Efficient detection of somatic UBA1 variants and clinical scoring system predicting patients with variants in VEXAS syndrome.

OBJECTIVES: To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. METHODS: Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited [81 males and 8 females; median onset age (IQR) 69.3 years (62.1-77.6)]. Peptide nucleic acid-clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants, and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR (pdPCR) or targeted amplicon deep sequencing (TAS) was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and ­negative patients and assessed the diagnostic value of our system using receiver operating characteristic (ROC) curve analysis. RESULTS: Forty patients with reported pathogenic UBA1 variants (40/89, 44.9%) were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering >50 years of age, cutaneous lesions, lung involvement, chondritis, and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). CONCLUSIONS: Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants.

Mediation Effects of Social Cognition on the Relationship between Neurocognition and Social Functioning in Major Depressive Disorder and Schizophrenia Spectrum Disorders.

BACKGROUND: In schizophrenia spectrum disorders (SSD), social cognition mediates the relationship between neurocognition and social functioning. Although people with major depressive disorder (MDD) also exhibit cognitive impairments, which are often prolonged, little is known about the role of social cognition in MDD. METHODS: Using data obtained through an internet survey, 210 patients with SSD or MDD were selected using propensity score matching based on their demographics and illness duration. Social cognition, neurocognition, and social functioning were evaluated using the Self-Assessment of Social Cognition Impairments, Perceived Deficits Questionnaire, and Social Functioning Scale, respectively. The mediation effects of social cognition on the relationship between neurocognition and social functioning were examined in each group. Invariances of the mediation model across the two groups were then analyzed. RESULTS: The SSD and MDD groups had mean ages of 44.49 and 45.35 years, contained 42.0% and 42.8% women, and had mean illness durations of 10.76 and 10.45 years, respectively. In both groups, social cognition had significant mediation effects. Configural, measurement, and structural invariances across the groups were established. CONCLUSION: The role of social cognition in patients with MDD was similar to that in SSD. Social cognition could be a common endophenotype for various psychiatric disorders.

[A case of giant cell arteritis after prednisolone dose reduction during treatment of polymyalgia rheumatica].

Giant cell arteritis (GCA) is closely associated with polymyalgia rheumatica (PMR). We herein report an 82-year-old woman who developed GCA during PMR treatment. She initially presented with shoulder pain and was diagnosed with PMR based on elevated serum C-reactive protein (CRP) levels and bursitis detected in both shoulders on ultrasonography (US). Treatment was initiated with a daily dose of 15 mg prednisolone (PSL), which led to rapid symptom alleviation, and the dosage was tapered to 1 mg/day. One month later, she developed myalgia extending from the lumbar region to the thigh and tenderness in the left temporal region. However, no abnormalities in the temporal artery were observed on US. Although the PSL dose was increased to 2 mg for relapse of PMR, the symptoms did not improve. One week later, she developed occipital pain with an increased CRP level of 9 mg/dL. She was diagnosed with GCA based on the 1990 ACR Classification Criteria. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) detected anomalous accumulations in the bilateral superficial temporal and vertebral arteries, but not in the larger vessels. We therefore diagnosed her with cranial-type GCA. At this time point, we repeated US and found a halo sign in the temporal artery. Although epithelioid and giant cells were not observed in the temporal artery biopsy, vascular inflammatory findings such as disruption of the internal elastic lamina and chronic inflammatory cell infiltration were noted. Symptoms improved immediately and CRP levels decreased after the PSL dose was increased to 30 mg daily. To mitigate the risk of steroid-induced diabetes, tocilizumab was introduced, and gradual tapering of PSL was implemented. In conclusion, we encountered a case of GCA that developed after PSL reduction during the course of PMR. PET/CT confirmed intracranial artery inflammation and facilitated a definitive diagnosis. Although PET/CT cannot be routinely performed for diagnose in Japan, we consider it useful as an adjunctive diagnostic tool.

Perceptions of and subjective difficulties with social cognition in schizophrenia from an internet survey: Knowledge, clinical experiences, and awareness of association with social functioning.

