Search

Alcohol dependence is a disorder with a high recurrence rate that leads to a considerable public health burden. The risk of relapse appears to be related to a complex interplay of multiple factors. Herein, we aimed to explore the potential neural predictors of relapse in Chinese male patients with alcohol dependence. This study enrolled 58 male patients with alcohol dependence who had undergone acute detoxification. General demographic information and clinical features were collected. Magnetic resonance imaging data were used to measure cortical thickness across 34 regions of the brain. Patients were followed up at six months, and 51 patients completed the follow-up visit. These patients were divided into a relapser and an abstainer group. A binary logistic regression analysis was performed to investigate the potential risk factors of relapse. Compared to abstainers, relapsers showed higher inattention and non-planning impulsivity on the 11th version of the Barratt Impulsive Scale. The cortical thicknesses of the inferior-parietal lobules were significantly higher in abstainers compared with those in relapsers. Furthermore, binary logistic regression analysis showed that the thickness of the inferior parietal lobule predicted relapse, and lower non-planning impulse was a protective factor against relapse. Relapsers show poorer impulse control than abstainers, and structural magnetic resonance imaging revealed a decreased thickness of the inferior parietal lobule in relapsers. Our results indicate the thickness of the inferior parietal lobule as a potential relapse predictor in male patients with alcohol dependence., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Patients with schizophrenia have patterns of brain deficits including reduced cortical thickness, subcortical gray matter volumes, and cerebral white matter integrity. We proposed the regional vulnerability index (RVI) to translate the results of Enhancing Neuro Imaging Genetics Meta-Analysis studies to the individual level. We calculated RVIs for cortical, subcortical, and white matter measurements and a multimodality RVI. We evaluated RVI as a measure sensitive to schizophrenia-specific neuroanatomical deficits and symptoms and studied the timeline of deficit formations in: early (≤5 years since diagnosis, N = 45, age = 28.8 ± 8.5); intermediate (6-20 years, N = 30, age 43.3 ± 8.6); and chronic (21+ years, N = 44, age = 52.5 ± 5.2) patients and healthy controls (N = 76, age = 38.6 ± 12.4). All RVIs were significantly elevated in patients compared to controls, with the multimodal RVI showing the largest effect size, followed by cortical, white matter and subcortical RVIs (d = 1.57, 1.23, 1.09, and 0.61, all p < 10 -6 ). Multimodal RVI was significantly correlated with multiple cognitive variables including measures of visual learning, working memory and the total score of the MATRICS consensus cognitive battery, and with negative symptoms. The multimodality and white matter RVIs were significantly elevated in the intermediate and chronic versus early diagnosis group, consistent with ongoing progression. Cortical RVI was stable in the three disease-duration groups, suggesting neurodevelopmental origins of cortical deficits. In summary, neuroanatomical deficits in schizophrenia affect the entire brain; the heterochronicity of their appearance indicates both the neurodevelopmental and progressive nature of this illness. These deficit patterns may be useful for early diagnosis and as quantitative targets for more effective treatment strategies aiming to alter these neuroanatomical deficit patterns., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Background: Animal and neuroimaging studies suggest that the volume of the motor-circuit region decreases in tardive dyskinesia (TD). This study examined the differences in functional connectivity within the motor circuit of patients with schizophrenia with and without TD to further clarify how the dysfunction is related to the pathogenesis of TD., Methods: Functional magnetic resonance images were taken of 56 schizophrenic patients with TD (TD group), 64 without TD (non-TD group), and 68 healthy controls (HC group). The motor-circuit area was selected as the seed region for a whole brain resting-state functional connectivity (rsFC) analysis. Psychopathological symptoms and TD severity were assessed with the Positive and Negative Syndrome Scale (PANSS) and Abnormal Involuntary Movement Scale (AIMS), respectively. Group differences and correlations among 18 brain regions of interest (e.g., the global strength of connectivity between two regions) were analyzed., Results: The analysis of variance results were as follows: The three groups exhibited rsFC losses in the left primary motor cortex, bilateral parietal cortices, right postcentral gyrus, right putamen, right superior parietal lobule, right supplementary motor area and bilateral thalami (false discovery rate,p < 0.05). The TD group showed a significant rsFC loss between the right postcentral gyrus and the inferior frontal gyrus of the left triangular part when compared with the non-TD group (AlphaSim, p < 0.001), which was negatively correlated with the AIMS total score (r=-0.259, p = 0.03)., Conclusions: These findings may suggest dysfunction of the postcentral and inferior frontal gyri of the triangular part in patients with schizophrenia and TD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning)., Competing Interests: Declaration of competing interest AB has consulting fees from Biogen and lecture fees from Lundbeck, Otsuka and Janssen. AP has served as a consultant for Boehringer Ingelheim. AS: Advisory board (DSP), Research grants (CynK, DSP, MTPC, and Ono). CA has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. CH is faculty member, Lundbeck Psychiatric Institute. CP is on an advisory board for Lundbeck, Australia Pty Ltd and also received honoraria for talks presented at educational meetings organized by Lundbeck. CSW is on an advisory board for Lundbeck, Australia Pty Ltd and in collaboration with Astellas Pharma Inc., Japan. DJS has received research grants or consultancy honoraria from Lundbeck and Sun. EV has received grants and served as a consultant, advisor or CME speaker for the following entities (work unrelated to the topic of this manuscript): AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Galenica, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, and Takeda. IN has no conflicts of interest to declare. RTS has received consulting fees from Genentech and Roche. SL has received consulting fees and speaking honoraria from Roche, Novartis, Biogen and Merck., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Schizophrenia is associated with widespread cortical and subcortical abnormalities. Studies examining cognitive deficits in schizophrenia have historically focused on cortical deficits; however, many subcortical areas also support cognition. We sought to determine whether deficits in subcortical gray matter are linked to neurocognitive dysfunction in patients with first-episode schizophrenia. This study included 170 patients with first-episode schizophrenia and 88 healthy controls. Clinical symptoms, neurocognitive function, and structural images were assessed. Subcortical volumes were recorded. Patients had significant deficits in all cognitive domains, including processing speed, attention, memory, executive function and social cognition. Patients also demonstrated significantly smaller volumes in the amygdala, hippocampus, thalamus, and total cortical gray matter than did controls after Bonferroni correction for multiple comparisons. Reasoning/problem solving was significantly and positively correlated with the volume of the amygdala and nucleus accumbens in patients. Positive symptoms of psychosis were positively correlated with the volume of the amygdala and nucleus accumbens. In addition, the dose of antipsychotic medication was positively correlated with the volume of the amygdala, nucleus accumbens, caudate, putamen, and pallidum. In conclusion, schizophrenia is associated with profound cognitive deficits. Our findings suggest that subcortical structures contribute to specific domains of cognitive dysfunction in first-episode schizophrenia., (Copyright © 2019. Published by Elsevier B.V.)

