Olfactory Reference Syndrome: Its Relationship to Comorbidity of Social Anxiety Disorder and Obsessive-Compulsive Disorder.

ABSTRACT: Olfactory reference syndrome (ORS) is known to have the clinical features of both obsessive-compulsive disorder (OCD) and social anxiety disorder (SAD). However, there has been no clear explanation as to why ORS has the characteristics of two different disorders. In the present study, the comorbidity rates of ORS in patients with SAD (without OCD, n = 83), ORS in patients with OCD (without SAD, n = 42), and patients with SAD and OCD comorbidity (n = 17) were compared. Of all 142 patients studied, 11 were diagnosed with ORS. The comorbidity rate of ORS in comorbid SAD/OCD group was significantly higher than those in both SAD and OCD groups. Logistic regression analysis of 100 cases of SAD and selected 69 cases of generalized SAD showed that the risk of ORS was significantly higher in patients with OCD and bulimia nervosa. Of 59 cases with OCD, the risk of ORS was significantly higher in patients with SAD. The results of the present study suggest that the comorbidity of SAD and OCD most likely explains the development of ORS.

A diet supplemented with cholic acid elevates blood pressure accompanied by albuminuria in rats.

A diet supplemented with cholic acid (CA), the primary 12α-hydroxylated bile acid, can induce hepatic lipid accumulation in rats without obesity. This study examined the effects of a CA-supplemented diet on blood pressure (BP). After acclimation, WKAH/HkmSlc rats (3 weeks old) were divided into two groups and fed with a control AIN-93-based diet or a CA-supplemented diet (0.5 g CA/kg) for 13 weeks. The CA diet increased systolic and diastolic BP as well as hepatic lipid concentrations in the rats. No changes were found in the blood sodium concentration. Urinary albumin concentration increased in CA-fed rats. An increase was observed in the hepatic expression of ATP-binding cassette subfamily B member 1B that correlated BPs and urinary albumin concentration accompanied by an increase in portal taurocholic acid concentration. These results suggest that 12α-hydroxylated bile acids are involved in increased BP and albuminuria via alteration of hepatic function.

Taurocholic acid, a primary 12α-hydroxylated bile acid, induces leakiness in the distal small intestine in rats.

A high-fat diet increases 12α-hydroxylated (12αOH) bile acid (BA) secretion in rats, and secondary BAs are responsible for the leaky gut. This study aimed to examine the role of primary 12αOH BAs in gut barrier impairment in rats using dietary cholic acid (CA) supplementation (0.5 g/kg diet). The CA diet increased the 12αOH BAs concentrations in the small and large intestine, accompanied by gut barrier impairment. Based on the luminal 12αOH BAs concentrations, ex vivo gut leakiness was determined. Deoxycholic acid increased permeability in the large intestine, whereas taurocholic acid (TCA) increased the ileal permeability, but not jejunal permeability. A Rho kinase inhibitor attenuated TCA-induced ileal permeability. Administration of vancomycin, which abolishes secondary BAs, did not influence the gut leakiness induced by the CA diet. Changes in the gut permeation marker in the tail vein blood suggested the possibility that the CA-induced leakiness occurred in the small intestine. The CA diet enhanced the phosphorylation of myosin light chain 2 and reduced claudins expressions in rat ileal epithelia. Reductions in barrier function-related genes were observed in the ileum, but not in the colon of the CA-fed rats. Overall, the present study demonstrated the significance of TCA in proximal gut leakiness.

12α-Hydroxylated bile acid enhances accumulation of adiponectin and immunoglobulin A in the rat ileum.

