Identification of schizophrenia by applying interpretable radiomics modeling with structural magnetic resonance imaging of the cerebellum.

AIMS: The cerebellum is involved in higher-order mental processing as well as sensorimotor functions. Although structural abnormalities in the cerebellum have been demonstrated in schizophrenia, neuroimaging techniques are not yet applicable to identify them given the lack of biomarkers. We aimed to develop a robust diagnostic model for schizophrenia using radiomic features from T1-weighted magnetic resonance imaging (T1-MRI) of the cerebellum. METHODS: A total of 336 participants (174 schizophrenia; 162 healthy controls [HCs]) were allocated to training (122 schizophrenia; 115 HCs) and test (52 schizophrenia; 47 HCs) cohorts. We obtained 2568 radiomic features from T1-MRI of the cerebellar subregions. After feature selection, a light gradient boosting machine classifier was trained. The discrimination and calibration of the model were evaluated. SHapley Additive exPlanations (SHAP) was applied to determine model interpretability. RESULTS: We identified 17 radiomic features to differentiate participants with schizophrenia from HCs. In the test cohort, the radiomics model had an area under the curve, accuracy, sensitivity, and specificity of 0.89 (95% confidence interval: 0.82-0.95), 78.8%, 88.5%, and 75.4%, respectively. The model explanation by SHAP suggested that the second-order size zone non-uniformity feature from the right lobule IX and first-order energy feature from the right lobules V and VI were highly associated with the risk of schizophrenia. CONCLUSION: The radiomics model focused on the cerebellum demonstrates robustness in diagnosing schizophrenia. Our results suggest that microcircuit disruption in the posterior cerebellum is a disease-defining feature of schizophrenia, and radiomics modeling has potential for supporting biomarker-based decision-making in clinical practice.

Altered DNA Methylation of the Serotonin Transporter Gene Associated with Early Life Stress and White Matter Microalterations in Korean Patients with Panic Disorder.

INTRODUCTION: Changes in the DNA methylation of 5-HTTLPR are associated with the pathophysiology of panic disorder (PD). This study was conducted to investigate the association between stressful life events and the level of 5-HTTLPR methylation in patients with PD. We also examined whether these factors were associated with white matter alterations in psychological trauma-related regions. METHODS: The participants comprised 232 patients with PD and 93 healthy adults of Korean descent. DNA methylation levels of five cytosine-phosphate-guanine (CpG) sites in the 5-HTTLPR region were analyzed. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the trauma-related regions. RESULTS: PD patients showed significantly lower levels of the DNA methylation at 5-HTTLPR 5 CpG sites than healthy controls. In patients with PD, the DNA methylation levels at 5-HTTLPR 5 CpG sites showed significant negative association with the parental separation-related psychological distress, and positive correlations with the fractional anisotropy values of the superior longitudinal fasciculus (SLF) which might be related to trait anxiety. CONCLUSION: Early life stress was significantly associated with DNA methylation levels at 5-HTTLPR related to the decreased white matter integrity in the SLF region in PD. Decreased white matter connectivity in the SLF might be related to trait anxiety and is vital to the pathophysiology of PD.

Long-term benefits of mindfulness on white matter tracts underlying the cortical midline structures in panic disorder: A 2-year longitudinal study.

AIMS: We aimed to examine the long-term benefits of mindfulness-based cognitive therapy (MBCT) on white matter plasticity in the cortical midline structures (CMS) for a period of 2 years in patients with panic disorder and the relationships between white matter changes in the CMS and severity of state and trait symptoms. METHODS: Seventy-one participants were enrolled and underwent diffusion tensor imaging at baseline and after 2 years (26 who received MBCT as an adjunct to pharmacotherapy [MBCT+PT], 20 treated with pharmacotherapy alone [PT-alone], and 25 healthy controls [HCs]). The severity of symptoms and fractional anisotropy (FA) in white matter regions underlying the CMS were assessed at baseline and 2-year follow-up. RESULTS: The MBCT+PT group showed better outcomes after 2 years than the PT-alone group. The groups showed different FA changes: the MBCT+PT group showed decreased FA in the left anterior cingulate cortex (ACC); the PT-alone group showed increased FA in the bilateral dorsomedial prefrontal cortex, posterior cingulate cortex (PCC), and precuneus. Decreased white matter FA in the ACC, PCC, and precuneus was associated with improvements in the severity of state and trait symptoms in patients with panic disorder. CONCLUSION: Alleviation of excessive white matter connectivity in the CMS after MBCT leads to improvements in clinical symptoms and trait vulnerability in patients with panic disorder. Our study provides new evidence for the long-term benefits of MBCT on white matter plasticity and its clinical applicability as a robust treatment for panic disorder.