AIM: Social cognition impacts social functioning in schizophrenia; however, little is known about how patients with schizophrenia themselves perceive social cognition. This study, using an internet survey, aimed to investigate their knowledge of social cognition, clinical experiences related to social cognition, awareness of social cognition's role in one's social life, and the relationships between subjective difficulties with social cognition and social functioning. METHODS: Data from 232 outpatients with schizophrenia (SZ) and 494 healthy controls (HC) were obtained through an internet survey and were weighted according to the demographics of the national population. A newly developed survey questionnaire on knowledge, experience, and awareness of social cognition was administered. Subjective difficulties were evaluated using the Self-Assessment of Social Cognition Impairments and the Observable Social Cognition Rating Scale. RESULTS: Less than a quarter of both groups were familiar with the term or concept of social cognition. Less than 5% of both groups had experienced being assessed or treated for social cognition. More than half of both groups were aware of the relationship between social cognition and social functioning. The SZ group had higher levels of subjective difficulties than the HC group across all social cognitive domains. The attributional bias domain of subjective difficulties was negatively associated with social functioning. CONCLUSION: Patients with schizophrenia had substantial subjective difficulties in social cognition, which they perceived as being related to social functioning. However, their knowledge of social cognition was limited, and the assessment and treatment might not be widespread in regular clinical practice.

COVID-19 in an Adult with Down Syndrome: Impact on Autoimmune Response.

We here report a case of COVID-19 with effusion prior to the development of pneumonia in an adult with Down syndrome. Serositis due to rheumatic disease was initially suspected because of a high titer of serum autoantibodies and leukocytopenia; however, SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction on admission after previous negative tests. Several cases of COVID-19 have been associated with autoimmune responses along with some cases of COVID-19 with autoimmune manifestations. Furthermore, patients with Down syndrome have a higher mortality risk from COVID-19 than the general population, and it is believed that a high sensitivity to the interferon response may contribute to the increased severity of the disease. Thus, careful attention should be paid to autoimmune manifestations due to SARS-CoV-2 infection for ensuring a proper and timely diagnosis, especially in patients with Down syndrome.

[A case of methotrexate-associated diffuse large B-cell lymphoma with splenial lesions of the corpus callosum on brain MRI after complete remission with chemotherapy].

An 86-year-old woman in a wheelchair was accompanied by her husband and son as she visited our outpatient clinic due to disturbed consciousness and fever. Twenty-seven years earlier, she had been diagnosed with rheumatoid arthritis and had been treated with methotrexate (MTX) and low-dose prednisolone (PSL). She stopped taking MTX four years previously when she was diagnosed with diffuse large B cell lymphoma of the paranasal sinus. Her lymphoma went into remission after six cycles of systemic immunochemotherapy. MRI after hospitalization revealed a lesion in the splenium of the corpus callosum that was hyperintense on diffusion-weighted imaging and which had low apparent diffusion coefficient values. An analysis of the cerebrospinal fluid revealed no atypical cells. The MRI findings were atypical, but her consciousness disturbance improved, leading to the diagnosis of mild encephalitis/encephalopathy with a reversible splenial lesion, which would be associated with a transient consciousness disturbance with a good course. However, her consciousness worsened over the next 3 weeks. One month later, a contrast-enhanced MRI showed an enlarged lesion in the callosum as well as new lesions, and the diagnosis of secondary CNS lymphoma was made. Brain biopsy is often not feasible. Less invasive and highly accurate diagnostic methods are needed, such as the identification of a spinal fluid tumor marker.

Eustachian tube involvement in a patient with relapsing polychondritis detected by magnetic resonance imaging: A case report.

BACKGROUND: Relapsing polychondritis (RP) is a rare inflammatory disease involving the systemic cartilage, such as the auricle, trachea, and bronchiole, among others. A patient with RP shows variable symptoms based on the involved cartilage. CASE SUMMARY: A 72-year-old Japanese woman with a history of redness of the bilateral auricles for 3 d was referred to a clinician. The clinician prescribed antibiotics to the patient; however, the symptoms worsened; thus, she was referred to our hospital. Head and neck magnetic resonance imaging (MRI) showed edematous auricle with remarkable contrast, fluid collection in the bilateral mastoid cells, suggesting otitis media. The eustachian tube (ET) on the right side was also edematous with contrast enhancement. The patient was suspected of RP according to the diagnostic criteria. A biopsy of the auricular cartilage was performed by an otorhinolaryngologist, confirming pathological proof of RP. Treatments with steroids were immediately administered thereafter. CONCLUSION: We highlight a rare case of RP with radiologically confirmed involvement of ET in the MRI.

COVID-19 survivors with calcineurin-inhibitors-treated rheumatoid arthritis.

