柳橋 達彦

<h4>Objective</h4>This study aimed to evaluate the dynamics of the neutrophil-to-lymphocyte ratio (NLR) during the initial hospitalization of patients with eating disorders (EDs) and to assess its potential as a biomarker for monitoring disease severity and treatment response.<h4>Methods</h4>A retrospective chart review was conducted with 55 patients aged ≤ 16 years diagnosed with anorexia nervosa or avoidant/restrictive food intake disorder and admitted to Jichi Medical University Hospital between 2015 and 2021. Sociodemographic and clinical characteristics including sex, age, rate of weight gain, percentage of ideal body weight (%IBW), tube feeding treatment, and NLR were obtained. Statistical analyses used a mixed model for repeated measures to assess NLR changes regarding %IBW and other clinical factors.<h4>Results</h4>The NLR at admission was lower in the malnourished state but increased with weight recovery. MMRM revealed that tube feeding treatment (β = 0.538) and restoration of %IBW (β = 0.029) significantly predicted an increase in the NLR. The interaction between tube feeding and the quadratic term of %IBW was also significant, indicating distinct patterns of NLR changes: without tube feeding, NLR increased linearly with weight recovery, whereas with tube feeding, NLR exhibited a non-linear, upward-convex parabolic trend.<h4>Discussion</h4>These findings suggest that NLR may offer an objective recovery marker less influenced by patient self-report. Monitoring NLR before and after tube feeding may help distinguish true physiological recovery from transient stress responses, providing complementary information to conventional assessments. Further research is warranted to establish its clinical relevance.

<h4>Purpose</h4>There is no consensus regarding the optimal target weight for discharge during the hospitalization of children with eating disorders (EDs). We attempted to identify the ideal discharge weight for children receiving their first inpatient treatment for anorexia nervosa (AN) or avoidant/restrictive food intake disorder (ARFID).<h4>Patients and methods</h4>Sixty children (mean age: 12.8 years) diagnosed with either AN (49 children) or ARFID (11 children) were followed for 1 year after discharge from a psychiatric ward. We analyzed the percent of ideal body weight (%IBW) at discharge, along with physical and social factors, to predict weight outcomes and rehospitalization risk during the first year after discharge. Longitudinal weight trends were assessed, and Cox proportional hazards modeling was used to analyze the time to rehospitalization.<h4>Results</h4>Single and multiple regression analyses identified the %IBW at discharge as the sole significant predictor of %IBW at 1 year. A receiver operating characteristic curve determined that 86.4%IBW at discharge was the optimal predictor of achieving 90%IBW by 1-year post-discharge. Patients who had achieved ≥ 86.4%IBW at discharge showed better weight trajectories compared with those discharged at < 86.4%IBW. A higher discharge %IBW was associated with prolonged time to rehospitalization, indicating a reduced risk of readmission.<h4>Conclusions</h4>Discharging pediatric patients at a higher weight is associated with improved weight recovery and a reduced risk of rehospitalization. A target discharge weight of 86.4%IBW may serve as an effective criterion for children with EDs.<h4>Level of evidence</h4>III, case-control analytic studies.

<h4>Background</h4>Although differential diagnosis between autoimmune encephalitis and schizophrenia spectrum disorders is crucial for a good outcome, the psychiatric symptoms that distinguish these two conditions have not been identified even though psychiatric symptoms are often the main manifestation of autoimmune encephalitis. Also, there are many situations in clinical psychiatry in which laboratory testing and imaging studies are not available. Because no comparative study of the psychiatric symptoms between these two conditions has been carried out, we explored diagnostically useful psychiatric symptoms in a retrospective case-control study.<h4>Methods</h4>We recruited 187 inpatients with first-episode psychosis who were admitted to our psychiatric unit and categorized them into two groups: the autoimmune encephalitis group (n = 10) and the schizophrenia spectrum disorders group (n = 177). Differences in the symptoms and signs between the two groups were investigated.<h4>Results</h4>Schneider's first-rank symptoms (e.g., verbal commenting hallucinations and delusional self-experience) were observed only in the schizophrenia spectrum disorders group, whereas altered perception was found more frequently in the autoimmune encephalitis group. Functional status was worse in the autoimmune encephalitis group, and neurological and neuropsychological signs were revealed almost exclusively in this group. A history of mental illness was more frequently reported in the schizophrenia spectrum disorders group than in the autoimmune encephalitis group.<h4>Conclusions</h4>The psychiatric symptoms, i.e., Schneider's first-rank symptoms and altered perception, together with neurological and neuropsychological signs, functional status, and past history, may help clinicians accurately differentiate these two conditions among patients with first-episode psychosis.

