Effectiveness and Changes in Brain Functions by an Occupational Therapy Program Incorporating Mindfulness in Outpatients with Anxiety and Depression: A Randomized Controlled Trial.

INTRODUCTION: This study examined the efficacy of an 8-week occupational therapy program incorporating mindfulness (MOT) as a form of psychiatric rehabilitation to ameliorate residual social and occupational impairment in patients with anxiety disorders and depression. The objective was to evaluate the effects of MOT on their personal well-being and to assess the impact of MOT on brain function using quantitative electroencephalography (qEEG). METHODS: This study was a randomized, wait-list control trial with assessments performed at baseline, post-intervention (9 weeks), and follow-up (18 weeks) in outpatients with anxiety disorders and depression. The MOT was conducted in small groups, comprising eight weekly 1.5-h sessions. The primary outcome was the mean score change between the pre- and post-interventions with Questionnaire about the Process of Recovery (QPR) scale. Other clinical assessments and qEEG served as secondary and biological outcomes, respectively. RESULTS: A total of 25 patients (mean age: 44.1) were included in the analysis. The MOT group demonstrated a significantly improved QPR compared to the control group after adjusting for baseline covariates (p < 0.01). This improvement was sustained for 9 weeks after the 8-week intervention. In the qEEG analysis, a significant increase in current source density in the ß2 band of the left dorsolateral prefrontal cortex was observed in the MOT group compared to the control group (p < 0.02). CONCLUSION: This study demonstrates that MOT improves subjective well-being and potentially, global function. This suggests that MOT may serve as a viable option for those whose symptoms have abated but who still struggle with social and occupational functioning.

Association between the Rostral Anterior Cingulate Cortex and Anterior Insula in the Salience Network on Response to Antidepressants in Major Depressive Disorder as Revealed by Isolated Effective Coherence.

INTRODUCTION: Functional connectivity is attracting increasing attention for understanding the pathophysiology of depression and predicting the therapeutic efficacy of antidepressants. In this study, we evaluated effective connectivity using isolated effective coherence (iCoh), an effective functional connectivity analysis method developed from low-resolution brain electromagnetic tomography (LORETA) and estimated its practical usefulness for predicting the reaction to antidepressants in theta and alpha band iCoh values. METHODS: We enrolled 25 participants from a depression treatment randomized study (the GUNDAM study) in which electroencephalography was performed before treatment. We conducted iCoh between the rostral anterior cingulate cortex (rACC) and anterior insula (AI), which are associated with the salience network. The patients were divided into responder and nonresponder groups at 4 weeks after the start of treatment, and iCoh values were compared between the two groups. Additionally, the sensitivity and specificity of iCoh were calculated using the receiver-operating characteristic (ROC) curve. RESULTS: The Mann-Whitney U test showed significantly weaker connectivity flow from the rACC to the left AI in the alpha band in the responder group. The ROC curve for the connectivity flow from the rACC to the left AI in the alpha band showed 82% sensitivity and 86% specificity. DISCUSSION/CONCLUSION: These findings suggest the pathological importance of effective connectivity flow from the rACC to the left AI in the alpha and theta bands and suggest its usefulness as a biomarker to distinguish responders to antidepressants.

Machine-Learning- and Knowledge-Based Scoring Functions Incorporating Ligand and Protein Fingerprints.

We propose a novel machine-learning-based scoring function for drug discovery that incorporates ligand and protein structural information into a knowledge-based PMF score. Molecular docking, a simulation method for structure-based drug design (SBDD), is expected to reduce the enormous costs associated with conventional experimental methods in terms of rational drug discovery. Molecular docking has two main purposes: to predict ligand-binding structures for target proteins and to predict protein-ligand binding affinity. Currently available programs of molecular docking offer an accurate prediction of ligand binding structures for many systems. However, the accurate prediction of binding affinity remains challenging. In this study, we developed a new scoring function that incorporates fingerprints representing ligand and protein structures as descriptors in the PMF score. Here, regression analysis of the scoring function was performed using the following machine learning techniques: least absolute shrinkage and selection operator (LASSO) and light gradient boosting machine (LightGBM). The results on a test data set showed that the binding affinity delivered by the newly developed scoring function has a Pearson correlation coefficient of 0.79 with the experimental value, which surpasses that of the conventional scoring functions. Further analysis provided a chemical understanding of the descriptors that contributed significantly to the improvement in prediction accuracy. Our approach and findings are useful for rational drug discovery.

Mindfulness augmentation for anxiety through concurrent use of transcranial direct current stimulation: a randomized double-blind study.

Transcranial direct current stimulation (tDCS) have revealed the capability to augment various types of behavioural interventions. We aimed to augment the effects of mindfulness, suggested for reducing anxiety, with concurrent use of tDCS. We conducted a double-blind randomized study with 58 healthy individuals. We introduced treadmill walking for focused meditation and active or sham tDCS on the left dorsolateral prefrontal cortex for 20 min. We evaluated outcomes using State-Trait Anxiety Inventory-State Anxiety (STAI) before the intervention as well as immediately, 60 min, and 1 week after the intervention, and current density from electroencephalograms (EEG) before and after the intervention. The linear mixed-effect models demonstrated that STAI-state anxiety showed a significant interaction effect between 1 week after the intervention and tDCS groups. As for alpha-band EEG activity, the current density in the rostral anterior cingulate cortex (rACC) was significantly reduced in the active compared with the sham stimulation group, and a significant correlation was seen between changes in STAI-trait anxiety and the current density of the rACC in the active stimulation group. Our study provided that despite this being a one-shot and short intervention, the reduction in anxiety lasts for one week, and EEG could potentially help predict its anxiolytic effect.

