Systematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study.

Although brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, we conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HC). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 ANBP) and 92 HC using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303 .

Comprehensive elucidation of resting-state functional connectivity in anorexia nervosa by a multicenter cross-sectional study.

BACKGROUND: Previous research on the changes in resting-state functional connectivity (rsFC) in anorexia nervosa (AN) has been limited by an insufficient sample size, which reduced the reliability of the results and made it difficult to set the whole brain as regions of interest (ROIs). METHODS: We analyzed functional magnetic resonance imaging data from 114 female AN patients and 135 healthy controls (HC) and obtained self-reported psychological scales, including eating disorder examination questionnaire 6.0. One hundred sixty-four cortical, subcortical, cerebellar, and network parcellation regions were considered as ROIs. We calculated the ROI-to-ROI rsFCs and performed group comparisons. RESULTS: Compared to HC, AN patients showed 12 stronger rsFCs mainly in regions containing dorsolateral prefrontal cortex (DLPFC), and 33 weaker rsFCs primarily in regions containing cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between anterior cingulate cortex (ACC) and thalamus (p < 0.01, false discovery rate [FDR] correction). Comparisons between AN subtypes showed that there were stronger rsFCs between right lingual gyrus and right supracalcarine cortex and between left temporal occipital fusiform cortex and medial part of visual network in the restricting type compared to the binge/purging type (p < 0.01, FDR correction). CONCLUSION: Stronger rsFCs in regions containing mainly DLPFC, and weaker rsFCs in regions containing primarily cerebellum, within temporal lobe, between posterior fusiform cortex and lateral part of visual network, and between ACC and thalamus, may represent categorical diagnostic markers discriminating AN patients from HC.

Role of Gut Microbiota in the Pathophysiology of Stress-Related Disorders: Evidence from Neuroimaging Studies.

BACKGROUND: The brain and gut communicate bidirectionally via immune, neurological, and endocrine pathways, which is termed the "brain-gut interaction." Recent studies of gut microbiota as a mediator of this interaction have provided a growing body of scientific evidence that suggests that the gut microbiota influences stress and emotional responses and stress-related disorders. SUMMARY: Major advances in analytical methods have led to an increased number of studies that combine gut microbiota and neuroimaging, mainly magnetic resonance imaging, to elucidate the mechanisms. Observational studies have been done to examine brain characteristics related to gut microbiota profiles, and intervention studies have examined brain changes related to probiotic intake. Studies of healthy subjects using negative emotional stimuli have shown that the pattern of emotional response differs depending on the gut microbiota profile and that probiotic intervention can modulate emotional response and be a buffer against the negative effects of stress. In studies on irritable bowel syndrome (IBS), a typical psychosomatic disorder, IBS-specific gut microbiota were reported to contribute to visceral irritability and pain by affecting the subcortical regions. Studies on psychiatric disorders revealed that a relative abundance of Bacteroides that produce γ-aminobutyric acid in feces was associated with a change in brain function specific to depression and that gut microbiota have an influence on abnormalities in the reward system of attention-deficit/hyperactivity disorder.

QseC inhibition as an antivirulence approach for colitis-associated bacteria.

Hosts and their microbes have established a sophisticated communication system over many millennia. Within mammalian hosts, this dynamic cross-talk is essential for maintaining intestinal homeostasis. In a genetically susceptible host, dysbiosis of the gut microbiome and dysregulated immune responses are central to the development of inflammatory bowel disease (IBD). Previous surveys of stool from the T-bet-/-Rag2-/- IBD mouse model revealed microbial features that discriminate between health and disease states. Enterobacteriaceae expansion and increased gene abundances for benzoate degradation, two-component systems, and bacterial motility proteins pointed to the potential involvement of a catecholamine-mediated bacterial signaling axis in colitis pathogenesis. Enterobacteriaceae sense and respond to microbiota-generated signals and host-derived catecholamines through the two-component quorum-sensing Escherichia coli regulators B and C (QseBC) system. On signal detection, QseC activates a cascade to induce virulence gene expression. Although a single pathogen has not been identified as a causative agent in IBD, adherent-invasive Escherichia coli (AIEC) have been implicated. Flagellar expression is necessary for the IBD-associated AIEC strain LF82 to establish colonization. Thus, we hypothesized that qseC inactivation could reduce LF82's virulence, and found that an absence of qseC leads to down-regulated flagellar expression and motility in vitro and reduced colonization in vivo. We extend these findings on the potential of QseC-based IBD therapeutics to three preclinical IBD models, wherein we observe that QseC blockade can effectively modulate colitogenic microbiotas to reduce intestinal inflammation. Collectively, our data support a role for QseC-mediated bacterial signaling in IBD pathogenesis and indicate that QseC inhibition may be a useful microbiota-targeted approach for disease management.

