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Abstract Alterations in the white matter have been implicated in schizophrenia. Myelin basic protein (MBP), a component of the myelin sheath, in the cerebrospinal fluid (CSF) has been suggested as a biomarker for white matter damage in demyelinating diseases. This prompted us to examine the CSF‐MBP levels in patients with schizophrenia. We analyzed the CSF‐MBP levels in 152 patients with schizophrenia and 117 age‐ and sex‐matched controls. A significant positive correlation between age and CSF‐MBP levels was observed both in the patients (p

Infrastructure operation and maintenance is essential for societal safety, particularly in Japan where the aging of infrastructures built during the period of high economic growth is advancing. However, there are issues such as a shortage of engineers and inefficiencies in work, requiring improvements in efficiency and automation for their resolution. Nevertheless, there are still many inefficiencies in the current procedures for bridge inspections. Usually, inspection engineers check for damage on bridges through close visual inspections at the site, then photograph the damaged parts, measure the size by touch, and create a report. A three-dimensional representation, considering the front and back of the structural elements, is needed for identifying damage, necessitating the creation of multi-directional three-dimensional drawings. However, this process is labor-intensive and prone to errors. Furthermore, due to the lack of uniformity in records, it is challenging to refer to past inspection histories. Especially for long bridges, without resolving such issues, the required labor and the number of mistakes could exceed acceptable limits, making proper management difficult. Therefore, in this study, we developed a method for automatically measuring the position and area of corroded parts by capturing images of the lower surface of the stiffening girder using a bridge inspection vehicle and utilizing image diagnosis technology. By integrating these results into a 3D model called BIM (Building Information Modeling), it becomes possible to manage the bridge more efficiently. We verified this method on actual long bridges and confirmed its effectiveness.

Schizophrenia is a syndrome with multiple etiologies, one of which is the potential for an autoimmune disease of the brain such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, which can induce psychosis resembling schizophrenia. Here, we examined anti-neuronal autoantibodies related to psychosis using both cell- (CBA) and tissue-based assays (TBA) in the cerebrospinal fluid (CSF) of patients with chronic schizophrenia and control participants. First, we screened for the antibodies against leucine-rich glioma-inactivated 1 (LGI1), γ-aminobutyric acid B receptor (GABABR), dipeptidyl aminopeptidase-like protein 6 (DPPX), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR1/R2), and contactin-associated protein-like 2 (CASPR2) in 148 patients with schizophrenia. No antibodies were detected. Next, we performed CBA for NMDAR antibodies in 148 patients with schizophrenia and 151 age- and sex-matched controls. Although we detected relatively weak immunoreactivity for NMDAR in the CSFs of two patients with schizophrenia and three controls, no samples were positive when strict criteria were applied. For TBA in the rat hippocampus and cerebellum, we detected positive signals in the CSFs of 13 patients with schizophrenia and eight controls. Positive samples were analyzed for paraneoplastic syndrome and antinuclear antibodies using immunoblotting. The CSFs of nine patients and six controls were positive for dense fine speckle 70 (DFS70) antibodies. Additionally, antibodies against centromere protein (CENP)-A and CENP-B were detected in patients with schizophrenia. Our results suggest that autoantibodies against NMDAR, LG1, GABABR, DPPX, AMPAR1/R2, and CASPR2 are not associated with the pathogenesis of chronic schizophrenia. Moreover, we emphasize the importance of considering the effect of anti-DFS70 antibodies when analyzing autoantibodies in CSF samples. Conclusively, we obtained no evidence suggesting that the most frequent neuronal autoantibodies in the CSF play a role in the pathogenesis of schizophrenia, even in our sample.

Purpose: Achromatopsia (ACHM) is an early-onset cone dysfunction caused by 5 genes with cone-specific functions (CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H) and by ATF6, a transcription factor with ubiquitous expression. To improve the relatively low variant detection ratio in these genes in a cohort of exome-sequenced Japanese patients with inherited retinal diseases (IRD), we performed genome sequencing to detect structural variants and intronic variants in patients with ACHM. Methods: Genome sequencing of 10 ACHM pedigrees was performed after exome sequencing. Structural, non-coding, and coding variants were filtered based on segregation between the affected and unaffected in each pedigree. Variant frequency and predicted damage scores were considered in identifying pathogenic variants. Results: A homozygous deletion involving exon 18 of RPGRIP1 was detected in 5 of 10 ACHM probands, and variant inheritance from each parent was confirmed. This deletion was relatively frequent (minor allele frequency = 0.0023) in the Japanese population but was only homozygous in patients with ACHM among the 199 Japanese IRD probands analyzed by the same genome sequencing pipeline. Conclusion: The deletion involving exon 18 of RPGRIP1 is a prevalent cause of ACHM in Japanese patients and contributes to the wide spectrum of RPGRIP1-associated IRD phenotypes, from Leber congenital amaurosis to ACHM.