Self-evaluation plays an important role in adaptive functioning and is a process that is typically impaired in patients with schizophrenia. Underlying neural mechanisms for this dysfunction may be associated with manifested psychosis. However, the brain substrates underlying this deficit are not well known. The present study used brain blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and gray matter voxel-based morphometry to explore the functional and structural brain correlates of self-evaluation deficits in schizophrenia. Eighteen patients with schizophrenia and 17 healthy controls were recruited and asked to judge whether a set of personality-trait adjectives were appropriate for describing themselves, a familiar other, or whether the adjectives were of positive or negative valence. Patients had slower response times for negative trait attributions than controls did; responses to positive trait attributions were faster than those for negative traits among the patient group, while no differences were observed in the control group. Control subjects showed greater activation within the dorsal medial prefrontal cortex (dMPFC) and the anterior cingulate cortex (ACC) than the patient group during the self-evaluation > semantic positivity-evaluation contrast. Patients showed greater activation mainly within the posterior cingulate gyrus (PCC) as compared to controls for the other-evaluation > semantic positivity-evaluation contrast. Furthermore, gray matter volume was reduced in the MPFC, temporal lobe, cuneus, and the dorsal lateral prefrontal cortex (DLPFC) among the patient group when compared to controls. The present study adds to previous findings regarding self- and other-referential processing in schizophrenia, providing support for neurobiological models of self-reflection impairment.

