The relationship between gray/white matter contrast and cognitive performance in first-episode schizophrenia.

Previous postmortem brain studies have revealed disturbed myelination in the intracortical regions in patients with schizophrenia, possibly reflecting anomalous brain maturational processes. However, it currently remains unclear whether this anomalous myelination is already present in early illness stages and/or progresses during the course of the illness. In this magnetic resonance imaging study, we examined gray/white matter contrast (GWC) as a potential marker of intracortical myelination in 63 first-episode schizophrenia (FESz) patients and 77 healthy controls (HC). Furthermore, we investigated the relationships between GWC findings and clinical/cognitive variables in FESz patients. GWC in the bilateral temporal, parietal, occipital, and insular regions was significantly higher in FESz patients than in HC, which was partly associated with the durations of illness and medication, the onset age, and lower executive and verbal learning performances. Because higher GWC implicates lower myelin in the deeper layers of the cortex, these results suggest that schizophrenia patients have less intracortical myelin at the time of their first psychotic episode, which underlies lower cognitive performance in early illness stages.

Tropomyosin induces the synthesis of magnesian calcite in sea urchin spines.

Calcium carbonate is present in many biominerals, including in the exoskeletons of crustaceans and shells of mollusks. High Mg-containing calcium carbonate was synthesized by high temperatures, high pressures or high molecular organic matter. For example, biogenic high Mg-containing calcite is synthesized under strictly controlled Mg concentration at ambient temperature and pressure. The spines of sea urchins consist of calcite, which contain a high percentage of magnesium. In this study, we investigated the factors that increase the magnesium content in calcite from the spines of the sea urchin, Heliocidaris crassispina. X-ray diffraction and inductively coupled plasma mass spectrometry analyses showed that sea urchin spines contain about 4.8% Mg. The organic matrix extracted from the H. crassispina spines induced the crystallization of amorphous phase and synthesis of magnesium-containing calcite, while amorphous was synthesized without SUE (sea urchin extract). In addition, aragonite was synthesized by SUE treated with protease-K. HC tropomyosin was specifically incorporated into Mg precipitates. Recombinant HC-tropomyosin induced calcite contained 0.1-2.5% Mg synthesis. Western blotting of sea urchin spine extracts confirmed that HC tropomyosin was present in the purple sea urchin spines at a protein weight ratio of 1.5%. These results show that HC tropomyosin is one factor that increases the magnesium concentration in the calcite of H. crassispina spines.

Glucose controls manganese homeostasis through transcription factors regulating known and newly identified manganese transporter genes in Bacillus subtilis.

Mn2+ is an essential nutrient whose concentration is tightly controlled in bacteria. In Bacillus subtilis, the Mn2+-activated transcription factor MntR controls Mn2+ transporter genes. However, factors regulating intracellular Mn2+ concentration are incompletely understood. Here, we found that glucose addition induces an increase in intracellular Mn2+ concentration. We determined this upshift was mediated by glucose induction of the major Mn2+ importer gene mntH by the transcription factor AhrC, which is known to be involved in arginine metabolism and to be indirectly induced by glucose. In addition, we identified novel AhrC-regulated genes encoding the Mn2+ importer YcsG and the ABC-type exporter YknUV. We found the expression of these genes was also regulated by glucose and contributes to the glucose induction of Mn2+ concentrations. ycsG expression is regulated by MntR as well. Furthermore, we analyzed the interaction of AhrC and MntR with the promoter driving ycsG expression and examined the Mn2+-dependent induction of this promoter to identify the transcription factors responsible for the Mn2+ induction. RNA-Seq revealed that disruption of ahrC and mntR affected the expression of 502 and 478 genes, respectively (false discovery rate, <0.001, log2[fold change] ≥ |2|. The AhrC- and/or MntR-dependent expression of twenty promoters was confirmed by LacZ analysis, and AhrC or MntR binding to some of these promoters was observed via EMSA. The finding that glucose promotes an increase in intracellular Mn2+ levels without changes in extracellular Mn2+ concentrations is reasonable for the bacterium, as intracellular Mn2+ is required for enzymes and pathways mediating glucose metabolism.

Diversification of von Willebrand Factor A and Chitin-Binding Domains in Pif/BMSPs Among Mollusks.

