Structural Brain Alterations in Individuals at Ultra-high Risk for Psychosis: A Review of Magnetic Resonance Imaging Studies and Future Directions

정위훈,장준환,변민수,안석균,권준수 대한의학회 2010 Journal of Korean medical science Vol.25 No.12

Individuals at ultra-high-risk (UHR) for psychosis have become a major focus for research designed to explore markers for early detection of and clinical intervention in schizophrenia. In particular, structural magnetic resonance imaging studies in UHR individuals have provided important insight into the neurobiological basis of psychosis and have shown the brain changes associated with clinical risk factors. In this review, we describe the structural brain abnormalities in magnetic resonance images in UHR individuals. The current accumulated data demonstrate that abnormalities in the prefrontal and temporal cortex and anterior cingulate cortex occur before illness onset. These regions are compatible with the regions of structural deficits found in schizophrenia and firstepisode patients. In addition, the burgeoning evidence suggests that such structural abnormalities are potential markers for the transition to psychosis. However, most findings to date are limited because they are from cross-sectional rather than longitudinal studies. Recently, researchers have emphasized neurodevelopmental considerations with respect to brain structural alterations in UHR individuals. Future studies should be conducted to characterize the differences in the brain developmental trajectory between UHR individuals and healthy controls using a longitudinal design. These new studies should contribute to early detection and management as well as provide more predictive markers of later psychosis.

휴지기 두뇌의 네트워크와 지연할인율의 개인차

정위훈 한국인지및생물심리학회 2021 한국심리학회지 인지 및 생물 Vol.33 No.1

Though many investigations have reported associations between brain and behavioral phenotypes (e.g., delay discount as a measure of impulsive choice), our current understanding of such associations in terms of functional connectivity (FC) is limited due to the limiting factors of the most commonly used mass univariate approach. Here, we thus examine the association between impulsive choice and resting-state FC using a recently introduced, data-driven multivariate analysis (multivariate distance-based matrix regression) in 142 young healthy adults. This connectome-wide analysis identified regions associated with delay discount rates based on multifocal FC patterns, including medial temporal lobe, precuneus, premotor cortex, and ventromedial prefrontal cortex (VMPFC). Follow-up seed-based and network-level analyses revealed that high impulsivity was associated with greater inter-network connectivity between default mode and attention networks, correlated respectively with VMPFC and premotor cortex. These results provide novel insights for functional connectivities and networks associated with impulsive choice and target regions for its intervention. These results suggest an important role of large-scale brain network balance in impulsive choice. 이전 여러 연구들이 뇌의 기능적 연결성과 행동적 표현형(예: 충동적 행동의 지표인 지연할인율) 간의 연관성을 보고하였다. 그럼에도 불구하고 대부분의 연구들이 사용한 다중-단변량 접근법(mass-univariate approach)으로 인해 이러한 연관성에 대한 우리의 지식 및 이해는 여전히 제한되어 있다. 본 연구에서는 최근 개발된 자료 기반 다변량 분석기법을 사용하여 142명의 젊고 건강한 성인의 지연할인율과 휴지기 기능적 연결성 간의 연관성을 조사하였다. 분석을 통해 내측 측두엽, 설전부(precuneus), 전운동피질, 복내측 전전두피질의 다변량 기능적 연결성 패턴이 지연할인율과 연합되어 있음을 발견하였다. 또한 seed 기반 기능적 연결성(seed-based functional connectivity) 분석과 네트워크 분석을 통해 지연할인율과 네트워크 간 연결성 사이의 정적 상관을 관찰하였다. 특별히 내측 전전두피질과 연합된 디폴트 모드 네트워크와 전운동피질과 연합된 주의네트워크들 사이의 네트워크 간 연결성이 지연할인율과 연관성을 보였다. 현 결과는 충동적인 선택에 연합된 특정한 기능적 연결성 및 네트워크에 대한 우리의 지식을 확장시켜준다. 특별히 충동적인 선택에 있어 뇌 네트워크들 간 연결성의 균형이 중요한 역할을 함을 제안한다. 또한 현 결과는 충동적 행동의 중재와 관련하여 새로운 통찰을 제공해준다.