Hymenobacter translucens sp. nov. and Hymenobacter pini sp. nov. isolated from soil.

Two novel bacterial strains BT175T and BT728T were isolated from soil collected in the Republic of Korea. Both strains were Gram stain negative, rod shaped, and had circular, convex, and pink-colored colonies. The 16S rRNA gene sequence similarity between the strains BT175T and BT728T was 93.6%, indicating that they represent a distinct species. 16S rRNA sequence analysis indicated that strains BT175T and BT728T belong to a distinct lineage within the genus Hymenobacter (family Hymenobacteraceae, order Cytophagales, class Cytophagia, phylum Bacteroidetes). Strain BT175T was closely related to Hymenobacter persicinus 1-3-3-3T (97.2%, 16S rRNA gene similarity), Hymenobacter knuensis 16F7C-2T (96.6%), and Hymenobacter daejeonensis PB105T (96.1%). Strain BT728T was closely related to Hymenobacter rigui KCTC 12533T (98.4%), Hymenobacter metallilatus 9PBR-2T (97.6%), and Hymenobacter perfusus LMG26000T (97.4%). Strain BT175T and BT728T were found to have the MK-7 as the major respiratory quinone. The DNA G + C content of strain BT175T was 61.6 mol% and BT728T was 59.6 mol%, respectively. Characterization based on polyphasic analysis indicated that strains BT175T and BT728T represent novel species of the genus Hymenobacter and the names Hymenobacter translucens sp. nov. and Hymenobacter pini sp. nov. are proposed. The type strain of Hymenobacter translucens is BT175T (= KCTC 72330T = NBRC 115441T) and Hymenobacter pini is BT728T (= KACC 22629T = NBRC 115444T).

Microvirga jeongseonensis sp. nov., isolated from soil in South Korea.

A novel Gram-stain-negative, aerobic, rod-shaped, convex, and light pink-colored strain BT688T was isolated from a soil sample collected in Jeongseon City, South Korea. Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain BT688T belongs to a distinct lineage within the genus Microvirga (family Methylobacteriaceae, order Rhizobiales, class Alphaproteobacteria, phylum Proteobacteria). The 16S rRNA gene sequence similarity between strain BT688T and Microvirga aerilata 5420S-16T was 98.5%. Strain BT688T had Q-10 as a major respiratory quinone and the major polar lipids were diphosphatidilglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and phosphatidylcholine (PC). The major cellular fatty acids of strain BT688T were C18:1 ω7c (76.0%) and summed feature 3 (9.6%). Based on the polyphasic characteristics, strain BT688T represents a novel bacterial species within the genus Microvirga and the proposed name is Microvirga jeongseonensis. The type strain of Microvirga jeongseonensis is BT688T (= KCTC 82701T = NBRC 114857T).

Microvirga terrestris sp. nov., and Microvirga arvi sp. nov., isolated from soil in South Korea.

Two novel Gram-stain-negative, aerobic, rod shaped bacterial strains BT290T and BT689T were isolated from soil collected in South Korea. Colony morphologies of both strains were circular and convex while the colors of BT290T and BT689T were light-pink and white, respectively. Phylogenetic analysis based on 16S rRNA gene sequences revealed that BT290T and BT689T belong to a distinct lineage within the genus Microvirga (family Methylobacteriaceae, order Rhizobiales, class Alphaproteobacteria, phylum Proteobacteria, kingdom Bacteria). The 16S rR NA gene sequence similarity between two strains was 97.9%. Both strains had the similar quinone system, with ubiquinone 10 (Q-10) as the major respiratory quinone. The major polar lipids of strains BT290T and BT689T were phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), phosphatidylcholine (PC), and phosphatidylglycerol (PG). The major cellular fatty acids of strain BT290T were C18:1 ω7c (58.2%) and C16:0 (17.7%), while those of strain BT689T were C18:1 ω7c (61.8%) and C16:0 (10.8%). On the bases of polyphasic analysis (phylogenetic, chemotaxonomic, and biochemical), strains BT290T and BT689T can be suggested as novel bacterial species within the genus Microvirga and the proposed names are Microvirga terrestris and Microvirga arvi, respectively. The type strain of Microvirga terrestris is BT290T (= KCTC 72367T = NBRC 114844T) and the type strain of Microvirga arvi is BT689T (= KACC 22016T = NBRC 114858T), respectively.

