Differences in neural responses to reward and punishment processing between anorexia nervosa subtypes: An fMRI study.

AIM: Anorexia nervosa (AN) includes the restricting (AN-r) and binge-eating/purging (AN-bp) subtypes, which have been reported to differ regarding their underlying pathophysiologies as well as their behavioral patterns. However, the differences in neural mechanisms of reward systems between AN subtypes remain unclear. The aim of the present study was to explore differences in the neural processing of reward and punishment between AN subtypes. METHODS: Twenty-three female patients with AN (11 AN-r and 12 AN-bp) and 20 healthy women underwent functional magnetic resonance imaging while performing a monetary incentive delay task. Whole-brain one-way analysis of variance was conducted to test between-group differences. RESULTS: There were significant group differences in brain activation in the rostral anterior cingulate cortex and right posterior insula during loss anticipation, with increased brain activation in the AN-bp group relative to the AN-r and healthy women groups. No significant differences were found during gain anticipation. CONCLUSION: AN-bp patients showed altered neural responses to punishment in brain regions implicated in emotional arousal. Our findings suggest that individuals with AN-bp are more sensitive to potential punishment than individuals with AN-r and healthy individuals at the neural level. The present study provides preliminary evidence that there are neurobiological differences between AN subtypes with regard to the reward system, especially punishment processing.

Rapid induction of an immune response in rat Peyer's patch after oral administration of Enterococcus faecalis strain EC-12.

A rapid and sharp immune response induced in Peyer's patches (PPs) by a single gavage of a heat-killed Enterococcus faecalis strain EC-12 (EC-12) was demonstrated. EC-12 was observed inside the PPs 2.5 h post administration and induction of TNF-α and CD69 gene expression was observed at the same time. The immune response in PPs disappeared 24 h post administration.

[Neuroimaging studies of social cognition in schizophrenia].

In various social situations, individuals with schizophrenia often have difficulties in keeping appropriate relationships with others. To elucidate the neural basis of such difficulties, we explored associations between brain morphological alterations and dysfunction of social cognition in schizophrenia, using MRI. Several important findings have been yielded: For instance, amygdala volume reduction was correlated with impaired facial emotion recognition ability, while reductions in the medial prefrontal cortex was correlated with impairment in emotion attribution to protagonists in social situations. These results suggest that individuals with schizophrenia have various domains of impaired social cognition. Moreover, in schizophrenia, the brain regions involved in such impairments might differ according to the domains of social cognition.

Anorexic behavior and elevation of hypothalamic malonyl-CoA in socially defeated rats.

Suppression of body weight and eating disorders, such as anorexia, are one of the major symptoms of psychiatric disorders such as depression. However, the mechanisms of weight loss and reduced appetite in depressive patients and in animal models of depression are largely unknown. In this study, we characterized the mechanism of anorexia resulting from depression using socially defeated rats as an animal model of depression. Socially defeated rats showed suppressed body weight gain, enlarged adrenal glands, decreased home cage activity, decreased food intake, and increased immobility in the forced swim test. These results are representative of some of the core symptoms of depression. Simultaneously, we observed decreased levels of phosphorylated AMP-activated protein kinase (AMPK) and acetyl-coenzyme A (CoA) carboxylase (ACC) and increased levels of malonyl-CoA in the hypothalamus of socially defeated rats. Hypothalamic malonyl-CoA controlled feeding behavior and elevation of malonyl-CoA in the hypothalamus induced inhibition of food intake. Our findings suggest that the suppression of body weight gain caused by social defeat stress is caused by anorexic feeding behavior via an increased concentration of malonyl-CoA in the hypothalamus.

The effects of oral taurine administration on behavior and hippocampal signal transduction in rats.

