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Gamma oscillations, thought to arise from the activity of ɣ‐aminobutyric acid (GABA)ergic interneurons, have potential as a biomarker for schizophrenia. Gamma‐band auditory steady‐state responses (ASSRs) are notably reduced in both chronic and early‐stage schizophrenia patients. Furthermore, alterations in gamma‐band ASSRs have been demonstrated in animal models through translational research. However, the 40‐Hz harmonic responses of the 20‐Hz ASSR are not as well‐characterized, despite the possibility that these harmonic oscillatory responses may reflect resonant activity in neural circuits. In this study, we investigated the 40‐Hz harmonic response to the 20‐Hz ASSR in the early stages of schizophrenia. The study recruited 49 participants, including 15 individuals at ultra‐high‐risk (UHR) for psychosis, 13 patients with first‐episode schizophrenia (FES), and 21 healthy controls (HCs). The 40‐Hz harmonic responses of the 20‐Hz ASSR were evident in all groups. Interestingly, while previous report observed reduced 40‐Hz ASSRs, the 40‐Hz harmonic responses of the 20‐Hz ASSR were not reduced in the UHR or FES groups. These findings suggest that the gamma‐band ASSR and its harmonic responses may represent distinct aspects of pathophysiology in the early stages of schizophrenia. [ABSTRACT FROM AUTHOR]

Schizophrenia is a heterogeneous psychiatric disorder characterized by positive symptoms such as hallucinations and delusions, negative symptoms such as anhedonia and flat affect, and cognitive impairment. Recently, glucuronate (GlucA) levels were reported to be significantly higher in serum of patients with schizophrenia than those in healthy controls. The accumulation of GlucA is known to be related to treatment-resistant schizophrenia, since GlucA is known to promote drug excretion by forming conjugates with drugs. However, the cause of GlucA accumulation remains unclear. Aldo-keto reductase family one member A1 (AKR1A1) is an oxidoreductase that catalyzes the reduction of GlucA. Genetic loss of AKR1A1 function is known to result in the accumulation of GlucA in rodents. Here, we aimed to explore genetic defects in AKR1A1 in patients with schizophrenia, which may result in the accumulation of GlucA. We identified 28 variants of AKR1A1 in patients with schizophrenia and control subjects. In particular, we identified a silent c.753G > A (rs745484618, p. Arg251Arg) variant located at the first position of exon 8 to be associated with schizophrenia. Using a minigene assay, we found that the c.753G > A variant induced exon 8 skipping in AKR1A1, resulting in a frameshift mutation, which in turn led to truncation of the AKR1A1 protein. Using the recombinant protein, we demonstrated that the truncated AKR1A1 completely lost its activity. Furthermore, we showed that AKR1A1 mRNA expression in the whole blood cells of individuals with the c.753G > A variant tended to be lower than that in those without the variants, leading to lower AKR activity. Our findings suggest that AKR1A1 carrying the c.753G > A variant induces exon skipping, leading to a loss of gene expression and enzymatic activity. Thus, GlucA patients with schizophrenia with the c.753G > A variant may show higher GlucA levels, leading to drug-resistant schizophrenia, since drug excretion by GlucA is enhanced. [ABSTRACT FROM AUTHOR]

Aim: Neuroimaging studies have revealed that patients with schizophrenia exhibit reduced gray matter volume in various regions. With these findings, various studies have indicated that structural MRI can be useful for the diagnosis of schizophrenia. However, multisite studies are limited. Here, we evaluated a simple model that could be used to differentiate schizophrenia from control subjects considering MRI scanner differences employing voxel‐based morphometry. Methods: Subjects were 541 patients with schizophrenia and 1252 healthy volunteers. Among them, 95 patients and 95 controls (Dataset A) were used for the generation of regions of interest (ROI), and the rest (Dataset B) were used to evaluate our method. The two datasets were comprised of different subjects. Three‐dimensional T1‐weighted MRI scans were taken for all subjects and gray‐matter images were extracted. To differentiate schizophrenia, we generated ROI for schizophrenia from Dataset A. Then, we determined volume within the ROI for each subject from Dataset B. Using the extracted volume data, we calculated a differentiation feature considering age, sex, and intracranial volume for each MRI scanner. Receiver–operator curve analyses were performed to evaluate the differentiation feature. Results: The area under the curve ranged from 0.74 to 0.84, with accuracy from 69% to 76%. Receiver–operator curve analysis with all samples revealed an area under the curve of 0.76 and an accuracy of 73%. Conclusion: We moderately successfully differentiated schizophrenia from control using structural MRI from differing scanners from multiple sites. This could be useful for applying neuroimaging techniques to clinical settings for the accurate diagnosis of schizophrenia. [ABSTRACT FROM AUTHOR]