사회비교 경향성의 개인차에 대한 신경 기질: 확산텐서영상 연구

정위훈 한국인지및생물심리학회 2023 한국심리학회지 인지 및 생물 Vol.35 No.2

People vary considerably in their social comparison orientation (SCO), which the extent (tendency) to which they compare themselves with others. Understanding individual differences in SCO is important, because it is associated with various types of rea-life outcomes. Therefore, using diffusion tensor imaging data from healthy young adults, I investigated not only the correlation between individual SCO and the fractional anisotropy (FA) and mean diffusivity (MD) values of the uncinate fasciculus (UF), associated with social-emotional processing, but also the correlation between individual SCO and each of demographic characteristics (age, sex, and duration of education). Multiple regression analyses were also preformed to test the ability of models with only demographic variables and models with demographic and brain variables to predict SCO. Correlation analyses revealed significant relationships between SCO and the FA and MD of UF. Additionally, age and duration of education were negative correlated with individual SCO, and women had higher SCO score than men. Multiple regression analyses revealed the model with sex, education, and UF FA better predicted individual SCO than others. These results provide novel insights into the predictors of individual SCO, showing the involvement of UF and some demographic information in individual differences in SCO. 사회비교 경향성(social comparison orientation, SCO)은 자신을 다른 사람과 비교하는 정도(경향)를 의미하는데 이 같은 사회비교 경향성은 사람들 간에 상당히 다르다. 개인의 사회비교 경향성은 실생활의 다양한 결과들과 연관이 있기 때문에 사회비교 경향성의 개인차를 이해하는 것은 매우 중요하다. 따라서 본 연구에서는 건강한 젊은 성인의 확산텐서영상(diffusion tensor imaging) 자료를 이용하여 개인의 사회비교 경향성과 사회적-정서적 처리와 관련된 갈고리섬유다발(uncinate fasciculus, UF)의 분할 비등방도(factional anisotropy, FA) 및 평균확산도(mean diffusivity, MD) 간의 상관관계 뿐만 아니라 개인의 사회비교 경향성과 각각의 인구통계학적 특성들(나이, 성별, 교육기간) 간의 상관관계를 조사하였다. 또한 인구통계학적 변수만 있는 모델과 인구통계학적 변수 및 뇌 변수가 함께 있는 모델이 개인의 사회비교 경향성을 예측하는 능력을 조사하고자 다중회귀분석을 수행하였다. 상관분석을 통해 사회비교 경향성과 갈고리섬유다발의 FA 및 MD 간에 중요한 관계가 있음이 관찰되었다. 또한 나이와 교육년수는 개인의 사회비교 경향성과 부적 상관을 지녔고, 여성이 남성보다 사회비교 경향성이 높은 것을 확인하였다. 다중회귀분석결과 성별, 교육년수, 그리고 갈고리섬유다발의 FA가 함께한 모델이 개인의 사회비교경향성을 가장 잘 예측하였다. 이러한 결과들은 사회비교 경향성에 있어 갈고리섬유다발 및 다양한 인구통계학적 정보와의 관련성을 보여줌으로써 개인의 사회비교 경향성의 예측 마커에 대한 새로운 통찰력을 제공해준다.

정신분열병, 정신증 임상적 고위험군 및 대조군에서의 시상 용적에 관한 연구

전명욱,정위훈,최정석,정명훈,김지원,최치훈,권준수 대한신경정신의학회 2009 신경정신의학 Vol.48 No.5

Objectives: To investigate the changes in thalamic volumes in subjects at ultra-high risk (UHR) for psychosis. Subjects manifest changes which are similar to but different from those found in subjects with schizophrenia, and thalamic structural changes were often reported in schizophrenic subjects. MethodsZZThalamic volumes of 29 UHR subjects, 31 subjects with schizophrenia and 29 healthy controls, were measured from their T1-weighted coronal magnetic resonance (MR) images using manual tracing. Results: UHR subjects showed greater right (6.243±0.848 cm3) and total (12.254±1.532 cm3) thalamic volumes compared to healthy control subjects (right thalamic volume=5.527±0.715 cm3, total thalamic volume=11.058±1.490 cm3) or patients with schizophrenia (right thalamic volume=5.855±0.938 cm3, total thalamic volume=11.513±1.784 cm3). The difference was significant for right (F=5.837, p=0.004) and total (F=4.217, p=0.018) thalamic volumes after intracranial volume had been accounted for as a covariate in ANCOVA. However, thalamic volume of subjects with schizophrenia showed no significant difference from controls. This difference was not affected by the presence of major depressive disorder or the magnitude of psychotic symptoms. Those among the UHR subjects taking antipsychotic agents did not show enlarged thalamic volume compared to controls. Conclusion: Our findings suggest that the possibility of a volumetric alteration of the thalamus characteristic of the UHR state. 결론적으로, 본 연구에서는 정신증 고위험군에서의 우측 시상 용적 증가가 관찰되었다. 이는 고위험군 시기에 특징적으로 나타날 수 있는 뇌의 용적 변화의 가능성을 제시하며, 또한 정신증의 경과 중 동적인 용적 변화가 병태생리와 연관되 어 있을 가능성도 있음을 시사한다.