The LRP5 gene encodes a Wnt signaling receptor to which Wnt binds directly. In humans, pathogenic monoallelic variants in LRP5 have been associated with increased bone density and exudative vitreoretinopathy. In mice, LRP5 plays a role in tooth development, including periodontal tissue stability and cementum formation. Here, we report a 14-year-old patient with a de novo non-synonymous variant, p.(Val1245Met), in LRP5 who exhibited mildly reduced bone density and mild exudative vitreoretinopathy together with a previously unreported phenotype consisting of dental abnormalities that included fork-like small incisors with short roots and an anterior open bite, molars with a single root, and severe taurodontism. In that exudative vitreoretinopathy has been reported to be associated with heterozygous loss-of-function variants of LRP5 and that our patient reported here with the p.(Val1245Met) variant had mild exudative vitreoretinopathy, the variant can be considered as an incomplete loss-of-function variant. Alternatively, the p.(Val1245Met) variant can be considered as exerting a dominant-negative effect, as no patients with truncating LRP5 variants and exudative vitreoretinopathy have been reported to exhibit dental anomalies. The documentation of dental anomalies in the presently reported patient strongly supports the notion that LRP5 plays a critical role in odontogenesis in humans, similar to its role in mice.

<h4>Background/aim</h4>To our knowledge, no case-control study has investigated the relationships between stealing, clinical implications, and psychiatric diagnosis among child and adolescent psychiatric patients with or without a history of stealing. Thus, the associations between child and adolescent psychiatric disorders and a history of stealing remain unclear. Therefore, the aim of the present study was to evaluate the relationships between stealing, clinical implications, and psychiatric diagnosis among child and adolescent psychiatric patients with or without a history of stealing.<h4>Methods</h4>In this retrospective case-control study, the proportions of clinical implications among child and adolescent psychiatric patients with and without a history of stealing were compared. Data regarding age, sex, primary diagnosis, junior high school student or not, both father and mother are the caregivers or not, family history, abuse history, school refusal, depressive state, and obsessive-compulsive symptoms were retrieved from medical records. Participants consisted of Japanese junior high school students and younger patients (maximum age, 15 years) at the first consultation. All patients were examined and diagnosed by psychiatrists according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, or the Fifth Edition. Stealing was reported by the patients or caregivers to the psychiatrist, or the psychiatrist had inquired about a history of stealing at the first consultation.<h4>Results</h4>Among 1972 patients who consulted the clinic, at the first consultation, 56 (2.84%) had a history of stealing (cases), and 1916 (97.16%) did not (controls). Multivariate logistic regression analyses revealed that the proportions of males, junior high school students, abuse history, autism spectrum disorder (ASD), and conduct disorder were significantly higher, and the proportions of adjustment disorders and school refusal were significantly lower in cases than in controls. The multivariate adjusted odds ratio increased further when the two factors were considered together, such as ASD with abuse history and attention deficit-hyperactivity disorder (ADHD) with abuse history.<h4>Conclusions</h4>Children with a history of stealing were more likely to be diagnosed with ASD or ADHD with abuse history. Child and adolescent psychiatric outpatients with a history of stealing were more likely to be older and male. Our study should be understood without prejudice because this study is reporting associations, not causality. Therefore, a prospective study to investigate causality among ADHD, ASD, abuse history, and stealing is needed. If ADHD and ASD with abuse history can be correlated to a history of stealing, interventions can be more effective by understanding the mechanisms underlying these connections.