We report two cases recovered from coronavirus disease 2019 with rheumatoid arthritis which had been in remission or low disease activity by taking calcineurin inhibitor (CNI). Both cases had moderate to severe pneumonia treated with intravenous dexamethasone or in the severe case remdesivir in addition to it. These cases suggest that the use of CNI may have affected the improvement of severe pneumonia.

An integrated youth mental health service in a densely populated metropolitan area in Japan: Clinical case management bridges the gap between mental health and illness services.

AIMS: A global movement, including in Asia, is seeking to establish integrated youth mental health services that provide early intervention in the continuum from mental health to mental illness. Clinical case management (CCM), in which a case manager becomes not only a coordinator of services but also a provider of psychosocial support, can establish a 'one-stop network' that supports youth in densely populated areas with various social resources. In 2019, we opened a community-based centre called 'SODA' in front of a metropolitan railway station, which was designed to be highly accessible, stigma-free and youth-friendly to provide CCM. We aimed to clarify its services and effectiveness of CCM. METHODS: Data from 105 youths were investigated in a case-controlled study, dividing them into two groups: those who had received CCM for 6 months, and those whose needs were met in fewer sessions. RESULTS: Twenty-one subjects who received CCM for 6 months had difficulties in more domains than the others. The mean of the total service minutes for the subjects who received CCM for 6 months was 491.3 min: psychological support (accounted for 24.8% of the time), support for community living (31.2%), work support (13.8%), family support (10.5%) and support for cooperation with other organizations (19.8%). Global Assessment of Functioning (GAF) score improved significantly, from 46.6 at baseline to 59.3 at 6 months. CONCLUSION: Even in metropolitan areas with numerous medical facilities, young people can face high barriers to access. CCM can be effective as an early intervention for subjects developing mental illness.

Predictors of long-term therapy with glucocorticoid in polymyalgia rheumatica.

OBJECTIVES: To investigate the response of glucocorticoid (GC) therapy for patients with polymyalgia rheumatica (PMR) and predictive factors which correspond to the long-term GC. METHODS: We reviewed 93 patients with PMR who were treated with GC for more than 6 months. We compared the clinical findings between patients who achieved remission within 24 months (early-remission group, n = 40) and those who required GC therapy for more than 24 months (long-therapy group, n = 24). RESULTS: Among 93 patients, 49 have achieved a remission, 35 were undergoing treatment, and 9 have transferred to other hospitals or died. Rate of remission of patients treated for one year GC therapy was in 12% and 53% after 2 years. Serum CRP of long-therapy group was significantly higher than those of the early-remission group. The ratio of patients who experienced more than one relapse within 6 months was 37.5% of long-therapy group and 7.5% of early-remission group. Multivariate logistic regression analysis showed that the history of relapse until 6 months was a significant predictor of long therapy. CONCLUSIONS: Some patients need the long-term therapy for more than 4 years. The history of relapse till 6 months is a significant predictor of the long-term GC therapy.

Prevalence and curriculum of sexual and gender minority education in Japanese medical school and future direction.

Background: In Japan, sexual and gender minorities (SGM) remain stigmatized, provoking hospital access barriers and health disparities from judgmental care. Japan's Western-influenced introduction of SGM course content into medical education for future physicians addresses these disparities, although often perfunctorily and inconsistently.Objective: To examine the prevalence and characteristics of medical education curriculum with respect to SGM patients, we surveyed medical schools.Methods: A medical education faculty member from each of 80 Japanese medical schools received double postcards to identify relevant SGM coursework. Upon acknowledgement, 43 schools received seven-item anonymous questionnaires in March 2018. Survey results were analyzed from the perspective of three of the qualities and abilities required of a physician - Patient Care, Knowledge for Practice, and Professionalism from Japan's Medical Core Curriculum - to develop recommendations for outcomes-based SGM curriculum through the lens of Van Melle's medical education framework.Results: The response rate was 46%, with 22 schools providing SGM lectures mostly to first- and third-year students. Obstetrics and Gynecology, Neuropsychiatry, and Introduction to Medicine lectures were the top three subjects offering SGM lectures, primarily consisting of basic knowledge of SGM and Differences in Sex Development. Several lectures addressed the health challenges of SGM. Primary reasons for not offering SGM lectures were lack of suitable instructors or no school policies.Conclusions: Students can best experience the humanity of SGM patients and employ more appropriate diagnostic practices and modes of treatment with targeted curriculum to address SGM health disparities and inclusion of SGM patients in clinical practice training. To disseminate SGM education in Japanese medical schools, development of qualified instructors and policies is essential, employing currently active experts. The Van Melle reforms framework can guide in the development of recommended tailored learning experiences and lectures for improved and expanded SGM education, integrating appropriate coursework within current medical core curriculum structure.

