Cognitive behavioral therapy for a Japanese woman with olfactory reference disorder (ORD) comorbid with schizophrenia: A case study.

Background: Olfactory reference disorder (ORD) is a mental illness in which individuals overestimate their sense of smell and worry about the negative impact of odors. Little is known about its successful treatment. A new cognitive behavioral model was developed based on cognitive behavioral therapy (CBT) for obsessive-compulsive disorder. Using this model, this study reports a successful treatment process of a 53-year-old female with ORD. Case Presentation: The patient's initial diagnosis was schizophrenia, and improvements were observed, such as the disappearance of persecutory delusions, through medication therapy. During this treatment process, it became clear that the patient's preoccupation with her own offensive body odor was not a hallucination or delusion caused by schizophrenia but rather a symptom of ORD. Within a limited 4-week hospitalization period, high-intensity CBT was provided by a clinical psychologist and a psychiatrist. Multiple CBT techniques were employed, including case formulation to identify her beliefs, reviewing safety-seeking behaviors, attention shift training, behavioral experiments, public opinion polls, mindfulness meditation, and exposure and response prevention. Conclusion: Following a seven-sessions intensive intervention over 3 weeks, her symptoms of ORD, anxiety, and depression reduced. High-frequency CBT practices could be beneficial in treatment of patients with severe ORD, addressing severe ORD cases, facilitating rapid improvement in both ORD symptoms and functioning.

Vortioxetine as a potential alternative for patients with escitalopram-induced jitteriness/anxiety syndrome: A report of three cases.

Background: Jitteriness/anxiety syndrome is a recognized adverse effect observed during the initiation or change of dose in antidepressant treatment. Managing patients who develop this syndrome remains a challenge. While escitalopram is a widely used antidepressant known to cause these symptoms, this report explores vortioxetine as a therapeutic alternative. Case Presentation: Three distinct clinical scenarios were observed in patients who manifested jitteriness/anxiety syndrome while on escitalopram treatment for depression. Patient A was initiated on escitalopram and experienced an initial alleviation in depressive symptoms, but 3 months later displayed mood elevation, talkativeness, and increased activity, which disturbed his daily life. A transition to vortioxetine subsequently resolved the mood elevation. Patient B exhibited elevated mood, hyperactivity, irritability, and talkativeness just 6 days post-initiation of treatment with escitalopram. After the discontinuation of escitalopram and unsuccessful trials with aripiprazole, lurasidone, and lamotrigine, her depressive mood intensified, culminating in suicidal ideation. Starting vortioxetine led to a consistent improvement of her symptoms, and she resumed work and was emotionally stable. Patient C was initially diagnosed with bipolar disorder and faced a relapse into depression despite undergoing various treatments. After 2 weeks on escitalopram, she exhibited irritability and self-harm urges. Three months later, after being re-diagnosed with depressive disorders with anxious distress, vortioxetine was administered, which significantly reduced her depressive symptoms and allowed her to continue her education. Conclusion: Vortioxetine presents as a promising therapeutic alternative that is worth considering for patients with escitalopram-induced jitteriness/anxiety syndrome.

PKCη deficiency improves lipid metabolism and atherosclerosis in apolipoprotein E-deficient mice.

Genomewide association studies have shown that a nonsynonymous single nucleotide polymorphism in PRKCH is associated with cerebral infarction and atherosclerosis-related complications. We examined the role of PKCη in lipid metabolism and atherosclerosis using apolipoprotein E-deficient (Apoe-/- ) mice. PKCη expression was augmented in the aortas of mice with atherosclerosis and exclusively detected in MOMA2-positive macrophages within atherosclerotic lesions. Prkch+/+ Apoe-/- and Prkch-/- Apoe-/- mice were fed a high-fat diet (HFD), and the dyslipidemia observed in Prkch+/+ Apoe-/- mice was improved in Prkch-/- Apoe-/- mice, with a particular reduction in serum LDL cholesterol and phospholipids. Liver steatosis, which developed in Prkch+/+ Apoe-/- mice, was improved in Prkch-/- Apoe-/- mice, but glucose tolerance, adipose tissue and body weight, and blood pressure were unchanged. Consistent with improvements in LDL cholesterol, atherosclerotic lesions were decreased in HFD-fed Prkch-/- Apoe-/- mice. Immunoreactivity against 3-nitrotyrosine in atherosclerotic lesions was dramatically decreased in Prkch-/- Apoe-/- mice, accompanied by decreased necrosis and apoptosis in the lesions. ARG2 mRNA and protein levels were significantly increased in Prkch-/- Apoe-/- macrophages. These data show that PKCη deficiency improves dyslipidemia and reduces susceptibility to atherosclerosis in Apoe-/- mice, showing that PKCη plays a role in atherosclerosis development.

