Publications by authors named "Jun Soo Kwon"

354 Publications

Mapping thalamocortical functional connectivity with large-scale brain networks in patients with first-episode psychosis.

Sci Rep 2021 Oct 6;11(1):19815. Epub 2021 Oct 6.

Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea.

Abnormal thalamocortical networks involving specific thalamic nuclei have been implicated in schizophrenia pathophysiology. While comparable topography of anatomical and functional connectivity abnormalities has been reported in patients across illness stages, previous functional studies have been confined to anatomical pathways of thalamocortical networks. To address this issue, we incorporated large-scale brain network dynamics into examining thalamocortical functional connectivity. Forty patients with first-episode psychosis and forty healthy controls underwent T1-weighted and resting-state functional magnetic resonance imaging. Independent component analysis of voxelwise thalamic functional connectivity maps parcellated the cortex into thalamus-related networks, and thalamic subdivisions associated with these networks were delineated. Functional connectivity of (1) networks with the thalamus and (2) thalamic subdivision seeds were examined. In patients, functional connectivity of the salience network with the thalamus was decreased and localized to the ventrolateral (VL) and ventroposterior (VP) thalamus, while that of a network comprising the cerebellum, temporal and parietal regions was increased and localized to the mediodorsal (MD) thalamus. In patients, thalamic subdivision encompassing the VL and VP thalamus demonstrated hypoconnectivity and that encompassing the MD and pulvinar regions demonstrated hyperconnectivity. Our results extend the implications of disrupted thalamocortical networks involving specific thalamic nuclei to dysfunctional large-scale brain network dynamics in schizophrenia pathophysiology.
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http://dx.doi.org/10.1038/s41598-021-99170-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494789PMC
October 2021

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

Neuropsychopharmacology 2021 Oct 4. Epub 2021 Oct 4.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.1038/s41386-021-01180-6DOI Listing
October 2021

Effects of Oxytocin on Social Comparisons in Intergroup Situations.

Brain Sci 2021 Sep 17;11(9). Epub 2021 Sep 17.

Department of Psychology, Korea University, Seoul 02841, Korea.

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.
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http://dx.doi.org/10.3390/brainsci11091227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466309PMC
September 2021

Eye movement as a biomarker of impaired organizational strategies during visual memory encoding in obsessive-compulsive disorder.

Sci Rep 2021 Sep 15;11(1):18402. Epub 2021 Sep 15.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

The symptoms of obsessive-compulsive disorder (OCD) are largely related to impaired executive functioning due to frontostriatal dysfunction. To better treat OCD, the development of biomarkers to bridge the gap between the symptomatic-cognitive phenotype and brain abnormalities is warranted. Therefore, we aimed to identify biomarkers of impaired organizational strategies during visual encoding processes in OCD patients by developing an eye tracking-based Rey-Osterrieth complex figure test (RCFT). In 104 OCD patients and 114 healthy controls (HCs), eye movements were recorded during memorization of the RCFT figure, and organizational scores were evaluated. Kullback-Leibler divergence (KLD) scores were calculated to evaluate the distance between a participant's eye gaze distribution and a hypothetical uniform distribution within the RCFT figure. Narrower gaze distributions within the RCFT figure, which yielded higher KLD scores, indicated that the participant was more obsessed with detail and had less organizational strategy. The OCD patients showed lower organizational scores than the HCs. Although no group differences in KLD scores were noted, KLD scores were significantly associated with organization T scores in the OCD group. The current study findings suggest that eye tracking biomarkers of visual memory encoding provide a rapidly determined index of executive functioning, such as organizational strategies, in OCD patients.
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http://dx.doi.org/10.1038/s41598-021-97885-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443551PMC
September 2021

Predictive protein markers for depression severity in mood disorders: A preliminary trans-diagnostic approach study.