Aim: Utena's Brief Objective Measures (UBOM) was developed to assess psychophysiological functions proximal to real‐world functioning in individuals with psychiatric disorders, including schizophrenia (SCZ), to facilitate shared decision‐making. However, the validity of UBOM has not been fully examined. Methods: We conducted a cross‐sectional observational study to evaluate the validity of each of the three tests in UBOM: UBOM‐Pulse, UBOM‐Ruler, and UBOM‐Random. We investigated associations: (i) between UBOM and existing cognitive‐ and autonomic‐function tests; and (ii) between UBOM and daily social functioning. The participants included SCZ individuals and healthy controls. We evaluated the cognitive and autonomic function using UBOM, the heart rate variability test, the simple reaction time test, and the Brief Assessment of Cognition in Schizophrenia, Japanese version. We also assessed the daily social functioning using the WHO Disability Assessment Schedule 2.0 and the modified Global Assessment of Functioning, Japanese version. Results: Thirty‐one SCZ individuals and 35 healthy control individuals participated in this study. In the SCZ group, UBOM‐Ruler was significantly associated with the Cognition and Getting Along domains of WHO Disability Assessment Schedule 2.0. UBOM‐Random was significantly associated with the Brief Assessment of Cognition in Schizophrenia's Working Memory, Verbal Fluency and Attention domains, and the modified Global Assessment of Functioning in the SCZ group. Conclusion: The validity of the current version of UBOM is imperfect and further improvements will be necessary to attain the originally intended goal of developing a brief assessment tool for real‐world functioning in SCZ. [ABSTRACT FROM AUTHOR]

Altered expression of mitochondria-related genes in postmortem brains of patients with bipolar disorder or schizophrenia, as revealed by large-scale DNA microarray analysis. Epigenetics reflects complex interactions between genes and the environment and plays a role in long-lasting gene expression changes. DNA methylation profiles were obtained with promoter tiling arrays covering 25 500 human promoters. We identified 91 DMRs and 69 DMR-associated genes in nonneurons and 74 DMRs and 59 DMR-associated genes in neurons (Tables S2 and S3). [Extracted from the article]

Aim Studies have shown that eye movement abnormalities are possible neurophysiological biomarkers for schizophrenia. The aim of this study was to investigate the utility of eye movement abnormalities in identifying patients with schizophrenia from healthy controls. Methods Eighty-five patients with schizophrenia and 252 healthy controls participated in this study. Eye movement measures were collected from free viewing, fixation stability, and smooth pursuit tests. In an objective and stepwise method, eye movement measures were extracted to create an integrated eye movement score. Results The discriminant analysis resulted in three eye movement measures; the scanpath length during the free viewing test, the horizontal position gain during the fast Lissajous paradigm of the smooth pursuit test, and the duration of fixations during the far distractor paradigm of the fixation stability test. An integrated score using these variables can distinguish patients with schizophrenia from healthy controls with 82% accuracy. The integrated score was correlated with Wechsler Adult Intelligence Scale-Third Edition full scale IQ, Positive and Negative Syndrome Scale scores, and chlorpromazine equivalents, with different correlation patterns in the three eye movement measures used. The discriminant analysis in subgroups matched for age, sex, years of education, and premorbid IQ revealed a sustained classification rate. Conclusion We established an integrated eye movement score with high classification accuracy between patients with schizophrenia and healthy controls, although there was a significant effect of medication. This study provides further evidence of the utility of eye movement abnormalities in schizophrenia pathology and treatment. [ABSTRACT FROM AUTHOR]

