Personality disorders are not granted the same clinical attention accorded Axis I disorders despite their instrumental role in treatment and outcome. Even when standardized assessments are used, their clinical utility may be limited by an overly favorable self-presentation. The current study focused on defensiveness, the intentional denial of symptomatology, by examining individuals’ ability to minimize their presentation on personality disorder diagnostic measures. Using a within-subjects simulation design, dually diagnosed inpatients were assessed under both honest and defensive conditions. The study used self-report (Structured Clinical Interview for DSM-IV – Axis II – Personality Questionnaire, SCID-II-PQ) and interview-based (Structured Interview for DSM-IV Personality, SIDP-IV) diagnostic measures and a self-report measure of favorable self-presentation (Paulhus Deception Scales, PDS). The inpatients were quite capable of hiding maladaptive personality traits on diagnostic measures, with similarly large effect sizes on both the SCID-II-PQ and SIDP-IV. In addition to the PDS, two new detection strategies for identifying defensiveness showed promise.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / Primary Sclerosing Cholangitis (PSC) is a rare and slow progressing cholangiopathy characterized by hepatic inflammation, fibrosis and ductular reaction with liver transplantation as the sole therapeutic option. PSC patients are at high risk of auto-immune comorbidities like irritable bowel disease (IBD), found in up to 80% of PSC patients (PSC-IBD). There are indications of genetic and environmental components for auto-immune development in IBD; however, its etiology remains unclear. Mast cells (MCs) infiltrate the liver and can become activated leading to degranulation and release of mediators, like histamine (HA), which result in increased intrahepatic bile duct mass, biliary senescence, hepatic inflammation, and hepatic stellate cell activation. Similarly, MCs infiltrate the intestine and increase inflammation which alters host-microbiome communication. MCs are necessary for successful liver regeneration and the combat of intestinal pathogens; however, chronic HA signaling exacerbates damage in cholangiopathies and IBD. Bile acid synthesis is tightly regulated by Farnesoid X Receptor (FXR) and its downstream mediator, fibroblast growth factor 15 (FGF15, -19 in humans). Cholangiocytes (i) are the target of cholangiopathies, (ii) modify and recycle bile acids through Apical Sodium Bile Acid Transporter (ASBT)-mediated cholehepatic shunting, which functions outside of enterohepatic circulation of bile acids and (iii) are capable of autocrine HA signaling. The complex relationship between hepatic and intestinal MC infiltration and bile acid signaling has not been established; therefore, identifying MC regulation of bile acid pool and FXR/FGF15 signaling pathway will provide insight into therapeutic treatment of PSC-IBD. Under the rationale that (i) cholestatic liver diseases are positively correlated with auto-immune comorbidities like IBD, (ii) during disease, MCs infiltrate the liver and intestine and release signaling factors like HA, and (iii) MCs express FXR and secrete FGF15/19; we propose the central hypothesis that MC activation regulates bile acid signaling and PSC progression through paracrine crosstalk with cholangiocytes in the liver and intestinal inflammation.

A life event is as an occurrence that involves a subsequent change in the life pattern of an individual (Holmes & Rahe, 1967). The current study investigated whether exposure to life events over the past year influenced hypothalamic-pituitary-adrenocortical (HPA) axis function in healthy children and adolescents, and explored whether sex, age, behavioural inhibition, trait anxiety, anxiety sensitivity, perceived parental bonding, and parental history of anxiety moderated this relationship. The sample included 147 healthy children and adolescents. Participants were administered Coddington’s Life Events Scale (CLES) and salivary cortisol was collected for the determination of the cortisol awakening response (CAR), diurnal cortisol, and cortisol reactivity to a laboratory stressor. Separate linear regression models were conducted for each cortisol profile. Results revealed that life events significantly predicted total CAR output, diurnal cortisol response, and cortisol reactivity to a laboratory stressor. Further, behavioural inhibition, trait anxiety, not having a parental history of anxiety, and paternal caring positively moderated some of the relationships between life events and cortisol profiles. Considering the physiological and psychological effects of early exposure to stress, this study is significant in understanding the impact of life events to improve the health of children and adolescents.