Taurine, 2-aminoethylsulfonic acid, is one of the most abundant amino acids in the brain. It has various important physiological functions as a neuromodulator and antioxidant. Taurine is expected to be involved in depression; however, knowledge regarding its function in relation to depression is limited. In this study, we attempted to elucidate the effects of oral taurine administration on antidepressant-like behaviors in rats and depression-related signal transduction in the hippocampus. In behavioral tests, rats fed a high taurine (HT: 45.0 mmol/kg taurine) diet for 4 weeks (HT4w) showed decreased immobility in the forced swim test (FS) compared to controls. However, rats fed a low taurine (LT: 22.5 mmol/kg taurine) diet for 4 weeks or an HT diet for 2 weeks (HT2w) did not show a significant difference in FS compared to controls. In biochemical analyses, the expression of glutamic acid decarboxylase (GAD) 65 and GAD67 in the hippocampus was not affected by taurine administration. However, the phosphorylation levels of extracellular signal-regulated kinase1/2 (ERK1/2), protein kinase B (Akt), glycogen synthase kinase3 beta (GSK3ß) and cAMP response element-binding protein (CREB) were increased in the hippocampus of HT4w and HT2w rats. Phospho-calcium/calmodulin-dependent protein kinase II (CaMKII) was increased in the hippocampus of HT4w rats only. Moreover, no significant changes in these molecules were observed in the hippocampus of rats fed an HT diet for 1 day. In conclusion, our findings suggest that taurine has an antidepressant-like effect and an ability to change depression-related signaling cascades in the hippocampus.

[Pathology of social brain and social cognitive impairments in schizophrenia].

Schizophrenia patients often have a difficulty in constructing appropriate relationships with others in social situations. This impairment of social cognition is also found in autism-spectrum disorder (ASD). To elucidate the neural basis of such commonality between these two disorders, we explored the association between Autism-Spectrum Quotient (AQ) and gray matter (GM) alterations measured by MRI in schizophrenia subjects. Schizophrenia patients showed significantly higher scores in total AQ compared with control subjects. In addition, the total AQ score in schizophrenia subjects showed significant negative correlation with GM volume in the cortical area surrounding the left superior temporal sulcus (STS). As STS is the area which has been reported to be pathological in ASD, our findings suggest a partial neuroanatomical commonality between ASD and schizophrenia.

Cortical changes in patients with schizophrenia across two ethnic backgrounds.

While it is known that cultural background influences the healthy brain, less is known about how it affects cortical changes in schizophrenia. Here, we tested whether schizophrenia differentially affected the brain in Japanese and German patients. In a sample of 155 patients with a diagnosis of schizophrenia and 191 healthy controls from Japan and Germany, we acquired 3 T-MRI of the brain. We subsequently compared cortical thickness and cortical surface area to identify whether differences between healthy controls and patients might be influenced by ethnicity. Additional analyses were performed to account for effects of duration of illness and medication. We found pronounced interactions between schizophrenia and cultural background in the cortical thickness of several areas, including the left inferior and middle temporal gyrus, as well as the right lateral occipital cortex. Regarding cortical surface area, interaction effects appeared in the insula and the occipital cortex, among others. Some of these brain areas are related to the expression of psychotic symptoms, which are known to differ across cultures. Our results indicate that cultural background impacts cortical structures in different ways, probably resulting in varying clinical manifestations, and call for the inclusion of more diverse samples in schizophrenia research.

Improvement of bone strength and dermal thickness due to dietary edible bird's nest extract in ovariectomized rats.

Oral administration of edible bird's nest extract (EBNE) improved bone strength and calcium concentration in the femur of ovariectomized rats. Dermal thickness was also increased by EBNE supplementation, whereas EBNE administration did not affect the serum estradiol concentration. These results suggest that EBNE is effective for the improvement of bone loss and skin aging in postmenopause all women.

Suppressive effects of the marine carotenoids, fucoxanthin and fucoxanthinol on triglyceride absorption in lymph duct-cannulated rats.

BACKGROUND: Fucoxanthin isolated from edible seaweeds and its metabolite fucoxanthinol have been recently found to have anti-obesity effects, but the mechanism is not fully understood. AIM OF STUDY: We investigated the effects of these carotenoids on the absorption of triglycerides in conscious rats implanted with cannulae into a lymph duct and the portal or jugular vein. METHODS: A duodenal infusion of 1 ml of test oil emulsion with or without 2 mg of fucoxanthin or fucoxanthinol was administered in the lymph duct and the portal (Experiment 1) or the jugular vein (Experiment 2) cannulated rats. The test oil contained 10% soybean oil (Experiment 1) and pre-digested 10% soybean oil (Experiment 2). The inhibitory activities of these carotenoids on pancreatic lipase activity were measured in vitro. RESULTS: Increases in lymphatic and blood triglyceride levels were much lower in the two carotenoid-treated groups than in the carotenoid-free group, indicating that these carotenoids inhibit triglyceride absorption. The total amounts of triglycerides released into the lymph after 4 h in the carotenoid-free, fucoxanthin and fucoxanthinol groups were 113.5, 59.4 and 53.1 micromol, respectively. The inhibitory effects of carotenoids were completely abolished after an infusion of pre-digested soybean oil containing carotenoids. Furthermore, these carotenoids inhibited pancreatic lipase activity in vitro. Regarding absorptive route, we found that fucoxanthinol, but not fucoxanthin, appeared in lymph fluid, whereas neither carotenoid was detected in portal blood. CONCLUSION: These results show that these two marine carotenoids inhibit lipase activity in the gastrointestinal lumen and suppress triglyceride absorption, and fucoxanthin was converted to fucoxanthinol in the intestine and released into the lymph.