Aim Go/No-go derived event-related potential ( ERP) signals have been widely used in schizophrenia research to monitor self-control deficits in this disorder. However, no study to date has associated Go/No-go-related ERP with global functioning. Methods Participants consisted of 21 patients with schizophrenia and 22 healthy controls. We used a visual Go/No-go paradigm to measure Go/No-go-related N2/P3 ERP components by means of a 64-electrode cap for electroencephalogram recording. We used the Global Assessment of Functioning to evaluate global functioning and analyzed the correlation between ERP indices and global functioning scores. Results N2 amplitudes were reduced in patients with schizophrenia, but not influenced by either of the Go/No-go conditions. P3 amplitudes were influenced by the Go/No-go conditions, but not reduced in patients with schizophrenia. Global functioning was correlated with the No-go P3 amplitudes, but not N2 amplitudes, in patients with schizophrenia. Conclusion These results indicate that global functioning is associated with intact neural activity rather than impaired neural activity during Go/No-go response inhibition tasks in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

Aim Auditory mismatch negativity ( MMN) and its magnetoencephalographic ( MEG) counterpart ( MMNm) are an established biological index in schizophrenia research. MMN in response to duration and frequency deviants may have differential relevance to the pathophysiology and clinical stages of schizophrenia. MEG has advantage in that it almost purely detects MMNm arising from the auditory cortex. However, few previous MEG studies on schizophrenia have simultaneously assessed MMNm in response to duration and frequency deviants or examined the effect of chronicity on the group difference. Methods Forty-two patients with chronic schizophrenia and 74 matched control subjects participated in the study. Using a whole-head MEG, MMNm in response to duration and frequency deviants of tones was recorded while participants passively listened to an auditory sequence. Results Compared to healthy subjects, patients with schizophrenia exhibited significantly reduced powers of MMNm in response to duration deviant in both hemispheres, whereas MMNm in response to frequency deviant did not differ between the two groups. These results did not change according to the chronicity of the illness. Conclusion These results, obtained by using a sequence-enabling simultaneous assessment of both types of MMNm, suggest that MEG recording of MMN in response to duration deviant may be a more sensitive biological marker of schizophrenia than MMN in response to frequency deviant. Our findings represent an important first step towards establishment of MMN as a biomarker for schizophrenia in real-world clinical psychiatry settings. [ABSTRACT FROM AUTHOR]

Epidemiological studies have revealed that schizophrenia is highly heritable. However, genetic studies have not fully elucidated its etiology. Accumulating evidence suggests that epigenetic alterations may provide an additional explanation of its pathophysiology. We investigated the methylation profiles of DNA in peripheral blood cells from 18 patients with first-episode schizophrenia (FESZ) and from 15 normal controls. Schizophrenia patients were confined to those at the stage of first-episode psychosis. We analyzed the DNA methylation status of 27 578 CpG sites by means of the Illumina Infinium HumanMethylation27 BeadChip array. Differentially methylated CpG sites, which were particularly abundant within CpG islands, were enriched in genes related to the nuclear lumen, to transcription factor binding, and to nucleotide binding. We also observed differential methylation of the promoters of HTR1E and COMTD1, which are functionally related to genes found to be differentially methylated in schizophrenia patients in previous studies. Our results indicate the site-specific epigenetic alterations in patients with FESZ. [ABSTRACT FROM AUTHOR]

In alphabet-based language-speaking patients with schizophrenia, category fluency is disproportionately disturbed as compared with phonological fluency. Deficits in category and phonological fluency observed in Japanese patients, however, were similar. The aim of the present study was to replicate these findings by modifying the task to minimize the influence of lack of motivation and concentration in the patients. Similar deficits were found in both types of fluency in Japanese patients. Patients who speak Japanese have deficits in phonological fluency, compared with patients who speak alphabet-based languages, suggesting that the pattern of impairment in verbal fluency in schizophrenia is dependent on the specific language system. [ABSTRACT FROM AUTHOR]