Background: Self-disturbances in schizophrenia have recently been explained by an abnormality in the sense of agency (SoA). The cerebral structures of SoA in healthy people are considered to mainly include the insula and inferior parietal lobule. In contrast, the functional lesion of aberrant SoA in schizophrenia is not yet fully understood. Considering the recent explanation of establishing SoA from the standpoint of associative learning, the "agency network" may include not only the insula and inferior parietal lobule but also the striatum. We hypothesized that aberrant SoA in schizophrenia is based on a deficit in the "agency network." Methods: Functional magnetic resonance imaging data were acquired while patients with schizophrenia (n = 15) and matched controls (n = 15) performed our adaptation method of agency attribution task on a trial-by-trial basis to assess participants' explicit experience of the temporal causal relationship between an action and an external event with temporal biases. Analysis of functional connectivity was done using the right supramarginal gyrus and the right middle frontal gyrus as seed regions. Results: In healthy controls, analyses revealed increased activation of the right inferior parietal lobule (mainly the supramarginal gyrus), right insula, and right middle frontal gyrus as an activation of the agency condition. We defined activated Brodmann areas shown in the agency condition of healthy controls as the seed region for connectivity analysis. The connectivity analysis revealed lower connectivity between the head of the left caudate nucleus and right supramarginal gyrus in the patients compared to healthy controls. Conclusions: This dysconnectivity of the agency network in schizophrenia may lead to self-disturbance through deficits in associative learning of SoA. These findings may explain why pathological function of the striatum in schizophrenia leads to self-disturbance.

Higher brain dysfunction, such as language delay, is a major concern among preterm infants. Cerebral substrates of cognitive development in preterm infants remain elusive, partly because of limited methods. The present study focuses on hemodynamic response patterns for brain function by using near-infrared spectroscopy. Specifically, the study investigates gestational differences in the hemodynamic response pattern evoked in response to phonetic changes of speech and cerebral hemispheric specialization of the auditory area in preterm infants (n = 60) and term infants (n = 20). Eighty neonates born between 26 and 41 weeks of gestational age (GA) were tested from 33 to 41 weeks of postmenstrual age (PMA). We analyzed the hemodynamic response pattern to phonemic and prosodic contrasts for multiple channels on temporal regions and the laterality index of the auditory area. Preterm infants younger than 39 weeks of PMA showed significantly atypical hemodynamic patterns, with an inverted response shape. Partial correlation analysis of the typicality score of hemodynamic response revealed a significant positive correlation with PMA. The laterality index of preterm infants from 39 weeks of PMA demonstrated a tendency rightward dominance for prosodic changes similar to term infants. We provide new evidence that alterations in hemodynamic regulation and the functional system for phonemic and prosodic processing in preterm infants catch up by their projected due dates.

<h4>Background</h4>Young children undergoing magnetic resonance imaging (MRI) require sedation. In June 2013, Tokyo Metropolitan Ohtsuka Hospital (TMOH) introduced an oral sedation protocol for young children undergoing MRI; the protocol included instructions on fasting before sedation, and recommended a shorter duration of sleep the night before MRI. We compared the MRI success rate before and after the introduction of this protocol.<h4>Methods</h4>The eligible subjects were children under 3 years old who underwent MRI by appointment at TMOH between October 2012 and March 2014, under sedation with triclofos sodium. All those who underwent MRI in or after June 2013 were enrolled prospectively as a post-protocol group. All patients who underwent MRI before June 2013 were enrolled retrospectively as a pre-protocol group, with data collected from chart review.<h4>Results</h4>Seventy-four patients were enrolled in the post-protocol group, and 42 in the pre-protocol group. The MRI success rate was significantly higher in the post-protocol group than in the pre-protocol group (98.7% vs 88.1%), as was the rate of on-time starting of MRI (86.5% vs 71.4%). The post-protocol group woke up earlier on the day of examination (6:18 a.m. vs 6:43 a.m.), resulting in a significantly longer time between awakening and the beginning of sedation (289.8 min vs 265.9 min), and a significantly shorter average duration of sleep on the previous night (504.8 min vs 532.3 min).<h4>Conclusions</h4>Implementation of a hospital-wide sedation protocol for young children undergoing MRI significantly improved the MRI success rate.

