In Vivo Reactive Astrocyte Imaging in Patients With Schizophrenia Using Fluorine 18-Labeled THK5351.

Importance: In vivo imaging studies of reactive astrocytes are crucial for understanding the pathophysiology of schizophrenia because astrocytes play a critical role in glutamate imbalance and neuroinflammation. Objective: To investigate in vivo reactive astrocytes in patients with schizophrenia associated with positive symptoms using monoamine oxidase B (MAO-B)-binding fluorine 18 ([18F])-labeled THK5351 positron emission tomography (PET). Design, Setting, and Participants: In this case-control study, data were collected from October 1, 2021, to January 31, 2023, from the internet advertisement for the healthy control group and from the outpatient clinics of Seoul National University Hospital in Seoul, South Korea, for the schizophrenia group. Participants included patients with schizophrenia and age- and sex-matched healthy control individuals. Main Outcomes and Measures: Standardized uptake value ratios (SUVrs) of [18F]THK5351 in the anterior cingulate cortex (ACC) and hippocampus as primary regions of interest (ROIs), with other limbic regions as secondary ROIs, and the correlation between altered SUVrs and Positive and Negative Syndrome Scale (PANSS) positive symptom scores. Results: A total of 68 participants (mean [SD] age, 32.0 [7.0] years; 41 men [60.3%]) included 33 patients with schizophrenia (mean [SD] age, 32.3 [6.3] years; 22 men [66.7%]) and 35 healthy controls (mean [SD] age, 31.8 [7.6] years; 19 men [54.3%]) who underwent [18F]THK5351 PET scanning. Patients with schizophrenia showed significantly higher SUVrs in the bilateral ACC (left, F = 5.767 [false discovery rate (FDR)-corrected P = .04]; right, F = 5.977 [FDR-corrected P = .04]) and left hippocampus (F = 4.834 [FDR-corrected P = .04]) than healthy controls. Trend-level group differences between the groups in the SUVrs were found in the secondary ROIs (eg, right parahippocampal gyrus, F = 3.387 [P = .07]). There were positive correlations between the SUVrs in the bilateral ACC and the PANSS positive symptom scores (left, r = 0.423 [FDR-corrected P = .03]; right, r = 0.406 [FDR-corrected P = .03]) in patients with schizophrenia. Conclusions and Relevance: This case-control study provides novel in vivo imaging evidence of reactive astrocyte involvement in the pathophysiology of schizophrenia. Reactive astrocytes in the ACC may be a future target for the treatment of symptoms of schizophrenia, especially positive symptoms.

Psychometrics of the Korean Version of the screen for adult anxiety related disorders (SCAARED).

BACKGROUND: For enhanced management of anxiety disorders, early screening and accurate diagnostic differentiation are essential. The Screen for Adult Anxiety Related Disorders (SCAARED) has been developed to identify and categorize anxiety disorders, thereby facilitating timely and appropriate interventions. In line with this, we aimed to translate and validate the Korean version of the SCAARED questionnaire for the Korean population. METHODS: The original SCAARED was translated into Korean and administered to community adult population (N = 119) ages 18-45 years old in South Korea. The internal consistency and test-retest reliability of the SCAARED were evaluated. In addition, its factor structure was examined using confirmatory and exploratory factor analysis. Concurrent validity was evaluated by comparing SCAARED with the Depression, Anxiety and Stress Scale-21 (DASS), the Beck's Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI). Test-retest reliability was evaluated one week after the first assessment. RESULTS: The SCAARED showed good internal consistency (Cronbach's α = 0.945) and test-retest reliability (γ = 0.883). The SCAARED had significant correlation with DASS-21 subscales (γ = 0.655-0.701), BAI (γ = 0.788) and STAI subscales (γ = 0.548-0.736), confirming good concurrent validity. The results of the Exploratory Factor Analysis showed four factors comparable to the original SCAARED (Generalized anxiety, Somatic/Panic/Agoraphobia, Social anxiety, and Separation anxiety). The area under the curve of the receiver operating characteristic of total and each of the factor scores ranged from 0.724 to 0.942. CONCLUSIONS: The Korean version of the SCAARED is a reliable and valid instrument to screen for anxiety disorders in the Korean adult populations.