The lateral intercalated cell mass of the amygdala is activated during social buffering of conditioned fear responses in male rats.

The presence of an affiliative conspecific reduces stress responses to a wide variety of stimuli. This phenomenon is termed "social buffering". We previously found that the presence of another Wistar rat (associate) suppressed activation of the lateral amygdala (LA) and ameliorated stress responses to an auditory conditioned stimulus (CS) in a fear-conditioned Wistar subject rat. Subsequent analyses suggested that activation of the posterior complex of the anterior olfactory nucleus (AOP) is responsible for the suppression of the LA. However, it remains unclear how the AOP suppresses the LA. To clarify this issue, a fear-conditioned Wistar subject was exposed to the CS either alone or with a Wistar associate. We also prepared a fear-conditioned Wistar subject that was tested with a Fischer344 (F344) associate as an additional control because F344 associates do not induce social buffering. We found that the presence of a Wistar associate induced a reduction of behavioral responses and Fos expression in the paraventricular nucleus of the hypothalamus (PVN) of the subject. Although Fos expression in the AOP was increased, the expression was not biased towards the GABAergic cells. In addition, Fos expression in the lateral intercalated cell mass of the amygdala (lITC) was increased. In contrast, the presence of a F344 associate did not affect Fos expression in subjects' PVN or lITC, whereas behavioral responses were slightly reduced. These results suggest that the lITC was activated during social buffering. Based on these findings, we propose that the AOP indirectly suppresses the LA by activating the lITC.

Hyperactivation of the Frontal Control Network Revealed by Symptom Provocation in Obsessive-Compulsive Disorder Using EEG Microstate and sLORETA Analyses.

The aim of this study was to investigate the changes of brain electric field induced by symptom provocation in patients with obsessive-compulsive disorder (OCD) in comparison to healthy controls in the resting state. For this purpose, EEG recordings in conditions of initial rest, clean control, symptom provocation by imaginal exposure, and final rest were used for computing spatiotemporal activity characteristics based on microstate segmentation. Within-group comparisons were significant for the symptom provocation condition: OCD showed high global field power (GFP) and transition rates into a medial frontal microstate, whereas healthy controls showed high frequency of occurrence and high percent of dwelling time for a medial occipitoparietal microstate. Between-group comparisons demonstrated significantly lower GFP and dwelling time for the medial occipitoparietal microstate in OCD in several conditions including initial rest and symptom provocation. In addition, OCD compared to healthy controls showed significant instability of the medial occipitoparietal microstate, with high preference for transitions into the medial frontal microstate. In conclusion, during rest and symptom provocation, OCD patients make preferential use of a medial frontal brain network, with concomitant reduction of use of a medial occipitoparietal network, as shown by dwelling times, explained variance, and dynamic transition rates. These findings support the idea of a possible biological marker for OCD, which might correspond to pathological hyperactivation of the frontal control network.

Involvement of the leaf-specific multidrug and toxic compound extrusion (MATE) transporter Nt-JAT2 in vacuolar sequestration of nicotine in Nicotiana tabacum.

Alkaloids play a key role in higher plant defense against pathogens and herbivores. Following its biosynthesis in root tissues, nicotine, the major alkaloid of Nicotiana species, is translocated via xylem transport toward the accumulation sites, leaf vacuoles. Our transcriptome analysis of methyl jasmonate-treated tobacco BY-2 cells identified several multidrug and toxic compound extrusion (MATE) transporter genes. In this study, we characterized a MATE gene, Nicotiana tabacum jasmonate-inducible alkaloid transporter 2 (Nt-JAT2), which encodes a protein that has 32% amino acid identity with Nt-JAT1. Nt-JAT2 mRNA is expressed at a very low steady state level in whole plants, but is rapidly upregulated by methyl jasmonate treatment in a leaf-specific manner. To characterize the function of Nt-JAT2, yeast cells were used as the host organism in a cellular transport assay. Nt-JAT2 was localized at the plasma membrane in yeast cells. When incubated in nicotine-containing medium, the nicotine content in Nt-JAT2-expressing cells was significantly lower than in control yeast. Nt-JAT2-expressing cells also showed lower content of other alkaloids like anabasine and anatabine, but not of flavonoids, suggesting that Nt-JAT2 transports various alkaloids including nicotine. Fluorescence assays in BY-2 cells showed that Nt-JAT2-GFP was localized to the tonoplast. These findings indicate that Nt-JAT2 is involved in nicotine sequestration in leaf vacuoles following the translocation of nicotine from root tissues.

A tolerance gene for prenylated flavonoid encodes a 26S proteasome regulatory subunit in Sophora flavescens.

Yeast functional screening with a Sophora flavescens cDNA library was performed to identify the genes involved in the tolerant mechanism to the self-producing prenylated flavonoid sophoraflavanone G (SFG). One cDNA, which conferred SFG tolerance, encoded a regulatory particle triple-A ATPase 2 (SfRPT2), a member of the 26S proteasome subunit. The yeast transformant of SfRPT2 showed reduced SFG accumulation in the cells.