Protective Role of the Hepatic Vagus Nerve against Liver Metastasis in Mice.

OBJECTIVE(S): Although accumulating evidence has shown that the autonomic nervous system is involved in liver pathology, its role in regulating cancer development remains unclear. The purpose of this study was to elucidate its detailed mechanisms. METHODS: A mouse model of liver metastasis of colorectal cancer was used. To elucidate the potential mechanisms involved, we examined the effect of selective hepatic vagotomy on the survival rate and liver-to-body weight. We further evaluated the possible involvement of the hepatic sympathetic nerve fibers in this model. RESULTS: The mortality rate and the liver-to-body weight ratio after cancer inoculation were significantly higher in the vagotomized mice than in the sham-operated mice. The vagotomized mice exhibited a transient decrease in hepatic norepinephrine levels following cancer inoculation. Interestingly, the vagotomy-induced exacerbation of liver metastasis was attenuated by supplementary norepinephrine or phenylephrine, a selective α1-adrenoceptor agonist, but not by clonidine, a selective α2-adrenoceptor agonist. CONCLUSION: Collectively, these results suggest that the hepatic vagus nerve may play a protective role against liver metastasis. Hepatic sympathetic nerves may also be involved as a protective efferent loop, possibly acting through the α1-adrenoceptor.

Neural correlates of fear-induced sympathetic response associated with the peripheral temperature change rate.

Activation of the sympathetic nervous system is essential for coping with environmental stressors such as fearful stimuli. Recent human imaging studies demonstrated that activity in some cortical regions, such as the anterior cingulate cortex (ACC) and anterior insula cortex (aIC), is related to sympathetic activity. However, little is known about the functional brain connectivity related to sympathetic response to fearful stimuli. The participants were 32 healthy, right-handed volunteers. Functional magnetic resonance imaging (fMRI) was used to examine brain activity when watching horror and control movies. Fingertip temperature was taken during the scanning as a measure of sympathetic response. The movies were watched a second time, and the degree of fear (9-point Likert-type scale) was evaluated every three seconds. The brain activity of the ACC, bilateral aIC, and bilateral anterior prefrontal cortex (aPFC) was correlated with the change rate of fingertip temperature, with or without fearful stimuli. Functional connectivity analysis revealed significantly greater positive functional connectivity between the amygdala and the ACC and between the amygdala and the aIC when watching the horror movie than when watching the control movie. Whole-brain psycho-physiological interaction (PPI) analysis revealed that the functional connectivity between the left amygdala and the ACC was modulated according to the fear rating. Our results indicate that the increased functional connectivity between the left amygdala and the ACC represents a sympathetic response to fearful stimuli.

Structural and functional associations of the rostral anterior cingulate cortex with subjective happiness.