Neurocomputational model of compulsivity: deviating from an uncertain goal-directed system.

Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how this occurs during arbitration between the two systems in obsessive-compulsive disorder. Inspired by a brain model in which the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to examine whether disruptions in the arbitration process via the fronto-striatal circuit would underlie imbalanced decision-making and compulsions in patients. Thirty patients with obsessive-compulsive disorder [mean (standard deviation) age = 26.93 (6.23) years, 12 females (40%)] and 30 healthy controls [mean (standard deviation) age = 24.97 (4.72) years, 17 females (57%)] underwent functional MRI scans while performing the two-step Markov decision task, which was designed to dissociate goal-directed behaviour from habitual behaviour. We employed a neurocomputational model to account for an uncertainty-based arbitration process, in which a prefrontal arbitrator (i.e. inferior frontal gyrus) allocates behavioural control to a more reliable strategy by selectively gating the putamen. We analysed group differences in the neural estimates of uncertainty of each strategy. We also compared the psychophysiological interaction effects of system preference (goal-directed versus habitual) on fronto-striatal coupling between groups. We examined the correlation between compulsivity score and the neural activity and connectivity involved in the arbitration process. The computational model captured the subjects' preferences between the strategies. Compared with healthy controls, patients had a stronger preference for the habitual system (t = -2.88, P = 0.006), which was attributed to a more uncertain goal-directed system (t = 2.72, P = 0.009). Before the allocation of controls, patients exhibited hypoactivity in the inferior frontal gyrus compared with healthy controls when this region tracked the inverse of uncertainty (i.e. reliability) of goal-directed behaviour (P = 0.001, family-wise error rate corrected). When reorienting behaviours to reach specific goals, patients exhibited weaker right ipsilateral ventrolateral prefronto-putamen coupling than healthy controls (P = 0.001, family-wise error rate corrected). This hypoconnectivity was correlated with more severe compulsivity (r = -0.57, P = 0.002). Our findings suggest that the attenuated top-down control of the putamen by the prefrontal arbitrator underlies compulsivity in obsessive-compulsive disorder. Enhancing fronto-striatal connectivity may be a potential neurotherapeutic approach for compulsivity and adaptive decision-making.

Alteration in left frontoparietal connectivity correlates with impaired cognitive reappraisal in early psychosis.

BACKGROUND: Impaired cognitive reappraisal is a notable symptom of early psychosis, but its neurobiological basis remains underexplored. We aimed to identify the underlying neurobiological mechanism of this impairment by using resting-state functional connectivity (FC) analyses focused on brain regions related to cognitive reappraisal. METHODS: Resting-state functional magnetic resonance images were collected from 36 first-episode psychosis (FEP) patients, 32 clinical high-risk (CHR) individuals, and 48 healthy controls (HCs). Whole-brain FC maps using seed regions associated with cognitive reappraisal were generated and compared across the FEP, CHR and HC groups. We assessed the correlation between resting-state FC, reappraisal success ratio, positive symptom severity and social functioning controlling for covariates. RESULTS: FEP patients showed higher FC between the left superior parietal lobe and left inferior frontal gyrus than HCs. Higher FC between the left superior parietal lobe and left inferior frontal gyrus negatively correlated with the reappraisal success ratio in the FEP group after controlling for covariates. Lower FC correlated with lower positive symptom severity and improved global functioning in the FEP group. CONCLUSIONS: Alteration in left frontoparietal connectivity reflects impaired cognitive reappraisal in early psychosis, and such alteration correlates with increased positive symptoms and decreased global functioning. These findings offer a potential path for interventions targeting newly emerging symptoms in the early stages of psychosis.

Magnetic resonance texture analysis reveals stagewise nonlinear alterations of the frontal gray matter in patients with early psychosis.