We previously reported that dietary supplementation with cholic acid (CA), the primary 12α-hydroxylated (12αOH) bile acid (BA), reduces plasma adiponectin concentration in rats. The aim of this study was to examine the distribution of adiponectin in the body of CA-fed rats and its influence on mucosal immunoglobulin A concentration in the intestine. Rats were fed a diet supplemented with or without CA (0.5 g CA/kg diet) for 13 weeks. A reduction in plasma adiponectin level was observed from week 3. At the end of the experiment, the CA diet reduced plasma adiponectin concentration both in the portal and aortic plasma. Accumulation of adiponectin was accompanied by an increase in cadherin-13 mRNA expression in the ileal mucosa of CA-fed rats. No increase was observed in adiponectin mRNA expression in the ileal and adipose tissues of the CA-fed rats. Immunoglobulin A concentration in the ileal mucosa was elevated in the CA-fed rats and was correlated with the ileal adiponectin concentration. 12αOH BAs may modulate mucosal immune response that are involved in the accumulation of adiponectin in the ileum.

12α-Hydroxylated bile acid induces hepatic steatosis with dysbiosis in rats.

There is an increasing need to explore the mechanism of the progression of non-alcoholic fatty liver disease. Steroid metabolism is closely linked to hepatic steatosis and steroids are excreted as bile acids (BAs). Here, we demonstrated that feeding WKAH/HkmSlc inbred rats a diet supplemented with cholic acid (CA) at 0.5 g/kg for 13 weeks induced simple steatosis without obesity. Liver triglyceride and cholesterol levels were increased accompanied by mild elevation of aminotransferase activities. There were no signs of inflammation, insulin resistance, oxidative stress, or fibrosis. CA supplementation increased levels of CA and taurocholic acid (TCA) in enterohepatic circulation and deoxycholic acid (DCA) levels in cecum with an increased ratio of 12α-hydroxylated BAs to non-12α-hydroxylated BAs. Analyses of hepatic gene expression revealed no apparent feedback control of BA and cholesterol biosynthesis. CA feeding induced dysbiosis in cecal microbiota with enrichment of DCA producers, which underlines the increased cecal DCA levels. The mechanism of steatosis was increased expression of Srebp1 (positive regulator of liver lipogenesis) through activation of the liver X receptor by increased oxysterols in the CA-fed rats, especially 4ß-hydroxycholesterol (4ßOH) formed by upregulated expression of hepatic Cyp3a2, responsible for 4ßOH formation. Multiple regression analyses identified portal TCA and cecal DCA as positive predictors for liver 4ßOH levels. The possible mechanisms linking these predictors and upregulated expression of Cyp3a2 are discussed. Overall, our observations highlight the role of 12α-hydroxylated BAs in triggering liver lipogenesis and allow us to explore the mechanisms of hepatic steatosis onset, focusing on cholesterol and BA metabolism.

Influence of AHRR Pro189Ala polymorphism on kidney functions.

The function of aryl hydrocarbon receptor repressor (AHRR) in the kidney is unclear. The present study investigated associations between AHRR Pro189Ala polymorphism and estimated glomerular filtration rates (eGFR), serum creatinine, and hemoglobin levels in 2775 Japanese adults without diabetes. In addition, we examined whether AHRR expression levels in the kidney of control and chronic kidney disease (CKD) rats were changed. Multiple linear regression analyses showed that carriers of the Ala allele had increased eGFR and lower concentrations of serum creatinine and hemoglobin (p < 0.05). Immunohistochemical analysis showed that the expression of AHRR was upregulated in the kidneys of rats with CKD. These findings suggest that AHRR plays distinct roles in kidney functions and hemoglobin values. The effects of the AHRR polymorphism might be intensified in the kidneys of patients with CKD.

[Atypical depression in Japan--39 case series].