Happiness is one of the most fundamental human goals, which has led researchers to examine the source of individual happiness. Happiness has usually been discussed regarding two aspects (a temporary positive emotion and a trait-like long-term sense of being happy) that are interrelated; for example, individuals with a high level of trait-like subjective happiness tend to rate events as more pleasant. In this study, we hypothesized that the interaction between the two aspects of happiness could be explained by the interaction between structure and function in certain brain regions. Thus, we first assessed the association between gray matter density (GMD) of healthy participants and trait-like subjective happiness using voxel-based morphometry (VBM). Further, to assess the association between the GMD and brain function, we conducted functional magnetic resonance imaging (MRI) using the task of positive emotion induction (imagination of several emotional life events). VBM indicated that the subjective happiness was positively correlated with the GMD of the rostral anterior cingulate cortex (rACC). Functional MRI demonstrated that experimentally induced temporal happy feelings were positively correlated with subjective happiness level and rACC activity. The rACC response to positive events was also positively correlated with its GMD. These results provide convergent structural and functional evidence that the rACC is related to happiness and suggest that the interaction between structure and function in the rACC may explain the trait-state interaction in happiness.

Neural substrates of shared attention as social memory: A hyperscanning functional magnetic resonance imaging study.

During a dyadic social interaction, two individuals can share visual attention through gaze, directed to each other (mutual gaze) or to a third person or an object (joint attention). Shared attention is fundamental to dyadic face-to-face interaction, but how attention is shared, retained, and neutrally represented in a pair-specific manner has not been well studied. Here, we conducted a two-day hyperscanning functional magnetic resonance imaging study in which pairs of participants performed a real-time mutual gaze task followed by a joint attention task on the first day, and mutual gaze tasks several days later. The joint attention task enhanced eye-blink synchronization, which is believed to be a behavioral index of shared attention. When the same participant pairs underwent mutual gaze without joint attention on the second day, enhanced eye-blink synchronization persisted, and this was positively correlated with inter-individual neural synchronization within the right inferior frontal gyrus. Neural synchronization was also positively correlated with enhanced eye-blink synchronization during the previous joint attention task session. Consistent with the Hebbian association hypothesis, the right inferior frontal gyrus had been activated both by initiating and responding to joint attention. These results indicate that shared attention is represented and retained by pair-specific neural synchronization that cannot be reduced to the individual level.

Mind-body inter-relationship of bronchial asthma.

The mind-body inter-relationship of bronchial asthma and its pathological mechanisms have been clarified by the knowledge obtained from basic research studies, such as epide- miological investigations, animal experiments, and brain imaging studies. It is important to take advantage of the knowledge obtained from these researches to clarify the pathology of bronchial asthma and to extend the results to the clinical sphere by developing effective treatments. In the clinical setting, the 'Japanese Guidelines for the Diagnosis and Treatment of Psychosomatic Diseases' is useful for the assessment and treatment of bronchial asthma accompanied by psychosomatic related problems. This report outlines the mind-body inter-relationship of bronchial asthma and the assessment & treatment of bronchial asthma accompanied by psychosomatic related problems.

The brain network underlying the recognition of hand gestures in the blind: the supramodal role of the extrastriate body area.

The visual perception of others' body parts is critical for understanding and imitating their behavior. The visual cortex in humans includes the extrastriate body area (EBA), which is a large portion of the occipitotemporal cortex that is selectively responsive to visually perceived body parts. Previous neuroimaging studies showed that the EBA not only receives sensory inputs regarding others' body information but also receives kinesthetic feedback regarding one's own actions. This finding raised the possibility that the EBA could be formed via nonvisual sensory modalities. However, the effect of visual deprivation on the formation of the EBA has remained largely unknown. Here, we used fMRI to investigate the effect of vision loss on the development of the EBA. Blind and sighted human subjects performed equally well in a haptic-identification task involving three categories of objects (hand shapes, toy cars, and teapots). The superior part (i.e., the middle temporal gyrus and angular gyrus) of the EBA and the supramarginal gyrus showed greater sensitivity to recognized hand shapes than to inanimate objects, regardless of the sensory modality and visual experience. Unlike the superior part of the EBA, the sensitivity of the inferior part (i.e., the inferior temporal sulcus and middle occipital gyrus) depended on visual experience. However, this vision-dependent sensitivity explained minor individual differences in hand-recognition performance. These results indicate that nonvisual modalities drive the development of the cortical network underlying the recognition of hand gestures with a node in the visual cortex.