J Psychiatr Res 2021 Oct 24;142:63-72. Epub 2021 Jul 24.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea. Electronic address:

Depression is a common symptom of many mental disorders, especially major depressive disorder (MDD) and bipolar disorder (BD). Previous studies have reported that these diseases share common pathophysiological pathways; therefore, this study elucidated whether the plasma levels of protein markers related to common depressive symptoms differed between patients with BD and those with MDD. Plasma samples of 71 patients with mood disorders and clinical manifestations were analyzed in this study. After depleting the abundant proteins, liquid chromatography-tandem mass spectrometry and label-free quantification were performed. Five proteins, viz., cholesteryl ester transfer protein (CETP), apolipoprotein D (APOD), mannan-binding lectin serine protease 2 (MASP2), Ig lambda chain V-II region BO (IGLV2-8) and Ig kappa chain V-III region NG9 (IGKV3-20) were negatively associated with the total scores of the Hamilton depression rating scale (HAM-D), after adjusting for the covariates. CETP and APOD also showed significant negative correlations with the anhedonia/retardation and guilt/agitation scores of the HAM-D. Four proteins, namely, Ig kappa chain V-II region TEW (IGKC; IGKV2D-28), Ig lambda variable 5-45 (IGLV5-45), complement factor H (CFH) and attractin (ATRN), showed significant associations with anhedonia/retardation after adjusting for covariates. Proteins that significantly correlated with the symptoms could predict the remission state of depression (area under the curve [AUC], 0.83) and anhedonia/retardation (AUC, 0.80). Bioinformatics analysis revealed that complement activation, immune response, and lipid metabolism were significantly enriched pathways. Although our study design was cross-sectional and no controls were included, protein markers identified in this preliminary study will be further investigated in our subsequent longitudinal study.
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http://dx.doi.org/10.1016/j.jpsychires.2021.07.041DOI Listing
October 2021

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

Psychiatry Investig 2021 Jun 24;18(6):486-499. Epub 2021 Jun 24.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.30773/pi.2020.0438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256139PMC
June 2021

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

Neuroimage Clin 2021 21;30:102686. Epub 2021 Apr 21.

Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.1016/j.nicl.2021.102686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102624PMC
July 2021

Brain Activation of Patients With Obsessive-Compulsive Disorder During a Mental Rotation Task: A Functional MRI Study.

Front Psychiatry 2021 7;12:659121. Epub 2021 May 7.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.

Functional neuroimaging studies have implicated alterations in frontostriatal and frontoparietal circuits in obsessive-compulsive disorder (OCD) during various tasks. To date, however, brain activation for visuospatial function in conjunction with symptoms in OCD has not been comprehensively evaluated. To elucidate the relationship between neural activity, cognitive function, and obsessive-compulsive symptoms, we investigated regional brain activation during the performance of a visuospatial task in patients with OCD using functional magnetic resonance imaging (fMRI). Seventeen medication-free patients with OCD and 21 age-, sex-, and IQ-matched healthy controls participated in this study. Functional magnetic resonance imaging data were obtained while the subjects performed a mental rotation (MR) task. Brain activation during the task was compared between the two groups using a two-sample -test. Voxel-wise whole-brain multiple regression analyses were also performed to examine the relationship between obsessive-compulsive symptom severity and neural activity during the task. The two groups did not differ in MR task performance. Both groups also showed similar task-related activation patterns in frontoparietal regions with no significant differences. Activation in the right dorsolateral prefrontal cortex in patients with OCD during the MR task was positively associated with their total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores. This study identified the specific brain areas associated with the interaction between symptom severity and visuospatial cognitive function during an MR task in medication-free patients with OCD. These findings may serve as potential neuromodulation targets for OCD treatment.
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http://dx.doi.org/10.3389/fpsyt.2021.659121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138312PMC
May 2021

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

J Proteome Res 2021 06 7;20(6):3188-3203. Epub 2021 May 7.

Department of Psychiatry, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

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.
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http://dx.doi.org/10.1021/acs.jproteome.1c00058DOI Listing
June 2021

Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

JAMA Psychiatry 2021 Jul;78(7):753-766

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.

Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).

Design, Setting, And Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.

Main Outcomes And Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).

Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001).

Conclusions And Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.
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http://dx.doi.org/10.1001/jamapsychiatry.2021.0638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100913PMC
July 2021

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

Psychiatry Clin Neurosci 2021 Apr 17. Epub 2021 Apr 17.

Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.1111/pcn.13219DOI Listing
April 2021

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

Front Psychiatry 2021 5;12:617683. Epub 2021 Mar 5.

Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, South Korea.

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.
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http://dx.doi.org/10.3389/fpsyt.2021.617683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973210PMC
March 2021

White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.

Transl Psychiatry 2021 03 17;11(1):173. Epub 2021 Mar 17.

Department of Psychiatry, Oxford University, Oxford, UK.

Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
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http://dx.doi.org/10.1038/s41398-021-01276-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969744PMC
March 2021

Identification of altered protein expression in major depressive disorder and bipolar disorder patients using liquid chromatography-tandem mass spectrometry.

Psychiatry Res 2021 05 2;299:113850. Epub 2021 Mar 2.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea. Electronic address:

Emerging high-throughput proteomic technologies have recently been considered as a powerful means of identifying substrates involved in mood disorders. We performed proteomic profiling using liquid chromatography-tandem mass spectrometry to identify dysregulated proteins in plasma samples of 42 and 45 patients with major depressive disorder (MDD) and bipolar disorder (BD), respectively, in comparison to 51 healthy controls (HCs). Fourteen and six proteins in MDD and BD patients, respectively, were differentially expressed compared to HCs, among which coagulation factor XIII A chain (F13A1), platelet basic protein (PPBP), platelet facor 4 (PF4), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and thymosin beta-4 (TMSB4X) were altered in both disorders. For proteins dysregulated in both, except F13A1, higher fold changes were observed in MDD than in BD patients. These findings may help identify candidate biomarkers of mood disorders and elucidate their underlying pathophysiology and biochemical abnormalities.
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http://dx.doi.org/10.1016/j.psychres.2021.113850DOI Listing
May 2021

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

NPJ Schizophr 2021 Mar 1;7(1):17. Epub 2021 Mar 1.

Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.1038/s41537-021-00148-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921641PMC
March 2021

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

Early Interv Psychiatry 2021 Feb 4. Epub 2021 Feb 4.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.

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.
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http://dx.doi.org/10.1111/eip.13123DOI Listing
February 2021

Attenuated Resting-State Functional Anticorrelation between Attention and Executive Control Networks in Schizotypal Personality Disorder.

J Clin Med 2021 Jan 15;10(2). Epub 2021 Jan 15.

Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul 08826, Korea.

Exploring the disruptions to intrinsic resting-state networks (RSNs) in schizophrenia-spectrum disorders yields a better understanding of the disease-specific pathophysiology. However, our knowledge of the neurobiological underpinnings of schizotypal personality disorders mostly relies on research on schizotypy or schizophrenia. This study aimed to investigate the RSN abnormalities of schizotypal personality disorder (SPD) and their clinical implications. Using resting-state data, the intra- and inter-network of the higher-order functional networks (default mode network, DMN; frontoparietal network, FPN; dorsal attention network, DAN; salience network, SN) were explored in 22 medication-free, community-dwelling, non-help seeking individuals diagnosed with SPD and 30 control individuals. Consequently, while there were no group differences in intra-network functional connectivity across DMN, FPN, DAN, and SN, the SPD participants exhibited attenuated anticorrelation between the right frontal eye field region of the DAN and the right posterior parietal cortex region of the FPN. The decreases in anticorrelation were correlated with increased cognitive-perceptual deficits and disorganization factors of the schizotypal personality questionnaire, as well as reduced independence-performance of the social functioning scale for all participants together. This study, which links SPD pathology and social functioning deficits, is the first evidence of impaired large-scale intrinsic brain networks in SPD.
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http://dx.doi.org/10.3390/jcm10020312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829946PMC
January 2021

Association of mental disorders with SARS-CoV-2 infection and severe health outcomes: nationwide cohort study.

Br J Psychiatry 2021 Jan 7:1-8. Epub 2021 Jan 7.

School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; and Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Republic of Korea.

Background: Epidemiological data on the association between mental disorders and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity are limited.

Aims: To evaluate the association between mental disorders and the risk of SARS-CoV-2 infection and severe outcomes following COVID-19.

Method: We performed a cohort study using the Korean COVID-19 patient database based on national health insurance data. Each person with a mental or behavioural disorder (diagnosed during the 6 months prior to their first SARS-CoV-2 test) was matched by age, gender and Charlson Comorbidity Index with up to four people without mental disorders. SARS-CoV-2-positivity risk and the risk of death or severe events (intensive care unit admission, use of mechanical ventilation and acute respiratory distress syndrome) post-infection were calculated using conditional logistic regression analysis.