Pif is a shell matrix protein (SMP) identified in the nacreous layer of Pinctada fucata (Pfu) comprised two proteins, Pif97 and Pif 80. Pif97 contains a von Willebrand factor A (VWA) and chitin-binding domains, whereas Pif80 can bind calcium carbonate crystals. The VWA domain is conserved in the SMPs of various mollusk species; however, their phylogenetic relationship remains obscure. Furthermore, although the VWA domain participates in protein-protein interactions, its role in shell formation has not been established. Accordingly, in the current study, we investigate the phylogenetic relationship between PfuPif and other VWA domain-containing proteins in major mollusk species. The shell-related proteins containing VWA domains formed a large clade (the Pif/BMSP family) and were classified into eight subfamilies with unique sequential features, expression patterns, and taxa diversity. Furthermore, a pull-down assay using recombinant proteins containing the VWA domain of PfuPif 97 revealed that the VWA domain interacts with five nacreous layer-related SMPs of P. fucata, including Pif 80 and nacrein. Collectively, these results suggest that the VWA domain is important in the formation of organic complexes and participates in shell mineralisation.

Stacking Structure of Vaterite Revealed by Atomic Imaging and Diffraction Analysis.

Anhydrous calcium carbonate crystals exist as three polymorphs: calcite, aragonite, and vaterite. Although vaterite is a metastable phase rarely found in the geological environment, it is intriguing that various biominerals are composed of vaterite. The processes of stable vaterite formation in biological systems cannot be understood without elucidating the nature of vaterite. The crystal structure of vaterite has been discussed for nearly a century but is still an open question. Here we propose the actual structure of vaterite by combining atomic imaging and diffraction analysis with simulations of disordered stacking sequences. Vaterite basically appears as layers of hexagonal calcium planes and carbonate (CO3 2-)-containing sheets stacked with +60°, -60°, or 180° rotations from the underlying layer. However, equivalent carbonate positions in alternating layers are forbidden, and four-layer stacking in which the fourth layer rotates 180° relative to the first layer are predominant, forming an orthogonal reciprocal lattice in diffraction patterns. These stacking characteristics replicate the intensity distribution in the electron and X-ray diffraction patterns. This study has almost completely elucidated the crystal structure and stacking sequence of vaterite. Our findings provide insights into the thermodynamic stability of vaterite, which facilitates comprehension of the biomineralization processes and growth dynamics of calcium carbonate.

Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Cerebral cortical structural alteration patterns across four major psychiatric disorders in 5549 individuals.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

Structural and Functional Analysis of the Amorphous Calcium Carbonate-Binding Protein Paramyosin in the Shell of the Pearl Oyster, Pinctada fucata.

Amorphous calcium carbonate (ACC) is an important precursor phase for the formation of aragonite crystals in the shells of Pinctada fucata. To identify the ACC-binding protein in the inner aragonite layer of the shell, extracts from the shell were used in the ACC-binding experiments. Semiquantitative analyses using liquid chromatography-mass spectrometry revealed that paramyosin was strongly associated with ACC in the shell. We discovered that paramyosin, a major component of the adductor muscle, was included in the myostracum, which is the microstructure of the shell attached to the adductor muscle. Purified paramyosin accumulates calcium carbonate and induces the prism structure of aragonite crystals, which is related to the morphology of prism aragonite crystals in the myostracum. Nuclear magnetic resonance measurements revealed that the Glu-rich region was bound to ACC. Activity of the Glu-rich region was stronger than that of the Asp-rich region. These results suggest that paramyosin in the adductor muscle is involved in the formation of aragonite prisms in the myostracum.

Atmospheric CO2 Sequestration in Seawater Enhanced by Molluscan Shell Powders.

Carbon capture, utilization, and storage (CCUS) are widely recognized as a promising technology for mitigating climate change. CO2 mineralization using Ca-rich fluids and high-concentration CO2 gas has been studied extensively. However, few studies have reported CO2 mineralization with atmospheric CO2, owing to the difficulty associated with its low concentration. In seawater, the biomineralization process promotes Ca accumulation and CaCO3 precipitation, assisted by specific organic matter. In this study, we examined the conversion of atmospheric CO2 into CaCO3 in seawater using shell powders (Pinctada fucata, Haliotis discus, Crassostrea gigas, Mizuhopecten yessoensis, Turbo sazae, and Saxidomus purpurata). Among the six species, the shell powder of S. purpurata showed the highest rate of CaCO3 formation and recovery of CaCO3. NaClO treatment test revealed that the organic matter in the shells enhanced the CO2 mineralization. All materials used in this study, including atmospheric CO2, seawater, and shells, are economically feasible for large-scale applications. Using shell powder for CO2 mineralization in seawater embodies an innovative technological advancement to address climate change.

