Euitae Kim - Academia.edu (original) (raw)
Papers by Euitae Kim
![Research paper thumbnail of S145. Antipsychotic Discontinuation in First Episode Psychosis: [18F]DOPA and [11C]RACLOPRIDE Pet Study](https://attachments.academia-assets.com/110484112/thumbnails/1.jpg)
](Schizophrenia Bulletin, 2018
Background: Recent meta-analysis revealed that elevated presynaptic striatal dopaminergic functio... more Background: Recent meta-analysis revealed that elevated presynaptic striatal dopaminergic function is a robust feature of psychosis like schizophrenia. Considering increased dopaminergic capacity in psychotic disorders, it is not surprising that antipsychotic drugs, which primarily block dopaminergic neurotransmission, are mostly effective in the treatment of psychosis. However, it remains obscure what would happen to presynaptic dopaminergic function with antipsychotic treatment. This is an important issue addressing whether the current antipsychotic drugs are correcting the primary dopaminergic abnormality or not. In addition, the issue can give a clue regarding the mechanism of relapse in psychotic disorders. Methods: We measured presynaptic dopamine capacity using [18F]DOPA PET before and after the antipsychotic discontinuation in first episode psychosis. The binding potentials of [11C]raclopride were also measured after the discontinuation. Healthy controls had [18F]DOPA and [11C]raclopride scans at the corresponding date. First episode psychosis patients were carefully monitored in the aspects of symptomatic aggravations. Results: The presynaptic dopamine capacity and the density of dopamine receptors showed significant group effect and the interaction between group and time (p<0.005) Discussion: Dopaminergic function seems to play a critical role in relapse of first episode psychosis.
Psychiatry Investigation
Objective Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis ... more Objective Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC).Methods Twenty-four patients with schizophrenia and twelve HC underwent [18F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant Kicer) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between Kicer and FA in each grou...
Dialogues in Clinical Neuroscience, 2013
The Journal of Clinical Psychiatry, 2021
Objective: This study aimed to examine the degree of clinical and functional improvement after pa... more Objective: This study aimed to examine the degree of clinical and functional improvement after paliperidone long-acting injectable (LAI) administration according to the duration of illness. Methods: Patients with schizophrenia diagnosed by ICD-10 criteria who were planned to start once-monthly paliperidone LAI were recruited from 2010 to 2017. Clinical and functional changes were measured every 4 weeks using the Clinical Global Impressions-Severity of Illness scale (CGI-S) and Personal and Social Performance scale (PSP), respectively, for 6 months after paliperidone LAI initiation. Improvements after starting paliperidone LAI were compared among patients with duration of illness < 3 years, ≥ 3 and < 10 years, and ≥ 10 years. Results: A total of 1,166 participants (duration of illness < 3 years, n = 240; 3 ≤ duration of illness < 10 years, n = 442; duration of illness ≥ 10 years, n = 484) were enrolled. The total olanzapine-equivalent doses of antipsychotics and the LAI monotherapy proportion at the final visit were significantly different among the 3 duration of illness groups (dose: F 2,1163 = 18.41, P < .001; monotherapy: χ 2 2 = 11.73, P = .003). The changes in CGI-S score were significantly different according to the duration of illness, and those with duration of illness < 3 years showed the best improvement (group × week: χ 2 12 = 25.33, P = .013). All 3 groups showed significantly improved PSP scores (week: χ 2 6 = 294.2, P < .001). Conclusions: Starting paliperidone LAI significantly improved clinical and functional outcomes in patients with schizophrenia, especially those with shorter duration of illness. These findings suggest that LAI antipsychotic administration may be considered in early-stage schizophrenia for improved outcomes.
Psychiatry Investigation, 2021
Objective More attempts have been made recently to improve psychosocial functioning and quality o... more Objective More attempts have been made recently to improve psychosocial functioning and quality of life in patients with schizophrenia, due to their crucial role in long-term outcomes. Previous studies on the effects of clozapine on psychosocial functioning have been limited in terms of generalizability and application to clinical practice. This study examined the relationship of clozapine use with psychosocial functioning and quality of life in patients with schizophrenia in a real-world setting.Methods Data were obtained from a survey targeting community-dwelling patients with schizophrenia. The Behavior and Symptom Identification Scale (BASIS) and Satisfaction with Life Scale (SWLS) were administered to evaluate psychosocial functioning and quality of life, and patients were classified into Clozapine and Non-clozapine groups. Group differences were assessed using ANCOVA, with additional sensitivity analyses for participants on atypical antipsychotic medications only.Results Of 29...