The Japanese archipelago is a terminal location for human migration, and the contemporary Japanese people represent a unique population whose genomic diversity has been shaped by multiple migrations from Eurasia. We analyzed the genomic characteristics that define the genetic makeup of the modern Japanese population from a population genetics perspective from the genomic data of 9,287 samples obtained by high-coverage whole-genome sequencing (WGS) by the National Center Biobank Network. The dataset comprised populations from the Ryukyu Islands and other parts of the Japanese archipelago (Hondo). The Hondo population underwent two episodes of population decline during the Jomon period, corresponding to the Late Neolithic, and the Edo period, corresponding to the Early Modern era, while the Ryukyu population experienced a population decline during the shell midden period of the Late Neolithic in this region. Haplotype analysis suggested increased allele frequencies for genes related to alcohol and fatty acid metabolism, which were reported as loci that had experienced positive natural selection. Two genes related to alcohol metabolism were found to be 12,500 years out of phase with the time when they began to increase in the allele frequency; this finding indicates that the genomic diversity of Japanese people has been shaped by events closely related to agriculture and food production.

Abstract Aim We aimed to compare neuropeptide levels between patients with major psychiatric disorders and healthy controls and examine their association with symptoms and cognitive function. Methods The participants were 149 patients with schizophrenia, 115 patients with bipolar disorder (BD), 186 unremitted patients with major depressive disorder (MDD), and 350 healthy controls. Psychiatric (schizophrenic, manic, and depressive) symptoms, sleep state, and cognitive (premorbid intelligence quotient, general cognitive, and memory) functions were evaluated. A multiplex immunoassay kit was used to measure cerebrospinal fluid (CSF) and plasma α‐melanocyte‐stimulating hormone (MSH), β‐endorphin, neurotensin, oxytocin, and substance P levels. Results The verification assay revealed that CSF α‐MSH, β‐endorphin, neurotensin, oxytocin, and substance P levels were too low to be reliably measured, while plasma α‐MSH, β‐endorphin, neurotensin, oxytocin, and substance P levels could be successfully measured. Plasma α‐MSH, β‐endorphin, neurotensin, oxytocin, and substance P levels were not significantly different between patients with schizophrenia, BD, or MDD and healthy controls. Plasma α‐MSH, β‐endorphin, neurotensin, oxytocin, and substance P levels were not significantly correlated with psychiatric symptom scores in patients with schizophrenia, BD, or MDD and cognitive function scores in patients or healthy controls. Conclusion Our data suggest that plasma neuropeptide levels do not elucidate the involvement of neuropeptides in the pathology of schizophrenia, BD, or MDD.

Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

AimTo examine the association of body mass index (BMI) [kg/m2] and its classifications (underweight [BMI < 18.5], normal [18.5 ≤ BMI < 25], overweight [25 ≤ BMI < 30], and obese [BMI ≥ 30]) with brain structure in individuals with a wide range of BMI group.Materials and methodsThe participants included 382 right-handed individuals (mean age: 46.9 ± 14.3 years, 142 men and 240 women). The intelligence quotient was assessed using the Japanese Adult Reading Test. Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) were performed to analyze the association of BMI and its classifications with gray and white matter structures, respectively.ResultsAccording to VBM, BMI was significantly and negatively correlated with the bilateral cerebellum exterior volumes. In group comparisons, the right cerebellum exterior volume was significantly lower in the overweight or obese group than in the underweight or normal group, while the bilateral cuneus and calcarine cortex, left cuneus, and left precuneus volume was significantly lower in the underweight group than in the non-underweight group. Sex-related stratification analyses for VBM revealed that BMI was significantly and negatively correlated with the bilateral cerebellum exterior volumes only in women. In group comparisons, the left cerebellum exterior volume was significantly lower in obese women than in non-obese women. The left thalamus proper and the right cerebellum exterior volumes were significantly lower in overweight or obese group than in underweight or normal group in men and women, respectively. The bilateral cuneus and calcarine cortex, left cuneus and carcarine cortex, and bilateral cuneus volume was significantly lower in underweight men than in non-underweight men. In contrast, there were no notable findings on DTI.ConclusionOur results suggest association of continuous BMI, being overweight or obese, and being underweight with decreased gray matter volume in individuals with a wide range of BMI group. Furthermore, sex-related differences are seen in the association of BMI and its classifications with regional gray matter volume reductions. Abnormally high or low BMIs may have a negative influence on regional gray matter volumes.