A comprehensive screening system for damaged nucleotide-binding proteins.

To identify novel nucleotide pool sanitizing enzymes, we have established a comprehensive screening system for damaged nucleotide-binding proteins based on proteomics technology. In the screening system, affinity chromatography with resins carrying various damaged nucleotides is used for the purification of binding proteins, and the purified proteins are identified by mass-spectrometry. Inosine triphosphate (ITP) is a deleterious damaged nucleotide, and can be generated by nitrosative deamination of ATP or phosphorylation of inosine monophosphate (IMP). Using the above system, we performed screens for ITP-binding proteins from mouse and human cell extracts, and identified several ITP-binding enzymes. We identified both mouse inosine triphosphatase (ITPA) and human ITPA, well-known ITP hydrolyzing enzymes, as ITP-binding proteins. These results support the validity of this screening system. In addition to ITPA, we identified human nucleoside diphosphate linked moiety X-type motif 16 (NUDT16) protein as an ITP-binding protein. Biochemical analysis revealed that NUDT16 selectively hydrolyzes deoxyinosine diphosphate (dIDP) and IDP to deoxyinosine monophosphate (dIMP) and IMP, respectively. dITP and ITP are also hydrolyzed by NUDT16 to a lesser extent. The knockdown of NUDT16 in HeLa MR cells suppressed cell proliferation, and was accompanied by a significantly increased accumulation of strand breaks in nuclear DNA, suggesting that NUDT16 has an essential role in the maintenance of genome stability. RS21-C6, another ITP-binding protein identified in our screen, binds not only to ITP, but also to ATP. RS21-C6 hydrolyzes dCTP and 5-halo-dCTP, but does not hydrolyze ITP or ATP. It is likely that RS21-C6 may control dCTP levels or eliminate 5-halo-dCTP in the nucleotide pools. In conclusion, the results of these studies show that our screening system is applicable in studying the health effects of damaged nucleotides and cellular sanitizing systems for nucleotide pools.

NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest.

Nucleotides function in a variety of biological reactions; however, they can undergo various chemical modifications. Such modified nucleotides may be toxic to cells if not eliminated from the nucleotide pools. We performed a screen for modified-nucleotide binding proteins and identified human nucleoside diphosphate linked moiety X-type motif 16 (NUDT16) protein as an inosine triphosphate (ITP)/xanthosine triphosphate (XTP)/GTP-binding protein. Recombinant NUDT16 hydrolyzes purine nucleoside diphosphates to the corresponding nucleoside monophosphates. Among 29 nucleotides examined, the highest k(cat)/K(m) values were for inosine diphosphate (IDP) and deoxyinosine diphosphate (dIDP). Moreover, NUDT16 moderately hydrolyzes (deoxy)inosine triphosphate ([d]ITP). NUDT16 is mostly localized in the nucleus, and especially in the nucleolus. Knockdown of NUDT16 in HeLa MR cells caused cell cycle arrest in S-phase, reduced cell proliferation, increased accumulation of single-strand breaks in nuclear DNA as well as increased levels of inosine in RNA. We thus concluded that NUDT16 is a (deoxy)inosine diphosphatase that may function mainly in the nucleus to protect cells from deleterious effects of (d)ITP.

Mouse RS21-C6 is a mammalian 2'-deoxycytidine 5'-triphosphate pyrophosphohydrolase that prefers 5-iodocytosine.

Free nucleotides in living cells play important roles in a variety of biological reactions, and often undergo chemical modifications of their base moieties. As modified nucleotides may have deleterious effects on cells, they must be eliminated from intracellular nucleotide pools. We have performed a screen for ITP-binding proteins because ITP is a deaminated product of ATP, the most abundant nucleotide, and identified RS21-C6 protein, which bound not only ITP but also ATP. Purified, recombinant RS21-C6 hydrolyzed several canonical nucleoside triphosphates to the corresponding nucleoside monophosphates. The pyrophosphohydrolase activity of RS21-C6 showed a preference for deoxynucleoside triphosphates and cytosine bases. The k(cat)/K(m) (s(-1) m(-1)) values were 3.11 x 10(4), 4.49 x 10(3) and 1.87 x 10(3) for dCTP, dATP and dTTP, respectively, and RS21-C6 did not hydrolyze dGTP. Of the base-modified nucleotides analyzed, 5-I-dCTP showed an eightfold higher k(cat)/K(m) value compared with that of its corresponding unmodified nucleotide, dCTP. RS21-C6 is expressed in both proliferating and non-proliferating cells, and is localized to the cytoplasm. These results show that RS21-C6 produces dCMP, an upstream precursor for the de novo synthesis of dTTP, by hydrolyzing canonical dCTP. Moreover, RS21-C6 may also prevent inappropriate DNA methylation, DNA replication blocking or mutagenesis by hydrolyzing modified dCTP.