To reveal the relation between intellectual disability and the deleted intervals in Williams syndrome, we performed an array comparative genomic hybridization analysis and standardized developmental testing for 11 patients diagnosed as having Williams syndrome based on fluorescent in situ hybridization testing. One patient had a large 4.2-Mb deletion spanning distally beyond the common 1.5-Mb intervals observed in 10/11 patients. We formulated a linear equation describing the developmental age of the 10 patients with the common deletion; the developmental age of the patient with the 4.2-Mb deletion was significantly below the expectation (developmental age = 0.51 × chronological age). The large deletion may account for the severe intellectual disability; therefore, the use of array comparative genomic hybridization may provide practical information regarding individuals with Williams syndrome.

<h4>Objective</h4>The nutritive evaluation and the serum carnitine values were measured for persons with severe motor and intellectual disabilities with enteral (tube) feeding.<h4>Methods</h4>In Shimada Rehabilitation Center, twenty one people who had serum albumin levels of 3.4 g/dl or less, and were taking nutrition with enteral (tube) feeding, were tested. Body weight, blood samples, and serum carnitine levels were measured.<h4>Results</h4>The total carnitine value was less than the standard value in 19 patients. The total carnitine value decreased in the group taking valporate sodium (VPA), compared to the values from the group non-taking VPA.<h4>Conclusions</h4>From our evaluation, we think that daily carnitine supplements is essential for persons with sever motor and intellectual disabilities taking VPA to maintain carnitine levels in the blood, and regular urine test should be done for earlier detection secondary lack complications from the secondary lack of carnitine.

Rubinstein-Taybi syndrome (RTS) is characterized by developmental delay, postnatal growth retardation, typical facial appearance, and broad thumbs and big toes. The behavioral phenotype of children with RTS has been described as friendly and having good social contacts; however, a short attention span and hyperactivity are sometimes present. Little attention has been paid to the behavioral aspects of adults with RTS. We conducted an observational study focusing on behavioral problems in adolescents and adults with RTS compared with children with RTS. A total of 63 patients with RTS and their caretakers answered self-administered questionnaires regarding behavioral features including the Child Behavior Checklist (CBCL). High total CBCL scores were observed, and the mean score was beyond the clinical cut-off point. After stratification into two groups according to age, the older group (≥14 years) displayed statistically significant higher scores for Anxious/Depression (P = 0.002) and Aggressive Behavior (P = 0.036) than the younger group (≤13 years). In analyses of single items, statistically significant differences between the younger group and the older group were found for 'Nervous, high-strung, or tense' (31.3% vs 67.7%, P = 0.004) and 'Too fearful or anxious' (37.5% vs 64.5%, P = 0.032). Here, we showed that the specific behavioral phenotypes of RTS change during adolescence, with anxiety, mood instability, and aggressive behavior emerging as patients age. A clear need exists to follow-up patients with RTS to catch the eventual emergence of psychiatric problems with age. If necessary, pharmacological treatment should be considered.