Abstract Aim We compared the Interpersonal Sensitivity Measure (IPSM) scores between diagnostic groups and examined the relationship between IPSM scores and clinical variables. Methods This study included 166 patients with schizophrenia, 47 patients with bipolar disorder (BD) Ⅰ, 110 patients with BD Ⅱ, 380 patients with major depressive disorder (MDD), and 558 healthy individuals. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale, 21‐item Hamilton Depression Rating Scale (HAMD‐21), and Pittsburgh Sleep Quality Index (PSQI). Results The IPSM interpersonal awareness, separation anxiety, timidity, fragile inner self, and total scores were significantly higher in all the patient groups compared with healthy individuals (corrected p

Abstract Bipolar disorder (BD) is a mental disorder characterized by extreme changes in mood polarity. It is also characterized by cognitive and metabolic dysfunctions. Fibroblast growth factor 21 (FGF21) is an endocrine protein that has a multifaceted function such as glucose and lipid regulation in the periphery, and neuroprotection and induction of synaptic plasticity in the central nervous system. Previous studies reported inconsistent results concerning peripheral FGF21 levels in patients with BD. In this study, we compared plasma FGF21 levels between 26 patients with BD and 51 healthy controls using a human FGF21 ELISA Kit. There was no significant difference in plasma FGF21 levels between the patients and controls. We found significant positive correlations between plasma FGF21 levels and some cognitive parameters (word association and motor speed). If our results are replicated that higher peripheral FGF21 may be associated with better cognitive performance in patients with BD.

Abstract Aim The ε4 allele of apolipoprotein E gene (APOE) is a well‐known risk factor of late‐onset Alzheimer's disease. However, little is known why this variant confers a risk for Alzheimer's disease. The aim of this study was to examine the influence of the APOE genotype on cerebrospinal fluid (CSF) protein levels. Methods The present study performed a secondary analysis on our previously generated database to compare the CSF levels of 1128 proteins between APOE‐ε4 carriers (28 subjects) and noncarriers (104 subjects). All subjects were physically healthy Japanese individuals without dementia. Results CSF levels of apoE2, apoE3, and apoE4 were significantly higher (all nominal P

Background: : Behavioral inhibition, referred to as the harm avoidance (HA) trait, has been deemed a vulnerability factor for major depressive disorder (MDD). Previous studies tried to find brain structural biomarkers of HA by assessing the relationship between interindividual variability in this trait and brain morphology. However, only healthy participants were recruited for these studies, and the results were heterogeneous. Methods: : To clarify the neural link between HA and MDD, we obtained magnetic resonance imaging data from the brains of 331 healthy people and 89 patients with MDD. Voxel-based morphometry (VBM) analyses were conducted to identify brain regions in which the gray matter volume was correlated with the HA score across participants and was simultaneously reduced in MDD patients. Results: : We found that the ventral part of the medial preferential cortex (vMPFC) fulfilled these criteria. Limitations: : The majority of the patients in this study were medicated with antidepressants. Conclusions: : The present finding suggests that reduced gray matter volume in this region is the neuropathology of high HA observed among MDD patients and might be the underlying reason why people with high HA are vulnerable to developing depression. Our findings may contribute to a deeper understanding of the neuropathology of MDD and provide insight into the brain regions of interest for predicting the development of the illness in the future.

Aim: We aimed to investigate the involvement of premorbid intelligence quotient in higher prevalence of smoking in patients with schizophrenia. Methods: Participants included 190 patients with schizophrenia (mean ± standard deviation age: 37.7 ± 10.8 years; 88 males and 102 females) and 312 healthy individuals (mean ± standard deviation age: 38.1 ± 13.8; 166 males and 146 females), matched for age, sex, and ethnicity (Japanese). Premorbid intelligence quotient was estimated using the Japanese Adult Reading Test and distress symptoms were assessed using the Hopkins Symptom Check List. Current smoking information was collected according to self-declarations. Results: As expected, the smoking rate was higher, while mean education level and Japanese Adult Reading Test scores were significantly lower, in patients with schizophrenia than in healthy individuals (p