Background: Although structural magnetic resonance imaging (MRI) studies have repeatedly demonstrated regional brain structural abnormalities in patients with schizophrenia, relatively few MRI-based studies have attempted to distinguish between patients with first-episode schizophrenia and healthy controls. Method: Three-dimensional MR images were acquired from 52 (29 males, 23 females) first-episode schizophrenia patients and 40 (22 males, 18 females) healthy subjects. Multiple brain measures (regional brain volume and cortical thickness) were calculated by a fully automated procedure and were used for group comparison and classification by linear discriminant function analysis. Results: Schizophrenia patients showed gray matter volume reductions and cortical thinning in various brain regions predominantly in prefrontal and temporal cortices compared with controls. The classifiers obtained from 66 subjects of the first group successfully assigned 26 subjects of the second group with accuracy above 80%. Conclusion: Our results showed that combinations of automated brain measures successfully differentiated first-episode schizophrenia patients from healthy controls. Such neuroimaging approaches may provide objective biological information adjunct to clinical diagnosis of early schizophrenia. [ABSTRACT FROM AUTHOR]

The structural abnormality of planum temporale (PT), a part of the superior temporal heteromodal association cortex involved in auditory and language processing, has been implicated in the pathophysiology of schizophrenia. However, its relationship to clinical manifestations remains unclear. Magnetic resonance images were obtained from 17 right-handed Japanese men with schizophrenia and from 22 age-, handedness-, and parental socioeconomic-status-matched healthy Japanese men in order to manually evaluate grey matter volumes of Heschl’s gyrus (HG) and PT. Psychiatric symptoms were assessed using positive and negative syndrome scale among the patients. Compared with healthy participants, patients with schizophrenia were associated with a statistically significant PT grey matter volume reduction without left or right lateralization, whereas HG volume was preserved. Smaller right PT volume was significantly correlated with more severe delusional behaviour in the patients. Previous investigations have focused on smaller-than-normal left PT in the pathophysiology of schizophrenia; however, the present results suggest a possible role of the right PT, which is involved in social cognition such as understanding the intentions of others, in the production of psychotic experiences in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined whether mismatch negativity (MMN) shows association with underlying auditory cortex gray matter at first hospitalization and progressive reduction longitudinally in schizophrenia patients. At first hospitalization for schizophrenia, MMN indexed left hemisphere Heschl gyrus gray matter volume, which is consistent with variable progression of pre-hospitalization cortical reduction.

Background: The Heschl gyrus and planum temporale have crucial roles in auditory perception and language processing. Our previous investigation using magnetic resonance imaging (MRI) indicated smaller gray matter volumes bilaterally in the Heschl gyrus and in left planum temporale in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis. We sought to determine whether there are progressive decreases in anatomically defined MRI gray matter volumes of the Heschl gyrus and planum temporale in patients with first-episode schizophrenia and also in patients with first-episode affective psychosis. Methods: At a private psychiatric hospital, we conducted a prospective high spatial resolution MRI study that included initial scans of 28 patients at their first hospitalization (13 with schizophrenia and 15 with affective psychosis, 13 of whom had a manic psychosis) and 22 healthy control subjects. Follow-up scans occurred, on average, 1.5 years after the initial scan. Results: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left Heschl gyrus (6.9%) and left planum temporale (7.2%) compared with patients with first-episode affective psychosis or control subjects. Conclusions: These findings demonstrate a left-biased progressive volume reduction in the Heschl gyrus and planum temporale gray matter in patients with first-episode schizophrenia in contrast to patients with first-episode affective psychosis and control subjects. Schizophrenia but not affective psychosis seems to be characterized by a postonset progression of neocortical gray matter volume loss in the left superior temporal gyrus and thus may not be developmentally fixed. [ABSTRACT FROM AUTHOR]