Psychiatry Investigation, 2020
Objective The clozapine/N-desmethylclozapine (NDMC) ratio is proposed to be used as a predictor o... more Objective The clozapine/N-desmethylclozapine (NDMC) ratio is proposed to be used as a predictor of cognitive performance in clozapine-treated patients, as its principal metabolite, NDMC, has an opposite action with clozapine on the cholinergic system. The aim of this study is to determine whether clozapine has influence on cognitive performance in accordance with changes in the clozapine/NDMC in patients with schizophrenia.Methods The data of fifteen patients with schizophrenia, who had initial and follow-up assessments after starting clozapine treatment, were retrospectively collected. The assessments included clinical scale, cognitive battery, and pharmacological data including plasma concentrations of clozapine and NDMC. The data were analyzed with Pearson correlation and stepwise multiple regression analyses.Results ΔAttention/vigilance, Δsocial cognition, and Δcomposite score had a significant correlation with Δclozapine/NDMC ratio, while ΔWorking memory had correlation with Δc...
Korean Journal of Schizophrenia Research, 2018
Objectives : This study investigated whether long-acting injectable (LAI) paliperidone is differe... more Objectives : This study investigated whether long-acting injectable (LAI) paliperidone is different from its oral form in terms of the effect on cognitive function in schizophrenia spectrum and other psychotic disorders. Methods : We reviewed the medical records of patients in Seoul National University Bundang Hospital who were diagnosed as having schizophrenia and/or other psychotic disorders based on DSM-5 from 2016 to 2017. Seven patients were treated with oral paliperidone and 11 were treated with paliperidone palmitate. All patients underwent clinical and neuropsychological assessment, including the Korean version of the MATRICS Consensus Cognitive Battery (MCCB) at their first visit or within one month of their initial treatment. MCCB was repeated within three to 12 months after the initial assessment. Results : There was no significant difference between the two groups in most cognitive domains including speed of processing, attention and vigilance, working memory, verbal learning, visual learning and reasoning and problem solving domain. However, patients treated with paliperidone palmitate showed better improvement in social cognition domain than those taking oral paliperidone. The standardized values of social cognition domain scores had significantly improved over time in patients under paliperidone palmitate, demonstrating a significant time-by-group interaction. Conclusion : Our results show that long-acting injectable paliperidone could be helpful in some aspects of improving cognitive function in schizophrenia spectrum and other psychotic disorders. Further studies with other antipsychotics are necessary to generalize the results.
Journal of Korean Neuropsychiatric Association, 2020
Objectives There has been growing interest in the relationship between mental illness and premorb... more Objectives There has been growing interest in the relationship between mental illness and premorbid trauma recently. The purpose of this study was to examine the difference in symptoms, functions, and their outcomes according to the degree of trauma in patients with early psychosis. Methods The study involved 226 people who participated in the Korean Early Psychosis Cohort Study, and we divided the participants into two groups according to the degree of trauma. Positive and Negative Syndrome Scale (PANSS) and Social and Occupational Functioning Assessment Scale (SOFAS) were compared at the start of the study and at 12 months after the treatment using paired t-test and repeated measures analysis of variance. Results At the beginning of the study, there was no significant difference between the two groups. But after 12 months of treatment, the high trauma group showed less improvement in PANSS negative score, general psychopathological score, total score, and SOFAS than the low trauma group. Conclusion In patients with early psychosis and at least moderate severity of premorbid trauma, negative symptoms, general psychopathological, and social and occupational functional improvements after treatment are less.
Clinical and Experimental Otorhinolaryngology, 2020
Objectives. Although unilateral hearing loss (UHL) has been proven to be associated with educatio... more Objectives. Although unilateral hearing loss (UHL) has been proven to be associated with educational and behavioral problems, few studies have investigated psychopathological abnormalities in this population. The aim of this study was to evaluate the psychopathological influence of UHL among Korean 19-year-old males.Methods. The authors retrospectively compared the objective personality test profiles of 602 subjects with UHL with those of 23,790 peers with normal hearing. All participants in the current study were 19-year-old males who underwent a physical examination and completed the Korean Military Multiphasic Personality Inventory for conscription at the Military Manpower Administration from February 2015 to December 2016.Results. Significantly higher scores were found on neurosis scales in the UHL group than in the normal-hearing group (50.9± 10.8 vs. 44.9±6.0 for anxiety; 51.0±10.5 vs. 44.9±5.2 for depression; 51.1±10.4 vs. 45.1±6.81 for somatization, all P<0.001). The psyc...
Psychological Medicine, 2020
BackgroundObsession and delusion are theoretically distinct from each other in terms of reality t... more BackgroundObsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS).MethodsOur study sample comprised of 96 patients with obsessive–compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion severity and RFSC using multivariate distance-based matrix regression.ResultsObsession was associated with the supplementary motor area, precentral gyrus, and superior parietal lobule, while delusion was associ...