Abstract Objective Our previous metabolomics study showed that the plasma nervonic acid levels were higher in patients with major depressive disorder (MDD) than those in healthy controls and patients with bipolar disorder (BD). To examine whether the nervonic acid levels differ in the central nervous system, we investigated the levels in the cerebrospinal fluid (CSF) of patients with MDD, BD, and healthy controls. Methods Nervonic acid levels in CSF were measured by gas chromatography time‐of‐flight mass spectrometry. The participants included 30 patients with MDD, 30 patients with BD, and 30 healthy controls. Results In contrast to our previous study, no significant differences were found in the nervonic acid level in the CSF among the patients with MDD, BD, and the healthy controls. Though no significant state‐dependent changes were found among the three groups, we did observe a significant negative correlation between the nervonic acid levels and depressive symptoms in the depressive state of patients with MDD and BD (r = −0.38, p = .046). Further, a significant positive correlation was found between the nervonic acid levels and manic symptoms in the manic state of patients with BD (r = 0.79, p = .031). Conclusion The nervonic acid levels in the CSF did not differ among the patients with MDD, BD, and the healthy controls; however, a significant negative correlation with depressive symptoms and a positive correlation with manic symptoms was observed. Thus, the nervonic acid levels in the CSF may be a candidate biomarker for mood symptoms.

Aim: Accumulating evidence suggests that neural inflammation plays an important role in psychiatric disorders. We aimed to identify inflammatory cytokines involved in the pathophysiology of such disorders by quantifying them in cerebrospinal fluid (CSF) samples from a large sample of patients with major psychiatric disorders and healthy controls.Methods: The subjects included 94 patients with schizophrenia, 68 with bipolar disorder, 104 with major depressive disorder, and 118 healthy controls, matched for age, sex, and ethnicity (Japanese). Lumbar puncture was performed to collect these CSF samples. A multiplex immunoassay was then performed to measure CSF cytokine levels using magnetic on-bead antibody conjugation for 19 inflammatory cytokines.Results: CSF interferon-β level was significantly higher in total psychiatric patients than in healthy controls (corrected p = 0.000029). In diagnostic group comparisons, CSF interferon-β level was significantly higher in patients with schizophrenia, or bipolar disorder (corrected p = 0.000047 or 0.0034) than in healthy controls.Conclusion: We present novel evidence that CSF IFN-β level showed prominent statistical differences between psychiatric groups and healthy controls. This suggests IFN-β as the most important player among the 19 cytokines tested here in the inflammation-related pathophysiology of major psychiatric disorders.

Pure Ti and Ti-6Al-4V alloy show high specific strength, excellent fatigue strength and good corrosion resistance; however, their poor wear resistance limits potentially wider application. To improve the wear resistance of pure Ti and Ti-6Al-4V alloy, they were reinforced with two types of titanium carbonitrides (TiC1-xNx), TiC0.3N0.7 (N rich) and TiC0.7N0.3 (C rich). The composites with 2.5, 5.0, 7.5 and 10.0 vol.% reinforcement were fabricated by spark plasma sintering (SPS). Dry wear tests of the composites were performed against a 10 mm-diameter high-carbon-chromium steel ball under 23 N normal load, at a sliding speed of 100 mm/s and a sliding distance of 500 m using a ball-on-disk configuration. The pure Ti and Ti-6Al-4V alloy matrix composites with TiC0.3N0.7 showed good wear resistance compared to the composites with TiC0.7N0.3. For the TiC0.3N0.7 reinforcement, the pure Ti matrix composite showed better wear resistance than the Ti-6Al-4V alloy matrix composite. The specific wear rate of the pure Ti matrix composite containing 10 vol.% TiC0.3N0.7 was almost zero. The amount of nitrogen diffused into the titanium matrix was higher than that of carbon diffused into the matrix. The Vickers hardnesses of the composites with TiC0.3N0.7 were higher than those of the composites with TiC0.7N0.3, due to the solid solution strengthening of the nitrogen in the Ti matrix. Therefore, the dry sliding wear characteristics of the titanium matrix composites depended on the amount of nitrogen diffused into the Ti matrix.