Results: Among 230 565 people tested for SARS-CoV-2, 33 653 (14.6%) had mental disorders; 928/33 653 (2.76%) tested SARS-CoV-2 positive and 56/928 (6.03%) died. In multivariable analysis using the matched cohort, there was no association between mental disorders and SARS-CoV-2-positivity risk (odds ratio OR = 0.95; 95% CI 0.87-1.04); however, a higher risk was associated with schizophrenia-related disorders (OR = 1.50; 95% CI 1.14-1.99). Among confirmed COVID-19 patients, the mortality risk was significantly higher in patients with than in those without mental disorders (OR = 1.99, 95% CI 1.15-3.43).

Conclusions: Mental disorders are likely contributing factors to mortality following COVID-19. Although the infection risk was not higher for people with mental disorders overall, those with schizophrenia-related disorders were more vulnerable to infection.
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http://dx.doi.org/10.1192/bjp.2020.251DOI Listing
January 2021

The Role of Estrogen Receptors and Their Signaling across Psychiatric Disorders.

Int J Mol Sci 2020 Dec 31;22(1). Epub 2020 Dec 31.

Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 08826, Korea.

Increasing evidence suggests estrogen and estrogen signaling pathway disturbances across psychiatric disorders. Estrogens are not only crucial in sexual maturation and reproduction but are also highly involved in a wide range of brain functions, such as cognition, memory, neurodevelopment, and neuroplasticity. To add more, the recent findings of its neuroprotective and anti-inflammatory effects have grown interested in investigating its potential therapeutic use to psychiatric disorders. In this review, we analyze the emerging literature on estrogen receptors and psychiatric disorders in cellular, preclinical, and clinical studies. Specifically, we discuss the contribution of estrogen receptor and estrogen signaling to cognition and neuroprotection via mediating multiple neural systems, such as dopaminergic, serotonergic, and glutamatergic systems. Then, we assess their disruptions and their potential implications for pathophysiologies in psychiatric disorders. Further, in this review, current treatment strategies involving estrogen and estrogen signaling are evaluated to suggest a future direction in identifying novel treatment strategies in psychiatric disorders.
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http://dx.doi.org/10.3390/ijms22010373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794990PMC
December 2020

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

Psychol Med 2020 Dec 14:1-9. Epub 2020 Dec 14.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

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.
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http://dx.doi.org/10.1017/S0033291720004675DOI Listing
December 2020

Impaired Performance on the Reading the Mind in the Eyes Test in First-Episode Psychosis and Clinical High Risk for Psychosis.

Psychiatry Investig 2020 Dec 11. Epub 2020 Dec 11.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objective: Although previous studies have reported impaired performance in the reading the mind in the eyes test (RMET), which measures complex emotion recognition abilities, in patients with schizophrenia, reports regarding individuals at clinical high risk (CHR) for psychosis have been inconsistent, mainly due to the interacting confounding effects of general cognitive abilities and age. We compared RMET performances across first-episode psychosis (FEP) patients, CHR individuals, and healthy controls (HCs) while controlling for the effects of both general cognitive abilities and age.

Methods: A total of 25 FEP, 41 CHR, and 44 HC subjects matched for age participated in this study. RMET performance scores were compared across the groups using analysis of variance with sex and intelligence quotient as covariates. Exploratory Pearson's correlation analyses were performed to reveal the potential relationships of RMET scores with clinical symptom severity in the FEP and CHR groups.

Results: RMET performance scores were significantly lower among FEP and CHR participants than among HCs. FEP patients and CHR subjects showed comparable RMET performance scores. RMET scores were negatively correlated with Positive and Negative Syndrome Scale (PANSS) positive symptom subscale scores in the FEP patients. No significant correlation was identified between RMET scores and other clinical scale scores.