Although gray matter (GM) abnormalities are present from the early stages of psychosis, subtle/miniscule changes may not be detected by conventional volumetry. Texture analysis (TA), which permits quantification of the complex interrelationship between contrasts at the individual voxel level, may capture subtle GM changes with more sensitivity than does volume or cortical thickness (CTh). We performed three-dimensional TA in nine GM regions of interest (ROIs) using T1 magnetic resonance images from 101 patients with first-episode psychosis (FEP), 85 patients at clinical high risk (CHR) for psychosis, and 147 controls. Via principal component analysis, three features of gray-level cooccurrence matrix - informational measure of correlation 1 (IMC1), autocorrelation (AC), and inverse difference (ID) - were selected to analyze cortical texture in the ROIs that showed a significant change in volume or CTh in the study groups. Significant reductions in GM volume and CTh of various frontotemporal regions were found in the FEP compared with the controls. Increased frontal AC was found in the FEP group compared to the controls after adjusting for volume and CTh changes. While volume and CTh were preserved in the CHR group, a stagewise nonlinear increase in frontal IMC1 was found, which exceeded both the controls and FEP group. Increased frontal IMC1 was also associated with a lesser severity of attenuated positive symptoms in the CHR group, while neither volume nor CTh was. The results of the current study suggest that frontal IMC1 may reflect subtle, dynamic GM changes and the symptomatology of the CHR stage with greater sensitivity, even in the absence of gross GM abnormalities. Some structural mechanisms that may contribute to texture changes (e.g., macrostructural cortical lamina, neuropil/myelination, cortical reorganization) and their possible implications are explored and discussed. Texture may be a useful tool to investigate subtle and dynamic GM abnormalities, especially during the CHR period.

Forecasting prognostic trajectories with mismatch negativity in early psychosis.

BACKGROUND: Prognostic heterogeneity in early psychosis patients yields significant difficulties in determining the degree and duration of early intervention; this heterogeneity highlights the need for prognostic biomarkers. Although mismatch negativity (MMN) has been widely studied across early phases of psychotic disorders, its potential as a common prognostic biomarker in early periods, such as clinical high risk (CHR) for psychosis and first-episode psychosis (FEP), has not been fully studied. METHODS: A total of 104 FEP patients, 102 CHR individuals, and 107 healthy controls (HCs) participated in baseline MMN recording. Clinical outcomes were assessed; 17 FEP patients were treatment resistant, 73 FEP patients were nonresistant, 56 CHR individuals were nonremitters (15 transitioned to a psychotic disorder), and 22 CHR subjects were remitters. Baseline MMN amplitudes were compared across clinical outcome groups and tested for utility prognostic biomarkers using binary logistic regression. RESULTS: MMN amplitudes were greatest in HCs, intermediate in CHR subjects, and smallest in FEP patients. In the clinical outcome groups, MMN amplitudes were reduced from the baseline in both FEP and CHR patients with poor prognostic trajectories. Reduced baseline MMN amplitudes were a significant predictor of later treatment resistance in FEP patients [Exp(ß) = 2.100, 95% confidence interval (CI) 1.104-3.993, p = 0.024] and nonremission in CHR individuals [Exp(ß) = 1.898, 95% CI 1.065-3.374, p = 0.030]. CONCLUSIONS: These findings suggest that MMN could be used as a common prognostic biomarker across early psychosis periods, which will aid clinical decisions for early intervention.

Cortical gyrification differences between early- and late-onset obsessive-compulsive disorder: neurobiological evidence for neurodevelopmentally distinct subtypes.