BackgroundThe Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III) is widely used to evaluate the intelligence quotient (IQ). We aimed to investigate the correlation between the WAIS-III metrics and whole-brain structures using magnetic resonance imaging.MethodsThe participants were 266 healthy, right-handed individuals (age: 45.6 ± 12.9 years, 98 males and 168 females). IQs were evaluated using the WAIS-III and Japanese Adult Reading Test (JART). Voxel-based morphometry and diffusion tensor imaging were performed to analyze the correlation of the WAIS-III metrics and JART score with the gray matter volume and white matter integrity, respectively.ResultsThe verbal IQ significantly and positively correlated with the left gyrus rectus and anterior cingulate gyrus, left posterior insula and planum polare, and left superior and middle frontal gyri volumes (p < 0.05, corrected). The verbal comprehension group index significantly and positively correlated with the left superior and middle frontal gyri, left gyrus rectus and anterior cingulate gyrus, and left middle frontal gyrus volumes, while the processing speed group index significantly and positively correlated with the bilateral various regional white matter fractional anisotropy values (p < 0.05, corrected). In contrast, the JART score showed no correlation with any brain structure.ConclusionThese results suggested the neurostructural bases of the WAIS-III IQs and group indices in the brain of healthy individuals.

Abstract Background Alzheimer’s disease (AD) is a most common dementia in elderly people. Since AD symptoms resemble those of other neurodegenerative diseases, including idiopathic normal pressure hydrocephalus (iNPH), it is difficult to distinguish AD from iNPH for a precise and early diagnosis. iNPH is caused by the accumulation of cerebrospinal fluid (CSF) and involves gait disturbance, urinary incontinence, and dementia. iNPH is treatable with shunt operation which removes accumulated CSF from the brain ventricles. Methods We performed metabolomic analysis in the CSF of patients with AD and iNPH with capillary electrophoresis-mass spectrometry. We assessed metabolites to discriminate between AD and iNPH with Welch’s t-test, receiver operating characteristic (ROC) curve analysis, and multiple logistic regression analysis. Results We found significant increased levels of glycerate and N-acetylneuraminate and significant decreased levels of serine and 2-hydroxybutyrate in the CSF of patients with AD compared to the CSF of patients with iNPH. The ROC curve analysis with these four metabolites showed that the area under the ROC curve was 0.90, indicating good discrimination between AD and iNPH. Conclusions This study identified four metabolites that could possibly discriminate between AD and iNPH, which previous research has shown are closely related to the risk factors, pathogenesis, and symptoms of AD. Analyzing pathway-specific metabolites in the CSF of patients with AD may further elucidate the mechanism and pathogenesis of AD.

Abstract Background Because soluble (or secreted) amyloid precursor protein-β (sAPPβ) and -α (sAPPα) possibly reflect pathological features of Alzheimer’s disease (AD), they are potential biomarker candidates for dementia disorders, including AD and mild cognitive impairment (MCI) due to AD (MCI-AD). However, controversial results have been reported regarding their alterations in the cerebrospinal fluid (CSF) of AD and MCI-AD patients. In this study, we re-assessed the utility of sAPPα and sAPPβ in CSF as diagnostic biomarkers of dementia disorders. Methods We used a modified and sensitive detection method to analyze sAPPs levels in CSF in four groups of patients: AD (N = 33), MCI-AD (N = 17), non-AD dementia (N = 27), and disease controls (N = 19). Phosphorylated tau (p-tau), total tau, and Aβ42 were also analyzed using standard methods. Results A strong correlation was observed between sAPPα and sAPPβ, consistent with previous reports. Both sAPPα and sAPPβ were highly correlated with p-tau and total tau, suggesting that sAPPs possibly reflect neuropathological changes in the brain. Levels of sAPPα were significantly higher in MCI-AD cases compared with non-AD and disease control cases, and those of sAPPβ were also significantly higher in MCI-AD and AD cases relative to other cases. A logistic regression analysis indicated that sAPPα and sAPPβ have good discriminative power for the diagnosis of MCI-AD. Conclusions Our findings collectively suggest that both sAPPs are pathologically relevant and potentially useful biomarkers for early and accurate diagnosis of dementia disorders. We also suggest that careful measurement is important in assessing the diagnostic utility of CSF sAPPs.

Major depressive disorder (MDD) is the most common psychiatric disorders. However, a biochemical marker has yet to be established for clinical purposes. It is proposed that lysophosphatidic acid (LPA, 1-acyl-2-sn-glycerol-3-phosphoate) plays some important roles in emotional regulation of experimental animals. Therefore, in this study, we measured LPA levels using enzyme-linked immunosorbent assays of cerebrospinal fluid (CSF) and plasma samples from patients with MDD. The participants were 52 patients and 49 normal healthy controls for CSF study, and 47 patients and 44 controls for plasma study. We used the Japanese version of the GRID Hamilton Depression Rating Scale (17-item version) for the assessment of depressive symptoms. We found no associations between LPA levels (CSF or plasma) and either diagnosis or severity of MDD, or with psychotropic medication. In conclusion, our data suggest that LPA levels likely would not serve as a practical biomarker of MDD.