High biliary excretion levels of quercetin metabolites after administration of a quercetin glycoside in conscious bile duct cannulated rats.

Biliary excretion of quercetin metabolites in conscious rats was biphasic, a high peak within 3 h and a lower peak for next 6 h, after duodenal administration of soluble quercetin glycosides. We also found much higher biliary excretion of quercetin metabolites than urinary excretion on feeding a quercetin glycoside diet. These results suggest high levels of enterohepatic circulation of quercetin metabolites.

Gray matter volume reductions in patients with schizophrenia: A replication study across two cultural backgrounds.

Structural gray matter (GM) volume reductions in patients with schizophrenia have rarely been replicated across two different sites, the impact of culture and clinical characteristics remains unresolved. Hence, we assessed GM volume reductions in patients with schizophrenia using 3 T magnetic resonace imaging to replicate results across two independent and culturally different backgrounds (Germany, Japan), and to investigate the impact of brain volume reductions on clinical characteristics. In total, 163 German (80 patients) and 203 Japanese (83 patients) participants were included in the analysis. Voxel-based morphometry (VBM) was used to investigate structural differences between the groups and across the two sites, comparing local GM volumes. Clinical variables were used to analyze effects unrelated to the socio-cultural background. Across both data sets, widespread GM reductions in frontal and temporal cortical parts were found between patients and controls, indicating strong effects of diagnosis and only small effects of site. The investigation of clinical characteristics revealed the strongest effects for chlorpromazine equivalents on GM volume reductions primarily in the Japanese sample. Although the effects of site are small, several brain regions do not overlap between the two groups. Thus, GM may be affected differently at the two sites in patients with schizophrenia.

Central Histamine Boosts Perirhinal Cortex Activity and Restores Forgotten Object Memories.

BACKGROUND: A method that promotes the retrieval of lost long-term memories has not been well established. Histamine in the central nervous system is implicated in learning and memory, and treatment with antihistamines impairs learning and memory. Because histamine H3 receptor inverse agonists upregulate histamine release, the inverse agonists may enhance learning and memory. However, whether the inverse agonists promote the retrieval of forgotten long-term memory has not yet been determined. METHODS: Here, we employed multidisciplinary methods, including mouse behavior, calcium imaging, and chemogenetic manipulation, to examine whether and how the histamine H3 receptor inverse agonists, thioperamide and betahistine, promote the retrieval of a forgotten long-term object memory in mice. In addition, we conducted a randomized double-blind, placebo-controlled crossover trial in healthy adult participants to investigate whether betahistine treatment promotes memory retrieval in humans. RESULTS: The treatment of H3 receptor inverse agonists induced the recall of forgotten memories even 1 week and 1 month after training in mice. The memory recovery was mediated by the disinhibition of histamine release in the perirhinal cortex, which activated the histamine H2 receptor. Histamine depolarized perirhinal cortex neurons, enhanced their spontaneous activity, and facilitated the reactivation of behaviorally activated neuronal ensembles. A human clinical trial revealed that treatment of H3 receptor inverse agonists is specifically more effective for items that are more difficult to remember and subjects with poorer performance. CONCLUSIONS: These results highlight a novel interaction between the central histamine signaling and memory engrams.