BACKGROUND: Identifying more homogenous subtypes of patients with obsessive-compulsive disorder (OCD) using biological evidence is critical for understanding complexities of the disorder in this heterogeneous population. Age of onset serves as a useful subtyping scheme for distinguishing OCD into two subgroups that aligns with neurodevelopmental perspectives. The underlying neurobiological markers for these distinct neurodevelopmental differences can be identified by investigating gyrification changes to establish biological evidence-based homogeneous subtypes. METHODS: We compared whole-brain cortical gyrification in 84 patients with early-onset OCD, 84 patients with late-onset OCD, and 152 healthy controls (HCs) to identify potential markers for early neurodevelopmental deficits using the local gyrification index (lGI). Then, the relationships between lGI in clusters showing significant differences and performance in visuospatial memory and verbal fluency, which are considered trait-related neurocognitive impairments in OCD, were further examined in early-onset OCD patients. RESULTS: The early-onset OCD patients exhibited significantly greater gyrification than those with late-onset OCD patients and HCs in frontoparietal and cingulate regions, including the bilateral precentral, postcentral, precuneus, paracentral, posterior cingulate, superior frontal, and caudal anterior cingulate gyri. Moreover, impaired neurocognitive functions in early-onset OCD patients were correlated with increased gyrification. CONCLUSIONS: Our findings provide a neurobiological marker to distinguish the OCD population into more neurodevelopmentally homogeneous subtypes, which may contribute to the understanding of the neurodevelopmental underpinnings of an etiology in early-onset OCD consistent with the accumulated phenotypic evidence of greater neurodevelopmental deficits in early-onset OCD than in late-onset OCD.

Aberrant cortico-striatal white matter connectivity and associated subregional microstructure of the striatum in obsessive-compulsive disorder.

The striatum and its cortical circuits play central roles in the pathophysiology of obsessive-compulsive disorder (OCD). The striatum is subdivided by cortical connections and functions; however, the anatomical aberrations in different cortico-striatal connections and coexisting microstructural anomalies in striatal subregions of OCD patients are poorly understood. Thus, we aimed to elucidate the aberrations in cortico-striatal white matter (WM) connectivity and the associated subregional microstructure of the striatum in patients with OCD. From diffusion tensor/kurtosis imaging of 107 unmedicated OCD patients and 110 matched healthy controls (HCs), we calculated the cortico-striatal WM connectivity and segmented the striatum using probabilistic tractography. For the segmented striatal subregions, we measured average diffusion kurtosis values, which represent microstructural complexity. Connectivity and mean kurtosis values in each cortical target and associated striatal subregions were compared between groups. We identified significantly reduced orbitofrontal WM connectivity with its associated striatal subregion in patients with OCD compared to that in HCs. However, OCD patients exhibited significantly increased caudal-motor and parietal connectivity with the associated striatal subregions. The mean kurtosis values of the striatal subregions connected to the caudal-motor and parietal cortex were significantly decreased in OCD patients. Our results highlighted contrasting patterns of striatal WM connections with the orbitofrontal and caudal-motor/parietal cortices, thus supporting the cortico-striatal circuitry imbalance model of OCD. We suggest that aberrations in WM connections and the microstructure of their downstream regions in the caudal-motor-/parietal-striatal circuits may underlie OCD pathophysiology and further provide potential neuromodulation targets for the treatment of OCD.

Volume deficits in hippocampal subfields in unaffected relatives of schizophrenia patients with high genetic loading but without any psychiatric symptoms.

BACKGROUND: Hippocampal volume changes have been reported in schizophrenia patients and their relatives and are proposed to contribute to the pathophysiology of schizophrenia. However, volume changes in the total hippocampus have not been consistently reported in relatives. The hippocampus consists of multiple subregions, and based on previous inconsistent results, subtle changes in specific subregions may occur in relatives. Here, we examined the subregion volumes in unaffected, high-functioning relatives (URs) without any psychiatric symptoms with high genetic loading with at least one first-degree relative diagnosed with schizophrenia and at least one or more other affected first- to third-degree relatives. METHODS: We acquired structural magnetic resonance imaging data from 50 URs, 101 first-episode psychosis (FEP) patients, and 101 healthy controls (HCs). The cornu ammonis (CA), dentate gyrus, and subiculum subfields were automatically segmented using FreeSurfer 7.1.0. Each subregion volume was compared across the groups. RESULTS: Compared with the HCs, the URs had a significant volume reduction in the left anterior CA (p = 0.039, Cohen's d = 0.480). In addition, the URs had a significantly larger right posterior subiculum (p = 0.001, Cohen's d = 0.541) than the FEP. CONCLUSIONS: The smaller left anterior CA in the URs may reflect their genetic vulnerability to schizophrenia and supports previous findings suggesting specific vulnerability in this region. The volume differences between the URs and FEP patients in the right posterior subiculum may suggest that a smaller volume in this region may reflect a risk for schizophrenia other than genetic vulnerability.