Background: Resting-state fMRI is a novel approach to measure spontaneous brain activity in patients with major depressive disorder (MDD). Although most resting-state fMRI studies have focused on the examination of temporal correlations between low-frequency oscillations (LFOs), few studies have explored the amplitude of these LFOs in MDD. In this study, we applied the approaches of amplitude of low-frequency fluctuation (ALFF) and fractional ALFF to examine the amplitude of LFOs in MDD., Methodology/principal Findings: A total of 36 subjects, 18 first-episode, treatment-naive patients with MDD matched with 18 healthy controls (HCs) completed the fMRI scans. Compared with HCs, MDD patients showed increased ALFF in the right fusiform gyrus and the right anterior and posterior lobes of the cerebellum but decreased ALFF in the left inferior temporal gyrus, bilateral inferior parietal lobule, and right lingual gyrus. The fALFF in patients was significantly increased in the right precentral gyrus, right inferior temporal gyrus, bilateral fusiform gyrus, and bilateral anterior and posterior lobes of the cerebellum but was decreased in the left dorsolateral prefrontal cortex, bilateral medial orbitofrontal cortex, bilateral middle temporal gyrus, left inferior temporal gyrus, and right inferior parietal lobule. After taking gray matter (GM) volume as a covariate, the results still remained., Conclusions/significance: These findings indicate that MDD patients have altered LFO amplitude in a number of regions distributed over the frontal, temporal, parietal, and occipital cortices and the cerebellum. These aberrant regions may be related to the disturbances of multiple emotion- and cognition-related networks observed in MDD and the apparent heterogeneity in depressive symptom domains. Such brain functional alteration of MDD may contribute to further understanding of MDD-related network imbalances demonstrated in previous fMRI studies.

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).

BackgroundThe profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.MethodsThe study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.ResultsCompared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.ConclusionsThe findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Background: Microglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of schizophrenia. However, how microglia/brain macrophages contribute to schizophrenia is not well established. We hypothesized that effector molecules expressed in microglia/macrophages were involved in schizophrenia via regulating stress susceptibility. Methods: We recruited a cohort of first episode schizophrenia (FES) patients (n = 51) and age- and sex-paired healthy controls (HCs) (n = 46) with evaluated stress perception. We performed blood RNA-sequencing (RNA-seq) and brain magnetic resonance imaging, and measured plasma level of colony stimulating factor 1 receptor (CSF1R). Furthermore, we studied a mouse model of chronic unpredictable stress (CUS) combined with a CSF1R inhibitor (CSF1Ri) (n = 9 ~ 10/group) on anxiety behaviours and microglial biology. Results: FES patients showed higher scores of perceived stress scale (PSS, p < 0.05), lower blood CSF1R mRNA (FDR = 0.003) and protein (p < 0.05) levels, and smaller volumes of the superior frontal gyrus and parahippocampal gyrus (both FDR < 0.05) than HCs. In blood RNA-seq, CSF1R-associated differentially expressed blood genes were related to brain development. Importantly, CSF1R facilitated a negative association of the superior frontal gyrus with PSS (p < 0.01) in HCs but not FES patients. In mouse CUS+CSF1Ri model, similarly as CUS, CSF1Ri enhanced anxiety (both p < 0.001). Genes for brain angiogenesis and intensity of CD31+-blood vessels were dampened after CUS-CSF1Ri treatment. Furthermore, CSF1Ri preferentially diminished juxta-vascular microglia/macrophages and induced microglia/macrophages morphological changes (all p < 0.05). Conclusion: Microglial/macrophagic CSF1R regulated schizophrenia-associated stress and brain angiogenesis. [ABSTRACT FROM AUTHOR]

Background: A dysfunctional default mode network (DMN) has been reported in patients with schizophrenia. However, the stability of the deficits has not been determined across different stages of the disorder. Methods: We examined the functional connectivity of the DMN subsystems of 125 patients with first-episode schizophrenia (FES) or recurrent schizophrenia (RES), compared to that of 82 healthy controls. We tested the robustness of the findings in an independent cohort of 158 patients and 39 healthy controls. We performed resting-state functional connectivity analysis, and examined the strength of the connections within and between the three subsystems of the DMN (core, dorsal medial prefrontal cortex [dMPFC], and medial temporal lobe [MTL]). We also analyzed the connectivity correlations to symptoms and illness duration. Results: We found reduced connectivity strength between the core and MTL subsystems in schizophrenia patients compared to controls, with no differences between the FES and RES patient groups; these findings were validated in the second sample. Schizophrenia patients also showed a significant reduction in connectivity within the MTL and between the dMPFC−MTL subsystems, similarly between FES and RES groups. The connectivity strength within the core subsystem was negatively correlated with clinical symptoms in schizophrenia. There was no significant correlation between the DMN subsystem connectivity and illness duration. Conclusions: DMN subsystem connectivity deficits are present in schizophrenia, and the homochronicity of their appearance indicates the trait-like nature of these alterations. The DMN deficit may be useful for early diagnosis, and MTL dysfunction may be a crucial mechanism underlying schizophrenia. [ABSTRACT FROM AUTHOR]