Coloboma and various ocular abnormalities have been described in CHARGE syndrome, although the severity of visual impairment varies from case to case. We conducted a multicenter study to clarify the ophthalmic features of patients with molecularly confirmed CHARGE syndrome. Thirty-eight eyes in 19 patients with CHARGE syndrome and confirmed CHD7 mutations treated at four centers were retrospectively studied. Colobomata affected the posterior segment of 35 eyes in 18 patients. Both retinochoroidal and optic disk colobomata were bilaterally observed in 15 patients and unilaterally observed in 3 patients. The coloboma involved the macula totally or partially in 21 eyes of 13 patients. We confirmed that bilateral large retinochoroidal colobomata represents a typical ophthalmic feature of CHARGE syndrome in patients with confirmed CHD7 mutations; however, even eyes with large colobomata can form maculas. The anatomical severity of the eye defect was graded according to the presence of colobomata, macula defect, and microphthalmos. A comparison of the severity in one eye with that in the other eye revealed a low-to-moderate degree of agreement between the two eyes, reflecting the general facial asymmetry of patients with CHARGE syndrome. The location of protein truncation and the anatomical severity of the eyes were significantly correlated. We suggested that the early diagnosis of retinal morphology and function may be beneficial to patients, since such attention may determine whether treatment for amblyopia, such as optical correction and patching, will be effective in facilitating the visual potential or whether care for poor vision will be needed.

This study focuses on the early cerebral base of speech perception by examining functional lateralization in neonates for processing segmental and suprasegmental features of speech. For this purpose, auditory evoked responses of full-term neonates to phonemic and prosodic contrasts were measured in their temporal area and part of the frontal and parietal areas using near-infrared spectroscopy (NIRS). Stimuli used here were phonemic contrast /itta/ and /itte/ and prosodic contrast of declarative and interrogative forms /itta/ and /itta?/. The results showed clear hemodynamic responses to both phonemic and prosodic changes in the temporal areas and part of the parietal and frontal regions. In particular, significantly higher hemoglobin (Hb) changes were observed for the prosodic change in the right temporal area than for that in the left one, whereas Hb responses to the vowel change were similarly elicited in bilateral temporal areas. However, Hb responses to the vowel contrast were asymmetrical in the parietal area (around supra marginal gyrus), with stronger activation in the left. These results suggest a specialized function of the right hemisphere in prosody processing, which is already present in neonates. The parietal activities during phonemic processing were discussed in relation to verbal-auditory short-term memory. On the basis of this study and previous studies on older infants, the developmental process of functional lateralization from birth to 2 years of age for vowel and prosody was summarized.

<h4>Rationale</h4>Treatment guidelines for major depressive disorder (MDD) recommend a continuous use of antidepressants for several weeks, while recent meta-analyses indicate that antidepressant efficacy starts to appear within 2 weeks and early treatment nonresponse is a predictor of subsequent nonresponse.<h4>Objectives</h4>We prospectively compared 8-week outcomes between switching antidepressants and maintaining the same antidepressant in early nonresponders, to generate a hypothesis on possible benefits of early switching strategy.<h4>Method</h4>Patients with MDD without any treatment history for the current episode were included. When subjects failed to show an early response (i.e., ≥20% improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS)) to the initial treatment with sertraline 50mg at week 2, they were randomly divided into two groups; in the Continuing group, sertraline was titrated at 50-100mg, whereas sertraline was switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure was a response rate (i.e., ≥50% improvement in the MADRS) at week 8.<h4>Results</h4>Among 132 subjects, 41 subjects showed early nonresponse. The Switching group (n=20) showed a higher rate of responders than the Continuing group (n=21) (75% vs. 19%: p=0.002). Further, the Switching group was also superior in the rate of remitters (total score of ≤10 in the MADRS) (60% vs. 14%: p=0.004) and continuous changes in the MADRS (19.0 vs. 7.5: p<0.001).<h4>Conclusions</h4>Our preliminary findings suggest that patients with MDD who fail to show early response to an initial antidepressant may derive benefits from the early switching antidepressants in the acute-phase treatment of depression.