Resting state hyperconnectivity of the default mode network in schizophrenia and clinical high-risk state for psychosis.

Disrupted functional connectivity (FC) of the default mode network (DMN) may have a pathophysiological role in schizophrenia. However, functional magnetic resonance imaging (fMRI) of the DMN in schizophrenia patients has shown inconsistent results. It also remains unclear whether individuals with at-risk mental state (ARMS) have an altered DMN connectivity and whether it is related to clinical characteristics. This fMRI study examined resting-state FCs of the DMN and its relevance to clinical/cognitive variables in 41 schizophrenia patients, 31 ARMS individuals, and 65 healthy controls. Compared with controls, schizophrenia patients had significantly increased FCs within the DMN and between the DMN and diverse cortical areas, whereas ARMS patients had increased FCs only between the DMN and occipital cortex. FC of the lateral parietal cortex with superior temporal gyrus was positively correlated with negative symptoms in schizophrenia, whereas FC of that with interparietal sulcus was negatively correlated with general cognitive impairment in ARMS. Our findings suggest that increased FCs between the DMN and visual network commonly seen in schizophrenia and ARMS subjects may reflect a network-level disturbance representing a general vulnerability to psychosis. In addition, FC changes related to the lateral parietal cortex may underpin clinical characteristics of ARMS and schizophrenia subjects.

Copy number variations in RNF216 and postsynaptic membrane-associated genes are associated with bipolar disorder: a case-control study in the Japanese population.

AIM: Bipolar disorder (BD) is a common psychiatric disorder characterized by alterations between manic/hypomanic and depressive states. Rare pathogenic copy number variations (CNVs) that overlap with exons of synaptic genes have been associated with BD. However, no study has comprehensively explored CNVs in synaptic genes associated with BD. Here, we evaluated the relationship between BD and rare CNVs that overlap with synaptic genes, not limited to exons, in the Japanese population. METHODS: Using array comparative genome hybridization, we detected CNVs in 1839 patients with BD and 2760 controls. We used the Synaptic Gene Ontology database to identify rare CNVs that overlap with synaptic genes. Using gene-based analysis, we compared their frequencies between the BD and control groups. We also searched for synaptic gene sets related to BD. The significance level was set to a false discovery rate of 10%. RESULTS: The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66-14.89], false discovery rate < 10%). The BD-associated CNV that corresponded with RNF216 also partially overlapped with the minimal critical region of the 7p22.1 microduplication syndrome. The integral component of the postsynaptic membrane (Gene Ontology:0099055) was significantly associated with BD. The CNV overlapping with the intron region of GRM5 in this gene set showed a nominal significant association between cases and controls (P < 0.05). CONCLUSION: We provide evidence that CNVs in RNF216 and postsynaptic membrane-related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD.

Structure-Guided Discovery of a Potent Inhibitor of the Ferric Citrate Binding Protein FecB in Vibrio Bacteria.

Infections caused by Gram-negative bacteria present a significant risk to human health worldwide. Novel strategies are needed to deal with the challenge caused by drug-resistant bacteria. Here, we report a new approach to combat infections by targeting iron-binding proteins to suppress bacterial growth. We investigated the function of the conserved periplasmic binding protein FecB from Vibrio alginolyticus. FecB was known to play a crucial role in the bacterial growth and to relate with biofilm formation. We then solved the crystal structures and elucidated the binding mechanism of FecB with ferric ion chelated by citrate. The results indicated that FecB binds weakly to one citrate molecule and strongly to the Fe3+-(citrate)2 complex. Based on these results, a structure-based virtual screening approach was conducted against FecB to identify small molecules that block ferric citrate uptake. Further evaluations in vivo and in vitro demonstrated that salvianolic acid C significantly suppressed bacterial growth, indicating that targeting bacterial nutrient absorption is a promising strategy for identifying potential antibacterial drugs.

Evolution of Epidermal Growth Factor (EGF)-like and Zona Pellucida Domains Containing Shell Matrix Proteins in Mollusks.