Hymenobacter telluris sp. nov., isolated from soil in South Korea.

Two novel bacterial strains, designated as BT186T and BT505, were isolated from a soil sample collected in South Korea and characterized. Both strains were Gram-stain-negative, rod-shaped, aerobic, circular, convex, and had red-colored colonies. The level of 16S rRNA gene sequence similarity between the strains BT186T and BT505 was 100%, indicating that they represent an identical species. 16S rRNA sequence analysis indicated that strains BT186T and BT505 belong to a distinct lineage within the genus Hymenobacter (family Hymenobacteraceae, order Cytophagales, class Cytophagia, phylum Bacteroidetes, Kingdom Bacteria). Both strains were closely related to Hymenobacter norwichensis DSM 15439T (98.3% 16S rRNA gene similarity), Hymenobacter aquaticus JCM 31653T (96.8%), and Hymenobacter perfusus LMG26000T (96.5%). Strain BT186T was found to have the MK-7 as the major respiratory quinone. The major polar lipid of strain BT186T was identified to be phosphatidylethanolamine (PE). The major cellular fatty acid profiles of strain BT186T were C16:1 ω5c (24.3%), iso-C15:0 (20.3%) and summed feature 3 (C16:1 ω6c/C16:1 ω7c) (19.9%). Characterization based on polyphasic analysis indicated that strains BT186T and BT505 represent novel species of the genus Hymenobacter and the name Hymenobacter telluris sp. nov. is proposed. The type strain of Hymenobacter telluris is BT186T (= KCTC 72338T = NBRC 114968T).

Microvirga splendida sp. nov., bacteria isolated from soil.

Two bacterial strains, BT325T and BT690, were isolated from soil samples collected in Korea. Both strains were Gram stain-negative, short rod-shaped, and formed light-pink colored colonies. The 16S rRNA sequence similarity of strains BT325T and BT690 shared a sequence similarity of 99.7%. Both strains shared the highest 16S rRNA gene similarity of 98.6% with Microvirga arabica SV2184PT, followed by Microvirga ossetica V5/3 M T (98.5% and 98.2%, respectively), Microvirga soli R491T (98.3% and 98.2%, respectively), Microvirga aerilata (98.2% and 98.08%, respectively), Microvirga makkahensis (98.08% and 97.8%, respectively). Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain BT325T and BT690 were positioned in a distinct lineage within the family Methylobacteriaceae (order Rhizobiales, class Alphaproteobacteria). The genome size of strain BT325T was 5,200,315 bp and the genomic DNA G + C content was 64.3 mol%. The sole respiratory quinone of strain BT325T was Q-10 and the predominant cellular fatty acids were summed feature 3 (C16:1 ω7c/C16:1 ω6c) and summed feature 8 (C18:1 ω7c/C18:1 ω6c). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, and phosphatidylcholine. Polyphasic taxonomic analysis of biochemical, chemotaxonomic, and phylogenetic analyses suggested that strains BT325T represents a novel bacterial species within the genus Microvirga, for which the name Microvirga splendida is proposed. The type strain of Microvirga splendida is BT325T (= KCTC 72406 T = NBRC 114847 T).

Quantitative Proteomic Approach for Discriminating Major Depressive Disorder and Bipolar Disorder by Multiple Reaction Monitoring-Mass Spectrometry.