Early Improvement and Marriage Are Determinants of the 12-Month Treatment Outcome of Paroxetine in Outpatients with Panic Disorder.

OBJECTIVE: In this study, we investigated the determinants of remission and discontinuation of paroxetine pharmacotherapy in outpatients with panic disorder (PD). METHODS: Subjects were 79 outpatients diagnosed with PD who took 10-40 mg/day of paroxetine for 12 months. The candidate therapeutic determinants included the serotonin transporter gene-linked polymorphic region and the -1019C/G promoter polymorphism of the serotonin receptor 1A as genetic factors, educational background and marital status as environmental factors, and early improvement (EI) at 2 weeks as a clinical factor were assessed. The Clinical Global Impression scale was used to assess the therapeutic effects of the pharmacotherapy. RESULTS: Cox proportional hazards regression was performed to investigate the significant predictive factors of remission and discontinuation. EI was only a significant predictive factor of remission. EI was a significant predictive factor of remission (hazard ratio [HR], 2.709; 95% confidence interval [CI], 1.177-6.235). Otherwise, EI and marital status were significant predictive factors of the discontinuation. EI (HR, 0.266; 95% CI, 0.115-0.617) and being married (HR, 0.437; 95% CI, 0.204-0.939) were considered to reduce the risk of treatment discontinuation. In married subjects, EI was a significant predictive factor of the discontinuation (HR, 0.160; 95% CI, 0.045-0.565). However, in unmarried subjects, EI was not a significantly predictive factor for the discontinuation. CONCLUSION: EI achievement appears to be a determinant of PD remission in paroxetine treatment. In married PD patients, EI achievement also appears to reduce a risk of discontinuation of paroxetine treatment.

Cognitive function, treatment response to lithium, and social functioning in Japanese patients with bipolar disorder.

OBJECTIVES: Patients with bipolar disorder often suffer from cognitive impairment that significantly influences their functional outcome. However, it remains unknown whether lithium has a central role in cognition and functional outcome. We examined whether cognition and functional outcome were predicted by demographic and clinical variables, including the response to lithium, in lithium-treated patients with bipolar disorder. METHODS: We evaluated 96 lithium-treated euthymic patients with bipolar disorder and 196 age- and-gender-matched healthy controls, using the Brief Assessment of Cognition in Schizophrenia (BACS). The patients were also assessed using the Social Functioning Scale (SFS) and "The Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" (Alda) scale, which was evaluated as either a continuous measure of the total scale or a dichotomous criterion. RESULTS: Multiple regression analysis revealed two key findings: first, that the premorbid intelligence quotient, age, and number of mood episodes were predictors of the BACS composite score; and, second, that the BACS composite score, negative symptoms, and continuous measure on the total Alda scale (but not its dichotomy) predicted the total SFS score. Structural equation modeling (SEM) was used to confirm these findings, and additionally revealed that the Alda scale was significantly associated with negative symptoms and also the number of mood episodes, regardless of how it was evaluated. CONCLUSIONS: SEM delineated how demographic and clinical variables, cognitive performance, and response to lithium treatment were causally associated with, and converged on, social function. The putative role of the Alda scale for social function warrants further study.

Genetic Polymorphism of 1019C/G (rs6295) Promoter of Serotonin 1A Receptor and Catechol-O-Methyltransferase in Panic Disorder.

OBJECTIVE: Family and twin studies have suggested genetic liability for panic disorder (PD) and therefore we sought to determine the role of noradrenergic and serotonergic candidate genes for susceptibility for PD in a Japanese population. METHODS: In this age- and gender-matched case-control study involving 119 PD patients and 119 healthy controls, we examined the genotype distributions and allele frequencies of the serotonin transporter gene linked polymorphic region (5-HTTLPR), -1019C/G (rs6295) promoter polymorphism of the serotonin receptor 1A (5-HT1A), and catechol-O-methyltransferase (COMT) gene polymorphism (rs4680) and their association with PD. RESULTS: No significant differences were evident in the allele frequencies or genotype distributions of the COMT (rs4680), 5-HTTLPR polymorphisms or the -1019C/G (rs6295) promoter polymorphism of 5-HT1A between PD patients and controls. Although there were no significant associations of these polymorphisms with in subgroups of PD patients differentiated by gender or in subgroup comorbid with agoraphobia (AP), significant difference was observed in genotype distributions of the -1019C/G (rs6295) promoter polymorphism of 5-HT1A between PD patients without AP and controls (p=0.047). CONCLUSION: In this association study, the 1019C/G (rs6295) promoter polymorphism of the 5-HT1A receptor G/G genotype was associated with PD without AP in a Japanese population.