Molecular Psychiatry, 2019
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Scientific Reports, 2017
Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, a... more Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [ 11 C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors. Cannabis is the world's most commonly used illicit substance 1. Although most recreational users smoke cannabis for its relaxing effects, the drug has a range of adverse effects including the induction of acute anxiety 2-5 and, development of anxiety disorders in regular users 6. While these effects of cannabis are mediated by its main psychoactive constituent, delta-9-tetrahydrocannabinol (delta-9-THC) 3 , the extract of the cannabis plant has many other ingredients, some of which e.g. Cannabidiol may have anxiolytic effects 3. Consistent with this, and evidence that many of the behavioural effects of exogenous cannabinoids can be linked to their effects on the endocannabinoid system 7 , a large body of preclinical evidence has accumulated implicating different components of the endocannabinoid system in emotional processing and anxiety 8. Preclinical studies suggest that contradictory evidence regarding the precise effect of exogenous cannabinoids on anxiety, in terms of an anxiolytic or anxiogenic response, may be linked to dose of the cannabinoid 7 as well as its site of action 9 , while there is less mechanistic
![Research paper thumbnail of {"__content__"=>"The relationship between dopamine receptor blockade and cognitive performance in schizophrenia: a [C]-raclopride PET study with aripiprazole.", "sup"=>{"__content__"=>"11"}}](https://attachments.academia-assets.com/91539878/thumbnails/1.jpg)
](Translational psychiatry, Apr 24, 2018
Aripiprazole's effects on cognitive function in patients with schizophrenia are unclear becau... more Aripiprazole's effects on cognitive function in patients with schizophrenia are unclear because of the difficulty in disentangling specific effects on cognitive function from secondary effects due to the improvement in other schizophrenic symptoms. One approach to address this is to use an intermediate biomarker to investigate the relationship between the drug's effect on the brain and change in cognitive function. This study aims to investigate aripiprazole's effect on working memory by determining the correlation between dopamine D2/3 (D2/3) receptor occupancy and working memory of patients with schizophrenia. Seven patients with schizophrenia participated in the study. Serial positron emission tomography (PET) scans with [C]raclopride were conducted at 2, 26, and 74 h after the administration of aripiprazole. The subjects performed the N-back task just after finishing the [C]raclopride PET scan. The mean (±SD) D2/3 receptor occupancies were 66.9 ± 6.7% at 2 h, 65.0 ± ...
Korean Journal of Schizophrenia Research, 2016
Objectives : This study investigated the prescribing patterns of atypical antipsychotics for the ... more Objectives : This study investigated the prescribing patterns of atypical antipsychotics for the various psychiatric disorders in the psychiatric ward of a University hospital. Methods : We reviewed the medical records of patients who were discharged from an open psychiatric ward from May, 2003 through April, 2014. The association between psychiatric disorders and prescription pattern of atypical antipsychotics was analyzed. Results : The study included 3091 patients' prescription of psychiatric medication. 60% of prescription included antipsychotics; quetiapine was the most frequently prescribed antipsychotics, but the average dosage was the lowest among all the atypical antipsychotics. According to the diagnoses, prescription rates and dosage of antipsychotics were different. Prescription rates of antipsychotics were the lowest in patients with anxiety disorders, and the mean dosage were the lowest in those with delirium, dementia, and amnestic and other cognitive disorders. Conclusion : This observational study shows prescription patterns of atypical antipsychotics for the treatment of psychiatric disorders in a University hospital; atypical antipsychotics were widely used for the treatment of the various disorders, and there were differences in prescription patterns for each disorders. The results of this study may be used to identify the proper atypical antipsychotics effective on certain psychiatric disorders and to propose expanding the indications of each atypical antipsychotics in the future.
![Research paper thumbnail of Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [(18)F]DOPA PET Study](https://attachments.academia-assets.com/91539874/thumbnails/1.jpg)
](Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, Jan 14, 2016
Some patients with schizophrenia show poor response to first-line antipsychotic treatments and th... more Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia. However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls...
NeuroImage. Clinical, 2013
Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward ... more Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward processing mediated by corticostriatal circuitry, a brain network implicated in the pathophysiology of OCD. Performing compulsive actions can be perceived as a reward to OCD patients because it temporarily reduces the anxiety provoked by obsessions. Although most OCD literature provides evidence of altered regional activity in these corticostriatal circuits, very little is known about the connectivity between individual regions of the corticostriatal-limbic circuits, including the cognitive and affective neural circuitry associated with OCD. Thus, this study investigated the differences in functional connectivity (FC) patterns in this network during resting-state and incentive processing. Nineteen patients with OCD and 18 well-matched healthy controls were scanned during resting-state and a monetary incentive delay task (task state). FC was assessed using both voxel-wise and region-of-in...
Clinical pharmacology and therapeutics, 2007
YKP1358 is a novel serotonin (5-HT(2A)) and dopamine (D(2)) antagonist that, in preclinical studi... more YKP1358 is a novel serotonin (5-HT(2A)) and dopamine (D(2)) antagonist that, in preclinical studies, fits the general profile of an atypical antipsychotic. We conducted a D(2) receptor occupancy study with YKP1358 in healthy volunteers using positron emission tomography (PET) to measure the D(2) receptor occupancy of YKP1358 and to characterize its relationship to plasma drug concentrations. A single oral dose, parallel group, dose-escalation (100, 200, and 250 mg) study was performed in 10 healthy male volunteers with the PET radiotracer [(11)C]raclopride. The D(2) receptor occupancy of striatum was measured pre-dose, and at 2, 5, and 10 h after YKP1358 administration. Serial blood samples were taken for measurement of plasma YKP1358 concentrations. D(2) receptor occupancy by YKP1358 increased to 53-83% at 2 h, and then decreased afterwards, ranging from 40-64% at 5 h to 20-51% at 10 h. The YKP1358 dose-plasma concentration relationship exhibited extensive variability, but there wa...