정신분열병, 정신증 임상적 고위험군 및 대조군에서의 시상 용적에 관한 연구

전명욱,정위훈,최정석,정명훈,김지원,최치훈,권준수 대한신경정신의학회 2009 신경정신의학 Vol.48 No.4

Objectives To investigate the changes in thalamic volumes in subjects at ultra-high risk (UHR) for psychosis. Subjects manifest changes which are similar to but different from those found in subjects with schizophrenia, and thalamic structural changes were often reported in schizophrenic subjects. Methods Thalamic volumes of 29 UHR subjects, 31 subjects with schizophrenia and 29 healthy controls, were measured from their T1-weighted coronal magnetic resonance (MR) images using manual tracing. Results UHR subjects showed greater right (6.243±0.848 cm3) and total (12.254±1.532 cm3) thalamic volumes compared to healthy control subjects (right thalamic volume=5.527±0.715 cm3, total thalamic volume=11.058±1.490 cm3) or patients with schizophrenia (right thalamic volume=5.855± 0.938 cm3, total thalamic volume=11.513±1.784 cm3). The difference was significant for right (F= 5.837, p=0.004) and total (F=4.217, p=0.018) thalamic volumes after intracranial volume had been accounted for as a covariate in ANCOVA. However, thalamic volume of subjects with schizophrenia showed no significant difference from controls. This difference was not affected by the presence of major depressive disorder or the magnitude of psychotic symptoms. Those among the UHR subjects taking antipsychotic agents did not show enlarged thalamic volume compared to controls. Conclusion Our findings suggest that the possibility of a volumetric alteration of the thalamus characteristic of the UHR state.

병적 도박 환자에서의 회백질 부피 변화 분석 : 화소 기반 형태분석 방법을 이용한 예비 연구

최정석,신영철,정위훈,정명훈,장준환,강도형,최치훈,권준수,이준영,Choi, Jung-Seok,Shin, Young-Chul,Jung, Wi Hoon,Jung, Myung Hun,Jang, Joon Hwan,Kang, Do-Hyung,Choi, Chi-Hoon,Kwon, Jun Soo,Lee, Jun-Young 대한생물정신의학회 2009 생물정신의학 Vol.16 No.3

Objectives : The purpose of this study was to examine structural abnormalities of brain in patients with pathological gambling(PG) using voxel-based morphometry. Methods : We compared gray matter(GM) volumes between 10 patients with PG and 14 age- and IQ-matched healthy controls and examined the relationship of GM volumes with clinical variables in patients with PG. Results : We found significant increase of GM volume in the superior, middle, and inferior frontal gyri, the midbrain, the middle temporal gyrus, the precuneus, and the fusiform gyrus of patients with PG. A significant decrease of GM volume was observed in the parahippocampal gyrus and the lingual gyrus of the patient group. In addition, GM volumes in some of these regions were positively associated with South Oaks Gambling Screen score and negatively with age of onset in patients with PG. Conclusion : Current findings indicate that structural abnormalities in the fronto-temporal cortex, the midbrain, and the precuneus might be involved in the pathophysiology of PG, and contribute to some of the behavioral changes observed in patients with PG.

Altered Brain Activation in Ventral Frontal–Striatal Regions Following a 16-week Pharmacotherapy in Unmedicated Obsessive–Compulsive Disorder

한지연,강도형,구본미,정위훈,최정석,최치훈,장준환,권준수 대한의학회 2011 Journal of Korean medical science Vol.26 No.5

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal–striatal circuit and parietal region is a core cognitive deficit of obsessive–compulsive disorder (OCD). However, few studies have examined progressive changes in these regions following clinical improvement in obsessive-compulsive symptoms. To determine if treatment changes the aberrant activation pattern associated with task switching in OCD, we examined the activation patterns in brain areas after treatment. The study was conducted on 10 unmedicated OCD patients and 20 matched controls using event-related functional magnetic resonance imaging. Treatment improved the clinical symptoms measured by the Yale-Brown Obsessive Compulsive Scale and behavioral flexibility indicated by the switching cost. At baseline, OCD showed significantly less activation in the dorsal and ventral frontal–striatal circuit and parietal regions under the task-switch minus task-repeat condition compared with controls. After treatment, the neural responses in the ventral frontal–striatal circuit in OCD were partially normalized,whereas the activation deficit in dorsal frontoparietal regions that mediate shifting attention or behavioral flexibility persisted. It is suggested that altered brain activation in ventral frontal-striatal regions in OCD patients is associated with their cognitive flexibility and changes in these regions may underlie the pathophysiology of OCD.