Exaggerated envy and guilt measured by economic games in Japanese women with anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) patients are assumed to express high levels of guilt and envy. Ultimatum game (UG) is a standard behavioral task that focuses on interpersonal behavior when splitting a sum of money between two players. UG studies consistently demonstrate that people tend to decrease their inequity in outcomes, one explanation being that economically irrational decision-making may partly arise from the emotions guilt and envy. We assumed that AN patients would perform excessively fair in UG, reflecting high guilt and envy. METHODS: We utilized UG to investigate the characteristics of guilt and envy among 24 Japanese AN patients and 22 age-matched healthy controls (HC). The relation between the outcome of UG and decision strategy confirmed by post-experimental questionnaires was analyzed. RESULTS: As proposer, AN offered a larger amount to the responder compared with HC (p = 0.002) while, on the other hand, as responder, AN demanded much higher allocation to accept the offer compared with HC (p = 0.026). Regarding the strategy as responder, AN put more emphasis on fairness and less emphasis on monetary reward compared with HC (p = 0.046, p = 0.042, respectively). CONCLUSIONS: The results indicate that Japanese AN patients demonstrate strong preference for fairness, with high guilt and high envy. High sensitivity to guilt and envy of AN patients can affect not only their own behavior concerning eating attitude and body shape, but also decision-making in interpersonal situations. Behavioral experimental settings among social situations will enable us to evaluate and help actual decision-making in the real life of patients.

A prediction model of working memory across health and psychiatric disease using whole-brain functional connectivity.

Working memory deficits are present in many neuropsychiatric diseases with diagnosis-related severity. However, it is unknown whether this common behavioral abnormality is a continuum explained by a neural mechanism shared across diseases or a set of discrete dysfunctions. Here, we performed predictive modeling to examine working memory ability (WMA) as a function of normative whole-brain connectivity across psychiatric diseases. We built a quantitative model for letter three-back task performance in healthy participants, using resting state functional magnetic resonance imaging (rs-fMRI). This normative model was applied to independent participants (N = 965) including four psychiatric diagnoses. Individual's predicted WMA significantly correlated with a measured WMA in both healthy population and schizophrenia. Our predicted effect size estimates on WMA impairment were comparable to previous meta-analysis results. These results suggest a general association between brain connectivity and working memory ability applicable commonly to health and psychiatric diseases.

Difructose anhydride III promotes absorption of the soluble flavonoid alphaG-rutin in rats.

A highly soluble quercetin glycoside, alphaG-rutin, is a glucose adduct of insoluble rutin. We examined the effects of difructose anhydride III (DFAIII; di-D-fructofuranosyl 1,2':2,3'-dianhydride) on intestinal absorption of alphaG-rutin by rat experiments. alphaG-rutin, rutin, quercetin, and the quercetin conjugate appeared in the portal blood after an intubation of alphaG-rutin (100 micromol), DFAIII effected higher portal concentrations of alphaG-rutin in portal cannulated rats. In ligated jejunal and ileal loops of rats, alphaG-rutin, rutin, quercetin, and the quercetin conjugate appeared in the intestinal mesenteric blood at both 30 and 60 min in both loops; the concentration of alphaG-rutin was 1.5-3 times higher when absorbed in the presence DFAIII. In the isolated mucosae of the jejunum and ileum, mucosal-to-serosal passage of alphaG-rutin increased with the addition of 100 micromol of DFAIII. These results indicate that alphaG-rutin is absorbed as the intact form and that DFAIII stimulates its absorption in the small intestine.

Ambiguity aversion in schizophrenia: An fMRI study of decision-making under risk and ambiguity.

When making decisions in everyday life, we often have to choose between uncertain outcomes. Economic studies have demonstrated that healthy people tend to prefer options with known probabilities (risk) than those with unknown probabilities (ambiguity), which is referred to as "ambiguity aversion." However, it remains unclear how patients with schizophrenia behave under ambiguity, despite growing evidence of their altered decision-making under uncertainty. In this study, combining economic tools and functional magnetic resonance imaging (fMRI), we assessed the attitudes toward risk/ambiguity and investigated the neural correlates during decision-making under risk/ambiguity in schizophrenia. Although no significant difference in attitudes under risk was observed, patients with schizophrenia chose ambiguity significantly more often than the healthy controls. Attitudes under risk and ambiguity did not correlate across patients with schizophrenia. Furthermore, unlike in the healthy controls, activation of the left lateral orbitofrontal cortex was not increased during decision-making under ambiguity compared to under risk in schizophrenia. These results suggest that ambiguity aversion, a well-established subjective bias, is attenuated in patients with schizophrenia, highlighting the need to distinguish between risk and ambiguity when assessing decision-making under these situations. Our findings, comprising important clinical implications, contribute to improved understanding of the mechanisms underlying altered decision-making in patients with schizophrenia.

Influence of Chronic Social Defeat Stress on Digestive System Functioning in Rats.