Conclusion: Impaired RMET performance is present from the risk stage of psychosis, which might be related to positive symptom severity in early psychosis. Longitudinal studies are necessary to confirm the stability of complex emotion recognition impairments and their relationship with social functioning in early psychosis patients.
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http://dx.doi.org/10.30773/pi.2020.0264DOI Listing
December 2020

The Neurobehavioral Mechanisms Underlying Attitudes Toward People With Mental or Physical Illness.

Front Behav Neurosci 2020 12;14:571225. Epub 2020 Nov 12.

Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul, South Korea.

Social factors play a significant role in the health outcomes of those struggling with mental or physical health issues. People with mental illness experience more social stigmatization and receive less concern for their welfare than do those with physical illness. However, the cognitive and neural mechanisms by which such a bias in attitude arises remain unclear. This functional MRI study examined whether a lack of self-other similarity during mental state attribution affects perceivers' theory of mind and, subsequently, how they value a patient's welfare. During scanning, participants were asked to respond to an expression of caring and sympathetic concern from either their own perspective or while adopting the perspective of patients labeled physically ill or mentally ill. Participants reported that physically ill patients would share their affective responses to the situations, but mentally ill patients would not. Furthermore, mentalizing about physically ill patients was associated with increased activity in the ventromedial prefrontal cortex (vmPFC), a critical region for empathic concern and value-based decisions. In contrast, mentalizing about mentally ill patients preferentially engaged the dorsal anterior cingulate cortex (dACC) and anterior insula, regions previously implicated in empathic distress, in which activity correlated with individual differences in prejudice control. The findings indicate that a lack of perceived self-other similarity poses a challenge to the theory of mind and thus requires greater cognitive resources and neural computations. This might give rise to stereotyped beliefs about and prejudice against the mentally ill and failure to respond with appropriate empathy and care.
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http://dx.doi.org/10.3389/fnbeh.2020.571225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689019PMC
November 2020

The effects of selective serotonin reuptake inhibitors on brain functional networks during goal-directed planning in obsessive-compulsive disorder.

Sci Rep 2020 11 26;10(1):20619. Epub 2020 Nov 26.

Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.

Whether brain network connectivity during goal-directed planning in patients with obsessive-compulsive disorder (OCD) is abnormal and restored by treatment with selective serotonin reuptake inhibitors (SSRIs) remains unknown. This study investigated whether the disrupted network connectivity during the Tower of London (ToL) planning task in medication-free OCD patients could be restored by SSRI treatment. Seventeen medication-free OCD patients and 21 matched healthy controls (HCs) underwent functional magnetic resonance imaging (fMRI) while performing the ToL task at baseline and again after 16 weeks of SSRI treatment. Internetwork connectivity was compared across the groups and treatment statuses (pretreatment versus posttreatment). At baseline, compared with the HCs, the OCD patients showed lower internetwork connectivity between the dorsal attention network and the default-mode network during the ToL planning task. After 16 weeks of SSRI treatment, the OCD patients showed improved clinical symptoms accompanied by normalized network connectivity, although their improved behavioral performance in the ToL task did not reach that of the HCs. Our findings support the conceptualization of OCD as a network disease characterized by an imbalance between brain networks during goal-directed planning and suggest that internetwork connectivity may serve as an early biomarker of the effects of SSRIs on goal-directed planning.
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http://dx.doi.org/10.1038/s41598-020-77814-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691328PMC
November 2020

Effectiveness of antipsychotic drugs in schizophrenia: a 10-year retrospective study in a Korean tertiary hospital.

NPJ Schizophr 2020 Nov 19;6(1):32. Epub 2020 Nov 19.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