Triple-Network Dysconnectivity in Patients With First-Episode Psychosis and Individuals at Clinical High Risk for Psychosis.

OBJECTIVE: In the triple-network model, the salience network (SN) plays a crucial role in switching between the default-mode network (DMN) and the central executive network (CEN). Aberrant patterns of triple-network connectivity have been reported in schizophrenia patients, while findings have been less consistent for patients in the early stages of psychotic disorders. Thus, the present study examined the connectivity among the SN, DMN, and CEN in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis. METHODS: Thirty-nine patients with FEP, 78 patients with CHR for psychosis, and 110 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. We compared the SN, DMN, and CEN connectivity patterns of the three groups. The role of the SN in networks with significant connectivity differences was examined by mediation analysis. RESULTS: FEP patients showed lower SN-DMN and SN-CEN (cluster-level F=5.83, false discovery rate [FDR] corrected-p=0.001) connectivity than HCs. There was lower SN-DMN connectivity (cluster-level F=3.06, FDR corrected-p=0.053) at a trend level in CHR subjects compared to HCs. Between HCs and FEP patients, mediation analysis showed that SN-DMN connectivity was a mediator between group and SN-CEN connectivity. Additionally, SN-CEN connectivity functioned as a mediator between group and SN-DMN connectivity. CONCLUSION: Aberrant connectivity between the SN and DMN/CEN suggests disrupted network switching in FEP patients, although CHR subjects showed trend-level SN-DMN dysconnectivity. Our findings suggest that dysfunctional triple-network dynamics centered on the SN can appear in patients in the early stages of psychotic disorders.

Prediction of psychosis: model development and internal validation of a personalized risk calculator.

BACKGROUND: Over the past two decades, early detection and early intervention in psychosis have become essential goals of psychiatry. However, clinical impressions are insufficient for predicting psychosis outcomes in clinical high-risk (CHR) individuals; a more rigorous and objective model is needed. This study aims to develop and internally validate a model for predicting the transition to psychosis within 10 years. METHODS: Two hundred and eight help-seeking individuals who fulfilled the CHR criteria were enrolled from the prospective, naturalistic cohort program for CHR at the Seoul Youth Clinic (SYC). The least absolute shrinkage and selection operator (LASSO)-penalized Cox regression was used to develop a predictive model for a psychotic transition. We performed k-means clustering and survival analysis to stratify the risk of psychosis. RESULTS: The predictive model, which includes clinical and cognitive variables, identified the following six baseline variables as important predictors: 1-year percentage decrease in the Global Assessment of Functioning score, IQ, California Verbal Learning Test score, Strange Stories test score, and scores in two domains of the Social Functioning Scale. The predictive model showed a cross-validated Harrell's C-index of 0.78 and identified three subclusters with significantly different risk levels. CONCLUSIONS: Overall, our predictive model showed a predictive ability and could facilitate a personalized therapeutic approach to different risks in high-risk individuals.

Thalamocortical dysrhythmia in patients with schizophrenia spectrum disorder and individuals at clinical high risk for psychosis.

Thalamocortical dysrhythmia (TCD) is a model characterized by abnormal resting-state thalamic oscillatory patterns where the alpha rhythm is replaced by cross-frequency coupling of low- and high-frequency rhythms. Although disrupted thalamic function is a suggested important pathophysiological mechanism underlying schizophrenia, knowledge regarding the TCD model in schizophrenia spectrum disorder (SSD) patients and individuals at clinical high risk (CHR) for psychosis is limited. A total of 169 SSD patients, 106 individuals at CHR for psychosis, and 105 healthy controls (HCs) underwent resting-state electroencephalography recordings. We performed mean global field power (MGFP) spectral analysis between 1 and 49 Hz as well as source-level theta phase-gamma amplitude coupling (TGC) analysis and compared resting-state oscillatory patterns across groups. Correlations between altered TGC values and psychotic symptom severity in the patient group were investigated. Spectral MGFP of low- and high-frequencies was larger in the SSD and CHR groups than in the HC group. The TGC of SSD patients was greater than that of HCs in the right frontal, right parietal, and left and right limbic lobes. Greater TGC in the right frontal and limbic lobes was associated with positive symptom severity in SSD patients. However, TGC in the CHR group was comparable to that in the HCs and was smaller than that in the SSD group in widespread cortical regions. The TCD pattern may be apparent after frank psychotic disorder onset in tandem with overt positive symptoms. A psychosis-risk state without overt psychotic symptoms could be characterized by abnormally increased low- and high-frequency activities with relatively preserved TGC.

