Predicting delirium and the effects of medications in hospitalized COVID-19 patients using machine learning: A retrospective study within the Korean Multidisciplinary Cohort for Delirium Prevention (KoMCoDe).

Objective: Delirium is commonly reported from the inpatients with Coronavirus disease 2019 (COVID-19) infection. As delirium is closely associated with adverse clinical outcomes, prediction and prevention of delirium is critical. We developed a machine learning (ML) model to predict delirium in hospitalized patients with COVID-19 and to identify modifiable factors to prevent delirium. Methods: The data set (n = 878) from four medical centers was constructed. Total of 78 predictors were included such as demographic characteristics, vital signs, laboratory results and medication, and the primary outcome was delirium occurrence during hospitalization. For analysis, the extreme gradient boosting (XGBoost) algorithm was applied, and the most influential factors were selected by recursive feature elimination. Among the indicators of performance for ML model, the area under the curve of the receiver operating characteristic (AUROC) curve was selected as the evaluation metric. Results: Regarding the performance of developed delirium prediction model, the accuracy, precision, recall, F1 score, and the AUROC were calculated (0.944, 0.581, 0.421, 0.485, 0.873, respectively). The influential factors of delirium in this model included were mechanical ventilation, medication (antipsychotics, sedatives, ambroxol, piperacillin/tazobactam, acetaminophen, ceftriaxone, and propacetamol), and sodium ion concentration (all p < 0.05). Conclusions: We developed and internally validated an ML model to predict delirium in COVID-19 inpatients. The model identified modifiable factors associated with the development of delirium and could be clinically useful for the prediction and prevention of delirium in COVID-19 inpatients.

Effects of Oxytocin on Social Comparisons in Intergroup Situations.

Oxytocin (OXT) is known to affect various social processes, including social comparisons and intergroup competition. In this study, we examined whether social comparisons in intergroup situations can be modulated by OXT and, if so, how this modulation manifests. Using a double-blind placebo-controlled design, we randomly assigned male participants to either OXT or placebo treatment and then asked them to play a card game with either an in-group or an out-group member. The OXT-treated participants showed a greater social comparison effect in the games with an out-group member than in games with an in-group member. Specifically, the participants in the OXT treatment condition showed a greater acceptance rate for relative gain (downward comparison) and a lower acceptance rate for relative loss (upward comparison) while playing with an out-group member rather than an in-group member. In contrast, no such effect was observed among placebo-treated participants. These findings demonstrate that OXT facilitates intergroup social comparisons with out-group versus in-group members.

Practice patterns of surgery for advanced ovarian cancer: analysis from international surveys.

BACKGROUND: We investigated the practice patterns of surgery for advanced ovarian cancer (AOC) through relevant international surveys. METHODS: After searching for 878 studies on surgery for AOC till 2017, we extracted 18 questions with similar query and answer formats from eight studies. Among them, 5 and 13 were classified as comprehensive and procedure information. RESULTS: In comprehensive information, there was a higher preference for optimal cytoreduction defined as no visible tumor (44%) compared with residual tumors <1 cm (38%) or <2 cm (2%) and omental disease involving the spleen or pancreas was more important as an intraoperative finding precluding optimal cytoreduction (35%) since 2010. The preference for neoadjuvant chemotherapy was the highest at its use for 1-10% (36%), which was preferred in Europe over USA. The positive expectation of preoperative determination of optimal cytoreduction was higher in Europe than in USA (44 vs. 27%; P < 0.05). In procedure information, conventional gynecological surgery was mainly performed by gynecological oncologists, whereas more than 50% of upper abdominal or urological surgeries were conducted by other surgeons. European clinicians showed a higher response rate of diaphragmatic stripping and resection than those from USA (88 vs. 60%; 69 vs. 24%; P < 0.05). CONCLUSION: No visible tumor as the criterion for optimal cytoreduction was preferred in AOC, and aggressive surgery beyond conventional gynecological surgery tended to be performed by other surgeons. Moreover, the preference of neoadjuvant chemotherapy and the positive expectation of preoperative determination of optimal cytoreduction were higher in Europe than in USA.

The Effects of Continuation-Maintenance Electroconvulsive Therapy on Reducing Hospital Re-Admissions in Patients with Treatment-Resistant Schizophrenia.