Depressive Symptoms and Brain Metabolite Alterations in Subjects at Ultra-high Risk for Psychosis: A Preliminary Study

변민수,최정석,유소영,강도형,장동표,정위훈,정명훈,장준환,이종민,권준수,최치훈 대한신경정신의학회 2009 PSYCHIATRY INVESTIGATION Vol.6 No.4

Objective: Recent neuroimaging studies have suggested that brain changes occur in subjects at ultra-high risk (UHR) for psychosis while experiencing prodromal symptoms, among which depression may increase the risk of developing a psychotic disorder. The goal of this study is to examine brain metabolite levels in the anterior cingulate cortex, the left dorsolateral prefrontal cortex and the left thalamus in subjects at UHR for psychosis and to compare brain metabolite levels between the UHR subjects with comorbid major depressive disorder and healthy controls. Methods: Proton magnetic resonance spectroscopy was used to examine brain metabolite levels. Twenty UHR subjects and 20 age- and intelligence quotient (IQ)-matched healthy controls were included in this study. Results: Overall, no significant differences were observed in any metabolite between the UHR and healthy control group. However, UHR subjects with major depressive disorder showed significantly higher myo-inositol (Ins) levels in the left thalamus, compared to the healthy control. Conclusion: Our results demonstrate that increased thalamic Ins level is associated with prodromal depressive symptoms. Further longitudinal follow-up studies with larger UHR sample sizes are required to investigate the function of Ins concentrations as a biomarker of vulnerability to psychosis.

소방공무원에서 부분 외상후 스트레스 장애의 심리적특성 및 기능적 자기공명영상 특징과 안구운동민감소실 및 재처리요법을 이용한 치료효과

정용호,김남희,김대호,배재현,권준수,장준환,정위훈,김석현,김준기,오동훈,신다정,조강익 대한신경정신의학회 2014 신경정신의학 Vol.53 No.2

Objectives This study investigated the clinical characteristics and functional magnetic resonanceimaging (fMRI) findings of firefighters suffering from partial posttraumatic stress disorder(partial PTSD). They were treated by eye movement desensitization and reprocessing (EMDR)and the treatment effect was evaluated. Methods A total of 116 firefighters were screened and 15 of them were diagnosed as partialPTSD. 1) We compared sociodemographic and psychological characteristics between the firefighterpartial PTSD group and the firefighter control group. 2) Subjects in the firefighter partialPTSD group (n=10), firefighter control group (n=8), and general control group (n=12) underwentfMRI with traumatic, negative, positive, and neutral picture stimuli. We compared clinical characteristicsand fMRI findings among these three groups. 3) Seven firefighters in the partial PTSD groupwere treated by EMDR and the treatment effect was evaluated according to psychological scales. Results In fMRI analysis, there was a left middle temporal/occipital activation in the order of thegeneral control group, firefighter control group, than the firefighter partial PTSD group for the Traumatic-Baseline contrast. For the Negative-Baseline contrast, there was an increased left middletemporal/occipital activation in the general control group versus decreased activation in the firefightercontrol group and the firefighter partial PTSD group. All firefighters in the partial PTSD grouptreated by EMDR showed significant improvement of Clinician-Administered PTSD Scale scores. Conclusion These results show high incidence rate of partial PTSD in firefighters. In addition,partial PTSD firefighters exhibited distinct clinical characteristics and fMRI findings and showed significant improvement by EMDR treatment. 소방공무원에서 부분 PTSD의 진단율이 높고, 이들은 다른 심리적 특성과 생물학적 특징을 보이며 EMDR 치료로 유의미한 호전을 보였다. 향후 이러한 소방공무원의 PTSD와이에 대한 효과적인 정신과적 개입을 위한 관심과 연구가 지속적으로 이루어져야 하며, 이는 양질의 체계적이고 효과적인 정신과적 치료와 정신건강 서비스를 소방공무원들에게제공하기 위한 체계 수립과 정책 개발에 도움이 될 것이다.