Because major depressive disorder (MDD) and bipolar disorder (BD) manifest with similar symptoms, misdiagnosis is a persistent issue, necessitating their differentiation through objective methods. This study was aimed to differentiate between these disorders using a targeted proteomic approach. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was performed to quantify protein targets regarding the two disorders in plasma samples of 270 individuals (90 MDD, 90 BD, and 90 healthy controls (HCs)). In the training set (72 MDD and 72 BD), a generalizable model comprising nine proteins was developed. The model was evaluated in the test set (18 MDD and 18 BD). The model demonstrated a good performance (area under the curve (AUC) >0.8) in discriminating MDD from BD in the training (AUC = 0.84) and test sets (AUC = 0.81) and in distinguishing MDD from BD without current hypomanic/manic/mixed symptoms (90 MDD and 75 BD) (AUC = 0.83). Subsequently, the model demonstrated excellent performance for drug-free MDD versus BD (11 MDD and 10 BD) (AUC = 0.96) and good performance for MDD versus HC (AUC = 0.87) and BD versus HC (AUC = 0.86). Furthermore, the nine proteins were associated with neuro, oxidative/nitrosative stress, and immunity/inflammation-related biological functions. This proof-of-concept study introduces a potential model for distinguishing between the two disorders.

Hymenobacter properus sp. nov., Hymenobacter ruricola sp. nov., and Hymenobacter jeongseonensis sp. nov., three new species isolated from mountain and beach soil in South Korea.

Three Gram-stain-negative, aerobic, circular, convex, red-colored and rod-shaped bacterial strains, designated BT439T, BT662T and BT683T were obtained from soil collected in South Korea. The phylogenetic analysis based on 16S rRNA gene sequences of the strains revealed a distinct lineage within the genus Hymenobacter. The complete genome sequence of strains BT439T, BT662T and BT683T is 5,542,738 bp, 5,964,541 bp, and 5,192,601 bp size, respectively. All three strains were found to have MK-7 as the major respiratory quinone. The major polar lipids of strains BT439T and BT662T were identified as phosphatidylethanolamine, aminophospholipids and amino lipids. Strain BT683T contained phosphatidylethanolamine. The major cellular fatty acids of strain BT439T were iso-C15:0, summed feature 3 (C16:1 ω6c/C16:1 ω7c) and anteiso-C15:0; strain BT662T possessed iso-C15:0 and summed feature 3 (C16:1 ω6c/C16:1 ω7c); strain BT683T were summed feature 3 (C16:1 ω6c/C16:1 ω7c), C16:1 ω5c, iso-C15:0 and anteiso-C15:0. Based on the polyphasic analysis, strains BT439T, BT662T and BT683T can be suggested as three novel bacterial species within the genus Hymenobacter and the proposed names are Hymenobacter properus sp. nov., Hymenobacter ruricola sp. nov. and Hymenobacter jeongseonensis sp. nov., respectively. The type strain of Hymenobacter properus is BT439T (= KCTC 72900T = NBRC 114849T), Hymenobacter ruricola is BT662T (= KACC 21966T = NBRC 114855T) and the type strain of Hymenobacter jeongseonensis is BT683T (= KACC 22013T = NBRC xxxxxT).

Hymenobacter puniceus sp. nov., radiation resistant bacteria isolated from soil in South Korea.

Two novel Gram-negative bacterial strains BT190T and BT191 were isolated from soil collected in Uijeongbu city (37°44'55″N, 127°02'20″E), Korea. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strains BT190T and BT191 belong to a distinct lineage within the genus Hymenobacter (family Hymenobacteraceae, order Cytophagales, class Cytophagia). The level of 16S rRNA gene sequence similarity between the strains BT190T and BT190 was 99.5%. The strains BT190T and BT191 were closely related to Hymenobacter swuensis DY53T (97.0% 16S rRNA gene similarity), Hymenobacter metallilatus 9PBR-2 T (96.8%), Hymenobacter tibetensis XTM003T (96.8%) and Hymenobacter yonginensis HMD1010T (96.6%). The genome size of strain BT190T was 4,859,864 bp. The DNA G+C content of strain BT190T was 55.3 mol%. Bacterial growth was observed at 4-30 °C (optimum 25 °C) and pH 6.0-9.0 (optimum, pH 6.0-7.0) on R2A agar. Colonies of strains BT190T and BT191 were raised, smooth, circular and red-pink colored. The sole respiratory quinone of strain BT190T was MK-7 and the predominant cellular fatty acids were iso-C15:0, C16:1 ω5c, summed feature 3 (C16:1 ω6c / C16:1 ω7c) and summed feature 4 (iso-C17:1 I / anteiso-C17:1 B). The major polar lipids of strain BT190T were aminophospholipid (APL) and phosphatidylethanolamine (PE). Based on the chemotaxonomic, biochemical, and phylogenetic analysis, strains BT190T and BT191 can be suggested as a novel bacterial species within the genus Hymenobacter, for which the name Hymenobacter puniceus sp. nov is proposed. The type strain of Hymenobacter puniceus is BT190T (= KCTC 72342 T = NBRC 114860 T).