Background: The fusiform gyrus (FG), or occipitotemporal gyrus, is thought to subserve the processing and encoding of faces. Of note, several studies have reported that patients with schizophrenia show deficits in facial processing. It is thus hypothesized that the FG might be one brain region underlying abnormal facial recognition in schizophrenia. The objectives of this study were to determine whether there are abnormalities in gray matter volumes for the anterior and the posterior FG in patients with chronic schizophrenia and to investigate relationships between FG subregions and immediate and delayed memory for faces. Methods: Patients were recruited from the Boston VA Healthcare System, Brockton Division, and control subjects were recruited through newspaper advertisement. Study participants included 21 male patients diagnosed as having chronic schizophrenia and 28 male controls. Participants underwent high-spatial-resolution magnetic resonance imaging, and facial recognition memory was evaluated. Main outcome measures included anterior and posterior FG gray matter volumes based on high-spatial-resolution magnetic resonance imaging, a detailed and reliable manual delineation using 3-dimensional information, and correlation coefficients between FG subregions and raw scores on immediate and delayed facial memory derived from the Wechsler Memory Scale III. Results: Patients with chronic schizophrenia had overall smaller FG gray matter volumes (10%) than normal controls. Additionally, patients with schizophrenia performed more poorly than normal controls in both immediate and delayed facial memory tests. Moreover, the degree of poor performance on delayed memory for faces was significantly correlated with the degree of bilateral anterior FG reduction in patients with schizophrenia. Conclusion: These results suggest that neuroanatomic FG abnormalities underlie at least some of the deficits associated with facial recognition in schizophrenia. [ABSTRACT FROM AUTHOR]

Investigates the abnormalities in the preattentive perception of speech sounds in schizophrenic patients. Level on the amplitude of mismatch negativity for schizophrenic patients; Indication on the weak left temporal combination of current sink and source of schizophrenics; Phase on the occurrence of language-related dysfunction in schizophrenia.

Near-infrared spectroscopy (NIRS) is a noninvasive functional neuroimaging modality that can detect changes in blood oxygenation levels by tracking cortical neural activity. We recorded the resting-state brain activity of 24 individuals with schizophrenia and 90 healthy controls for 8 min using a whole-head NIRS arrangement and then used partial correlation analysis to estimate the resting-state functional connectivity (RSFC) between 17 cortical regions. We found that the RSFC between the bilateral orbitofrontal cortices (OFCs) and between the right temporal and parietal lobes was significantly higher in patients with schizophrenia than in healthy controls. The RSFC between the bilateral OFCs was positively correlated with negative symptom severity, whereas the RSFC between the right temporal and parietal lobes was positively correlated with the chlorpromazine equivalent for antipsychotics prescribed to patients with schizophrenia. This finding was consistent with that for the RSFC calculated using the anterior 52-channel signals. Our results suggest that NIRS-based RSFC measurements have potential clinical applications. [ABSTRACT FROM AUTHOR]

The article examines the relationship between patients' reasoning about medication adherence and neurocognitive and clinical indices for a treatment-compliant sample of Japanese patients with schizophrenia. The Rating of Medication Influences scale was used to assess subjective reasoning about medication adherence. Higher prevention scores were associated with lower executive functioning and older age.

Eye movement abnormalities have been reported in schizophrenia; however, their influences on everyday life remain unknown. From data on 69 subjects with schizophrenia and 246 healthy subjects, we found positive correlations between eye movement measures and work hours, which were only significant in subjects with schizophrenia. This relationship was also confirmed in a multi-site dataset including 118 subjects with schizophrenia and 280 healthy subjects. These findings further strengthen our understanding of eye movement abnormalities and their relevance in clinical recovery. [ABSTRACT FROM AUTHOR]