Several types of shell matrix proteins (SMPs) have been identified in molluskan shells. Their diversity is the consequence of various molecular processes, including domain shuffling and gene duplication. However, the evolutionary origin of most SMPs remains unclear. In this study, we investigated the evolutionary process EGF-like and zona pellucida (ZP) domains containing SMPs. Two types of the proteins (EGF-like protein (EGFL) and EGF-like and ZP domains containing protein (EGFZP)) were found in the pearl oyster, Pinctada fucata. In contrast, only EGFZP was identified in the gastropods. Phylogenetic analysis and genomic arrangement studies showed that EGFL and EGFZP formed a clade in bivalves, and their encoding genes were localized in tandem repeats on the same scaffold. In P. fucata, EGFL genes were expressed in the outer part of mantle epithelial cells are related to the calcitic shell formation. However, in both P. fucata and the limpet Nipponacmea fuscoviridis, EGFZP genes were expressed in the inner part of the mantle epithelial cells are related to aragonitic shell formation. Furthermore, our analysis showed that in P. fucata, the ZP domain interacts with eight SMPs that have various functions in the nacreous shell mineralization. The data suggest that the ZP domain can interact with other SMPs, and EGFL evolution in pterimorph bivalves represents an example of neo-functionalization that involves the acquisition of a novel protein through gene duplication.

Directional fabrication and dissolution of larval and juvenile oyster shells under ocean acidification.

Biomineralization is one of the key biochemical processes in calcifying bivalve species such as oysters that is affected by ocean acidification (OA). Larval life stages of oysters are made of aragonite crystals whereas the adults are made of calcite and/or aragonite. Though both calcite and aragonite are crystal polymorphs of calcium carbonate, they have different mechanical properties and hence it is important to study the micro and nano structure of different life stages of oyster shells under OA to understand the mechanisms by which OA affects biomineralization ontogeny. Here, we have studied the larval and juvenile life stages of an economically and ecologically important estuarine oyster species, Crassostrea hongkongensis, under OA with focus over shell fabrication under OA (pHNBS 7.4). We also look at the effect of parental exposure to OA on larvae and juvenile microstructure. The micro and nanostructure characterization reveals directional fabrication of oyster shells, with more organized structure as biomineralization progresses. Under OA, both the larval and juvenile stages show directional dissolution, i.e. the earlier formed shell layers undergo dissolution at first, owing to longer exposure time. Despite dissolution, the micro and nanostructure of the shell remains unaffected under OA, irrespective of parental exposure history.

Dispersion Function of a Protein, DP-1, Identified in Collimonas sp. D-25, for the Synthesis of Gold Nanoparticles.

Collimonas sp. (D-25), found in the soil of Akita Prefecture, is a gram-negative bacterium with the ability to synthesize gold nanoparticles (AuNPs). During the synthesis of AuNPs, one specific protein (DP-1) was found to have disappeared in the sonicated solution of the bacterium. Recombinant DP-1 (rDP-1) from Escherichia coli BL21 (DE3) was used to study the effect of DP-1 on the synthesis of AuNPs. AuNPs synthesized with rDP-1 result in small, stabilized nanoparticles. AuNPs synthesized by DP-1 retained the stability of both the dispersion and nano-size particles under high salt concentrations. Isothermal titration calorimetry was employed to investigate the bonding ratio of rDP-1 to AuNPs. Several thousand rDP-1 proteins are attached to the surface of an AuNP to form a protein corona containing multiple layers. These results suggest that DP-1 obtained from D-25 has a size and stability control function during AuNP synthesis.

Capnocytophaga catalasegens sp. nov., isolated from feline oral cavities.

Three bacterial strains, KC07075, KC07079 and KC07084T, were isolated from the oral cavity of cats in 2007 in Japan. These strains were Gram-negative rods, exhibited gliding motility, grew in air with 5 % CO2, and showed oxidase activity, but not catalase activity. The 16S rRNA gene sequences of the three strains were 100 % identical. The 16S rRNA gene sequence of strain KC07084T showed 92.1 and 91.9% identity to the type strains of Capnocytophaga canis and Capnocytophaga felis, respectively, and showed 89.3-91.6% identity to other Capnocytophaga species. The major cellular fatty acids of strain KC07084T were iso-C15 : 0 (58.4 %) and summed feature 11 (13.1 %). The G+C content of DNA from strain KC07084T was 33.7 mol%, and the genome size was 2.92 Mbp. Strains KC07075, KC07079 and KC07084T showed digital DNA-DNA hybridization values (dDDH) values of 99.9 % and average nucleotide identity (ANI) values of 99.98 % with each other, strain KC07084T had dDDH values of 18.7-28.2 % and ANI values of 67.12-72.30 % to the type strains of other Capnocytophaga species. All known species of the genus Capnocytophaga inhabiting the oral cavity of dogs and cats have catalase activity, but the three strains, including type strain KC07084T, lacked catalase activity. These results of the phylogenetic analysis of the 16S rRNA gene sequence, biochemical characteristics, and dDDH and ANI values suggest that strain KC07084T represents a novel species. We propose the name Capnocytophaga catalasegens sp. nov., with KC07084T as the type strain (=JCM 32682T=DSM 107252T).