Multi-regression analysis revealed a relationship between l-serine and methionine, a component of one-carbon metabolism, in the normal control but not in the schizophrenia.

BACKGROUND: Alterations in one-carbon metabolism (OCM) have been observed in patients with schizophrenia (SZ), but a comprehensive study of OCM has not yet been conducted. A carbon atom is transferred from l-serine to methionine during OCM, but the relationship between l-serine and methionine in SZ is not yet known. We investigated the relationship between l-serine and methionine to obtain a comprehensive understanding of OCM in SZ. METHODS: We recruited forty-five patients with SZ and thirty normal controls (NC). Whole blood, plasma, and DNA specimens were obtained from all participants. Plasma l-serine, d-serine, glycine, methionine, and total homocysteine levels were measured using high-performance liquid chromatography. Plasma vitamin B12 and total folate were measured using a chemiluminescent protein-binding immunoassay. Clinical symptoms were estimated using the positive and negative syndrome scale (PANSS). The methylenetetrahydrofolate reductase (MTHFR) C667T genotype and A298C genotype, which are involved in MTHFR activity, were determined using the TaqMan genotyping assay system. RESULTS: Analysis of variance was used to confirm that the SZ cohort has higher plasma homocysteine levels and lower plasma folate levels than the NC group. Multi-regression analysis revealed a relationship between l-serine and methionine in the NC group but not in the SZ group. The MTHFR genotype did not affect the relationship between l-serine and methionine in each group. The total PANSS score was significantly related to d-serine and folate levels and to age. Positive PANSS scores were significantly related to both glycine and sex. In addition, both glycine and d-serine were significantly correlated with negative PANSS scores. CONCLUSIONS: We found impairment of the relationship between l-serine and methionine in SZ. Clinical symptoms of SZ were partially correlated with the OCM components. These findings contributed to our understanding of OCM alteration in SZ and may explain why the alteration occurs.

Influence of the cytochrome P450 2D6 *10/*10 genotype on the pharmacokinetics of paroxetine in Japanese patients with major depressive disorder: a population pharmacokinetic analysis.

OBJECTIVE: Although the reduced function of the cytochrome P450 2D6*10 (CYP2D6*10) allele is common among Asian populations, existing evidence does not support paroxetine therapy adjustments for patients who have the CYP2D6*10 allele. In this study, we attempted to evaluate the degree of the impact of different CYP2D6 genotypes on the pharmacokinetic (PK) variability of paroxetine in a Japanese population using a population PK approach. METHODS: This retrospective study included 179 Japanese patients with major depressive disorder who were being treated with paroxetine. CYP2D6*1, *2, *5, *10, and *41 polymorphisms were observed. A total of 306 steady-state concentrations for paroxetine were collected from the patients. A nonlinear mixed-effects model identified the apparent Michaelis-Menten constant (Km) and the maximum velocity (Vmax) of paroxetine; the covariates included CYP2D6 genotypes, patient age, body weight, sex, and daily paroxetine dose. RESULTS: The allele frequencies of CYP2D6*1, *2, *5, *10, and *41 were 39.4, 14.5, 4.5, 41.1, and 0.6%, respectively. There was no poor metabolizer who had two nonfunctional CYP2D6*5 alleles. A one-compartment model showed that the apparent Km value was decreased by 20.6% in patients with the CYP2D6*10/*10 genotype in comparison with the other CYP2D6 genotypes. Female sex also influenced the apparent Km values. No PK parameters were affected by the presence of one CYP2D6*5 allele. CONCLUSION: Unexpectedly, elimination was accelerated in individuals with the CYP2D6*10/*10 genotype. Our results show that the presence of one CYP2D6*5 allele or that of any CYP2D6*10 allele may have no major effect on paroxetine PKs in the steady state.

Japanese physicians' preferences for decision making in rheumatoid arthritis treatment.