OBJECTIVE: Continuation-maintenance electroconvulsive therapy (C/M-ECT) is used to prevent relapse or recurrence in patients with severe mental illnesses. We aimed to investigate the effect of C/M-ECT on reducing hospital re-admissions in patients with treatment-resistant schizophrenia. METHODS: We applied a mirror-image design by retrospectively examining re-hospitalization rates of 18 patients with schizophrenia spectrum disorders. We compared the numbers of psychiatric admissions during the actual period over which C/M-ECT was administered with the same period prior to the beginning of C/M-ECT. RESULTS: The number of psychiatric admissions was reduced significantly during C/M-ECT (0.33±0.77) compared with that of the same period prior to C/M-ECT (2.67±1.33) (Wilcoxon signed rank Z=-3.663; p＜0.001). CONCLUSION: This finding shows that C/M-ECT augmentation could successfully reduce the re-hospitalization rates in patients with treatment-resistant schizophrenia.

Increased Attentional Bias Toward Visual Cues in Internet Gaming Disorder and Obsessive-Compulsive Disorder: An Event-Related Potential Study.

Internet gaming disorder (IGD) is a newly identified potential addiction disorder associated with compulsive internet-game playing behavior and attentional bias toward online gaming- related cues. Attentional bias toward addiction-related cues is the core feature of addiction that is associated with craving, but the pathophysiology of attentional bias in IGD is not well-understood, such as its relationship to compulsivity. In this study, we used the electrophysiological marker of late positive potential (LPP) to compare attentional bias in IGD and obsessive compulsive disorder (OCD). Twenty patients with IGD, 20 patients with OCD, and 23 healthy control (HC) subjects viewed a series of game-related, OCD-related, and neutral pictures while their event-related potentials (ERPs) were recorded. The game-related cues included in-game screen captures of popular internet games. The OCD-related cues included pictures which provokes obsessive and compulsive symptoms of contamination/washing or checking. LPPs were calculated as the mean value of amplitudes between 350 and 750 ms at the centro-parietal (CP1, CPz, CP2) and parietal (P1, Pz, P2) electrode sites. Higher LPP amplitudes were found for game-related cues in the IGD group than in the HCs, and higher LPP amplitudes were observed in the OCD group for OCD-related cues. The IGD group did not exhibit LPP changes in response to OCD-related cues. Subjective scales demonstrated increased arousal to game-related cues and OCD-related cues in both the IGD and OCD groups compared with the HC group. Increased LPPs in response to disorder-specific cues (game-related and OCD-related) were found in both IGD and OCD groups respectively, although the groups showed overlapping arousal on subjective scales. Our results indicate that LPP is a candidate neurophysiological marker for cue-related craving in IGD.

Longitudinal Changes in Neural Connectivity in Patients With Internet Gaming Disorder: A Resting-State EEG Coherence Study.

Aims: The present study investigated neural connectivity associated with treatment responses in patients with Internet gaming disorder (IGD) using resting-state electroencephalography (EEG) coherence analyses. Methods: We included 30 patients with IGD and 32 healthy control subjects (HCs). Of the IGD patients, 18 completed an outpatient treatment that included pharmacotherapy with selective serotonin reuptake inhibitors for 6 months. Resting-state EEG coherence and self-report questionnaires were used to evaluate clinical and psychological features pre- and post-treatment, and data were analyzed using generalized estimating equations. Results: Compared with HCs, patients with IGD showed increased beta and gamma intrahemispheric coherence and increased delta intrahemispheric coherence of the right hemisphere at baseline. After 6 months of outpatient management, patients with IGD exhibited improvements in IGD symptoms compared with baseline, but they continued to show increased beta and gamma intrahemispheric coherence compared with that of HCs. No significant EEG coherence changes between the pre- and post-treatment assessments were detected in any band in the IGD group. Conclusion: These findings suggest that significantly greater intrahemispheric fast-frequency coherence may be an important neurophysiological trait marker of patients with IGD.

Early referral and comorbidity as possible causes of the declining transition rate in subjects at clinical high risk for psychosis.

