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Allergen immunotherapy (AIT), including SCIT and SLIT, is a treatment that involves the administration of allergens to which patients with allergic diseases have been sensitized. HDM-SCIT for asthma is indicated in cases of HDM-sensitized allergic asthma with normal lung function. HDM-SCIT improves asthma symptoms and AHR, and decreases the medication dose. Importantly, AIT can improve other allergic diseases complicated by asthma, such as allergic rhinitis, which can also contribute to the improvement of asthma symptoms. Several studies have suggested that HDM-SLIT also attenuates the risk of asthma exacerbations, and improves lung function in asthma cases with allergic rhinitis. Furthermore, AIT can modify the natural course of allergic diseases, including asthma. For example, the effects of AIT are maintained for at least several years after treatment discontinuation. AIT can prevent the onset of asthma when introduced in allergic rhinitis, and can also inhibit or reduce new allergen sensitizations. Recent data have suggested that AIT may suppress non-targeted allergen-induced immune responses in addition to targeted allergen-induced responses, and suppress infections of the lower respiratory tract by enhancing IFN responses., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Cognitive impairment associated with schizophrenia predicts poor functional outcomes, but currently no approved pharmacotherapy is available. This study investigated whether the glycine transporter-1 inhibitor BI 425809 improves cognition in patients with schizophrenia., Methods: This phase 2, randomised, double-blind, placebo-controlled, parallel-group trial (81 centres, 11 countries), randomly assigned outpatients (aged 18-50 years) with schizophrenia on stable treatment to add-on once-daily oral BI 425809 2 mg, 5 mg, 10 mg, or 25 mg or placebo (1:1:1:1:2) for 12 weeks. Treatment was assigned in blocks using interactive response technology; patients, investigators, and all trial personnel were masked to group assignment. The primary endpoint was change from baseline in MATRICS Consensus Cognitive Battery (MCCB) overall composite T-score at week 12. Six predefined dose-response models were evaluated using a multiple comparison procedure and modelling approach with mixed model repeated measures to assess evidence for a non-flat dose-response relationship for cognitive improvements with BI 425809. Adverse events were monitored. Safety analyses included all randomly allocated patients who received one or more doses of trial medication; efficacy analyses included patients from this set who also had available baseline data and at least one post-baseline on-treatment measurement for the primary or secondary endpoint. This study is registered with ClinicalTrials.gov, number NCT02832037., Findings: 509 patients were randomly assigned between April 25, 2018, and Oct 4, 2019 (BI 425809 2 mg, n=85; 5 mg, n=84; 10 mg, n=85; 25 mg, n=85; placebo, n=170 444 (87%) completed the 12-week treatment. Five of six dose-response models showed a statistically significant benefit of BI 425809 over placebo (linear [t=2·55, p=0·015], linear in log [t=2·56, p=0·015]; Emax [t=2·75, p=0·0089], sigmoid Emax [t=2·98, p=0·0038], logistic [t=2·77, p=0·0085]). Pairwise comparisons showed greater mean improvement from baseline in MCCB overall composite T-score at week 12 with BI 425809 10 mg and 25 mg versus placebo (adjusted mean difference 1·98 [95% CI 0·43-3·53] for 10 mg and 1·73 [0·18-3·28] for 25 mg; standardised effect size 0·34 for 10 mg and 0·30 for 25 mg). Adverse events were balanced across groups, reported in 50 (59%) of 85 patients on BI 425809 2 mg, 44 (52%) of 84 on 5 mg, 35 (41%) of 85 on 10 mg, 36 (42%) of 85 on 25 mg, and 74 (44%) of 170 on placebo., Interpretation: BI 425809 improved cognition after 12 weeks in patients with schizophrenia; doses of 10 mg and 25 mg showed the largest separation from placebo. If these encouraging results are confirmed in phase 3 trials, BI 425809 could provide an effective treatment for cognitive impairment associated with schizophrenia., Funding: Boehringer Ingelheim., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Condition of asthma in patients with asthma and concomitant seasonal allergic rhinitis (SAR) deteriorates during the Japanese cedar pollen (JCP) season. However, the underlying mechanisms remain unclear., Methods: We analyzed seasonal variations in eicosanoid levels in the airways of patients with asthma and concomitant SAR sensitized to JCP (N = 29, BA-SAR-JCP group) and those not sensitized (N = 13, BA-AR-non-JCP group) during the JCP season. The association between changes in eicosanoid concentrations and pulmonary function was assessed. Exhaled breath condensate (EBC) was collected, and pulmonary function tests were performed during the JCP and non-JCP seasons. The cysteinyl leukotriene (CysLT), thromboxane B 2 (TXB 2 ), prostaglandin D 2 -methoxime (PGD 2 -MOX), and leukotriene B 4 (LTB 4 ) levels in the collected EBC were measured via enzyme-linked immunosorbent immunoassays., Results: The log CysLT levels significantly increased in the BA-SAR-JCP group during the JCP season compared with the non-JCP season (1.78 ± 0.55, 1.39 ± 0.63 pg/mL, mean ± standard deviation, respectively, p = 0.01) and those in the BA-AR-non-JCP group during the JCP season (1.39 ± 0.38 pg/mL, p = 0.04). Moreover, the log TXB 2 levels seemed to increase. However, the log LTB 4 and log PGD 2 -MOX levels did not increase. The changes in the log CysLT levels during the two seasons were negatively correlated to forced expiratory volume in one second (FEV 1 ) in the BA-SAR-JCP group (r = -0.52, p < 0.01)., Conclusions: In the BA-SAR-JCP group, seasonal increases in eicosanoid levels in the airway likely promoted deterioration in pulmonary function despite optimal maintenance treatment., (Copyright © 2020 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Severe asthma is a complex disease with heterogeneous features and involves type 2 airway inflammation, including eosinophil accumulation. Surrogate biomarkers, fraction of exhaled nitric oxide (FeNO) and blood eosinophil count (b-EOS), may predict eosinophilic airway inflammation. Here we investigated clinical characteristics of severe asthma phenotype using a combined analysis of FeNO and b-EOS., Methods: This retrospective study examined clinical data of patients with severe asthma (N = 107; median age, 64 years) treated at Saitama Medical University Hospital from 2009 to 2016. Thresholds of FeNO and b-EOS for sputum eosinophil ratio ≥2% were determined using receiver operating characteristic curve (ROC) analysis. Clinical characteristics were analyzed after classifying patients into four subgroups according to these thresholds., Results: Of 39 induced sputum samples examined, ROC area under the curve for predicting sputum eosinophilia was 82.0% (p = 0.001) for b-EOS and 77.0% (p = 0.006) for FeNO at optimal cut-off values of ≥300/μL and ≥25 ppb, respectively. The number of sensitized allergens was higher in the high FeNO/low b-EOS and high FeNO/high b-EOS subgroups (p < 0.05). The prevalence of chronic sinusitis was higher in the low FeNO/high b-EOS and high FeNO/high b-EOS subgroups (p = 0.04). The high FeNO/high b-EOS subgroup included the largest proportion (approximately 40%) of patients experiencing frequent severe exacerbations. Both low FeNO/low b-EOS and high FeNO/low b-EOS subgroups showed less severe exacerbations., Conclusions: Combined evaluation of FeNO and b-EOS can identify patients with frequent exacerbations and stratify the appropriate therapy for type 2 inflammation-predominant severe asthma., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Inflammation has been implicated in a variety of psychiatric disorders. We aimed to determine whether levels of complement C5 protein in the cerebrospinal fluid (CSF), which may reflect activation of the complement system in the brain, are altered in patients with major psychiatric disorders. Additionally, we examined possible associations of CSF C5 levels with clinical variables. Subjects comprised 89 patients with major depressive disorder (MDD), 66 patients with bipolar disorder (BPD), 96 patients with schizophrenia, and 117 healthy controls, matched for age, sex, and ethnicity (Japanese). Diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria. CSF C5 levels were measured by enzyme-linked immunosorbent assay. CSF C5 levels were significantly increased in the patients with MDD (p < 0.001) and in the patients with schizophrenia (p = 0.001), compared with the healthy controls. The rate of individuals with an "abnormally high C5 level" (i.e., above the 95th percentile value of the control subjects) was significantly increased in all psychiatric groups, relative to the control group (all p < 0.01). Older age, male sex, and greater body mass index tended to associate with higher C5 levels. There was a significantly positive correlation between C5 levels and chlorpromazine-equivalent dose in the patients with schizophrenia. Thus, we found, for the first time, elevated C5 levels in the CSF of patients with major psychiatric disorders. Our results suggest that the activated complement system may contribute to neurological pathogenesis in a portion of patients with major psychiatric disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Recent evidence has suggested that the innate immune response may play a role in the development of eosinophilic airway inflammation. We previously reported that uric acid (UA) and adenosine triphosphate (ATP), two important damage-associated molecular pattern molecules (DAMPs), activate eosinophil functions, suggesting that these molecules may be involved in the development of eosinophilic airway inflammation. The objective of this study was to measure the concentrations of DAMPs including UA and ATP in the bronchoalveolar lavage fluid (BALF) of patients with eosinophilic pneumonia (EP)., Methods: BAL was performed in patients with EP including acute and chronic eosinophilic pneumonia, and in patients with hypersensitivity pneumonia, and sarcoidosis. UA, ATP, and cytokine concentrations in the BALF were then measured., Results: The UA concentration was increased in the BALF of EP patients. UA concentrations correlated with eosinophil numbers, and with eosinophil-derived neurotoxin and interleukin (IL)-5 concentrations. Furthermore, the ATP concentration was increased in the BALF of EP patients and ATP concentrations correlated with UA concentrations. Moreover, IL-33 was increased in EP patients and IL-33 concentrations correlated with UA and ATP concentrations., Conclusions: The UA and ATP concentration was increased in the BALF of EP patients. UA concentrations correlated with eosinophil numbers, and with ATP and IL-33 concentrations. Our findings suggest that DAMPs such as UA and ATP play a role in the pathogenesis of EP., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