<h4>Background</h4>One severe side effect of calcineurin inhibitors (CNIs: such as cyclosporine [CsA] and tacrolimus [FK506]) is neurotoxicity. CNIs are substrates for CYP3A5 and P-glycoprotein (P-gp), encoded by ABCB1 gene. In the present study, we hypothesized that genetic variability in CYP3A5 and ABCB1 genes may be associated with CNI-related neurotoxicity.<h4>Methods</h4>The effects of the polymorphisms, such as CYP3A5 A6986G, ABCB1 C1236T, G2677T/A, and C3435T, associated with CNI-related neurotoxicity were evaluated in 63 patients with hematopoietic stem cell transplantation.<h4>Results</h4>  Of the 63 cases, 15 cases developed CNI-related neurotoxicity. In the CsA patient group (n = 30), age (p = 0.008), hypertension (p = 0.017), renal dysfunction (p < 0.001), ABCB1 C1236T (p < 0.001), and G2677T/A (p = 0.014) were associated with neurotoxicities. The CC genotype at ABCB1 C1236T was associated with it, but not significantly so (p = 0.07), adjusted for age, hypertension, and renal dysfunction. In the FK506 patient group (n = 33), CYP3A5 A6986G (p < 0.001), and ABCB1 C1236T (p = 0.002) were associated with neurotoxicity. At least one A allele at CYP3A5 A6986G (expressor genotype) was strongly associated with it according to logistic regression analysis (p = 0.01; OR, 8.5; 95% CI, 1.4-51.4).<h4>Conclusion</h4>  The polymorphisms in CYP3A5 and ABCB1 genes were associated with CNI-related neurotoxicity. This outcome is probably because of CYP3A5 or P-gp functions or metabolites of CNIs.

Patients with Down syndrome (DS) and a left-to-right shunt often develop early severe pulmonary hypertension (PH) and pulmonary vascular obstructive disease (PVOD); the pathophysiological mechanisms underlying the development of these complications are yet to be determined. To investigate the mechanisms, we evaluated the biosynthesis of thromboxane (TX) A(2) and prostacyclin (PGI(2)) in four groups of infants, cross-classified as shown below, by measuring the urinary excretion levels of 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha): DS infants with a left-to-right shunt and PH (D-PH, n = 18), DS infants without congenital heart defect (D-C, n = 8), non-DS infants with a left-to-right shunt and PH (ND-PH, n = 12), and non-DS infants without congenital heart defect (ND-C, n = 22). The urinary excretion ratios of 11-dehydro-TXB(2) to 2,3-dinor-6-keto-PGF(1alpha) in the D-PH, D-C, ND-PH, and ND-C groups were 7.69, 4.71, 2.10, and 2.27, respectively. The ratio of 11-dehydro-TXB(2) to 2,3-dinor-6-keto-PGF(1alpha) was higher in the presence of DS (P < 0.001), independently of the presence of PH (P = 0.297). The predominant biosynthesis of TXA(2) over PGI(2), leading to vasoconstriction, was observed in DS infants, irrespective of the presence/absence of PH. This imbalance in the biosynthesis of vasoactive eicosanoids may account for the rapid progression of PVOD in DS infants with a left-to-right shunt.

CHARGE syndrome is an autosomal dominant congenital anomaly syndrome, and the causative gene is CHD7. We report a patient with a CHD7 mutation who presented with juvenile muscular atrophy of a unilateral upper extremity, a presumably heterogeneous condition that is also known as Hirayama disease. This association has not been previously described. Weakness and atrophy of the hands should be carefully examined in patients with CHARGE syndrome, since Hirayama disease might be a possible complication in adolescent patients with this syndrome.