Insufficient or lack of response to antipsychotic medications in some patients with schizophrenia is a major challenge in psychiatry, but the underlying mechanisms remain unclear. Two seemingly unrelated observations, cerebral white matter and N-methyl-D-aspartate receptor (NMDAR) hypofunction, have been linked to treatment-resistant schizophrenia (TRS). As NMDARs are critical to axonal myelination and signal transduction, we hypothesized that NMDAR antibody (Ab), when present in schizophrenia, may impair NMDAR functions and white matter microstructures, contributing to TRS. In this study, 50 patients with TRS, 45 patients with nontreatment-resistant schizophrenia (NTRS), 53 patients with schizophrenia at treatment initiation schizophrenia (TIS), and 90 healthy controls were enrolled. Serum NMDAR Ab levels and white matter diffusion tensor imaging fractional anisotropy (FA) were assessed. The white matter specificity effects by NMDAR Ab were assessed by comparing with effects on cortical and subcortical gray matter. Serum NMDAR Ab levels of the TRS were significantly higher than those of the NTRS (P =.035). In patients with TRS, higher NMDAR Ab levels were significantly associated with reduced whole-brain average FA (r = −.37; P =.026), with the strongest effect at the genu of corpus callosum (r = −.50; P =.0021, significant after correction for multiple comparisons). Conversely, there was no significant correlation between whole-brain or regional cortical thickness or any subcortical gray matter structural volume and NMDAR Ab levels in TRS. Our finding highlights a potential NMDAR mechanism on white matter microstructure impairment in schizophrenia that may contribute to their treatment resistance to antipsychotic medications. [ABSTRACT FROM AUTHOR]

A disruption in the connectivity between brain regions may underlie the core pathology in schizophrenia. One of the most consistent observations in human functional imaging is a network of brain regions referred to as the default network (DMN) that contains core subsystem, the dorsomedial prefrontal cortex (dMPFC) subsystem and the medial temporal lobe (MTL) subsystem, with differential contributions. The goal of this study was to examine abnormalities of different DMN subsystems in first episode schizophrenia and associations between these abnormalities and individual psychopathology. We recruited 203 patients and 131 healthy controls. A seed-based resting-state functional connectivity (RSFC) analysis on the 2D surface was conducted. Individual DMN functional connectivity matrices were then obtained by calculating spatial correlations between pairs of RSFC maps, characterizing the functional fractionation of the DMN. Patients showed patterns similar to controls but markedly reduced strength of DMN fractionation, with the degree centrality of the MTL subsystem significantly reduced, including the posterior inferior parietal lobule (pIPL), parahippocampal cortex (PHC) and lateral temporal cortex (LTC). Patients also exhibited hypo-connectivity within the MTL subsystem and between the MTL and dMPFC subsystems. Clinical symptoms were negatively correlated with degree centrality of LTC, pIPL and PHC in patients. Hyper-fractionation of different DMN components implied that communication and coordination throughout the dissociated components of the DMN are functionally over-segregated in schizophrenia. The associations between the hyper-fractionation with clinical symptoms suggest a role of the high fractionation in the DMN in the abnormal neuropathology observed in schizophrenia. [ABSTRACT FROM AUTHOR]