Schizophrenia Research, 2011
Background: While deficits in cognitive functions are frequently reported in psychotic disorders,... more Background: While deficits in cognitive functions are frequently reported in psychotic disorders, further longitudinal research is needed to confirm the specific risk factors for the development of psychosis. We examined longitudinally the social-cognitive and neurocognitive function of individuals at ultra-high risk for schizophrenia who developed psychosis later as predictive markers. Method: The investigators studied 49 subjects at ultra-high risk (UHR) for psychosis and 45 healthy controls. The UHR subjects were followed for up 5.2 years (mean:2.8 years) and 13 of these subjects developed psychosis. Theory of mind (ToM) tasks and neuropsychological tests were administered at baseline. Analyses compared the UHR patients who later developed psychosis, those who did not develop, and healthy controls. To examine the cognitive variables to predict transition to psychosis, Cox regression analyses were conducted. Results: At baseline, we found significant differences among the three groups in social cognition according to the False Belief and cartoon tasks and in neurocognition according to tasks measuring executive function, working memory, verbal memory, and visual memory. Our study showed that a model combining working memory, visual memory, executive function, and ToM tasks was significantly predictive of time to conversion to psychosis. Conclusion: This study indicated that UHR patients who later converted to psychosis performed more poorly on tasks involving social cognition and neurocognition than did those who did not convert. We suggest that these deficits can serve as specific markers to predict the development of psychosis.
![Research paper thumbnail of Dopaminergic Function in the Psychosis Spectrum: An [18F]-DOPA Imaging Study in Healthy Individuals With Auditory Hallucinations](https://attachments.academia-assets.com/91539821/thumbnails/1.jpg)
](Schizophrenia Bulletin, 2012
Background: The psychosis phenotype appears to exist in the population as a continuum, but it is ... more Background: The psychosis phenotype appears to exist in the population as a continuum, but it is not clear if subclinical psychotic symptoms and psychotic disorders share the same neurobiology. We investigated whether the dopaminergic dysfunction seen in psychotic disorders is also present in healthy, well-functioning people with hallucinations. Methods: We compared dopamine synthesis capacity (using 6-[ 18 F]fluoro-L-DOPA [[ 18 F]-DOPA] positron emission tomography imaging) in 16 healthy individuals with frequent persistent auditory verbal hallucinations (hallucinating group) with that in 16 matched controls. Results: There was no significant difference in dopamine synthesis capacity in the striatum, or its functional subdivisions, between groups and no relationship between subclinical psychotic symptom severity or schizotypal traits and dopamine synthesis capacity in the hallucinating group. Conclusions: Altered dopamine synthesis capacity is unlikely to underlie subclinical hallucinations, suggesting that although there may be a phenomenological psychosis continuum, there are distinctions at the neurobiological level.
PLoS ONE, 2011
Background: Recent studies have reported that the insular cortex is involved in the pathophysiolo... more Background: Recent studies have reported that the insular cortex is involved in the pathophysiology of obsessivecompulsive disorder (OCD). However, specific morphometric abnormalities of the insular subregions remain unclear. In this study, we examined insular cortical volume to determine whether the volume of the anterior and posterior insular cortices of unmedicated OCD patients differed according to different symptom dimensions. Methods/Principal Findings: Using magnetic resonance imaging, we measured the gray matter volumes of the insular cortex and its subregions (anterior and posterior divisions) in 41 patients with OCD (31 drug-naïve and 10 non-medicated) and 53 healthy controls. Volumetric measures of the insular cortex were compared according to different OC symptoms. Enlarged anterior and reduced posterior insular cortices were observed in OCD patients. The insular volumetric alterations were more significant in OCD patients with predominant checking rather than cleaning symptoms when compared with healthy controls. Conclusions/Significance: Our results suggest the presence of unbalanced anterior and posterior insular volumetric abnormalities in unmedicated OCD patients and emphasize the distinct role of the insular cortex in different OC symptoms. We propose that the insular morphometric alterations may influence the modulation of interoceptive processing, the insular functional role, in OCD patients with different symptoms.