Differences in the presentation of COVID-19-related psychosocial stress and general psychological distress and the relation between the number of care days and these symptoms among Japanese ward staff working exclusively with COVID-19 and support staff.

BACKGROUND: Psychological distress has been frequently observed in frontline healthcare workers under stress during the coronavirus disease 2019 (COVID-19) epidemic; however, it is unclear if there are differences in the stress and symptoms experienced by staff members who work exclusively in a COVID-19 ward and support staff temporarily deployed to a COVID-19 ward. The present study investigated psychosocial stress specific to the care for patients with COVID-19 and psychological distress among ward staff working exclusively with COVID-19 and temporary support staff. METHODS: The participants were full-time nurses and doctors working in COVID-19 wards or the ICU who provided face-to-face care to patients with COVID-19 during the COVID-19 outbreak in February of 2021. The data of 67 staff members (21 exclusively working with Covid-19 patients (group A) and 46 in the temporary support group (group B)) was available for study. Psychosocial stress specific to healthcare professionals during this COVID-19 outbreak (Tokyo Metropolitan Distress Scale for Pandemic [TMDP]) and general psychological distress (K6) were assessed. RESULTS: The K6 score was significantly lower in group B than in group A (p = .006), but no significant difference was found in the total score of TMDP or its subscales. Positive correlations were found between TMDP and K6 for group B (p = .011), as was the number of days of care on TMDP-social (rs = .456, p = .001). CONCLUSION: Even though support staff members experienced lower psychological distress than staff working exclusively with COVID-19, COVID-19-related psychosocial stress specific to HCWs was comparable. The support staff also presented psychological distress associated with psychosocial stress specific to healthcare professionals during this COVID-19 outbreak, and the COVID-19-related social stress was enhanced as the number of working days increased. Our results show that all staff, not only those working exclusively with COVID-19 patients but also other support staff should be provided with care focusing on COVID-19-related psychosocial occupational stress.

Dietary supplementation with 1-kestose induces altered locomotor activity and increased striatal dopamine levels with a change in gut microbiota in male mice.

1-Kestose (KES), a dietary fiber and prebiotic carbohydrate, benefits various physiological functions. This study aimed to examine whether diets supplemented with KES over three consecutive generations could significantly affect some host physiological aspects, including behavioral phenotypes and gut microbial ecology. Mice that received KES-supplemented diets for three generations demonstrated increased activity compared with those fed diets lacking KES. Furthermore, the KES group showed increased striatal dopamine (DA) and serotonin (5-HT) levels. The observed increase in DA levels within the striatum was positively correlated with locomotor activity in the KES group but not in the control (CON) group. The α-diversities were significantly lower in the KES group compared to the CON group. The three-dimensional principal coordinate analysis revealed a substantial distinction between the KES and CON groups across each generation. At the genus level, most gut microbiota genera exhibited lower abundances in the KES group than in the CON group, except for Bifidobacteria and Akkermansia. Spearman's rank-order analysis indicated significant negative correlations between the striatal DA levels and α-diversity values. These findings suggest that prolonged supplementation with KES may stimulate increased locomotor activity along with elevated striatal DA levels, which are potentially associated with KES-induced alterations in the gut microbiota.

Alexithymia characteristics are associated with salience network activity in healthy participants: an arterial spin labeling study.