Sex differences in the behavioral inhibition system and ventromedial prefrontal cortex connectivity.

The reinforcement sensitivity theory proposes brain-behavioral systems that underlie individual differences in sensitivity to punishment and reward. Such trait sensitivity is assessed using the behavioral inhibition/activation system (BIS/BAS) scales. Recent studies have reported sex-linked neuroanatomical correlates of the BIS/BAS, especially in the regions belonging to the valuation and salience networks that are associated with the representation of subjective value (SV), whereas less effort has been focused on investigating the neurofunctional aspects associated with sex differences in the BIS/BAS. We tested whether functional connectivity (FC) of the regions associated with the representation of SV mediates the relationship between sex and BIS sensitivity in healthy young adults by using resting-state functional magnetic resonance imaging data and self-reported BIS/BAS measures. Compared with males, females had heightened BIS sensitivity and increased FC between the ventromedial prefrontal cortex (vmPFC) seed and posterior parietal areas; this FC mediated the impact of sex on BIS sensitivity. Given that the observed vmPFC FC maps are considered part of the default-mode network, which is involved in ruminative processes, and that the BIS is associated with rumination and negative affect, our results may have implications for psychiatric disorders such as depression and anxiety, both of which have high incidence in females.

Intrinsic cerebellar functional connectivity of social cognition and theory of mind in first-episode psychosis patients.

Neuroimaging studies have revealed how intrinsic dysconnectivity among cortical regions of the mentalizing network (MENT) and the mirror neuron system (MNS) could explain the theory of mind (ToM) deficit in schizophrenia patients. However, despite the concurrent involvement of the cerebellum with the cortex in social cognition, the dysfunction in intrinsic interplay between the cerebellar nodes of MENT/MNS and the cortex in schizophrenia patients remains unknown. Thus, we aimed to investigate whether resting-state cerebello-cortical dysconnectivity exists in first-episode psychosis (FEP) patients in relationship with their ToM deficit. A total of 37 FEP patients and 80 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Using a priori-defined cerebellar seeds that functionally connect to the MENT (right crus II) and MNS (right crus I), we compared cerebello-cortical functional connectivities (FCs) in FEP patients and HCs. Correlations between cerebello-parietal connectivities and ToM performance were investigated in FEP patients. FEP patients showed hyperconnectivity between the right crus II and anterior cingulate gyrus and between the right crus I and supplementary motor area, bilateral postcentral gyrus, and right central/parietal operculum (CO/PO). Hypoconnectivity was found between the right crus II and left supramarginal gyrus (SMG) in FEP patients. FCs between the right crus II and left SMG and between the right crus I and right CO/PO were significantly correlated with ToM scores in FEP patients. In accordance with the "cognitive dysmetria" hypothesis, our results highlight the importance of cerbello-cortical dysconnectivities in understanding social cognitive deficits in schizophrenia patients.

Systematic Review of the Neural Effect of Electroconvulsive Therapy in Patients with Schizophrenia: Hippocampus and Insula as the Key Regions of Modulation.