Schizophrenia Bulletin, 2018
Background: Recent meta-analysis revealed that elevated presynaptic striatal dopaminergic functio... more Background: Recent meta-analysis revealed that elevated presynaptic striatal dopaminergic function is a robust feature of psychosis like schizophrenia. Considering increased dopaminergic capacity in psychotic disorders, it is not surprising that antipsychotic drugs, which primarily block dopaminergic neurotransmission, are mostly effective in the treatment of psychosis. However, it remains obscure what would happen to presynaptic dopaminergic function with antipsychotic treatment. This is an important issue addressing whether the current antipsychotic drugs are correcting the primary dopaminergic abnormality or not. In addition, the issue can give a clue regarding the mechanism of relapse in psychotic disorders. Methods: We measured presynaptic dopamine capacity using [18F]DOPA PET before and after the antipsychotic discontinuation in first episode psychosis. The binding potentials of [11C]raclopride were also measured after the discontinuation. Healthy controls had [18F]DOPA and [11C]raclopride scans at the corresponding date. First episode psychosis patients were carefully monitored in the aspects of symptomatic aggravations. Results: The presynaptic dopamine capacity and the density of dopamine receptors showed significant group effect and the interaction between group and time (p<0.005) Discussion: Dopaminergic function seems to play a critical role in relapse of first episode psychosis.
Psychiatry Investigation
Objective Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis ... more Objective Striatal dopamine dysfunction caused by cortical abnormalities is a leading hypothesis of schizophrenia. Although prefrontal cortical pathology is negatively correlated with striatal dopamine synthesis, the relationship between structural frontostriatal connectivity and striatal dopamine synthesis has not been proved in patients with schizophrenia with different treatment response. We therefore investigated the relationship between frontostriatal connectivity and striatal dopamine synthesis in treatment-responsive schizophrenia (non-TRS) and compared them to treatment-resistant schizophrenia (TRS) and healthy controls (HC).Methods Twenty-four patients with schizophrenia and twelve HC underwent [18F] DOPA PET scans to measure dopamine synthesis capacity (the influx rate constant Kicer) and diffusion 3T MRI to measure structural connectivity (fractional anisotropy, FA). Connectivity was assessed in 2 major frontostriatal tracts. Associations between Kicer and FA in each grou...
Dialogues in Clinical Neuroscience, 2013
The Journal of Clinical Psychiatry, 2021
Objective: This study aimed to examine the degree of clinical and functional improvement after pa... more Objective: This study aimed to examine the degree of clinical and functional improvement after paliperidone long-acting injectable (LAI) administration according to the duration of illness. Methods: Patients with schizophrenia diagnosed by ICD-10 criteria who were planned to start once-monthly paliperidone LAI were recruited from 2010 to 2017. Clinical and functional changes were measured every 4 weeks using the Clinical Global Impressions-Severity of Illness scale (CGI-S) and Personal and Social Performance scale (PSP), respectively, for 6 months after paliperidone LAI initiation. Improvements after starting paliperidone LAI were compared among patients with duration of illness < 3 years, ≥ 3 and < 10 years, and ≥ 10 years. Results: A total of 1,166 participants (duration of illness < 3 years, n = 240; 3 ≤ duration of illness < 10 years, n = 442; duration of illness ≥ 10 years, n = 484) were enrolled. The total olanzapine-equivalent doses of antipsychotics and the LAI monotherapy proportion at the final visit were significantly different among the 3 duration of illness groups (dose: F 2,1163 = 18.41, P < .001; monotherapy: χ 2 2 = 11.73, P = .003). The changes in CGI-S score were significantly different according to the duration of illness, and those with duration of illness < 3 years showed the best improvement (group × week: χ 2 12 = 25.33, P = .013). All 3 groups showed significantly improved PSP scores (week: χ 2 6 = 294.2, P < .001). Conclusions: Starting paliperidone LAI significantly improved clinical and functional outcomes in patients with schizophrenia, especially those with shorter duration of illness. These findings suggest that LAI antipsychotic administration may be considered in early-stage schizophrenia for improved outcomes.
Psychiatry Investigation, 2021
Objective More attempts have been made recently to improve psychosocial functioning and quality o... more Objective More attempts have been made recently to improve psychosocial functioning and quality of life in patients with schizophrenia, due to their crucial role in long-term outcomes. Previous studies on the effects of clozapine on psychosocial functioning have been limited in terms of generalizability and application to clinical practice. This study examined the relationship of clozapine use with psychosocial functioning and quality of life in patients with schizophrenia in a real-world setting.Methods Data were obtained from a survey targeting community-dwelling patients with schizophrenia. The Behavior and Symptom Identification Scale (BASIS) and Satisfaction with Life Scale (SWLS) were administered to evaluate psychosocial functioning and quality of life, and patients were classified into Clozapine and Non-clozapine groups. Group differences were assessed using ANCOVA, with additional sensitivity analyses for participants on atypical antipsychotic medications only.Results Of 29...
Psychiatry Investigation, 2020
Objective The clozapine/N-desmethylclozapine (NDMC) ratio is proposed to be used as a predictor o... more Objective The clozapine/N-desmethylclozapine (NDMC) ratio is proposed to be used as a predictor of cognitive performance in clozapine-treated patients, as its principal metabolite, NDMC, has an opposite action with clozapine on the cholinergic system. The aim of this study is to determine whether clozapine has influence on cognitive performance in accordance with changes in the clozapine/NDMC in patients with schizophrenia.Methods The data of fifteen patients with schizophrenia, who had initial and follow-up assessments after starting clozapine treatment, were retrospectively collected. The assessments included clinical scale, cognitive battery, and pharmacological data including plasma concentrations of clozapine and NDMC. The data were analyzed with Pearson correlation and stepwise multiple regression analyses.Results ΔAttention/vigilance, Δsocial cognition, and Δcomposite score had a significant correlation with Δclozapine/NDMC ratio, while ΔWorking memory had correlation with Δc...