A core feature of schizophrenia (SCZ) is impairment in intrinsic motivation. Although intrinsic motivation plays an important role in enhancing improvement of the social functioning, its neural mechanisms of impairment have yet to be clarified. We hypothesized that abnormal function of the frontostriatal loop consisting of the striatum and lateral prefrontal cortex (LPFC) may be related to impaired intrinsic motivation in SCZ. We tested this by comparing the brain activity measured by functional magnetic resonance imaging and behavioral parameters associated with movement, motivation, and cognitive control between 18 stable SCZ patients and 17 healthy control (HC) participants during a task that elicits intrinsic motivation. We also compared the functional connectivity during resting-state and the fractional anisotropy using diffusion tensor imaging analysis between the two groups. We adopted an enjoyable timing task to stop a stopwatch at an exact time, which in our previous study has demonstrated to elicit intrinsic motivation. Although the performance level in general was not different between groups, the SCZ group performed worse than the HC group in trials following "overshoot" errors (i.e., the response was too late). SCZ participants showed lower intrinsic motivation to the task than the HC group in an inventory report. The striatal activity during the prediction at the task cue period was consistently lower in SCZ participants than in HC. The LPFC activity at the task cue period positively correlated with intrinsic motivation and also with the rate of success following overshoot errors in the HC group, but not in the SCZ group. The LPFC activity at the task cue period was also positively correlated with the striatal activity in both groups. The striatal activity during the feedback period was not significantly different between groups. These results suggest that, unlike HC, the neural activity in the LPFC fails to mediate between prediction of hedonic events and cognitive control of action plans in SCZ, whereas the hedonic response is retained.