Reduced activation of the ventromedial prefrontal cortex during self-referential processing in individuals at ultra-high risk for psychosis.

OBJECTIVE: Defects in self-referential processing and perspective-taking are core characteristics that may underlie psychotic symptoms and impaired social cognition in schizophrenia. Here, we investigated the neural correlates of self-referential processing regardless of the perspective taken and third-person perspective-taking regardless of the target person to judge relevance in individuals at ultra-high risk for psychosis. We also explored relationships between alterations in neural activity and neurocognitive function and basic self ('ipseity') disorder. METHODS: Twenty-two ultra-high-risk individuals and 28 healthy controls completed a functional magnetic resonance imaging task. While being scanned, participants were asked to take a first-person perspective or to put themselves in their close relative's place thereby adopting a third-person perspective during judgments of the relevance of personality trait adjectives to one's self and a close relative. RESULTS: For self-referential (vs other-referential) processing, ultra-high-risk individuals showed less neural activity in the left ventromedial prefrontal cortex/medial orbitofrontal cortex, which was correlated with poor working memory performance. When taking a third-person perspective (vs first-person perspective), ultra-high-risk individuals showed more activity in the middle occipital gyrus. CONCLUSION: Taken together, our findings suggest that ultra-high-risk individuals already show aberrant neural activity during self-referential processing which may possibly be related to engagement of working memory resources.

Associations of systemic inflammation with frontotemporal functional network connectivity and out-degree social-network size in community-dwelling older adults.

Increasing evidence suggests that systemic inflammation adversely affects social experiences and behaviors of older adults by changing the functional state of the brain. In this study, we investigated the relationships among systemic inflammation, functional network connectivity (FNC) of the whole brain, and social-network size using complete social-network data of older adults residing in a Korean village. Sixty-one participants were recruited from the Korean Social Life, Health, and Aging Project (KSHAP). Participants underwent a resting-state functional magnetic resonance imaging scan. High sensitivity C-reactive protein (hs-CRP) levels were measured as an inflammation marker. In-degree and out-degree network sizes were calculated based on the total number of intimate social relationships per participant. We demonstrated that hs-CRP levels were associated with decreased frontotemporal FNC. Stronger frontotemporal FNC was significantly correlated with a larger out-degree network size, suggesting that impaired frontotemporal communication in older adults decreases perceived social connectedness with other people. An exploratory mediation analysis supported the observation that increased systemic inflammation contributes to reduced out-degree social-network size among older adults by changing frontotemporal FNC. The present findings provide meaningful insight into the complex relationship between systemic inflammation and social quality of life.

Tyrosine kinase Fyn regulates iNOS expression in LPS-stimulated astrocytes via modulation of ERK phosphorylation.

The high concentrations of nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) in activated glial cells in response to neuroinflammatory stimuli have neurotoxic effects on the brain. At basal levels, iNOS expression is low, and proinflammatory stimuli induce iNOS expression in astrocytes, microglia, and oligodendrocytes. Fyn, a non-receptor tyrosine kinase, regulates iNOS expression in several types of immune cells. However, its role in stimulated astrocytes is less clear. In this study, we investigated the role of Fyn in the regulation of lipopolysaccharide (LPS)-induced iNOS expression in astrocytes from mice and rats. Intracerebroventricular LPS injections in cortical regions enhanced iNOS mRNA and protein levels, which were increased in Fyn-deficient mice. Accordingly, LPS-induced nitrite production was enhanced in primary astrocytes cultured from Fyn-deficient mice or rats. Similar results were observed in cultured astrocytes after the siRNA-induced knockdown of Fyn expression. Finally, we observed increased LPS-induced extracellular signal-regulated protein kinase (ERK) activation in Fyn-deficient astrocytes. These results suggested that Fyn has a regulatory role in iNOS expression in astrocytes during neuroinflammatory responses.

Neurocognitive impairments in individuals at ultra-high risk for psychosis: Who will really convert?