Korean Journal of Schizophrenia Research, 2018
Objectives : This study investigated whether long-acting injectable (LAI) paliperidone is differe... more Objectives : This study investigated whether long-acting injectable (LAI) paliperidone is different from its oral form in terms of the effect on cognitive function in schizophrenia spectrum and other psychotic disorders. Methods : We reviewed the medical records of patients in Seoul National University Bundang Hospital who were diagnosed as having schizophrenia and/or other psychotic disorders based on DSM-5 from 2016 to 2017. Seven patients were treated with oral paliperidone and 11 were treated with paliperidone palmitate. All patients underwent clinical and neuropsychological assessment, including the Korean version of the MATRICS Consensus Cognitive Battery (MCCB) at their first visit or within one month of their initial treatment. MCCB was repeated within three to 12 months after the initial assessment. Results : There was no significant difference between the two groups in most cognitive domains including speed of processing, attention and vigilance, working memory, verbal learning, visual learning and reasoning and problem solving domain. However, patients treated with paliperidone palmitate showed better improvement in social cognition domain than those taking oral paliperidone. The standardized values of social cognition domain scores had significantly improved over time in patients under paliperidone palmitate, demonstrating a significant time-by-group interaction. Conclusion : Our results show that long-acting injectable paliperidone could be helpful in some aspects of improving cognitive function in schizophrenia spectrum and other psychotic disorders. Further studies with other antipsychotics are necessary to generalize the results.
Journal of Korean Neuropsychiatric Association, 2020
Objectives There has been growing interest in the relationship between mental illness and premorb... more Objectives There has been growing interest in the relationship between mental illness and premorbid trauma recently. The purpose of this study was to examine the difference in symptoms, functions, and their outcomes according to the degree of trauma in patients with early psychosis. Methods The study involved 226 people who participated in the Korean Early Psychosis Cohort Study, and we divided the participants into two groups according to the degree of trauma. Positive and Negative Syndrome Scale (PANSS) and Social and Occupational Functioning Assessment Scale (SOFAS) were compared at the start of the study and at 12 months after the treatment using paired t-test and repeated measures analysis of variance. Results At the beginning of the study, there was no significant difference between the two groups. But after 12 months of treatment, the high trauma group showed less improvement in PANSS negative score, general psychopathological score, total score, and SOFAS than the low trauma group. Conclusion In patients with early psychosis and at least moderate severity of premorbid trauma, negative symptoms, general psychopathological, and social and occupational functional improvements after treatment are less.
Clinical and Experimental Otorhinolaryngology, 2020
Objectives. Although unilateral hearing loss (UHL) has been proven to be associated with educatio... more Objectives. Although unilateral hearing loss (UHL) has been proven to be associated with educational and behavioral problems, few studies have investigated psychopathological abnormalities in this population. The aim of this study was to evaluate the psychopathological influence of UHL among Korean 19-year-old males.Methods. The authors retrospectively compared the objective personality test profiles of 602 subjects with UHL with those of 23,790 peers with normal hearing. All participants in the current study were 19-year-old males who underwent a physical examination and completed the Korean Military Multiphasic Personality Inventory for conscription at the Military Manpower Administration from February 2015 to December 2016.Results. Significantly higher scores were found on neurosis scales in the UHL group than in the normal-hearing group (50.9± 10.8 vs. 44.9±6.0 for anxiety; 51.0±10.5 vs. 44.9±5.2 for depression; 51.1±10.4 vs. 45.1±6.81 for somatization, all P<0.001). The psyc...
Psychological Medicine, 2020
BackgroundObsession and delusion are theoretically distinct from each other in terms of reality t... more BackgroundObsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS).MethodsOur study sample comprised of 96 patients with obsessive–compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion severity and RFSC using multivariate distance-based matrix regression.ResultsObsession was associated with the supplementary motor area, precentral gyrus, and superior parietal lobule, while delusion was associ...