Russell-Silver syndrome (RSS) is characterized by prenatal and postnatal growth retardation, triangular facies, and fifth-finger clinodactyly. Half of all patients with RSS have hypomethylation of the differentially methylated region of the H19 gene on chromosome 11p15.5. Hence, a quantitative methylation analysis of this region can be useful for the molecular diagnosis of RSS. However, conventional assays based on bisulfite clone sequencing are rather time and labor consuming and are not suitable for clinical use. In the present study, we investigated a possible method of quantitatively determining H19 hypomethylation in RSS patients using a combined bisulfite restriction analysis (COBRA)-denaturing high-performance liquid chromatography (DHPLC) assay; in this combined assay, polymerase chain reaction products amplified from the H19 differentially methylated region of bisulfite-treated genomic DNA were analyzed using a COBRA assay, which detects methylation-dependent sequence differences in the bisulfite-treated genomic DNA using a restriction enzyme analysis. We designed the assay so that a restriction enzyme (HinfI) would cut the methylated, but not the unmethylated, template. The molar ratio between the cut and uncut fragments was measured using DHPLC, and the construction of a calibration curve enabled the methylation index for the original genomic DNA to be estimated. An analysis of seven RSS patients using the COBRA-DHPLC assay demonstrated that three of the seven RSS patients had a low methylation index of around 10%. A comparison of the methylation indices obtained using COBRA-DHPLC and conventional bisulfite clone sequencing revealed an excellent intermethod agreement. In summary, we have developed a robust, rapid, and cost-effective COBRA-DHPLC-based screening system for RSS.

A cross-sectional comparative study among women who underwent surgical treatment for endometriosis revealed that frequency of the Ala/Ala genotype at aryl hydrocarbon receptor repressor (AHRR) Pro185Ala polymorphism was three times higher (27.6% vs. 9.9%) in the younger group (<or=30 years) than in the older group (>30 years). AHHR genotyping may help to identify a subpopulation of women who are susceptible to the earlier onset of endometriosis.

<h4>Objective</h4>Risperidone is converted to 9-hydroxyrisperidone by CYP2D6. Two parameters were used to examine the influences of CYP2D6 polymorphism and of co-medication on risperidone metabolism: the risperidone:9-hydroxyrisperidone concentration ratio (R:9-OHR ratio) and the sum of the risperidone and 9-hydroxyrisperidone concentrations divided by the dose (C:D ratio). We evaluated the effect of the CYP2D6*10 allele, which is a prevalent mutant allele among East Asians.<h4>Methods</h4>Genotyping using the P450 microarray system was performed for 89 Japanese patients with schizophrenia receiving risperidone. The patients with CYP2D6*1/*1, *1/*2, or *2/*2 were classified as Group 1, those with one CYP2D6*10 allele (CYP2D6*1/*10 or *2/*10) were classified as Group 2, and those with two CYP2D6*10 alleles were classified as Group 3. The R:9-OHR and C:D ratios were analyzed using two-way ANOVAs with the CYP2D6 genotype and co-medication with CYP2D6-dependent drugs as independent variables.<h4>Results</h4>Both the "genotype" and the "co-medication" factors had significant impacts on the R:9-OHR ratio (p = 0.011, p < 0.001). The "genotype" factor also had a significant impact on the C:D ratio (p = 0.032). However, the "co-medication" factor did not have a significant impact on the C:D ratio (p = 0.129).<h4>Conclusions</h4>The CYP2D6*10 polymorphism and the presence of co-medication exerted significant influences on the pharmacokinetics of risperidone.

Mulvihill-Smith syndrome (MSS) is characterized by premature aging, multiple pigmented nevi, decreased facial subcutaneous fat, microcephaly, short stature, mental retardation and recurrent infections, however the adult phenotype of MSS has yet to be delineated. We report a 28-year-old woman with Mulvihill-Smith syndrome, who had a solid pseudopapillary cystic tumor of her pancreas at age 17 years. Her distinctive sleep pattern includes severe insomnia with disappearance of sleep spindles and K-complexes, persisting muscle tone, and loss of slow wave sleep. The clinical and neurophysiological studies are compatible with agrypnia excitata, a sleep disorder attributable to a dysfunction of the thalamo-limbic system. Brain magnetic resonance imaging and single photon emission computed tomography revealed structural and functional deficits in the dorsomedial region of the thalamus and indicated that an alteration in the thalamo-limbic system may underlie the sleep disturbances in MSS. Furthermore, the rapid and severe decline in acquired cognitive function showed the distinct cognitive impairments resembling dementia, including intellectual deficits, memory disorder and executive dysfunction. We posit that an early onset tumor, sleep disorder and cognitive decline are adult manifestations of Mulvihill-Smith syndrome.