AIM: A clinical high risk (CHR) for psychosis is regarded as the state of being at risk of developing psychosis. However, the rate of transition to psychosis among CHR subjects has been declining over time. We aimed to investigate the effects of the possible causes of the declining transition rate. METHODS: A total of 129 CHR subjects were divided into two groups according to the date of enrollment: the 2005-2009 group and the 2009-2013 group. Baseline demographic and clinical characteristics, including medication prescription, were compared. The duration of untreated prodromal positive symptoms (DUPP) was used to account for early referral. RESULTS: The transition rate to psychosis in the 2009-2013 group was significantly lower than that in the 2005-2009 group (χ2 = 4.664, P = 0.031), although the risk factors of transition, intelligence quotient and prodromal positive symptoms did not differ between the two groups. When the DUPP was added to the follow-up duration, the between-group difference in the transition rates was no longer significant; however, the P-value was low (χ2 = 2.761, P = 0.097). After adjusting for axis II comorbidities other than schizotypal personality disorder, the effect of group division on the transition rate disappeared; however, the P-value was also low (P = 0.072). The mean olanzapine equivalent dose and the proportion of subjects prescribed with antidepressant or anxiolytic did not differ between the two groups. CONCLUSIONS: Early referral and axis II comorbidities other than schizotypal personality disorder were associated with the declining transition rate.

Association of TNF-alpha G-308A gene polymorphism with depression: a meta-analysis.

BACKGROUND: Although many studies have investigated the association of a single nucleotide polymorphism in TNF-α G-308A gene with depression, their association is still controversial. To clarify this, we performed a meta-analysis. METHOD: Studies related to TNF-α G-308A and depression were retrieved from PubMed, Medline, Embase, and Scopus (up to April 18, 2017). The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in the models of allele comparison (G vs A), homozygote comparison (GG vs AA), dominant (GG vs GA + AA), and recessive (GG + GA vs AA) to estimate the strength of the associations. RESULTS: A total of 10 case-control studies were included in this meta-analysis. Overall, no significant association between TNF-α G-308A and depression was found (G vs A: OR [95% CI] =1.09 [0.92, 1.29]; GG vs AA: 1.24 [0.71, 2.15]; GG vs GA + AA: 1.01 [0.76, 1.35]; GG + GA vs AA: 1.22 [0.70, 2.13]). In subgroup analyses by ethnicity or age group, no statistically significant association between TNF-α G-308A polymorphisms and depression was shown. CONCLUSION: This meta-analysis revealed that TNF-α G-308A polymorphism is not associated with susceptibility to depression.

Impulsivity and compulsivity in Internet gaming disorder: A comparison with obsessive-compulsive disorder and alcohol use disorder.

Background and aims Internet gaming disorder (IGD) is characterized by a loss of control and a preoccupation with Internet games leading to repetitive behavior. We aimed to compare the baseline neuropsychological profiles in IGD, alcohol use disorder (AUD), and obsessive-compulsive disorder (OCD) in the spectrum of impulsivity and compulsivity. Methods A total of 225 subjects (IGD, N = 86; AUD, N = 39; OCD, N = 23; healthy controls, N = 77) were administered traditional neuropsychological tests including Korean version of the Stroop Color-Word test and computerized neuropsychological tests, including the stop signal test (SST) and the intra-extra dimensional set shift test (IED). Results Within the domain of impulsivity, the IGD and OCD groups made significantly more direction errors in SST (p = .003, p = .001) and showed significantly delayed reaction times in the color-word reading condition of the Stroop test (p = .049, p = .001). The OCD group showed the slowest reading time in the color-word condition among the four groups. Within the domain of compulsivity, IGD patients showed the worst performance in IED total trials measuring attentional set shifting ability among the groups. Conclusions Both the IGD and OCD groups shared impairment in inhibitory control functions as well as cognitive inflexibility. Neurocognitive dysfunction in IGD is linked to feature of impulsivity and compulsivity of behavioral addiction rather than impulse dyscontrol by itself.