Background: Although the pathophysiology of bipolar disorder remains elusive, growing evidence suggests the beneficial effects of Bifidobacterium and Lactobacillus in the gut microbiota on stress response and depressive symptoms. In the present study, we examined Bifidobacterium and Lactobacillus counts for association with bipolar disorder and serum cortisol levels.Methods: Bacterial counts in fecal samples were examined in 39 patients with bipolar disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edn. and 58 healthy controls using bacterial rRNA-targeted reverse transcription-quantitative polymerase chain reaction.Results: No significant difference was found in either bacterial counts between the two groups. However, we found a significantly negative correlation between Lactobacillus counts and sleep (ρ = −0.45, P = 0.01). Furthermore, a significant negative correlation was found between Bifidobacterium counts and cortisol levels (ρ = −0.39, P = 0.02) in the patients, although such a correlation was not found for Lactobacillus counts.Conclusions: Our results suggest that Bifidobacterium or Lactobacillus counts may not play a major role in the pathophysiology of bipolar disorder in our sample. However, the observed negative correlation between Lactobacillus counts and sleep and that between Bifidobacterium counts and serum cortisol levels point to the possible roles of these bacteria in sleep and stress response of the patients.

Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual’s background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases.

Cerebrospinal fluid (CSF) metabolites reflect biochemical diffusion/export from the brain and possibly serve as biomarkers related to brain disease severity, pathophysiology, and therapeutic efficacy/toxicity. Metabolomic studies using blood matrices have demonstrated interindividual and preanalytical variation of blood metabolites, whereas those of CSF metabolites remain unclear. In this study, we aimed to delineate the postprandial effects on CSF metabolites because fasting of patients with brain-related disorders is challenging. We collected pre- and postprandial (1.5, 3, and 6 h) plasma and CSF from nine healthy subjects. Using a mass-spectrometry-based global metabolomics approach, 150 and 130 hydrophilic metabolites and 263 and 340 lipids were detected in CSF and plasma, respectively. Principal component analysis of CSF hydrophilic metabolites and lipids primarily classified individual subjects at any time point, suggesting that the postprandial effects had a lower impact than interindividual variations on CSF metabolites. Individually, less than 10% of the CSF metabolites were putatively altered by postprandial effects (with either significant differences or over 2-fold changes, but not both) at any time point. Thus, global CSF metabolite levels are not directly associated with food intake, and except for several putatively altered CSF metabolites, postprandial effects are not a major concern when applying CSF metabolomics to screen biomarkers.

Background: The relationship between muscle strength and cognition in schizophrenia has not been well studied. We investigated the potential relationship of handgrip strength (HGS) score and body mass index (BMI) with cognitive function in patients with schizophrenia.Methods: Participants included 153 patients with schizophrenia (age: 36.9 ± 9.4 years; 82 males) and 328 healthy controls (age: 36.4 ± 10.7 years; 150 males), matched for age, sex, and ethnicity (Japanese). HGS was measured using a digital handgrip dynamometer. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia (BACS) test. A two-way multivariate analysis of covariance was used to compare HGS scores between the patient and control groups. Multiple regression analyses of BACS scores were performed in the patient and control groups using HGS and BMI scores as independent variables.Results: In the intergroup comparison, significantly lower HGS scores were observed in patients with schizophrenia than in healthy controls (p < 0.05, corrected). In the patient group, there was a significantly positive correlation between HGS scores and BACS composite score (male, p = 0.0014; female, p = 0.0051). However, BMI scores were significantly negatively correlated with the BACS composite score (male, p = 0.0022; female, p = 0.018). Furthermore, the ratio of HGS/BMI was significantly positively correlated with the BACS composite score in the patient group (p = 0.00000018).Conclusions: Cognitive function in patients with schizophrenia is correlated positively with HGS and negatively with BMI. HGS/BMI may thus be a good index for cognitive performance in schizophrenia.

Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition, modification of these metabolites by diet and/or medications may be a novel therapeutic target for depression. To clarify these aspects, clinical trials measuring metabolites before/after interventions should be conducted. Larger cohort studies including non-clinical subjects are also warranted to clarify our pilot findings.