Understanding the physiological response of marine mammals to anthropogenic stressors can inform marine ecosystem conservation strategies. Stress stimulates release of glucocorticoid (GC) hormones, which increase energy substrate availability while suppressing energy-intensive processes. Exposure to repeated stressors can potentially affect an animal’s ability to respond to and recover from subsequent challenges. To assess the endocrine response of a marine mammal to repeated stressors, we administered adrenocorticotropic hormone (ACTH) to free-ranging juvenile northern elephant seals (Mirounga angustirostris; n=7) once daily for four days. ACTH administration induced significant, but transient (<24 h) elevation in circulating cortisol levels (p < 0.0001). These increases did not vary in magnitude between the first ACTH challenge on day 1 and the last challenge on day 4. In contrast, aldosterone levels remained elevated above baseline for at least 24 hours after each ACTH injection (p < 0.001), and responses were greater on day 4 than day 1 (p < 0.01). Total triiodothyronine (tT3) levels were decreased on day 4 relative to day 1 (p < 0.01), while reverse triiodothyronine (rT3) concentrations increased relative to baseline on days 1 and 4 (p < 0.001) in response to ACTH, indicating a suppression of thyroid hormone secretion. There was no effect of ACTH on the sex steroid dehydroepiandrosterone (DHEA). These results suggest that elephant seals are able to mount adrenal responses to multiple ACTH challenges. However, repeated stress results in facilitation of aldosterone secretion and suppression of tT3, which may impact osmoregulation and metabolism. We propose that aldosterone and tT3 are informative additional indicators of repeated stress in marine mammals.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21634号 / 医博第4440号 / 新制||医||1034(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 生田 宏一, 教授 三森 経世, 教授 濵﨑 洋子 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Bacteria, especially symbiotic species in the gastrointestinal tract, have lived with human for long time and are involved in many aspects of host physiology. There is growing evidence that microbiota-gut-brain axis plays an important role in modulating the response to stress in both human and animals. Alterations in the gut microbiota can change the central nervous system function through effects on the endocrine, immune and nervous systems. Recent studies suggest that probiotic treatment may help to maintain resistance against the detrimental effects of stress though the microbiota-gut-brain axis. However, how potentially beneficial bacteria interact with specific immune and neural components, to mediate beneficial effects on behavior remain unclear. Using chronic social defeat stress, a model often used in post-traumatic stress disorder research, we found that administration of Lactobacillus rhamnosus JB-1 beginning 48 hours following chronic social defeat led to persistence of fear memory and social deficits. These effects were associated with changes in gene expression related to emotion and memory in the hippocampus. This was in contrast to previous studies showing that probiotic intervention during social defeat prevents stress induced deficits in social behavior. This indicates that timing of L. rhamnosus treatment in relation to stress exposure has important implications for effects of the bacteria on behavior. In relation to the mechanism of action of L. rhamnosus on behavior, we demonstrate through depletion and adoptive transfer experiments that CD4+CD25+ T cells in mice treated with JB-1 were necessary and sufficient for JB-1 induced anxiolytic and antidepressant-like effects. Evidence also suggested that Ly6Chi monocytes may be a downstream target inhibited by Tregs involved in the behavioral effects of the bacteria. We observed that JB-1 could also reduce the number of activated microglia in the hippocampus, and attenuate hypothalamic-pituitary-adrenal axis reactivity with the integrity of vagus nerve. Crucially we demonstrated that JB-1 induced promotion of peripheral Tregs, reduction in microglia activation in the hippocampus, and attenuation of HPA axis reactivity, were all inhibited following vagotomy indicating that vagus nerve integrity is required to maintain immune and endocrine linkages from gut microbes to the brain. These studies demonstrate prerequisites for beneficial probiotic effects on stress related behaviours including a specific time window in relation to stress