BACKGROUND: Alexithymia, a personality trait characterized by difficulties in identifying and expressing their emotions despite having a range of emotional experiences, can impact individuals' stress coping mechanisms. While many studies have investigated brain functions associated with specific tasks in relation to emotion processing, research focusing on resting-state brain functions has been limited. Thus, the aim of this study was to investigate the relationship between alexithymia and brain function by analyzing arterial spin labeling (ASL) data obtained during the resting state. METHODS: A brain structural and functional imaging study was conducted on 42 healthy adult men and women using ASL and the 20-item Toronto Alexithymia Scale (TAS-20) questionnaire survey. Cerebral blood flow and functional connectivity values were calculated for regions of interest in the default mode network, saliency network, and central executive network from the ASL data. Correlation analysis was performed with TAS20 scores, and partial correlation analysis was conducted to control for anxiety and depression. RESULTS: The functional connectivity analysis revealed a negative correlation between the functional connectivity of the right insular cortex and left anterior cingulate cortex and the total score of TAS, as well as difficulty identifying feelings and difficulty describing feeling subscores, indicating that the higher the scores, the weaker the functional connectivity between these regions (T = -3.830, p = 0.0013, R = -0.5180). This correlation remained significant even after controlling for anxiety and depression using partial correlation analysis. CONCLUSION: The present study revealed differences in the activity of the Saliency Network at rest as measured by ASL, which were independent of anxiety and depression, and varied depending on the severity of alexithymia. This functional change may underlie the neural basis of decreased emotional processing observed in alexithymia. These findings may contribute to the elucidation of the neural mechanisms of alexithymia, which can lead to social impairments, and suggest the usefulness of ASL measurement as a biomarker of alexithymia.

Effects of integrated hospital treatment on the default mode, salience, and frontal-parietal networks in anorexia nervosa: A longitudinal resting-state functional magnetic resonance imaging study.

The psychopathology of patients with anorexia nervosa has been hypothesized to involve inappropriate self-referential processing, disturbed interoceptive awareness, and excessive cognitive control, including distorted self-concern, disregard of their own starvation state, and extreme weight-control behavior. We hypothesized that the resting-state brain networks, including the default mode, salience and frontal-parietal networks, might be altered in such patients, and that treatment might normalize neural functional connectivity, with improvement of inappropriate self-cognition. We measured resting-state functional magnetic resonance images from 18 patients with anorexia nervosa and 18 healthy subjects before and after integrated hospital treatment (nourishment and psychological therapy). The default mode, salience, and frontal-parietal networks were examined using independent component analysis. Body mass index and psychometric measurements significantly improved after treatment. Before treatment, default mode network functional connectivity in the retrosplenial cortex and salience network functional connectivity in the ventral anterior insula and rostral anterior cingulate cortex were decreased in anorexia nervosa patients compared with those in controls. Interpersonal distrust was negatively correlated with salience network functional connectivity in the rostral anterior cingulate cortex. Default mode network functional connectivity in the posterior insula and frontal-parietal network functional connectivity in the angular gyrus were increased in anorexia nervosa patients compared with those in controls. Comparison between pre- and post-treatment images from patients with anorexia nervosa exhibited significant increases in default mode network functional connectivity in the hippocampus and retrosplenial cortex, and salience network functional connectivity in the dorsal anterior insula following treatment. Frontal-parietal network functional connectivity in the angular cortex showed no significant changes. The findings revealed that treatment altered the functional connectivity in several parts of default mode and salience networks in patients with anorexia nervosa. These alterations of neural function might be associated with improvement of self-referential processing and coping with sensations of discomfort following treatment for anorexia nervosa.

Psychological characteristics associated with the brain volume of patients with fibromyalgia.

Fibromyalgia (FM) is a disease characterized by chronic widespread pain concomitant with psychiatric symptoms such as anxiety and depression. It has been reported that FM patients engage in pain catastrophizing. In this study, we investigated characteristics of the brain volume of female FM patients and the association between psychological indices and brain volume. Thirty-nine female FM patients and 25 female healthy controls (HCs) were recruited for the study, and five FM patients were excluded due to white matter lesions. The following analyses were performed: (1) T1-weighted MRI were acquired for 34 FM patients (age 41.6 ± 7.4) and 25 HCs (age 39.5 ± 7.4). SPM12 was used to compare their gray and white matter volumes. (2) Data from anxiety and depression questionnaires (State-Trait Anxiety Inventory and Hospital Anxiety and Depression Scale), the Pain Catastrophizing Scale (subscales rumination, helplessness, magnification), and MRI were acquired for 34 FM patients (age 41.6 ± 7.4). Correlation analysis was done of the psychological indices and brain volume. We found that (1) The white matter volume of the temporal pole was larger in the FM patient group than in the HC group. (2) Correlation analysis of the psychological indices and gray matter volume showed a negative correlation between trait anxiety and the amygdala. For the white matter volume, positive correlations were found between depression and the brainstem and between magnification and the postcentral gyrus. Changes in the brain volume of female FM patients may be related to anxiety, depression, and pain catastrophizing.