The cost-effectiveness of deep brain stimulation for patients with treatment-resistant obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a chronic neuropsychiatric disorder with a 2% to 3% lifetime prevalence; in addition, 10% of OCD patients are resistant to conventional therapy. Deep brain stimulation (DBS) has been an effective treatment for treatment resistant OCD patients (TROCD). We aimed to determine the cost-effectiveness of DBS for TROCD. METHODS: We used a Markov model to estimate the cost-effectiveness of DBS compared to conventional treatment for TROCD with a 10-year time horizon. Published data were used to estimate the rates of treatment response and complications. Costs were calculated from the perspective of the third-party payer. Data on quality of life were obtained from a literature review and a survey of OCD patients. We applied the model separately to Korea and the United Kingdom (UK) to enhance the validity. RESULTS: Base-case analysis showed an incremental cost-effectiveness ratio of US$37,865 per quality-adjusted life-year in Korea and US$34,462 per quality-adjusted life-year in the UK. According to the World Health Organization's criteria, DBS for TROCD was "cost-effective" in Korea (<3x GDP per capita) and "highly cost-effective" in the UK (

Executive Dysfunction in Obsessive-Compulsive Disorder and Anterior Cingulate-Based Resting State Functional Connectivity.

OBJECTIVE: Executive dysfunction might be an important determinant for response to pharmacotherapy in obsessive-compulsive disorder (OCD), and could be sustained independently of symptom relief. The anterior cingulate cortex (ACC) has been indicated as a potential neural correlate of executive functioning in OCD. The present study examined the brain-executive function relationships in OCD from the ACC-based resting state functional connectivity networks (rs-FCNs), which reflect information processing mechanisms during task performance. METHODS: For a total of 58 subjects [OCD, n=24; healthy controls (HCs), n=34], four subdomains of executive functioning were measured using the Rey-Osterrieth Complex Figure Test (RCFT), the Stroop Color-Word Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Trail Making Test part B (TMT-B). To probe for differential patterns of the brain-cognition relationship in OCD compared to HC, the ACC-centered rs-FCN were calculated using five seed regions systemically placed throughout the ACC. RESULTS: Significant differences between the OCD group and the HCs with respect to the WCST perseverative errors, SCWT interference scores, and TMT-B reaction times (p<0.05) were observed. Moreover, significant interactions between diagnosis×dorsal ACC [S3]-based rs-FCN strength in the right dorsolateral prefrontal cortex for RCFT organization summary scores as well as between diagnosis×perigenual ACC [S7]-based rs-FCN strength in the left frontal eye field for SCWT color-word interference scores were unveiled. CONCLUSION: These network-based neural foundations for executive dysfunction in OCD could become a potential target of future treatment, which could improve global domains of functioning broader than symptomatic relief.

Brain network characteristics separating individuals at clinical high risk for psychosis into normality or psychosis.

We aimed to separate individuals at clinical high risk for psychosis (CHR) state into subgroups according to neurobiological characteristics using structural and functional network constructs and examine their clinical characteristics. Structural diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed in 61 healthy controls (HC), 57 individuals at CHR and 29 patients with schizophrenia (SZ). The main outcome was a likelihood ratio calculated from measures of structural and functional network efficiencies, coupling strength of structural and functional networks, and a disease-specific data analysis, resulting in the most probable classification of CHR into HC or SZ. The likelihood ratios revealed that 33 individuals at CHR were likely similar to HC (CHR-HC), and the remaining 24 CHR individuals were similar to SZ (CHR-SZ). The CHR subgroups were comparable to each other in demographic characteristics and clinical symptoms. However, the verbal and executive functions of CHR-HC were similar to those of HC, and those of CHR-SZ similar to SZ. Additionally, CHR-SZ was more responsive to treatment than CHR-HC during the follow-up period. By combining structural and functional data, we could detect the vulnerable population and provide an active intervention in the early phase of the CHR state.

Reconsidering Clinical Staging Model: A Case of Genetic High Risk for Schizophrenia.

The clinical staging model is considered a useful and practical method not only in dealing with the early stage of psychosis overcoming the debate about diagnostic boundaries but also in emerging mood disorder. However, its one limitation is that it cannot discriminate the heterogeneity of individuals at clinical high risk for psychosis, but lumps them all together. Even a healthy offspring of schizophrenia can eventually show clinical symptoms and progress to schizophrenia under the influence of genetic vulnerability and environmental stress even after the peak age of onset of schizophrenia. Therefore, individuals with genetic liability of schizophrenia may require a more intensive intervention than recommended by the staging model based on current clinical status.

Neurophysiological correlates of altered response inhibition in internet gaming disorder and obsessive-compulsive disorder: Perspectives from impulsivity and compulsivity.