OBJECTIVE: Electroconvulsive therapy (ECT) has been the most potent treatment option for treatment-resistant schizophrenia (TRS). However, the underlying neural mechanisms of ECT in schizophrenia remain largely unclear. This paper examines studies that investigated structural and functional changes after ECT in patients with schizophrenia. METHODS: We carried out a systematic review with following terms: 'ECT', 'schizophrenia', and the terms of various neuroimaging modalities. RESULTS: Among the 325 records available from the initial search in May 2020, 17 studies were included. Cerebral blood flow in the frontal, temporal, and striatal structures was shown to be modulated (n=3), although the results were divergent. Magnetic resonance spectroscopy (MRS) studies suggested that the ratio of N-acetyl-aspartate/creatinine was increased in the left prefrontal cortex (PFC; n=2) and left thalamus (n=1). The hippocampus and insula (n=6, respectively) were the most common regions of structural/functional modulation, which also showed symptom associations. Functional connectivity of the default mode network (DMN; n=5), PFC (n=4), and thalamostriatal system (n=2) were also commonly modulated. CONCLUSION: Despite proven effectiveness, there has been a dearth of studies investigating the neurobiological mechanisms underlying ECT. There is preliminary evidence of structural and functional modulation of the hippocampus and insula, functional changes in the DMN, PFC, and thalamostriatal system after ECT in patients with schizophrenia. We discuss the rationale and implications of these findings and the potential mechanism of action of ECT. More studies evaluating the mechanisms of ECT are needed, which could provide a unique window into what leads to treatment response in the otherwise refractory TRS population.

Smaller volume of posterior thalamic nuclei in patients with obsessive-compulsive disorder.

AIM: Although the thalamus is a key structure in the pathophysiology of obsessive-compulsive disorder (OCD), reports regarding thalamic volume alterations in OCD patients have been inconsistent. Because the thalamus has a complex structure with distinct functions, we investigated subregional volume changes in the thalamus and their relationship with clinical attributes in a large sample of medication-free OCD patients. METHODS: We collected T1-weighted magnetic resonance imaging data from 177 OCD patients and 152 healthy controls (HCs). Using FreeSurfer, we segmented the thalamus into 12 nuclei groups; subregional volumes were compared between groups using an analysis of covariance. The relationships between altered thalamic volumes and OC symptom severity and OCD onset age were investigated. RESULTS: Compared to HCs, OCD patients showed a smaller volume of the left posterior thalamic nuclei. Other thalamic subregions did not show significant group differences. There was a significant negative correlation between the volume of the left posterior thalamic nuclei and the age of OCD onset but no significant correlation with OC symptom severity. CONCLUSIONS: This is the first study to report reduced volume of the posterior thalamic nuclei in a large sample of medication-free OCD patients. Our results suggest that the volume of posterior thalamic nuclei may reflect different pathophysiological mechanisms of OCD subtypes related to the age of onset. Additional studies with pediatric samples are required to clarify the relationship between thalamic alterations and the onset age of OCD.

Impaired error-related processing in patients with first-episode psychosis and subjects at clinical high risk for psychosis: An event-related potential study.

AIM: Impaired event-related potential (ERP) indices reflecting performance-monitoring systems have been consistently reported in patients with schizophrenia. However, whether these impairments exist from the beginning of the early phase of psychosis, such as in first-episode psychosis (FEP) patients and individuals at clinical high risk (CHR) for psychosis, has not yet been clearly ascertained. METHODS: Thirty-seven FEP patients, 22 CHR subjects, and 22 healthy controls (HC) performed a visual go/no-go task so that three ERP components associated with performance monitoring-error-related negativity (ERN), correct response negativity (CRN), and error positivity (Pe) -could be assessed. Repeated-measures analysis of variance (ANOVA) with age and sex as covariates was used to compare ERN, CRN, and Pe across the groups. RESULTS: Repeated-measures ANOVA with age and sex as covariates revealed that compared with HC, FEP patients and CHR subjects showed significantly smaller ERN amplitudes at the Fz (F = 4.980, P = 0.009) and FCz (F = 3.453, P = 0.037) electrode sites. Neither CRN nor Pe amplitudes showed significant differences across the FEP, CHR, and HC groups. CONCLUSION: These findings suggest that performance monitoring is already compromised during the early course of psychotic disorders, evident in FEP patients and CHR subjects, as reflected in the reduced ERN amplitude. Considering these findings, ERN could serve as a potential indicator of early-stage psychosis.

Reduced cortical gyrification in the posteromedial cortex in unaffected relatives of schizophrenia patients with high genetic loading.