OBJECTIVE: Impairments in neurocognitive function are considered as core features of schizophrenia. Individuals at ultra-high risk (UHR) for psychosis, the 'putative' prodrome of schizophrenia, generally show levels of impairments intermediate between schizophrenia patients and healthy controls. We investigated the neurocognitive performance of individuals at UHR for psychosis, comparing them with patients with first-episode schizophrenia (FES) and healthy controls (HC), and explored the predictivity of baseline neurocognitive function in the UHR group for transition to overt psychosis. METHOD: Individuals at UHR for psychosis (n = 60), patients with FES (n = 39), and HC subjects (n = 94) participated in the present study. All participants performed a comprehensive neurocognitive battery, consisting of tests for five separate neurocognitive domains (executive function, attention/working memory, processing speed, verbal memory, and spatial memory). UHR subjects were assessed for transition every month during 24 months of follow-up. RESULTS: Neurocognitive performance in the UHR group was largely at intermediate levels. Attention/working memory and verbal memory were significantly different from both the FES and HC groups. In the UHR group, processing speed was decreased to the level of the FES group, while executive function and spatial memory were relatively preserved. In the Cox regression model, spatial memory significantly predicted the transition to overt psychosis in the UHR group. CONCLUSIONS: The present study showed that neurocognitive impairments were evident in UHR individuals prior to the onset of overt psychosis. Our findings generally support the neurodevelopmental model of schizophrenia and suggest that there could be different developmental trajectories between converters and non-converters.

Cerebro-cerebellar gray matter abnormalities associated with cognitive impairment in patients with recent-onset and chronic schizophrenia.

Although the role of the cerebellum in schizophrenia has gained attention, its contribution to cognitive impairment remains unclear. We aimed to investigate volumetric alterations in the cerebro-cerebellar gray matter (GM) in patients with recent-onset schizophrenia (ROS) and chronic schizophrenia (CS) compared with healthy controls (HCs). Seventy-two ROS, 43 CS, and 127 HC participants were recruited, and high-resolution T1-weighted structural magnetic resonance images of the brain were acquired. We compared cerebellar GM volumes among the groups using voxel-based morphometry and examined the cerebro-cerebellar GM volumetric correlations in participants with schizophrenia. Exploratory correlation analysis investigated the functional relevance of cerebro-cerebellar GM volume alterations to cognitive function in the schizophrenia group. The ROS and CS participants demonstrated smaller cerebellar GM volumes, particularly in Crus I and II, than HCs. Extracted cerebellar GM volumes demonstrated significant positive correlations with the cerebral GM volume in the fronto-temporo-parietal association areas engaged in higher-order association. The exploratory analysis showed that smaller cerebellar GM in the posterior lobe regions was associated with poorer cognitive performance in participants with schizophrenia. Our study suggests that cerebellar pathogenesis is present in the early stages of schizophrenia and interconnected with structural abnormalities in the cerebral cortex. Integrating the cerebellum into the pathogenesis of schizophrenia will help advance our understanding of the disease and identify novel treatment targets concerning dysfunctional cerebro-cerebellar interactions.

Positive Effects of Uric Acid on White Matter Microstructures and Treatment Response in Patients With Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia involves microstructural changes in white matter (WM) tracts. Oxidative stress is a key factor causing WM damage by hindering oligodendrocyte development and myelin maturation. Uric acid (UA), an endogenous antioxidant, may protect against oxidative stress. We investigated the effect of UA on WM connectivity in antipsychotic-naive or -free patients with early- or chronic-stage schizophrenia. STUDY DESIGN: A total of 192 patients with schizophrenia (122 recent-onset [ROS] and 70 chronic [CS]) and 107 healthy controls (HCs) participated in this study. Diffusion tensor imaging data and serum UA levels at baseline were obtained. STUDY RESULTS: Fractional anisotropy was lower in the widespread WM regions across the whole brain, and diffusivity measures were higher in both schizophrenia groups than in HCs. The CS group showed lower diffusivity in some WM tracts than the ROS or HC groups. The linear relationship of serum UA levels with axial and mean diffusivity in the right frontal region was significantly different between schizophrenia stages, which was driven by a negative association in the CS group. WM diffusivity associated with serum UA levels correlated with 8-week treatment responses only in patients with CS, suggesting UA to be protective against long-term schizophrenia. CONCLUSIONS: UA may protect against the WM damage associated with the progression of schizophrenia by reducing oxidative stress and supporting WM repair against oxidative damage. These results provide insights into the positive role of UA and may facilitate the development of novel disease-modifying therapies.