exposure, the activation of regulatory immune cells, and undisrupted vagal nerve signalling. These findings highlight the inter-systemic communication of the microbiota-gut-brain axis in the stress response, and might help to unveil more therapeutic opportunities in relation to stress-related mood disorders. / Thesis / Doctor of Philosophy (PhD) / Excessive exposure or dysregulated responses to stress in human and animals induces behavioral changes and the development of mood disorders. The Microbiota-gut-brain axis plays an important role in maintenance of homeostasis. However, crosstalk between the different components of microbiota-gut-brain axis, and how specific microbes can modulate these interactions, remains unclear. Thus, we sought to understand the mechanism of inter-systemic communication linking a specific gut microbe to changes in stress response and behavior. We observed immunoregulation by regulatory T cells were essential in Lactobacillus rhamnosus JB-1 induced anxiolytic and antidepressant-like effects. We also found the integrity of vagus nerve was necessary for JB-1 induced promotion of regulatory T cells and decrease in microglial activation and attenuation of hypothalamic-pituitary-adrenal axis that are associated with the anxiolytic effects of the bacteria. We also identified that the temporal relationship between exposures to stress and the bacteria is important as ingestion of JB-1 directly after chronic social defeat lead to persistence of fear memory and social deficits. This work will help us to understand mechanisms underlying the microbiota-gut-brain axis, which may allow for the development of novel microbe based therapeutic intervention against mood disorders.

Introduction: Irritable bowel syndrome (IBS) is characterized by gastrointestinal (GI) symptoms, and as a consequence of dysregulated communication via the gut-brain axis, is highly comorbid with mental illnesses such as anxiety and depression. With no known cure, IBS patients must manage their symptoms through lifestyle factors. Physical activity is one such lifestyle factor that reduces GI symptoms and improves mental health; however, it remains unclear whether physical activity buffers against the acute worsening of IBS symptoms following a stressor. Method: To investigate this, we evaluated the stress reactivity and recovery of 9 IBS patients and 13 healthy controls following exposure to acute stress. We exposed participants to an electronic Trier Social Stress Test (e-TSST) and measured changes in psychological stress (state anxiety), physiological stress (sympathovagal balance, where higher LF/HF ratio indicates greater stress system activation), and GI symptom severity before, during and every 20 minutes for one hour after. Physical activity was measured using the Stanford Seven-Day Physical Activity Recall questionnaire and quantified as weekly energy expenditure. Results: IBS patients had higher state anxiety (p = .05), LF/HF ratio (p = .01) and GI symptom severity (p = .01) than healthy controls. Although the e-TSST did not exacerbate these group differences, higher state anxiety at baseline (p = .03) and higher LF/HF ratio in response to an acute stressor (p < .001) were associated with more severe GI symptoms within the first 20 minutes following the e-TSST. Importantly, IBS patients who were more physically active experienced less severe GI symptoms during that same timeframe (p = .03). Conclusion: Physical activity may be a promising lifestyle factor for lessening GI symptom severity in response to an acute stressor. / Thesis / Master of Science in Kinesiology

5軸制御マシニングセンターの運動精度の向上に向けた新たなキャリブレーション手法の開発に取り組んだ．また、直進および旋回軸の各種の運動誤差要因を診断する手法を構築した．さらにサーボ系の位置フィードバックで，サーボ系に起因する運動誤差の診断法も提案した.旋回軸にDDモータ方式を採用することで機械全体のサーボ特性を大きく改善できることも解明した．最後に，複雑形状の実加工により開発機で高い加工精度を確認することができた． / A new calibration method to improve the motion accuracy of a 5-axis control machining center has been developed. A method to diagnose various causes of motion errors on linear and rotary axes has been also established. Furthermore, a diagnosis method of motion errors caused by servo motors using the position feedback function is suggested in this paper. This study also figured out employing the direct drive motor for the rotary axes improved the characteristics of all the servo motors on the machine. Finally, the development test machine proved its high machining accuracy through actual machining of a complex-shaped workpiece. / 博士(工学) / Doctor of Philosophy in Engineering / 同志社大学 / Doshisha University