Background: Eosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins, complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood., Methods: We examined migration, adhesion, superoxide production and degranulation of human eosinophils. Isolated eosinophils were incubated with monosodium urate (MSU) crystals and ATPγS, a non-hydrolysable ATP analogue. To determine the involvement of P2 or P2Y2 receptors in eosinophil responses to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP (oATP), or anti-P2Y2 antibody before incubation with MSU crystals or ATPγS., Results: MSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced production of superoxide. oATP abolished eosinophil responses to MSU crystals, suggesting involvement of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATPγS, induced migration of eosinophils through a model basement membrane, adhesion to rh-ICAM-1, superoxide generation, and degranulation of eosinophil-derived neurotoxin (EDN). oATP and anti-P2Y2 significantly reduced these eosinophil responses., Conclusions: ATP serves as an essential mediator of functional responses in human eosinophils. Eosinophil responses to ATP may be implicated in airway inflammation in patients with asthma., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Eosinophils play important roles in the development of asthma exacerbation. Viral infection is a major cause of asthma exacerbation, and the expression of IFN-γ-inducible protein of 10 kDa (IP-10) and cysteinyl leukotrienes (cysLTs) is up-regulated in virus-induced asthma. As β2-adrenergic agonists, such as formoterol or salbutamol, are used to treat asthma exacerbation, we examined whether formoterol or salbutamol could modify eosinophil functions such as adhesiveness, particularly those activated by cysLTs or IP-10., Methods: Eosinophils were isolated from the blood of healthy subjects and were pre-incubated with either formoterol or salbutamol, and subsequently stimulated with IL-5, LTD4, or IP-10. Adhesion of eosinophils to intercellular cell adhesion molecule (ICAM)-1 was measured using eosinophil peroxidase assays. The generation of eosinophil superoxide anion (O2(-)) was examined based on the superoxide dismutase-inhibitable reduction of cytochrome C. Eosinophil-derived neurotoxin (EDN) release was evaluated by ELISA as a marker of degranulation., Results: Neither formoterol nor salbutamol suppressed the spontaneous adhesion of eosinophils to ICAM-1. However, when eosinophils were activated by IL-5, LTD4, or IP-10, formoterol, but not salbutamol, suppressed the adhesion to ICAM-1. Formoterol also suppressed IL-5, LTD4, or IP-10 induced eosinophil O2(-) generation or EDN release., Conclusions: These findings suggest that formoterol, but not salbutamol, suppresses eosinophil functions enhanced by IL-5, LTD4, or IP-10. As these factors are involved in the development of asthma exacerbation, our results strongly support the hypothesis that administration of formoterol is a novel strategy for treating asthma exacerbation., (Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Perillyl alcohol (POH) is an isoprenoid which inhibits farnesyl transferase and geranylgeranyl transferase, key enzymes that induce conformational and functional changes in small G proteins to conduct signal production for cell proliferation. Thus, it has been tried for the treatment of cancers. However, although it affects the proliferation of immunocytes, its influence on immune responses has been examined in only a few studies. Notably, its effect on antigen-induced immune responses has not been studied. In this study, we examined whether POH suppresses Ag-induced immune responses with a mouse model of allergic airway inflammation. POH treatment of sensitized mice suppressed proliferation and cytokine production in Ag-stimulated spleen cells or CD4(+) T cells. Further, sensitized mice received aerosolized OVA to induce allergic airway inflammation, and some mice received POH treatment. POH significantly suppressed indicators of allergic airway inflammation such as airway eosinophilia. Cytokine production in thoracic lymph nodes was also significantly suppressed. These results demonstrate that POH suppresses antigen-induced immune responses in the lung. Considering that it exists naturally, POH could be a novel preventive or therapeutic option for immunologic lung disorders such as asthma with minimal side effects., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Many neuropsychological studies demonstrate impairment of working memory in patients with major depressive disorder (MDD). However, there are not enough functional neuroimaging studies of MDD patients seeking for the underlying brain activity relevant to working memory function. The objective of this study is to evaluate prefrontal hemodynamic response related to working memory function in patients with MDD. Twenty-four subjects with MDD and 26 age- and gender-matched healthy subjects were recruited for the present study. We measured hemoglobin concentration changes in the prefrontal and superior temporal cortical surface areas during the execution of working memory task (WM; 2-back, letter version) using 52-channel near-infrared spectroscopy (NIRS), which enables real-time monitoring of task-related changes in cerebral blood volumes in the cortical surface areas. MDD patients showed a smaller increase in lateral prefrontal and superior temporal cortex activation during the 2-back task and associated poorer task performance than healthy controls. The results coincided with previous findings in terms of working memory deficits and prefrontal cortex dysfunction in MDD patients, but contradicted with some previous fMRI studies that suggested increased cortical activity during the working memory task in patients with depression. The contradiction may, in part, be explained by a relatively low level of cognitive demand imposed on the subjects in the present study., (Copyright © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.)