Mental disorders are caused by chronic psychosocial stress, and can cause various symptoms related to the digestive system. We focused on the conjugation of intestinal absorptive and enzymatic mechanisms between chronic social defeat stress (CSDS) model rats and healthy controls to obtain general biochemical data about the intestine of the model in this study. The small intestine was divided into three regions: proximal (PI), middle (MI), and distal (DI); mRNA expression associated with a nutrient absorption, glucose absorption activity, and activities of the digestive enzymes such as maltase, sucrase and lactase was measured. Expression of both sodium-dependent glucose transporter 1 (Sglt1) and glucose transporter 2 gene tended to be higher in the stress group compared to the control group in PI. Glucose absorption was also higher in PI of the CSDS group. Sglt1 and peptide transporter 1 gene expressions in the CSDS group were significantly higher than those in the control group in DI. Furthermore, in PI, expression of the aquaporin 1 gene was significantly higher in the CSDS group compared to the control group. Thus, absorption of some nutrients might be higher in the small intestine of the CSDS rat.

Effects of chronic mild food restriction on behavior and the hypothalamic malonyl-CoA signaling pathway.

Depression induces anorexia, leading to suppressed feeding behaviors and energy intake. Previously, we revealed that chronic social defeat induced a mild suppression of feeding in rats with elevated levels of hypothalamic malonyl-CoA which regulates feeding. Therefore, we attempted to elucidate the effects of chronic mild food restriction on behavior and on hypothalamic malonyl-CoA. The chronic mild food restricted rats were fed a restricted diet approximately 80% to 90% amount of diet compared to the control for 5 weeks. Ratios of restriction were adjusted with feed consumption in the chronic social defeat stressed rats. Chronic mild food restricted rats exhibited a suppression of body weight gain similar to that of the chronic social defeat stressed rats. Also these rats showed increased time spent in the center area of an open field (OF), prolonged immobility time in forced swim, increased phosphorylation of hypothalamic adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase and a decreased concentration of hypothalamic malonyl-CoA. Weight of the adrenal glands, locomotion in an OF, mitogen-activated protein kinase cascade and calcium/calmodulin-dependent protein kinases II in the hippocampus were not affected by chronic mild food restriction. Our findings suggest that chronic mild food restriction activates AMPK following a decreased hypothalamic malonyl-CoA.

Anterior cingulate volume predicts response to cognitive behavioral therapy in major depressive disorder.

BACKGROUND: Cognitive behavioral therapy (CBT) is widely used to treat major depressive disorder (MDD). Although improved response prediction could facilitate the development of individualized treatment plans, few studies have investigated whether underlying brain structure is related to CBT response in MDD. METHODS: Ten MDD patients who received individual CBT were studied in this study. We investigated the relationship between the regional gray matter (GM) volume and subsequent responses to CBT using voxel-based morphometry. RESULTS: The degree of improvement in depressive symptoms was positively correlated with GM volume in the caudal portion of the anterior cingulate cortex. LIMITATIONS: The sample size was small, and the effects of medication on the results could not be excluded. CONCLUSIONS: Our results, although preliminary, suggest that the anterior cingulate cortex is a key structure whose volume can be used to predict responses to CBT and is thus a potential prognostic marker in MDD.

High-sensitivity detection of short-chain fatty acids in porcine ileal, cecal, portal and abdominal blood by gas chromatography-mass spectrometry.

Short-chain fatty acids (SCFA), such as acetate, propionate and n-butyrate, are the main end-products of fermentation in the large intestine. SCFA are rapidly absorbed from the large intestinal mucosa to provide energy to the host. In this study, high-sensitivity detection of SCFA was demonstrated in blood using the gas chromatometry with mass spectrometry (GC-MS). Few studies have measured SCFA in porcine blood. Therefore, SCFA concentrations in the ileal (IV), cecal (CV), portal (PV) and abdominal (AV) vein blood, urine (Ur) and saliva (Sa) were measured by GC-MS. All body fluids were collected from four 5-month-old pigs. Cecal (CD) and ileal (ID) digesta, and cecal (CM) and ileal (IM) mucosa were also collected and their corresponding SCFA concentrations were measured using ion-exclusion high-performance liquid chromatography. GC-MS analyses were successful to determine the SCFA concentrations in the porcine body fluids. n-Butyrate concentration was surprisingly high in CV and its proportion remained higher in CV than that in CD and CM. Acetate showed a constantly high proportion in all porcine body fluids. Propionate was detected at a relatively high proportion in CV, IV and PV, but was low in AV.