Extensive research has been carried out on the comparative effectiveness of antipsychotic medications. Most studies, however, have been performed in Western countries. The purpose of this study was to compare the effectiveness, indicated by time to any-cause discontinuation, of antipsychotic drugs in a large number of patients with schizophrenia in South Korea. We identified 1458 patients with schizophrenia or schizophreniform disorder who were treated with antipsychotic medications using a clinical data warehouse at the Seoul National University Hospital between March 2005 and February 2014. Kaplan-Meier survival analyses were used to estimate the time to discontinuation of antipsychotic drugs. We compared the survival curves of different antipsychotics using log-rank tests. Overall, the median time to discontinuation for any cause was 133 days (95% CI, 126-147). The longest time to discontinuation was observed for clozapine, followed by aripiprazole, paliperidone, olanzapine, amisulpride, risperidone, quetiapine, ziprasidone, and haloperidol. Specifically, clozapine was significantly different from all other antipsychotic drugs (all p < 0.001). Aripiprazole also had a significantly longer time to discontinuation than amisulpride (p = 0.001), risperidone (p < 0.001), quetiapine (p < 0.001), ziprasidone (p < 0.001), and haloperidol (p < 0.001). In Asian patients with schizophrenia, clozapine was the most effective antipsychotic in terms of time to discontinuation, followed by aripiprazole. This study extends the findings of previous effectiveness studies from Western populations and suggests the need to develop guidelines for the pharmacotherapy of schizophrenia tailored to Asian individuals.
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http://dx.doi.org/10.1038/s41537-020-00122-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677553PMC
November 2020

In vivo gamma-aminobutyric acid-A/benzodiazepine receptor availability and genetic liability in asymptomatic individuals with high genetic loading of schizophrenia: A [11C]flumazenil positron emission tomography study.

Hum Psychopharmacol 2021 Mar 13;36(2):e2766. Epub 2020 Nov 13.

Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.

Objectives: Whilst reduced signalling and gene expression related to gamma-aminobutyric acid (GABA) play a role in the presumed pathophysiology of schizophrenia, its origin is unclear. Studying asymptomatic individuals with high genetic liability to schizophrenia (AIs) would provide insights. Therefore, this study aimed to investigate the role of genetic liability in GABAergic dysfunction of schizophrenia by exploring in vivo GABA-A/benzodiazepine receptor (GABAR) availability in AIs.

Methods: A total of 10 AIs with multiple relatives diagnosed as schizophrenia and 11 healthy controls underwent [11C]flumazenil positron emission tomography and neurocognitive function tests.

Results: There was no significant difference in [11C]flumazenil availability based on the groups. GABAR availability in caudate nuclei had positive correlations with genetic liability of AIs. GABAR availability in caudate nuclei and verbal memory measures of AIs revealed positive correlations. Only the correlation between right caudate and short-term verbal memory survived multiple-comparison correction (p = 0.030).

Conclusions: This study, for the first time, reports correlations between the genetic liability of schizophrenia and GABAR availability. Correlations between [11C]flumazenil binding in caudate of individuals with high genetic liability to schizophrenia suggests that the GABAergic dysfunction may arise from shared genetic factors and also that it may be responsible for cognitive impairment of AIs.
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http://dx.doi.org/10.1002/hup.2766DOI Listing
March 2021

Defining data-driven subgroups of obsessive-compulsive disorder with different treatment responses based on resting-state functional connectivity.

Transl Psychiatry 2020 10 26;10(1):359. Epub 2020 Oct 26.

Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.

Characterization of obsessive-compulsive disorder (OCD), like other psychiatric disorders, suffers from heterogeneities in its symptoms and therapeutic responses, and identification of more homogeneous subgroups may help to resolve the heterogeneity. We aimed to identify the OCD subgroups based on resting-state functional connectivity (rsFC) and to explore their differences in treatment responses via a multivariate approach. From the resting-state functional MRI data of 107 medication-free OCD patients and 110 healthy controls (HCs), we selected rsFC features, which discriminated OCD patients from HCs via support vector machine (SVM) analyses. With the selected brain features, we subdivided OCD patients into subgroups using hierarchical clustering analyses. We identified 35 rsFC features that achieved a high sensitivity (82.74%) and specificity (76.29%) in SVM analyses. The OCD patients were subdivided into two subgroups, which did not show significant differences in their demographic and clinical backgrounds. However, one of the OCD subgroups demonstrated more impaired rsFC that was involved either within the default mode network (DMN) or between DMN brain regions and other network regions. This subgroup also showed both lower improvements in symptom severity in the 16-week follow-up visit and lower responder percentage than the other subgroup. Our results highlight that not only abnormalities within the DMN but also aberrant rsFC between the DMN and other networks may contribute to the treatment response and support the importance of these neurobiological alterations in OCD patients. We suggest that abnormalities in these connectivity may play predictive biomarkers of treatment response, and aid to build more optimal treatment strategies.
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http://dx.doi.org/10.1038/s41398-020-01045-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589530PMC
October 2020

Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters.