In Japan, schizophrenia was renamed in 2002 to reduce the stigma that people with schizophrenia are dangerous. However there has been little research on the potential anti-stigma effect of renaming. The present study aimed to examine whether portrayals of schizophrenia in newspapers as dangerous have been varied across renaming of the disease. To achieve this goal, newspaper articles containing the previous and new Japanese names for schizophrenia, published in the decades before and after the renaming, were identified through the database of the three largest Japanese national broadsheets. Identified articles were divided into two categories: a negative category, including a subcategory "danger"; and a positive category. Articles containing bipolar disorder were adopted as a control. The ratio of the number of articles on schizophrenia and danger to that of bipolar disorder was analysed as a variable of interest. The trend of this ratio was investigated to examine whether portrayals of schizophrenia changed after renaming. The search identified 4677 articles on schizophrenia, 53.0% of which were categorised as negative and 38.9% as danger. The search identified 525 articles on bipolar disorder, 24.6% of which were categorised as negative and 11.2% as danger. There was an increase of the ratio before schizophrenia was renamed (r=0.54, p=0.104), and a significant decrease after renaming (r=-0.69, p=0.028). Fisher's r-to-z transformation demonstrated a significant change in the trend of the ratio across renaming (Z=2.72, p=0.007). Renaming schizophrenia might be associated with mitigation in potentially stigmatised depiction of schizophrenia associated with violence in newspaper reports. [ABSTRACT FROM AUTHOR]

Abstract: The early growth response 3 (EGR3) gene is an immediate early gene that is expressed throughout the brain and has been suggested as a potential susceptibility gene for schizophrenia (SZ). EGR3 impairment is associated with various neurodevelopmental dysfunctions, and some animal studies have reported a role for EGR3 function in the prefrontal cortex. Therefore, EGR3 genotype variation may be reflected in prefrontal function. By using multi-channel near-infrared spectroscopy (NIRS) in an imaging genetics approach, we tested for an association between the EGR3 gene polymorphism and prefrontal hemodynamic response during a cognitive task in patients with SZ. We assessed 73 chronic patients with SZ and 73 age-, gender-, and genotype-matched healthy controls (HC) who provided written informed consent. We used NIRS to measure changes in prefrontal oxygenated hemoglobin concentration (oxyHb) during the letter version of a verbal fluency task (VFT). Statistical comparisons were performed among EGR3 genotype subgroups (rs35201266, GG/GA/AA). The AA genotype group showed significantly smaller oxyHb increases in the left dorsolateral prefrontal cortex (DLPFC) during the VFT than the GG and GA genotype groups; this was true for both patients with SZ and HC. Our findings provide in vivo human evidence of a significant influence of EGR3 polymorphisms on prefrontal hemodynamic activation level in healthy adults and in patients with SZ. Genetic variation in EGR3 may affect prefrontal function through neurodevelopment. This study illustrates the usefulness of NIRS in imaging genetics investigations on psychiatric disorders. [Copyright &y& Elsevier]

Abstract: Thought disorder is one of the primary symptoms in schizophrenia, yet the neural correlates and related semantic processing abnormalities remain unclear. We aimed to investigate the relationship between functional prefrontal abnormalities and thought disorder in schizophrenia using 2 types of verbal fluency tasks: the letter fluency task (LFT) and the category fluency task (CFT). Fifty-six adult patients with schizophrenia and 56 healthy controls matched for age, gender, and IQ participated in the study. During completion of the 2 types of verbal fluency tasks, we measured oxy- and deoxy-hemoglobin concentration ([oxy-Hb] and [deoxy-Hb]) signal changes over a wide area of the bilateral prefrontal cortex, using a 52-channel near-infrared spectroscopy (NIRS) system. Thought disorder scores were evaluated using the positive and negative syndrome scale. CFT performance was significantly higher than LFT performance in both groups, while there was no significant difference in any prefrontal NIRS signal changes between the 2 tasks in either group. In both versions of verbal fluency task, healthy controls exhibited a significantly greater NIRS signal change than did patients with schizophrenia. On the CFT only, left ventrolateral prefrontal NIRS [deoxy-Hb] signals were significantly associated with thought disorder scores in patients with schizophrenia. Our results suggest that left ventrolateral prefrontal abnormalities in category fluency might be related to thought disorder in schizophrenia. This could lead to an improved understanding of the neural mechanisms within the left ventrolateral prefrontal cortex involved in mediating semantic processing, as well as the relationship between semantic processing abnormalities and thought disorder in schizophrenia. [Copyright &y& Elsevier]

