. METHODS: We used nationally representative cohort data and included adults who registered as having a disability from 2004 to 2012, following up with them throughout 2013. We used the clinical diagnoses of all psychiatric disorders as an independent variable and death by suicide as a dependent variable to estimate the adjusted hazard ratio (AHR) of suicide risk using a Cox proportional hazards model. RESULTS: Among adults with disabilities (n = 30,386), those who had any psychiatric disorder were at an increased risk of death by suicide compared to those without mental illness (AHR 1.42; 95% confidence interval [CI] 1.02-1.99). Adults with mild disabilities who had psychiatric or mood disorders were more likely to commit suicide than the comparison group (AHR 1.67, 3.00; 95% CI 1.13-2.46, 1.95-4.61, respectively). LIMITATIONS: The actual time of disability onset could differ from the time of disability registration. CONCLUSIONS: Adults with disabilities who have psychiatric disorders are at increased risk of suicide compared to those without mental illness. During rehabilitation treatment after disability diagnosis, mental health support should be provided to those who have psychiatric illnesses to potentially reduce the risk of death by suicide.

Publisher Correction: An automated Raman-based platform for the sorting of live cells by functional properties.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.