Although internet gaming disorder (IGD) and obsessive-compulsive disorder (OCD) represent opposite ends of the impulsivity and compulsivity dimensions, the two disorders share common neurocognitive deficits in response inhibition. However, the similarities and differences in neurophysiological features of altered response inhibition between IGD and OCD have not been investigated sufficiently. In total, 27 patients with IGD, 24 patients with OCD, and 26 healthy control (HC) subjects participated in a Go/NoGo task with electroencephalographic recordings. N2-P3 complexes elicited during Go and NoGo condition were analyzed separately and compared among conditions and groups. NoGo-N2 latency at the central electrode site was delayed in IGD group versus the HC group and correlated positively with the severity of internet game addiction and impulsivity. NoGo-N2 amplitude at the frontal electrode site was smaller in OCD patients than in IGD patients. These findings suggest that prolonged NoGo-N2 latency may serve as a marker of trait impulsivity in IGD and reduced NoGo-N2 amplitude may be a differential neurophysiological feature between OCD from IGD with regard to compulsivity. We report the first differential neurophysiological correlate of the altered response inhibition in IGD and OCD, which may be a candidate biomarker for impulsivity and compulsivity.

Altered functional network architecture in orbitofronto-striato-thalamic circuit of unmedicated patients with obsessive-compulsive disorder.

Dysfunction of corticostriatal loops has been proposed to underlie certain cognitive and behavioral problems associated with various neuropsychiatric disorders, such as obsessive-compulsive disorder (OCD) characterized by repetitive, unwanted thoughts, and behaviors. Although functional abnormalities in the loops involving the orbitofronto-striato-thalamic (OFST) circuitry in patients with OCD have been reported, our understanding of a link between disruptions in the architecture of the intrinsic functional network of the OFST circuit and their symptoms remain incomplete. Using resting-state functional MRI in conjunction with unsupervised clustering and multilevel functional connectivity (FC) techniques, FC of the OFST network and its topological organization in 61 OCD patients versus 61 matched controls were characterized. Patients exhibited disruptions in small-world properties of the OFST circuit, which indicates an imbalance between functional integration and segregation. Patients also showed decreased FC between the central orbitofrontal cortex and dorsomedial striatum but increased FC between the medial thalamus and striatal areas. Using one of the largest samples of unmedicated OCD patients to date, our findings provide evidence supporting the OFST dysconnection hypothesis in OCD as a basic pathophysiological mechanism underlying the disorder, showing the disruption of FC between specific cortical, striatal, and thalamic clusters and aberrant topological patterns of the OFST circuit. Hum Brain Mapp 38:109-119, 2017. © 2016 Wiley Periodicals, Inc.

Internet-Based Cognitive Behavioral Therapy for Obsessive-Compulsive Disorder in Korea.

OBJECTIVE: Cognitive behavioral therapy (CBT) is regarded as one of the most effective intervention for obsessive-compulsive disorder (OCD). However, many patients remain untreated or inadequately treated due to time or geographical constraints. The purpose of this study was to develop an internet-based CBT (ICBT) for OCD, and to examine its efficacy in the Korean clinical setting. METHODS: The ICBT program ('COT') was developed from the same OCD manual in the standard CBT intervention. Twenty-seven participants of the total 42 patients completed all training sessions of the ICBT and the remainder (n=15) were classified as non-completers. Self-report measures of OCD, depression, anxiety, and work/social functioning, in addition to a neurocognitive test battery, were administered by face-to-face before and after treatment. RESULTS: The participants showed significant improvements in OCD and depressive symptoms, and in work/social functioning after ICBT completion. The presence of combined medication had no significant impact on treatment effect. The non-completers displayed more severe depressive and anxiety symptoms, and ICBT responders were younger and performed better in the Wisconsin Card Sorting Test. CONCLUSION: ICBT was found to be as effective for patients with moderate OC symptoms and little treatment experience. Considering the high accessibility and convenience of ICBT, it could be a helpful first treatment step for OCD patients when face-to-face treatment is unavailable. In the future a randomized controlled study will be necessary for verification and generalization of these results.

Decreased neural response for facial emotion processing in subjects with high genetic load for schizophrenia.