Abstract: Short forms (SF) of the Wechsler Intelligence Scale have been developed to enhance its practicality. However, only a few studies have addressed the Wechsler Intelligence Scale Revised (WAIS-R) SFs based on data from patients with schizophrenia. The current study was conducted to develop the WAIS-R SFs for these patients based on the intelligence structure and predictability of the Full IQ (FIQ). Relations to demographic and clinical variables were also examined on selecting plausible subtests. The WAIS-R was administered to 90 Japanese patients with schizophrenia. Exploratory factor analysis (EFA) and multiple regression analysis were conducted to find potential subtests. EFA extracted two dominant factors corresponding to Verbal IQ and Performance IQ measures. Subtests with higher factor loadings on those factors were initially nominated. Regression analysis was carried out to reach the model containing all the nominated subtests. The optimality of the potential subtests included in that model was evaluated from the perspectives of the representativeness of intelligence structure, FIQ predictability, and the relation with demographic and clinical variables. Taken together, the dyad of Vocabulary and Block Design was considered to be the most optimal WAIS-R SF for patients with schizophrenia, reflecting both intelligence structure and FIQ predictability. [Copyright &y& Elsevier]

Abstract: Background: A shorter duration of untreated psychosis in patients with schizophrenia results in better symptomatic and functional outcomes. Therefore, identifying biological markers in the early stages of psychosis is an important step toward early detection and intervention. Mismatch negativity (MMN) and P3a are leading candidate biomarkers. MMN measures differ in their sensitivity to varying deviants. However, this has not been fully addressed in assessing the early stages of psychosis. In the current study, we examined MMN/P3a to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of psychosis. To our knowledge, this is the first study that examined both MMN/P3a to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of psychosis. Methods: Participants consisted of 20 patients with first episode schizophrenia (FES), 21 ultra-high risk (UHR) individuals, and 22 healthy controls (HC). We measured dMMN/dP3a and fMMN/fP3a ERP components by means of a 64 electrodes-cap for EEG recording, and we used two-tone auditory oddball paradigms with 2000 stimuli. Results: The amplitude of dMMN was significantly reduced in FES and UHR compared to HC. The amplitude of fMMN showed no significant difference among the three groups. The amplitudes of dP3a and fP3a were significantly reduced in FES and UHR compared to HC. Conclusion: These findings suggest that dMMN may have higher sensitivity than fMMN whereas dP3a and fP3a may have similar sensitivity in the early stages of psychosis. [Copyright &y& Elsevier]

Abstract: Background: Patients with schizophrenia have auditory gating deficits; however, little is known about P50 auditory gating to human voices and its association with clinical symptoms. We examined the functioning of auditory gating and its relationship with the clinical symptoms in schizophrenia. Methods: Auditory evoked magnetoencephalography responses to the first and the second voices stimuli were recorded in 22 schizophrenia patients and 28 normal control subjects. The auditory gating ratios of P50m and N100m were investigated and P50m-symptom correlations were also investigated. Results: Patients showed significantly higher P50m gating ratios to human voices specifically in the left hemisphere. Moreover, patients with higher left P50m gating ratios showed more severe auditory hallucinations, while patients with higher right P50m gating ratios showed more severe negative symptoms. Conclusions: The present study suggests that schizophrenia patients have auditory gating deficits to human voices, specifically in the left hemisphere and auditory hallucinations of schizophrenia may be associated with sensory overload to human voices in the auditory cortex. [Copyright &y& Elsevier]