Molecular Psychiatry, 2019
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
Scientific Reports, 2017
Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, a... more Use of Cannabis, the most widely used illicit drug worldwide, is associated with acute anxiety, and anxiety disorders following regular use. The precise neural and receptor basis of these effects have not been tested in man. Employing a combination of functional MRI (fMRI) and positron emission tomography (PET), we investigated whether the effects of delta-9-tetrahydrocannabinol (delta-9-THC), the main psychoactive ingredient of cannabis, on anxiety and on amygdala response while processing fearful stimuli were related to local availability of its main central molecular target, cannabinoid-1 (CB1) receptors in man. Fourteen healthy males were studied with fMRI twice, one month apart, following an oral dose of either delta-9-THC (10 mg) or placebo, while they performed a fear-processing task. Baseline availability of the CB1 receptor was studied using PET with [ 11 C]MePPEP, a CB1 inverse agonist radioligand. Relative to the placebo condition, delta-9-THC induced anxiety and modulated right amygdala activation while processing fear. Both these effects were positively correlated with CB1 receptor availability in the right amygdala. These results suggest that the acute effects of cannabis on anxiety in males are mediated by the modulation of amygdalar function by delta-9-THC and the extent of these effects are related to local availability of CB1 receptors. Cannabis is the world's most commonly used illicit substance 1. Although most recreational users smoke cannabis for its relaxing effects, the drug has a range of adverse effects including the induction of acute anxiety 2-5 and, development of anxiety disorders in regular users 6. While these effects of cannabis are mediated by its main psychoactive constituent, delta-9-tetrahydrocannabinol (delta-9-THC) 3 , the extract of the cannabis plant has many other ingredients, some of which e.g. Cannabidiol may have anxiolytic effects 3. Consistent with this, and evidence that many of the behavioural effects of exogenous cannabinoids can be linked to their effects on the endocannabinoid system 7 , a large body of preclinical evidence has accumulated implicating different components of the endocannabinoid system in emotional processing and anxiety 8. Preclinical studies suggest that contradictory evidence regarding the precise effect of exogenous cannabinoids on anxiety, in terms of an anxiolytic or anxiogenic response, may be linked to dose of the cannabinoid 7 as well as its site of action 9 , while there is less mechanistic
Translational psychiatry, Apr 24, 2018
Aripiprazole's effects on cognitive function in patients with schizophrenia are unclear becau... more Aripiprazole's effects on cognitive function in patients with schizophrenia are unclear because of the difficulty in disentangling specific effects on cognitive function from secondary effects due to the improvement in other schizophrenic symptoms. One approach to address this is to use an intermediate biomarker to investigate the relationship between the drug's effect on the brain and change in cognitive function. This study aims to investigate aripiprazole's effect on working memory by determining the correlation between dopamine D2/3 (D2/3) receptor occupancy and working memory of patients with schizophrenia. Seven patients with schizophrenia participated in the study. Serial positron emission tomography (PET) scans with [C]raclopride were conducted at 2, 26, and 74 h after the administration of aripiprazole. The subjects performed the N-back task just after finishing the [C]raclopride PET scan. The mean (±SD) D2/3 receptor occupancies were 66.9 ± 6.7% at 2 h, 65.0 ± ...
Korean Journal of Schizophrenia Research, 2016
Objectives : This study investigated the prescribing patterns of atypical antipsychotics for the ... more Objectives : This study investigated the prescribing patterns of atypical antipsychotics for the various psychiatric disorders in the psychiatric ward of a University hospital. Methods : We reviewed the medical records of patients who were discharged from an open psychiatric ward from May, 2003 through April, 2014. The association between psychiatric disorders and prescription pattern of atypical antipsychotics was analyzed. Results : The study included 3091 patients' prescription of psychiatric medication. 60% of prescription included antipsychotics; quetiapine was the most frequently prescribed antipsychotics, but the average dosage was the lowest among all the atypical antipsychotics. According to the diagnoses, prescription rates and dosage of antipsychotics were different. Prescription rates of antipsychotics were the lowest in patients with anxiety disorders, and the mean dosage were the lowest in those with delirium, dementia, and amnestic and other cognitive disorders. Conclusion : This observational study shows prescription patterns of atypical antipsychotics for the treatment of psychiatric disorders in a University hospital; atypical antipsychotics were widely used for the treatment of the various disorders, and there were differences in prescription patterns for each disorders. The results of this study may be used to identify the proper atypical antipsychotics effective on certain psychiatric disorders and to propose expanding the indications of each atypical antipsychotics in the future.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, Jan 14, 2016
Some patients with schizophrenia show poor response to first-line antipsychotic treatments and th... more Some patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment-resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment-resistant schizophrenia. However, in this study, the treatment-resistant patients were highly symptomatic, whereas the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus, we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment-resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls...
NeuroImage. Clinical, 2013
Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward ... more Compulsive behaviors in obsessive-compulsive disorder (OCD) may be related to deficits in reward processing mediated by corticostriatal circuitry, a brain network implicated in the pathophysiology of OCD. Performing compulsive actions can be perceived as a reward to OCD patients because it temporarily reduces the anxiety provoked by obsessions. Although most OCD literature provides evidence of altered regional activity in these corticostriatal circuits, very little is known about the connectivity between individual regions of the corticostriatal-limbic circuits, including the cognitive and affective neural circuitry associated with OCD. Thus, this study investigated the differences in functional connectivity (FC) patterns in this network during resting-state and incentive processing. Nineteen patients with OCD and 18 well-matched healthy controls were scanned during resting-state and a monetary incentive delay task (task state). FC was assessed using both voxel-wise and region-of-in...