BACKGROUND: Patients with schizophrenia show impairment in facial emotion processing which is essential for successful social cognition. Using a functional magnetic resonance imaging (fMRI), this study aimed to investigate the implicit facial emotion recognition processing in participants with high genetic load for schizophrenia (GHR) as a possible trait marker of developing schizophrenia. METHODS: Block design fMRI of implicit facial emotion processing was used in 20 participants with GHR aged 16-35, and 17 age, sex, and education year-matched healthy controls (HC). During the facial emotional processing for fearful, happy, and neutral face stimuli, participants were asked to explicitly determine the gender per stimuli. RESULTS: Occipito-temporo-limbic area in fearful face condition and involvement of broader region including prefrontal cortex in neutral face condition revealed significant attenuation of BOLD signal activation in GHR compared to HC. The GHR demonstrated less activity in right amygdala during fearful and neutral face condition. CONCLUSION: The study presented that GHR displayed abnormal brain activity in occipito-temporo-limbic-frontal network implicated in facial emotion processing. It indicates that abnormal facial emotion processing may be influenced by a genetic factor and could be a trait marker in schizophrenia.

Correction: Increased Intra-Individual Variability of Cognitive Processing in Subjects at Risk Mental State and Schizophrenia Patients.

[This corrects the article DOI: 10.1371/journal.pone.0078354.].

Longitudinal change in neurocognition and its relation to symptomatic and functional changes over 2years in individuals at clinical high-risk for psychosis.

BACKGROUND: Negative symptoms and functional disability represent the core of schizophrenia and both are associated with cognitive impairments. We explored the course of cognitive change and its relation to symptomatic and functional changes in individuals at clinical high-risk (CHR) for psychosis to identify cognitive indicators of long-term course. Such attempts may offer insight into the pathological changes associated with the development of illness in the prodromal state. METHODS: Forty-seven CHR individuals completed neurocognitive, clinical, and functional assessments at baseline and 2-year follow-up; twenty-eight healthy controls were assessed for neurocognitive and functional measures at baseline and 2-year follow-up. The delta values of CHR individuals in neurocognitive, clinical, and functional domains were determined from differences between baseline and follow-up scores to estimate the degree of change. RESULTS: Although overall longitudinal cognitive performance of CHR individuals improved, the magnitude of improvement was not statistically different from that of normal controls at the group level. However, the individual data yielded two groups of CHR subjects showing opposite trajectories of cognitive change in semantic fluency (i.e., improvement or decline), which was significantly associated with changes in negative symptoms and functioning. Moreover, the relationships between negative symptoms and functioning were more strengthened over time than baseline. CONCLUSIONS: Our findings show that semantic fluency seems to be a neurocognitive indicator reflecting clinical courses in CHR individuals. The longitudinal relationship of negative symptoms and functioning with semantic fluency may represent ongoing pathological processes in neural systems involving aberrant fronto-temporal interaction in the early phase of schizophrenia.

Altered Thalamo-Cortical White Matter Connectivity: Probabilistic Tractography Study in Clinical-High Risk for Psychosis and First-Episode Psychosis.

Disrupted thalamo-cortical connectivity is regarded as a core psychopathology in patients diagnosed with schizophrenia. However, whether the thalamo-cortical white matter connectivity is disrupted before the onset of psychosis is still unknown. To determine this gap in knowledge, the strength of thalamo-cortical white matter anatomical connectivity in subjects at clinical-high risk for psychosis (CHR) was compared to that of first-episode psychosis (FEP) and healthy controls. A total of 37 CHR, 21 FEP, and 37 matched healthy controls underwent diffusion-weighted magnetic resonance imaging to examine the number of probabilistic tractography "counts" representing thalamo-cortical white matter connectivity. We also investigated the relationship with psychopathology. For FEP, the connectivity between the thalamus and parietal cortex was significantly increased (F= 5.65,P< .05) compared to that of healthy controls. However, the connectivity between thalamus and orbitofrontal cortex was significantly reduced compared to both healthy controls (F= 11.86,P< .005) and CHR (F= 6.63,P< .05). Interestingly, CHR exhibited a similar pattern as FEP, albeit with slightly reduced magnitude. Compared to healthy controls, there was a significant decrease (F= 4.16,P< .05) in CHR thalamo-orbitofrontal connectivity. Also, the strength of the thalamo-orbitofrontal connectivity was correlated with the Global Assessment of Functioning score in CHR (r= .35,P< .05). This observed pattern of white matter connectivity disruptions in FEP and in CHR suggests that this pattern of disconnectivity not only highlights the involvement of thalamus but also might be useful as an early biomarker for psychosis.