Although abnormal cortical gyrification has been consistently reported in patients with schizophrenia, whether gyrification abnormalities reflect a genetic risk for the disorder remains unknown. This study investigated differences in cortical gyrification between unaffected relatives (URs) with high genetic loading for schizophrenia and healthy controls (HCs) to identify potential genetic vulnerability markers. A total of 50 URs of schizophrenia patients and 50 matched HCs underwent T1-weighted magnetic resonance imaging to compare whole-brain gyrification using the local gyrification index (lGI). Then, the lGI clusters showing significant differences were compared between the UR subgroups based on the number of first-degree relatives with schizophrenia to identify the effect of genetic loading on cortical gyrification changes. The URs exhibited significantly lower cortical gyrification than the HCs in clusters including medial parieto-occipital and cingulate regions comprising the bilateral precuneus, cuneus, pericalcarine, lingual, isthmus cingulate, and posterior cingulate gyri. Moreover, URs who had two or more first-degree relatives with schizophrenia showed greater gyrification reductions in these clusters than those who had at least one first-degree relative with schizophrenia. Our findings of reduced gyrification in URs, which are consistent with accumulated evidence of hypogyria observed in regions showing patient-control differences in previous studies, highlight that such hypogyria in posteromedial regions may serve as a genetic vulnerability marker and reflect early neurodevelopmental abnormalities resulting from a genetic risk for schizophrenia.

White Matter Correlates of Theory of Mind in Patients With First-Episode Psychosis.

Deficits in theory of mind (ToM) are considered as a distinctive feature of schizophrenia. Functional magnetic resonance imaging (fMRI) studies have suggested that aberrant activity among the regions comprising the mentalizing network is related to observed ToM deficits. However, the white matter structures underlying the ToM functional network in schizophrenia remain unclear. To investigate the relationship between white matter integrity and ToM impairment, 35 patients with first-episode psychosis (FEP) and 29 matched healthy controls (HCs) underwent diffusion tensor imaging (DTI). Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) values of the two regions of interest (ROI)-the cingulum and superior longitudinal fasciculus (SLF)-were acquired, and correlational analysis with ToM task scores was performed. Among the patients with FEP, ToM strange story scores were positively correlated with the FA values of the left cingulum and left SLF. There was no significant correlation between FA and ToM task scores in HCs. These results suggest that the left cingulum and SLF constitute a possible neural basis for ToM deficits in schizophrenia. Our study is the first to demonstrate the white matter connectivity underlying the mentalizing network, as well as its relation to ToM ability in patients with FEP.

Reliability and validity of the Korean version of the comprehensive assessment of at-risk mental states.

AIM: Although the comprehensive assessment of at-risk mental states (CAARMS) is one of the most widely used instruments for identifying individuals meeting the criteria for ultra-high risk (UHR) of developing psychosis, the psychometric properties of the Korean version of the CAARMS (CAARMS-K) have not been studied to date. Thus, we tested the reliability, validity, and factor structure of the CAARMS-K in a Korean population. METHODS: The CAARMS-K was administered to 96 UHR individuals. The inter-rater reliability and internal consistency of the CAARMS-K were evaluated. In addition, its factor structure was investigated using principal-axis factor analysis. Concurrent validity was examined by comparing the extracted CAARMS-K factors with the five factors of the positive and negative syndrome scale (PANSS) using Spearman's correlation tests. The percentage of transition to psychosis was examined at 1- and 2-year. RESULTS: The inter-rater reliability was good (intraclass correlation = .89), and the internal consistency was acceptable (Cronbach's alpha = .812). A five-factor solution demonstrated the best simple structure and accounted for 43.1% of all-item variance. The five factors extracted from the factor analysis were similar to the PANSS five factors and significantly correlated with the factors of the PANSS. Among the 96 UHR individuals, 11 (11.5%) and 17 (17.7%) developed psychotic disorders during the 1- and 2-year follow-up, respectively. CONCLUSIONS: The CAARMS-K is a reliable and valid instrument for the assessment of UHR individuals in Korea.