• The TRS group had significantly higher salivary KYNA than the NTRS group, who in turn had higher salivary KYNA than HC. • Higher salivary KYNA was associated with larger choroid plexus volume in TRS patients. • Higher salivary KYNA related to worse cognitive performances worse and higher total PANSS score in TRS patients. • An enlarged choroid plexus was also related to worse cognitive performances and clinical symptoms in TRS patients only. Patients with treatment-resistant schizophrenia (TRS) suffer severe, long-term psychotic symptoms and chronic stress. Salivary kynurenic acid (KYNA) and choroid plexus were evidenced to relate to psychological stress. We hypothesized that TRS patients would have higher salivary KYNA levels than patients who respond to antipsychotics (NTRS) and healthy controls (HC), and increased salivary KYNA levels are associated with clinical phenotypes and choroid plexus volume. A total of 66 HC participants, 53 patients with TRS and 46 with NTRS were enrolled. Salivary KYNA levels were measured by liquid chromatography-tandem mass spectrometry, choroid plexus volume by magnetic resonance imaging, and cognitive functions with the MATRICS Consensus Cognitive Battery. The TRS group had significantly higher salivary KYNA levels than the NTRS group (p = 0.003), who in turn had higher salivary KYNA than HC (p = 0.02). Higher salivary KYNA levels were associated with larger choroid plexus volume (r = 0.48, p = 0.004); lower attention/vigilance (r = -0.44, p = 0.004), verbal learning (r = -0.44, p = 0.004), total MCCB score (r = -0.42, p = 0.005); and a higher total PANSS score (r = 0.48, p = 0.004) in TRS patients. An enlarged choroid plexus also related to worse attention/vigilance (r = -0.39, p = 0.03), verbal learning (r = -0.55, p = 0.001), total MCCB score (r = -0.41, p = 0.02) and clinical symptoms (r = 0.48, p = 0.004) in TRS patients only. We conclude that elevated salivary KYNA levels and associated choroid plexus enlargement are clinically relevant indicators of TRS, with salivary KYNA being particularly valuable as a peripheral marker. Our findings should benefit TRS research and benefit the improvement of personalized treatment. [ABSTRACT FROM AUTHOR]

About a third of patients with schizophrenia do not respond adequately to currently available antipsychotics and thus experiences symptoms of greater severity, known as treatment-resistant schizophrenia (TRS). Some evidence suggests that the tryptophan (TRP) pathway (comprising 5-HT and kynurenine sub-pathways) has an important influence on response to antipsychotics. We therefore hypothesized that TRS is linked to metabolites of TRP pathway. We measured TRP metabolites in 54 patients with TRS and compared them to 49 age- and sex-matched patients who responded to antipsychotics (NTRS), and 62 healthy controls using liquid chromatography-tandem mass spectrometry. Psychopathology and clinical symptoms were assessed by means of schizophrenia positive and negative scales. Working memory abilities, cortical thickness and white matter diffusion tensor imaging fractional anisotropy were appraised in enrolled subjects by neurophysiological tests, as spatial span and digital sequencing tests, and 3T magnetic resonance imaging. Patients with TRS had a significantly higher 5-HT/TRP ratio (p = 0.009) than patients with NTRS. However, the two groups did not differ in kynurenine-pathway metabolites or ratios. Additionally, 5-HT/TRP was positively correlated with disorganized symptoms in TRS (r = 0.59, p < 0.001), and negatively correlated with digit-sequencing test scores (r = −0.34, p = 0.02). These correlations were insignificant among patients with NTRS and healthy controls. In patients with TRS, 5-HT/TRP was strongly linked to the right supramarginal cortex (t = −3.2, p = 0.003), and in healthy controls, to the right transverse temporal (t = 3.40, p = 0.001), but significance disappeared after FDR correction. Present results indicate that an upregulated 5-HT biosynthetic pathway can be associated to TRS, suggesting that targeting mechanisms of 5-HT conversion from tryptophan could shed light on the development of new pharmacological approaches of TRS. [ABSTRACT FROM AUTHOR]