Multimodal neural correlates of dispositional resilience among healthy individuals.

Resilient individuals are less likely to develop psychiatric disorders despite extreme psychological distress. This study investigated the multimodal structural neural correlates of dispositional resilience among healthy individuals. Participants included 92 healthy individuals. The Korean version of the Connor-Davidson Resilience Scale and other psychological measures were used. Gray matter volumes (GMVs), cortical thickness, local gyrification index (LGI), and white matter (WM) microstructures were analyzed using voxel-based morphometry, FreeSurfer, and tract-based spatial statistics, respectively. Higher resilient individuals showed significantly higher GMVs in the inferior frontal gyrus (IFG), increased LGI in the insula, and lower fractional anisotropy values in the superior longitudinal fasciculus II (SLF II). These resilience's neural correlates were associated with good quality of life in physical functioning or general health and low levels of depression. Therefore, the GMVs in the IFG, LGI in the insula, and WM microstructures in the SLF II can be associated with resilience that contributes to emotional regulation, empathy, and social cognition.

Neural Correlates of Trait Impulsivity among Adult Healthy Individuals.

Objective: : Impulsivity can be observed in individuals with or without mental illness. The discovery of neural correlates responsible for trait impulsivity can therefore help to understand the severity of psychiatric symptoms, personality characteristics and social adjustment. In this study, we aimed to identify the gray matter substrates of trait impulsivity in healthy individuals. Methods: : Seventy-five healthy individuals were enrolled. At baseline, trait impulsivity was assessed using the Barratt Impulsiveness Scale (BIS) and all participants underwent T1-weighted magnetic resonance imaging scan. Beck Anxiety Inventory (BAI), World Health Organization Quality of Life (WHOQOL-BREF) and Connor-Davidson Resilience Scale (CD-RISC) were also assessed. Mean cortical thickness (CT) and the local gyrification index (LGI) were calculated to perform whole-brain vertex-wise correlation analysis, which were performed to investigate the relationship between BIS scores and CT or LGI in each brain region. We also revealed the relationship between brain regions and psychological measurements. Results: : Total BIS scores were significantly and negatively correlated with mean CT values in the left lateral occipital cortex (OC) and LGIs in the inferior frontal gyrus (IFG). Correlation analyses revealed that the lateral OC's mean CT values were negatively correlated with BAI scores and positively correlated with WHOQOL-BREF scores, while LGI in the IFG was positively correlated with CD-RISC scores. Conclusion: : Our study showed that trait impulsivity might be associated with the lateral OC and IFG in healthy individuals. Understanding the neural correlates of trait impulsivity could provide ways to expect high impulsivity, anxiety, and poor resilience in healthy adults.

Association of hair cortisol concentration with brain-derived neurotrophic factor gene methylation: The role of sex as a moderator.

Hair cortisol concentration (HCC) reflects the long-term activity of the hypothalamus-pituitary-adrenal (HPA) axis in response to stress. Brain-derived neurotrophic factor DNA methylation (BDNF DNAM) may affect HCC, and sex and Val66Met may contribute to this association. Thus, the aim of this study was to investigate the associations between HCC and Brain-derived neurotrophic factor (BDNF) DNAM, and the moderating effects of Val66Met and sex. We recruited 191 healthy young participants (96 women, mean age 23.0 ± 2.6 years) and collected body samples to evaluate HCC, and to determine BDNF DNAM and Val66Met genotypes. We analyzed the effects of BDNF DNAM, sex, and Val66Met on HCC. We also evaluated the associations between BDNF DNAM and HCC in groups separated by sex and genotypes. We found a marked association of BDNF DNAM with HCC across men and women. After dividing the data by sex, a positive correlation of HCC with BDNF DNAM was found only in women. There was no substantial moderation effect of Val66Met genotypes on the association between BDNF DNAM and HCC. Therefore, BDNF DNAM was found to have positive association with HCC only in healthy young women, indicating that sex moderates the association of BDNF DNAM with long-term HPA axis activity.