Persistence of gut dysbiosis in individuals with anorexia nervosa.

Recent evidence suggests a crucial role of the gut microbiota in the pathogenesis of anorexia nervosa (AN). In this study, we carried out a series of multiple analyses of the gut microbiota of hospitalized individuals with AN over three months using 16S or 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction (PCR) technology (YIF-SCAN®), which is highly sensitive and enables the precise quantification of viable microorganisms. Despite the weight gain and improvements in psychological features observed during treatment, individuals with AN exhibited persistent gut microbial dysbiosis over the three-month duration. Principal component analysis further underscored the distinct microbial profile of individuals with AN, compared with that of age-matched healthy women at all time points. Regarding the kinetics of bacterial detection, the detection rate of Lactiplantibacillus spp. significantly increased after inpatient treatment. Additionally, the elevation in the Bifidobacterium counts during inpatient treatment was significantly correlated with the subsequent body weight gain after one year. Collectively, these findings suggest that gut dysbiosis in individuals with AN may not be easily restored solely through weight gain, highlighting the potential of therapeutic interventions targeting microbiota via dietary modifications or live biotherapeutics.

Critical role of gut microbiota in the production of biologically active, free catecholamines in the gut lumen of mice.

There is increasing interest in the bidirectional communication between the mammalian host and prokaryotic cells. Catecholamines (CA), candidate molecules for such communication, are presumed to play an important role in the gut lumen; however, available evidence is limited because of the lack of actual data about luminal CA. This study evaluated luminal CA levels in the gastrointestinal tract and elucidated the involvement of gut microbiota in the generation of luminal CA by comparing the findings among specific pathogen-free mice (SPF-M), germ-free mice (GF-M), and gnotobiotic mice. Substantial levels of free dopamine and norepinephrine were identified in the gut lumen of SPF-M. The free CA levels in the gut lumen were lower in GF-M than in SPF-M. The majority of CA was a biologically active, free form in SPF-M, whereas it was a biologically inactive, conjugated form in GF-M. The association of GF-M with either Clostridium species or SPF fecal flora, both of which have abundant ß-glucuronidase activity, resulted in the drastic elevation of free CA. The inoculation of E. coli strain into GF-M induced a substantial amount of free CA, but the inoculation of its mutant strain deficient in the ß-glucuronidase gene did not. The intraluminal administration of DA increased colonic water absorption in an in vivo ligated loop model of SPF-M, thus suggesting that luminal DA plays a role as a proabsorptive modulator of water transport in the colon. These results indicate that gut microbiota play a critical role in the generation of free CA in the gut lumen.

Occupational stress, psychological distress, physical symptoms, and their interrelationships among frontline nurses caring for COVID-19 patients in Japan.

This study aimed to identify occupational stress, psychosomatic symptoms, psychological distress, and their correlations among frontline nurses during and after the first peak of the coronavirus disease 2019 (COVID-19) outbreak in Japan. Sixteen frontline nurses, aged 25 to 52 years, working in a ward with COVID-19 patients participated in this study. Two months after the peak of the first wave of the COVID-19 outbreak in Japan, the COVID-19-related occupational stress scale (COS; questionnaire items: fear of infection and increased workload) and physical symptom scale (PS; questionnaire items: gastrointestinal symptoms, pain, appetite loss, and insomnia) were assessed. The degree of general psychological distress was evaluated using the 6-item Kessler Scale (K6). Simultaneously, participants were asked to recall their condition during the peak period of the first wave and rate it using the same scale. K6 was positively correlated with COS and PS during the peak period (rs = 0.574, P = .020 and rs = 0.587, P = .017, respectively). Increased workload was positively correlated with the K6 score both during and after the peak period (rs = 0.869, P < .001 and rs = 0.732, P = <.001, respectively) and was positively correlated with insomnia during the peak period (rs = 0.498, P < .05). The COS, PS, and K6 scores during the peak period were significantly higher than those after the peak period. Psychological distress at the peak was associated with PS and occupational stress. An increased workload during peak periods can cause psychological distress and insomnia. The occupational stress, PS, and psychological distress of nurses working in COVID-19 wards improved after the peak of COVID-19.