Immune disturbance has been postulated to be one of the mechanisms underlying the pathogenesis of tardive dyskinesia (TD). Recently, the role of autoimmune abnormality in TD has been increasingly recognized. Autoantibodies against neuronal N-methyl-D-aspartate receptor (NMDAR) may be cross-reactive in the brain in neuropsychiatric disorders, and the choroid plexus (CP) is a crucial immune barrier in the central nervous system (CNS). We supposed that NMDAR antibodies might underlie the pathophysiological process of TD through the mediation of CP. Serum NMDAR antibody levels were assessed by enzyme-linked immunosorbent assay, CP and ventricle volumes were assessed by magnetic resonance imaging in schizophrenia patients with TD (n = 61), without TD (NTD, n = 61), and in healthy controls (n = 74). Psychopathology and TD severity were assessed by the Positive and Negative Syndrome Scale and Abnormal Involuntary Movement Scale (AIMS). NMDAR antibody levels were significantly higher, CP volumes were larger in the TD group than in the NTD group (p = 0.022; p = 0.019, respectively). In the TD group, higher NMDAR antibody level was correlated with larger CP volume (β = 0.406, p = 0.002). An elevated NMDAR antibody level and enlarged CP volume were correlated with orofacial AIMS score (β = 0.331 , p = 0.011; β = 0.459 , p = 3.34 × 10−4, respectively). In a mediation model, the effect of NMDAR antibody level on the orofacial AIMS score was mediated by the CP volume (indirect effect: β = 0.08, 95% confidence interval = 0.002–0.225; direct effect: β = 0.14, p = 0.154). Our findings highlight a potential NMDAR antibody-associated mechanism in orofacial TD, which may be mediated by increased CP volume. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is characterized by recurrent episodes of depression and mild mania. In this paper, to address the common issue of insufficient accuracy in existing methods and meet the requirements of clinical diagnosis, we propose a framework called Spatio-temporal Feature Fusion Transformer (STF2Former). It improves on our previous work — MFFormer by introducing a Spatio-temporal Feature Aggregation Module (STFAM) to learn the temporal and spatial features of rs-fMRI data. It promotes intra-modality attention and information fusion across different modalities. Specifically, this method decouples the temporal and spatial dimensions and designs two feature extraction modules for extracting temporal and spatial information separately. Extensive experiments demonstrate the effectiveness of our proposed STFAM in extracting features from rs-fMRI, and prove that our STF2Former can significantly outperform MFFormer and achieve much better results among other state-of-the-art methods. [Display omitted] An overview of the proposed method Spatio-temporal Feature Fusion Transformer (STF2Former). Resting-state functional magnetic resonance imaging (rs-fMRI) data undergoes feature extraction through 2D convolution layers with 1x3 and 3x1 kernels to extract temporal and spatial features. Residual structures are used to preserve useful information. T1w goes through five layers of 3D convolution and max pooling to obtain feature representation. In the final feature extraction stage, a transformer self-attention mechanism is introduced to learn intermediate representations that fuse across multiple modalities. After a series of feature extraction, the feature maps are concatenated and fed into two convolutional layers and an MLP, producing logits as the output. • We propose a new framework which significantly improves the performance compared to MFFormer. • We introduce a scheme to utilize the temporal and spatial features of rs-fMRI data fully. • Our results demonstrate that STF2Former achieves SOTA performance in BD disease diagnosis tasks. [ABSTRACT FROM AUTHOR]

• Patients with schizophrenia had higher HCY levels than healthy controls. • HCY levels were correlated with cognitive function in the patients. • Healthy controls had higher cortical thickness than the patients. • Cortical thickness had moderating effects on cognitive deficits in patients. The mechanism by which high homocysteine (HCY) may aggravate cognitive impairment in patients with schizophrenia is not well understood. We aimed to test the hypothesis that hyperhomocysteinaemia may exacerbate cognitive deficits by mediating the decrease in cortical thickness in patients with schizophrenia. One hundred and sixty-seven first-episode patients with schizophrenia (FEPS) and 120 healthy controls (HCs) were included. Psychopathology and cognitive function were assessed using the Positive and Negative Symptom Scale and Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB), respectively. Brain cortical thickness was measured by 3.0 T high-resolution magnetic resonance imaging. Serum HCY levels were tested using a sandwich enzyme-linked immunosorbent assay. Our findings showed that HCY levels in the FEPS were significantly higher than those in the HCs (P < 0.001). The MCCB total and subtest scores in the patients were significantly lower than those in the HCs (P < 0.001). The HCs had significantly higher cortical thickness than the patients (P < 0.001). Serum HCY levels were negatively correlated with Working Memory, Attention/Vigilance, and MCCB total scores in the FEPS (P < 0.05). Brain cortical thickness had positive moderating effects on cognitive impairment in FEPS with high HCY after controlling for sex, age, and education (P < 0.05). In HCs with high HCY, brain cortical thickness had no mediating or moderating effects on cognitive impairment. Compared with HCs, FEPS had thinner grey matter thickness, furthermore, the grey matter thickness might play a crucial role in relationship between high HCY and cognitive deficits. [ABSTRACT FROM AUTHOR]