Clinical pharmacology and therapeutics, 2007
YKP1358 is a novel serotonin (5-HT(2A)) and dopamine (D(2)) antagonist that, in preclinical studi... more YKP1358 is a novel serotonin (5-HT(2A)) and dopamine (D(2)) antagonist that, in preclinical studies, fits the general profile of an atypical antipsychotic. We conducted a D(2) receptor occupancy study with YKP1358 in healthy volunteers using positron emission tomography (PET) to measure the D(2) receptor occupancy of YKP1358 and to characterize its relationship to plasma drug concentrations. A single oral dose, parallel group, dose-escalation (100, 200, and 250 mg) study was performed in 10 healthy male volunteers with the PET radiotracer [(11)C]raclopride. The D(2) receptor occupancy of striatum was measured pre-dose, and at 2, 5, and 10 h after YKP1358 administration. Serial blood samples were taken for measurement of plasma YKP1358 concentrations. D(2) receptor occupancy by YKP1358 increased to 53-83% at 2 h, and then decreased afterwards, ranging from 40-64% at 5 h to 20-51% at 10 h. The YKP1358 dose-plasma concentration relationship exhibited extensive variability, but there wa...
Schizophrenia Research, 2011
Background: While deficits in cognitive functions are frequently reported in psychotic disorders,... more Background: While deficits in cognitive functions are frequently reported in psychotic disorders, further longitudinal research is needed to confirm the specific risk factors for the development of psychosis. We examined longitudinally the social-cognitive and neurocognitive function of individuals at ultra-high risk for schizophrenia who developed psychosis later as predictive markers. Method: The investigators studied 49 subjects at ultra-high risk (UHR) for psychosis and 45 healthy controls. The UHR subjects were followed for up 5.2 years (mean:2.8 years) and 13 of these subjects developed psychosis. Theory of mind (ToM) tasks and neuropsychological tests were administered at baseline. Analyses compared the UHR patients who later developed psychosis, those who did not develop, and healthy controls. To examine the cognitive variables to predict transition to psychosis, Cox regression analyses were conducted. Results: At baseline, we found significant differences among the three groups in social cognition according to the False Belief and cartoon tasks and in neurocognition according to tasks measuring executive function, working memory, verbal memory, and visual memory. Our study showed that a model combining working memory, visual memory, executive function, and ToM tasks was significantly predictive of time to conversion to psychosis. Conclusion: This study indicated that UHR patients who later converted to psychosis performed more poorly on tasks involving social cognition and neurocognition than did those who did not convert. We suggest that these deficits can serve as specific markers to predict the development of psychosis.
Schizophrenia Bulletin, 2012
Background: The psychosis phenotype appears to exist in the population as a continuum, but it is ... more Background: The psychosis phenotype appears to exist in the population as a continuum, but it is not clear if subclinical psychotic symptoms and psychotic disorders share the same neurobiology. We investigated whether the dopaminergic dysfunction seen in psychotic disorders is also present in healthy, well-functioning people with hallucinations. Methods: We compared dopamine synthesis capacity (using 6-[ 18 F]fluoro-L-DOPA [[ 18 F]-DOPA] positron emission tomography imaging) in 16 healthy individuals with frequent persistent auditory verbal hallucinations (hallucinating group) with that in 16 matched controls. Results: There was no significant difference in dopamine synthesis capacity in the striatum, or its functional subdivisions, between groups and no relationship between subclinical psychotic symptom severity or schizotypal traits and dopamine synthesis capacity in the hallucinating group. Conclusions: Altered dopamine synthesis capacity is unlikely to underlie subclinical hallucinations, suggesting that although there may be a phenomenological psychosis continuum, there are distinctions at the neurobiological level.
PLoS ONE, 2011
Background: Recent studies have reported that the insular cortex is involved in the pathophysiolo... more Background: Recent studies have reported that the insular cortex is involved in the pathophysiology of obsessivecompulsive disorder (OCD). However, specific morphometric abnormalities of the insular subregions remain unclear. In this study, we examined insular cortical volume to determine whether the volume of the anterior and posterior insular cortices of unmedicated OCD patients differed according to different symptom dimensions. Methods/Principal Findings: Using magnetic resonance imaging, we measured the gray matter volumes of the insular cortex and its subregions (anterior and posterior divisions) in 41 patients with OCD (31 drug-naïve and 10 non-medicated) and 53 healthy controls. Volumetric measures of the insular cortex were compared according to different OC symptoms. Enlarged anterior and reduced posterior insular cortices were observed in OCD patients. The insular volumetric alterations were more significant in OCD patients with predominant checking rather than cleaning symptoms when compared with healthy controls. Conclusions/Significance: Our results suggest the presence of unbalanced anterior and posterior insular volumetric abnormalities in unmedicated OCD patients and emphasize the distinct role of the insular cortex in different OC symptoms. We propose that the insular morphometric alterations may influence the modulation of interoceptive processing, the insular functional role, in OCD patients with different symptoms.