Allergen immunotherapy targets Th2 cells activated by specific allergens, which constitutes the basis of allergic disease. Therefore, this approach has therapeutic potential for a variety of allergic diseases, including asthma, and may modify their natural course. Immunotherapy results in systemic immunological changes to allergens, thereby providing clinical benefits in allergic asthma. For example, immunotherapy attenuates T-cell-mediated airway inflammation by down-modulating Th2 and inducing Th1 differentiation. In addition, immunotherapy induces regulatory T cells, which produce IL-10. Meta-analysis has demonstrated that allergen immunotherapy improves clinical symptoms and non-specific airway hyperresponsiveness in asthma, and decreases drug requirements. Clinical studies have supported the usefulness if immunotherapy in mild to moderate asthma cases, particularly in patients with concomitant rhinitis. Several promising novel approaches have emerged as future immunotherapeutic strategies for the treatment of asthma. Current pharmacotherapy, including inhalational corticosteroids, provides powerful anti-symptomatic benefits in asthma; however, pharmacotherapy cannot cure or modify the natural course of asthma. As immunotherapy targets the background immunological state in asthma, it is expected to lead to long-term amelioration or cure. It is hoped that the positioning of allergen immunotherapy as a treatment option will allow the comprehensive management of symptoms in allergic individuals, and the modification of disease course.