Abstract: Background: Brain morphometric measures from magnetic resonance imaging (MRI) have not been used to discriminate between first-episode patients with schizophrenia and healthy subjects. Methods: Magnetic resonance images were acquired from 34 (17 males, 17 females) first-episode schizophrenia patients and 48 (24 males, 24 females) age- and parental socio-economic status-matched healthy subjects. Twenty-nine regions of interest (ROI) were measured on 1-mm-thick coronal slices from the prefrontal and central parts of the brain. Linear discriminant function analysis was conducted using standardized z scores of the volumes of each ROI. Results: Discriminant function analysis with cross-validation procedures revealed that brain anatomical variables correctly classified 75.6% of male subjects and 82.9% of female subjects, respectively. The results of the volumetric comparisons of each ROI between patients and controls were generally consistent with those of the previous literature. Conclusions: To our knowledge, this study provides the first evidence of MRI-based successful classification between first-episode patients with schizophrenia and healthy controls. The potential of these methods for early detection of schizophrenia should be further explored. [Copyright &y& Elsevier]

Abstract: Previous diffusion tensor imaging (DTI) studies have shown structural abnormalities of the cingulum bundle (CB) in patients with schizophrenia. However, regional specificity and functional relevance of the pregenual and dorsal CB subdivisions has not been fully studied. In the current study, 31 patients with schizophrenia and 65 age- and gender-matched healthy subjects underwent DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) in cross sections of dorsal and pregenual CB tractography. To test the hypothesis of region-specific association with neurocognition, all of the patients and 31 controls performed the Stroop task, which is assumed to mainly involve dorsal cingulate function. The verbal memory subscale of Wechsler Memory Scale-Revised and premorbid IQs estimated from the Japanese version of the National Adult Reading Test, which were non-specific to dorsal cingulate function, were also employed as control neurocognitive indices. Significant bilateral FA reductions in the pregenual and dorsal CB, and bilateral MD increases in the dorsal CB were observed in the patients compared with the controls. As predicted, significant associations between DTI measures and neurocognition were found in the schizophrenia group only: double-dissociable correlation between higher MD in the dorsal, not in the pregenual CB, and a longer reaction time in the Stroop task, not verbal memory or premorbid IQs. The current DTI study suggests that structural disruption of the dorsal CB has region-specific functional relevance to selective attention deficits, although structural disruption also exists in the pregenual CB in patients with schizophrenia. [Copyright &y& Elsevier]

B Background: b Recent studies have revealed that the genome of human brain cells contains several kinds of somatic variations, such as single nucleotide variants (SNV), copy number variations (CNV) and novel insertions of retrotransposons. We isolated single neuronal nuclei from prefrontal cortex, amplified whole genomic DNA using microfluidic system (C1), and performed LINE-1 insertion analysis using DNA from single nuclei. [Extracted from the article]

Accumulating evidence suggests that aberrant epigenetic regulation is involved in the pathophysiology of major psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). We previously showed that the plasma level of betaine (N,N,N -trimethylglycine), a methyl-group donor, was significantly decreased in patients with first episode schizophrenia (FESZ). In this study, we identified decrease of global DNA methylation level in FESZ (N = 24 patients vs N = 42 controls), and found that global DNA methylation level was inversely correlated with scores on the global assessment of functioning (GAF) scale, and positively correlated with plasma betaine level. Notably, correlations between levels of betaine and its metabolites (N,N -dimethylglycine and sarcosine, N -methylglycine) were lower or lost in FESZ plasma, but remained high in controls. We further examined global DNA methylation levels in patients with chronic SZ (N = 388) and BD (N = 414) as well as controls (N = 430), and confirmed significant hypomethylation and decreased betaine level in SZ. We also found that patients with BD type I, but not those with BD type II, showed significant global hypomethylation. These results suggest that global hypomethylation associated with decreased betaine level in blood cells is common to SZ and BD, and may reflect common pathophysiology such as psychotic symptoms. • We identified decreased global DNA methylation in blood of patients with first episode schizophrenia (FESZ). • Methylation level in FESZ was inversely correlated with GAF, and positively correlated with plasma betaine level. • Decreased global DNA methylation and betaine levels were confirmed in chronic stage of schizophrenia. • Decreased global DNA methylation was also found in bipolar disorder I, suggesting an association with psychotic symptoms. [ABSTRACT FROM AUTHOR]