Transl Psychiatry 2020 10 8;10(1):342. Epub 2020 Oct 8.

Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06510, USA.

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
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http://dx.doi.org/10.1038/s41398-020-01013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598942PMC
October 2020

Intrinsic functional connectivity of blue and red brains: neurobiological evidence of different stress resilience between political attitudes.

Sci Rep 2020 09 28;10(1):15877. Epub 2020 Sep 28.

Department of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, Republic of Korea.

Conservatives are more sensitive to threatening/anxious situations in perceptual and cognitive levels, experiencing emotional responses and stress, while liberals are more responsive to but tolerant of ambiguous and uncertain information. Interestingly, conservatives have greater psychological well-being and are more satisfied with their lives than liberals despite their psychological vulnerability to stress caused by threat and anxiety sensitivities. We investigated whether conservatives have greater resilience and self-regulation capacity, which are suggested to be psychological buffers that enhance psychological well-being, than liberals and moderates. We also explored associations between intrinsic functional brain organization and these psychological resources to expand our neurobiological understanding of self-regulatory processes in neuropolitics. We found that conservatives, compared to liberals and moderates, had greater psychological resilience and self-regulation capacity that were attributable to greater impulse control and causal reasoning. Stronger intrinsic connectivities between the orbitofrontal cortex (OFC) and precuneus and between the insula and frontal pole/OFC in conservatives were correlated with greater resilience and self-regulation capacity. These results suggest the neural underpinnings that may allow conservatives to manage the psychological stress and achieve greater life satisfaction. This study provides neuroscientific evidence for the different responses of liberals and conservatives to politically relevant social issues.
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http://dx.doi.org/10.1038/s41598-020-72980-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522714PMC
September 2020

Dopamine dysregulation in psychotic relapse after antipsychotic discontinuation: an [F]DOPA and [C]raclopride PET study in first-episode psychosis.

Mol Psychiatry 2021 Jul 14;26(7):3476-3488. Epub 2020 Sep 14.

Department of Psychiatry, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.

Although antipsychotic drugs are effective for relieving the psychotic symptoms of first-episode psychosis (FEP), psychotic relapse is common during the course of the illness. While some FEPs remain remitted even without medication, antipsychotic discontinuation is regarded as the most common risk factor for the relapse. Considering the actions of antipsychotic drugs on presynaptic and postsynaptic dopamine dysregulation, this study evaluated possible mechanisms underlying relapse after antipsychotic discontinuation. Twenty five FEPs who were clinically stable and 14 matched healthy controls were enrolled. Striatal dopamine activity was assessed as K value using [F]DOPA PET before and 6 weeks after antipsychotic discontinuation. The D2/3 receptor availability was measured as BP using [C]raclopride PET after antipsychotic discontinuation. Healthy controls also underwent PET scans according to the corresponding schedule of the patients. Patients were monitored for psychotic relapse during 12 weeks after antipsychotic discontinuation. 40% of the patients showed psychotic relapse after antipsychotic discontinuation. The change in K value over time significantly differed between relapsed, non-relapsed patients and healthy controls (Week*Group: F = 4.827, df = 2,253.193, p = 0.009). In relapsed patients, a significant correlation was found between baseline striatal K values and time to relapse after antipsychotic discontinuation (R = 0.518, p = 0.018). BP were not significantly different between relapsed, non-relapsed patients and healthy controls (F = 1.402, df = 2,32.000, p = 0.261). These results suggest that dysfunctional dopamine autoregulation might precipitate psychotic relapse after antipsychotic discontinuation in FEP. This finding could be used for developing a strategy for the prevention of psychotic relapse related to antipsychotic discontinuation.
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http://dx.doi.org/10.1038/s41380-020-00879-0DOI Listing
July 2021

Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

JAMA Psychiatry 2021 Jan;78(1):47-63

Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University, the Netherlands.

Importance: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood.

Objective: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia.

Design, Setting, And Participants: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244.

Main Outcomes And Measures: Interregional profiles of group difference in cortical thickness between cases and controls.

Results: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders.

Conclusions And Relevance: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450410PMC
January 2021
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