BACKGROUND: Rheumatoid arthritis (RA) is a complex chronic illness requiring continued medical care. During the past decade, the therapeutic options for RA have increased significantly; these often have a higher risk of adverse effects and are more expensive than traditional drugs. Rheumatologists may hence face difficulties when deciding on the optimal modality in initiating or changing treatment. The aim of this study was to explore the Japanese physicians' usual style of and preferences for decision making regarding RA treatment. METHODS: This was a cross-sectional study conducted using an Internet survey. Respondents were asked about their usual style of making treatment decisions (perceived style), and their perception of the importance of physicians' actions and patients' attitudes. RESULTS: Of the 485 physicians who were sent the questionnaire, 157 responded completely (response rate: 32.3%). Ninety-two percent of the respondents were men, and 57% were clinicians with more than 20 years of experience. Their specialties were general medicine (29%), rheumatology (27%), orthopedics (31%), and rehabilitation (12%). Sixty-one (39%) stated that they usually presented multiple treatment options to their patients and selected a decision for them, 42 (27%) shared the decision making with their patients, 34 (22%) let their patients choose the treatment, and 20 (13%) made the treatment decision for the patients. Physicians using the shared decision making (SDM) style desired for their patients to have supportive family and friends, to discuss with nurses, and to follow the doctors' directions more strongly compared with physicians using the other styles. There were no significant differences in sex, duration of clinical experience, major place of clinical work, and number of patients per month by the styles. More number of rheumatologists and physicians with specialist qualifications stated that they practiced SDM. CONCLUSION: To enhance patient participation, physicians need to recognize the importance of discussing treatment options with patients in addition to giving them information.

Phosphoserine phosphatase activity is elevated and correlates negatively with plasma d-serine concentration in patients with schizophrenia.

The pathophysiology of schizophrenia may involve N-methyl-D-aspartate receptor (NMDAR) hypofunction. D-3serine and glycine are endogenous l-serine-derived NMDAR co-agonists. We hypothesized that the l-serine synthesis pathway could be involved in schizophrenia. We measured the activity of phosphoserine phosphatase (PSP), a rate-limiting enzyme in l-serine synthesis, in peripheral blood mononuclear cells of 54 patients with schizophrenia and 49 normal control subjects. Plasma amino acid (l-serine, d-serine, glycine, glutamine, and glutamate) levels were measured by high performance liquid chromatography. Peripheral blood mRNA expression levels of PHGDH, PSAT1, PSP, and SR, determined by quantitative real-time PCR were compared between patients and controls. PSP activity was higher in patients than in controls, especially in male patients. In male patients, the plasma l-serine concentration was higher than that in controls. In patients, PSP activity was negatively correlated with plasma d-serine and glycine levels. Furthermore, PSP activity was positively correlated with plasma l-serine concentration. These results were statistically significant only in male patients. PSP, PSAT1, and PHGDH mRNA levels were lower in patients than in controls, except when the PHGDH expression level was compared with ACTB expression. In summary, we found the l-serine synthesis system to be altered in patients with schizophrenia, especially in male patients.

[An elderly man presenting polyarthritis diagnosed as chronic tophaceous gout].

An 85-year-old man was admitted to our hospital for swollen and painful bilateral lower legs and a high fever. He was initially diagnosed with acute cellulitis and treated with antibiotics. Several days after the improvement of his swollen legs, he complained of both shoulder and arm pain. The laboratory data at this time were as follow: C-reactive protein 10.7 mg/dL, uric acid 8.7 mg/dL, and creatinine 1.07 mg/dL. Both rheumatoid factor and anti-CCP antibody were negative. Whole-body gallium scintigraphy showed a high pathological accumulation in both the shoulders and left wrist. As polymyalgia rheumatica was suspected, oral prednisolone (PSL) of 10 mg/day was started. The patient's shoulder pain improved and he was discharged. However, he was hospitalized twice in the next month because of left shoulder, left knee, right arm, and right wrist pain. During the third hospitalization, we found a subcutaneous nodule on right toe. Aspiration material from the nodule was a white paste, showing acicular crystals under the microscope. According to these findings, the nodule was diagnosed as a tophaceous nodule, and recurrent episodes of polyarthritis were diagnosed as chronic tophaceous gout. Low-dose PSL was continued and febuxostat was added. This patient had multiple risk factors for chronic tophaceous gout: obesity, a habit of drinking, diabetes mellitus, hyperlipidemia, congestive heart failure, and interruption of allopurinol treatment. We herein discuss the clinical course of the patient, the interruption of allopurinol treatment and polypharmacy in elderly patients.