Volume Reduction of the Dorsal Lateral Prefrontal Cortex Prior to the Onset of Frank Psychosis in Individuals with an At-Risk Mental State.

Although some individuals with at-risk mental states (ARMS) develop overt psychosis, surrogate markers which can reliably predict a future onset of psychosis are not well established. The dorsal lateral prefrontal cortex (DLPFC) is thought to be involved in psychotic disorders such as schizophrenia. In this study, 73 ARMS patients and 74 healthy controls underwent 1.5-T 3D magnetic resonance imaging scans at three sites. Using labeled cortical distance mapping, cortical thickness, gray matter (GM) volume, and surface area of DLPFC were estimated. These measures were compared across the diagnostic groups. We also evaluated cognitive function among 36 ARMS subjects to clarify the relationships between the DLPFC morphology and cognitive performance. The GM volume of the right DLPFC was significantly reduced in ARMS subjects who later developed frank psychosis (ARMS-P) relative to those who did not (P = 0.042). There was a positive relationship between the right DLPFC volume and the duration prior to the onset of frank psychosis in ARMS-P subjects (r = 0.58, P = 0.018). Our data may suggest that GM reduction of the DLPFC might be a potential marker of future onset of psychosis in individuals with ARMS.

Effect of phosphoproteins on intracellular calcification of bacteria.

This study aimed to evaluate the effects of phosphoproteins on bacterial mineralization. Dental calculus formation is attributed to bacterial mineralization in the oral cavity; however, the influence of phosphoproteins (which are abundant in saliva) is not clear. The model bacterium Escherichia coli was suspended in a calcification solution containing casein as a model phosphoprotein. To evaluate mineralization independent of bacterial metabolism, bacteria killed by heat treatment at 70°C were compared with viable bacteria. After incubation at 37°C for 24 h, the mode of calcification was observed using electron microscopy and energy dispersive x-ray spectroscopy. Solutions without casein produced precipitation in solution, which was identical to that in experiments without bacteria. In contrast, calcification solutions with 200 ppm casein only produced calcium phosphate deposition intracellularly. Without heat treatment, intracellular calcification rarely occurred, even when casein was added. Thus, phosphoproteins promoted intracellular calcification of dead bacteria; this is similar to the calcification of insoluble matrices, such as collagen fibrils, promoted by acidic polymers. We concluded that intracellular calcification is caused by the collagen fibril-like behavior of dead bacteria. The promotion of intracellular calcification of dead bacteria by phosphoproteins suggested a basic principle of dental calculus formation.

Midline brain structures in adult Niemann-Pick type C disease: a cross-sectional study.

OBJECTIVE: A range of neuropathological changes occur in the brains of individuals with adult Niemann-Pick type C disease (NPC), a recessive disorder of cholesterol trafficking that results in accumulation of cholesterol and gangliosides in lysosomes, particularly in neurons. One of the most significant regions of grey matter loss occurs in the thalami, which abut the midline. What is not known is whether these are neurodevelopmental in origin well prior to symptomatic onset. We aimed to examine other markers of midline developmental anomalies in adults with NPC. METHOD: We examined the size of adhesio interthalamica (AI) and cavum septum pellucidum (CSP) (if present) in nine individuals diagnosed with NPC and nine healthy comparison subjects, matched for age and gender, using a 3T magnetic resonance volumetric sequence and measured the length of the AI and CSP in mm. RESULTS: We found that 5/9 NPC patients and 0/9 controls had a missing AI. AI length was significantly shorter in the patient group. No subject in other group had a large CSP, and CSP length did not differ. Duration of illness showed a trend to a negative correlation with AI length in patients. CONCLUSIONS: Our findings suggest that adult NPC patients show some markers of early neurodevelopmental disturbance, matching findings seen in psychotic disorders. The differences in AI, but not CSP, suggest neurodevelopmental change may occur early in gestation rather than post-partum. The relationship with duration of illness suggests that there may be atrophy over time in these structures, consistent with prior analyses of grey matter regions in NPC.

Features of Duration Mismatch Negativity Around the Onset of Overt Psychotic Disorders: A Longitudinal Study.

Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2 years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.