UNLABELLED: In Japan, relatively little attention has been paid to atypical depression, which is defined as the presence of mood reactivity and two of four associated features: hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. The present study was undertaken to obtain detailed clinical information from patients with a diagnosis of atypical depression. We assessed clinical characteristics of each atypical feature, comorbidity of other psychiatric disorders, presence of a stressful life event, and underlying psychological stress in 39 psychiatric outpatients. We also examined the relationship of interpersonal sensitivity to each atypical feature. RESULTS AND DISCUSSION: Mean age of onset was 22 +/- 6, 74% were female, 20 patients (51%) had comorbid social phobia. Thirty (77%) had hyperphagia and 25 of these were women. Twenty (74%) had hypersomnia. Only seven patients reported daytime sleepiness and others (13) reported difficulty in staying awake due to lack of energy. Nineteen (49%) had leaden paralysis. Thirty-two patients (82%) had rejection sensitivity and this symptom correlated with scores of FNE (fears of negative evaluation), LSAS (Liebowits social anxiety scale) and Brief social phobia scale (BSPA). Seven patients reported disappointment in love as a stressful life event preceding the depressive episode. In patients with comorbid social phobia, loss of confidence due to hypersensitivity to rejection or criticism seemed to be the most important factor as a chronic psychologica stress. Seven patients met criteria for bipolar disorder and five out of seven had comorbid generalized social phobia. The clinical and theoretical implications of these findings were discussed.

Endogenous 5-HT inhibits firing activity of hippocampal CA1 pyramidal neurons during conditioned fear stress-induced freezing behavior through stimulating 5-HT1A receptors.

This study examines the activity of hippocampal CA, pyramidal neurons during conditioned fear stress (CFS)-induced freezing behavior in unanesthetized, unrestrained rats. The firing frequency of hippocampal CA1 pyramidal neurons was significantly decreased when conditioned rats exhibited freezing behavior. Firing frequency returned to the baseline after freezing behavior disappeared. The selective 5-hydroxytryptamine (5-HT)1A antagonists, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY-100635), and N-tert-butyl-3-[4-(2-methoxyphenyl)piperazine-1-yl]-2-phenylpropamide (WAY-100135) and 5-HT depletion with parachlorophenylalanine (PCPA) completely abolished the decrease in firing frequency during CFS-induced freezing behavior. These results suggested that endogenous 5-HT inhibited the firing activity of hippocampal CA1 pyramidal neurons during CFS-induced freezing behavior mainly through stimulating 5-HT1A receptors.

Effects of a benzodioxan derivative MKC-242 on the firing activity of the dorsal hippocampus CA1 pyramidal neurons in awake and urethane- anaesthetized rats: in vivo electrophysiological evidence for a 5-HT 1A agonistic property.

The aim of the present in vivo study was to determine whether a benzodioxan derivative MKC-242, (S)-5-[3-[(1,4-benzodioxan-2-ylmethyl)amino]propoxy]-1,3-benzodioxole hydrochloride, possesses an agonistic activity at postsynaptic serotonin (5-HT)1A receptors in the rat hippocampus when administered systemically. We examined the effects of acute administrations of MKC-242 on the firing activities of dorsal hippocampus CA1 pyramidal neurons. In quiet awake rats, s.c. administrations of MKC-242 significantly decreased the spontaneous firing activity in a dose-dependent manner at doses of 0.3-6 mg/kg. In urethane-anaesthetized rats, i.v. injections of MKC-242, at cumulative doses of 0.3-3 mg/kg, also significantly and dose-dependently inhibited the firing activity induced by microiontophoretically applied quisqualate. These decreasing effects were antagonized by the selective 5-HT1A antagonists WAY-100135 (5 mg/kg, s.c.) and WAY-100635 (0.2 mg/kg, s.c. to the awake rats and 0.4 mg/kg, i.v. to the anaesthetized rats), thereby confirming that MKC- 242 decreased the firing activities by stimulating 5-HT1A receptors. The selective depletion of 5-HT produced by the 3-d administration of the 5-HT synthesis inhibitor, parachlorophenylalanine (500 mg/kg.d, i.p.), did not affect the decreasing effect of MKC-242 in the awake animals, indicating that postsynaptic 5-HT1A receptors mediated the decreasing effect. The present results provided the first in vivo electrophysiological evidence that MKC-242, when systemically administered, exerts a 5-HT1A agonistic action at the postsynaptic level.