Dietary tryptophan, tyrosine, and phenylalanine depletion induce reduced food intake and behavioral alterations in mice.

Important precursors of monoaminergic neurotransmitters, dietary tryptophan (TRP), tyrosine, and phenylalanine (all referred to as TTP), play crucial roles in a wide range of behavioral and emotional functions. In the current study, we investigated whether diets devoid of TTP or diets deficient in TRP alone can affect body weight, behavioral characteristics, and gut microbiota, by comparing mice fed on these amino acids-depleted diets to mice fed on diets containing regular levels of amino acids. Both dietary TTP- and TRP-deprived animals showed a reduction in food intake and body weight. In behavioral analyses, the mice fed TTP-deprived diets were more active than mice fed diets containing regular levels of amino acids. The TRP-deprived group exhibited a reduction in serum TRP levels, concomitant with a decrease in serotonin and 5-hydroxyindoleacetic acid levels in some regions of the brain. The TTP-deprived group showed a reduction in TTP levels in the serum, concomitant with decreases in both phenylalanine and tyrosine levels in the hippocampus, as well as serotonin, norepinephrine, and dopamine concentrations in some regions of the brain. Regarding the effects of TRP or TTP deprivation on gut microbial ecology, the relative abundance of genus Roseburia was significantly reduced in the TTP-deprived group than in the dietary restriction control group. Interestingly, TTP was found even in the feces of mice fed TTP- and TRP-deficient diets, suggesting that TTP is produced by microbial or enzymatic digestion of the host-derived proteins. However, microbe generated TTP did not compensate for the systemic TTP deficiency induced by the lack of dietary TTP intake. Collectively, these results indicate that chronic dietary TTP deprivation induces decreased monoamines and their metabolites in a brain region-specific manner. The altered activities of the monoaminergic systems may contribute to increased locomotor activity.

Association Between Diabetes and Gray Matter Atrophy Patterns in a General Older Japanese Population: The Hisayama Study.

OBJECTIVE: To examine the association between diabetes and gray matter atrophy patterns in a general older Japanese population. RESEARCH DESIGN AND METHODS: In 2012, a total of 1,189 community-dwelling Japanese aged ≥65 years underwent brain MRI scans. Regional gray matter volumes (GMV) and intracranial volume (ICV) were measured by applying voxel-based morphometry (VBM) methods. The associations of diabetes and related parameters with the regional GMV/ICV were examined using an ANCOVA. The regional gray matter atrophy patterns in the subjects with diabetes or elevated fasting plasma glucose (FPG) or 2-h postload glucose (2hPG) levels were investigated using VBM. RESULTS: Subjects with diabetes had significantly lower mean values of GMV/ICV in the frontal lobe, temporal lobe, insula, deep gray matter structures, and cerebellum than subjects without diabetes after adjusting for potential confounders. A longer duration of diabetes was also significantly associated with lower mean values of GMV/ICV in these brain regions. The multivariable-adjusted mean values of the temporal, insular, and deep GMV/ICV decreased significantly with elevating 2hPG levels, whereas higher FPG levels were not significantly associated with GMV/ICV of any brain regions. In the VBM analysis, diabetes was associated with gray matter atrophy in the bilateral superior temporal gyri, right middle temporal gyrus, left inferior temporal gyrus, right middle frontal gyrus, bilateral thalami, right caudate, and right cerebellum. CONCLUSIONS: The current study suggests that a longer duration of diabetes and elevated 2hPG levels are significant risk factors for gray matter atrophy in various brain regions.