Objective: With the aim of investigating gender differences in the functional lateralization subserving preattentive processing of language stimuli, we compared auditory mismatch negativities (MMNs) using dichotic listening tasks., Methods: Forty-four healthy volunteers, including 23 males and 21 females, participated in the study. MMNs generated by pure-tone and phonetic stimuli were compared, to check for the existence of language-specific gender differences in lateralization. Both EEG amplitude and scalp current density (SCD) data were analyzed., Results: With phonetic MMNs, EEG findings revealed significantly larger amplitude in females than males, especially in the right hemisphere, while SCD findings revealed left hemisphere dominance and contralateral dominance in males alone. With pure-tone MMNs, no significant gender differences in hemispheric lateralization appeared in either EEG or SCD findings., Conclusion: While males exhibited left-lateralized activation with phonetic MMNs, females exhibited more bilateral activity. Further, the contralateral dominance of the SCD distribution associated with the ear receiving deviant stimuli in males indicated that ipsilateral input as well as interhemispheric transfer across the corpus callosum to the ipsilateral side was more suppressed in males than in females., Significance: The findings of the present study suggest that functional lateralization subserving preattentive detection of phonetic change differs between the genders. These results underscore the significance of considering the gender differences in the study of MMN, especially when phonetic stimulus is adopted. Moreover, they support the view of Voyer and Flight [Voyer, D., Flight, J., 2001. Gender differences in laterality on a dichotic task: the influence of report strategies. Cortex 37, 345-362.] in that the gender difference in hemispheric lateralization of language function is observed in a well-managed-attention condition, which fits the condition adopted in the MMN measurement; subjects are required to focus attention to a distraction task and thereby ignore the phonetic stimuli that elicit MMN.

Objective: Autism is a form of pervasive developmental disorder in which dysfunction in interpersonal relationships and communication is fundamental. This study evaluated neurophysiological abnormalities at the basic level of language processing, i.e. automatic change detection of speech and non-speech sounds, using magnetoencephalographic recording of mismatch response elicited by change in vowels and tones., Methods: The auditory magnetic mismatch field (MMF) was evaluated in 9 adults with autism and 19 control subjects using whole-head magnetoencephalography. The MMF in response to the duration change of a pure tone or vowel /a/ and that in response to across-phoneme change between vowels /a/ and /o/, were recorded., Results: The groups were not significantly different in MMF power under any conditions. However, the autism group showed a left-biased latency prolongation of the MMF particularly under the across-phoneme change condition, and this latency delay was significantly associated with greater symptom severity., Conclusions: These results suggest that adults with autism are associated with delayed processing for automatic change detection of speech sounds. These electrophysiological abnormalities at the earliest level of information processing may contribute to the basis for language deficits observed in autism., Significance: These results provide the first evidence for delayed latency of phonetic MMF in adults with autism.

We previously demonstrated that event-related potentials (ERPs), such as N1/N2b amplitudes in an auditory selective attention task, were significantly associated with communication skills of schizophrenia. The present study investigated the relationship between N1/N2b amplitudes and the quality of life (QOL) 5 years after ERP measurement. QOL of 15 patients with schizophrenia was assessed using the quality of life scale (QLS). Correlational analyses revealed a significant relationship between N2b, but not N1, amplitude and specific domains of QOL. N2b amplitude, an electrophysiological index of orienting response, may be associated with longitudinal social functioning outcome in schizophrenia.

This paper reviews recent empirical findings related to prefrontal and executive function in unipolar depression. While a number of reviews have dealt with either the neuropsychological literature or findings from imaging studies, the present review addresses both, as well as findings from studies that have combined brain-imaging techniques with neuropsychological measures. This combined approach is of great interest as the performance of a structured task may act to load the areas of interest and reduce variance, thus making the imaging evidence more valuable; while the use of imaging provides a check that the neuropsychological tasks are indeed engaging the structures whose performance they are intended to assess. Prominent models of the neurobiology of depression implicate involvement of the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). The evidence from combined imaging and neuropsychological studies supports the involvement of the ACC, but is less clear in the case of the DLPFC. However, the limited number of such studies conducted to date means that conclusions must be tentative and further studies employing this combined approach may be of great value.

Corollary discharge is a brain electrical activity associated with self-monitoring, which distinguishes self from others in thoughts or behaviors. Corollary discharge can be non-invasively assessed using event-related potential (ERP) recordings in humans. Previous studies have revealed that the amplitude of the N100 component elicited during an "odd-ball" task is reduced while a healthy subject is vocalizing, which may index the effect of corollary discharge on auditory ERPs. In this study, we attempted to assess the effect of vocalization on ERP components including N100, mismatch negativity (MMN), negative difference wave (Nd), and P300 during a selective attention task in 22 healthy adults. We also evaluated the possible contribution of gender to these effects. N100 amplitudes elicited by unattended standard stimuli were reduced under the vocalization condition compared with those under the baseline condition. However, there were no significant effects of vocalization on MMN, Nd or P300. Moreover, there was no significant effect of gender to the corollary discharge. These results suggest that the effect of corollary discharge on auditory ERPs is limited to the perceptual stage of information processing in healthy men and women.

The continuous performance test (CPT) provides a reliable index of cognitive function, but it is still unclear what aspects of processing this test measures. This study aimed to investigate the contribution of different aspects of cognitive function to the performance on degraded stimulus CPT (DSCPT), which requires a higher level of mental effort than the conventional CPT. Event-related potential (ERP) components, MMN, N2b, and early and late Nds were measured at 16 electrode sites in 19 right-handed normal volunteers using an auditory selective attention task. The association between CPT sensitivity ratings (sensitivity A') and amplitudes of each component was examined for each electrode site. The CPT sensitivity A' showed a significant positive correlation with the N2b amplitude in the fronto-central and temporal regions, predominantly in the right hemisphere and specifically to the right ear of stimulation. This finding suggests that the controlled deviance detection process was related to DSCPT performance.

Schizophrenia is a major mental disorder, characterized by their set of symptoms, including hallucinatory-delusional symptoms, thought disorder, emotional flattening, and social withdrawal. Since 1980s, advances in neuroimaging and neurophysiological techniques have provided tremendous merits for investigations into schizophrenia as a brain disorder. In this article, we first overviewed neuroanatomical studies using structural magnetic resonance imaging (s-MRI), MR spectroscopy (MRS), and postmortem brains, followed by neurophysiological studies using event-related potentials (ERPs) and magnetoencephalography (MEG), in patients with schizophrenia. Evidences from these studies suggest that schizophrenia is a chronic brain disorder, structurally and functionally affecting various cortical and subcortical regions involved in cognitive, emotional, and motivational aspects of human behavior. Second, we reviewed recent investigations into neurobiological basis for schizophrenic symptoms (auditory hallucinations and thought disorder) using these indices as well as hemodynamic assessments such as positron emission tomography (PET) and functional MRI (f-MRI). Finally, we addressed the issue of the heterogeneity of schizophrenia from the neurobiological perspective, in relation to the neuroanatomical and neurophysiological measures.

Objective: Many studies have demonstrated mismatch negativity (MMN) attenuation in schizophrenia. Recently, investigators have shown that GABAergic inhibitory neurons may regulate MMN generation. Considering that a substantial proportion of schizophrenic patients receive anxiolytics and hypnotics that have affinity to GABA(A) receptors to reduce their comorbid symptoms of anxiety and sleep disturbances, we need to assess whether anxiolytics/hypnotics might affect their MMN generation. The aim of this study is to assess the possibility that high or low doses of anxiolytics/hypnotics received by schizophrenic subjects affect their mismatch negativity (MMN), using event-related potentials (ERPs) and magnetoencephalography (MEG)., Methods: Twenty-three and 16 patients with schizophrenia participated in the ERP and MEG studies, respectively. Three types of MMN (MMN in response to a duration change of pure-tone stimuli, within-category vowel change (Japanese vowel /a/ with short versus long duration), and across-category vowel change (vowel /a/ versus /o/)) were recorded., Results: High or low doses of benzodiazepine had no significant effects on MMN amplitude/magnetic MMN power, topography/laterality, or latency under any conditions of the ERP or MEG study., Conclusions: These results suggest that chronic administration of anxiolytics/hypnotics does not significantly affect MMN in schizophrenia.