Additive Burden of Abnormal Diffusivity in the Brainwith Schizophrenia: A Diffusion Tensor Imaging Studywith Public Neuroimaging Data

Objective@#Diffusion tensor imaging has been extensively applied to schizophrenia research. In this study, we counted the number ofabnormal brain regions with altered diffusion measures in patients with schizophrenia to enumerate the burden of abnormal diffusivityin the brain. @*Methods@#The public neuroimaging data of the COBRE project from SchizConnect were used for the study. The studied dataset consistedof data from 57 patients with schizophrenia and 71 healthy participants. FreeSurfer and FSL were applied for image processingand analysis. After verifying 161 regions of interest (ROIs), mean diffusion measures in every single ROI in all study participants weremeasured and normalized into Z-scores. Each ROI was then defined as normal or abnormal on the basis of a cutoff absolute Z-score of1.96. The number of abnormal ROIs was obtained by each diffusion measure. @*Results@#The numbers of ROIs with increased radial diffusivity and increased trace were significantly larger in the patient group than inhealthy participants. @*Conclusion@#Thus, the patient group showed a significant increase in abnormal ROIs, strongly indicating that schizophrenia is notcaused by the pathology of a single brain region, but is instead attributable to the additive burden of structural alterations within multiplebrain regions. Psychiatry Investig 2020;17(4):341-349

Gray Matter Microstructural Abnormalities and Working Memory Deficits in Individuals with Schizophrenia

OBJECTIVE: Working memory impairments serve as prognostic factors for patients with schizophrenia. Working memory deficits are mainly associated with gray matter (GM) thickness and volume. We investigated the association between GM diffusivity and working memory in controls and individuals with schizophrenia. METHODS: T1 and diffusion tensor images of the brain, working memory task (letter number sequencing) scores, and the demographic data of 90 individuals with schizophrenia and 97 controls were collected from the SchizConnect database. T1 images were parcellated into the 68 GM Regions of Interest (ROI). Axial Diffusivity (AD), Fractional Anisotropy (FA), Radial Diffusivity (RD), and Trace (TR) were calculated for each of the ROIs. RESULTS: Compared to the controls, schizophrenia group showed significantly increased AD, RD, and TR in specific regions on the frontal, temporal, and anterior cingulate area. Moreover, working memory was negatively correlated with AD, RD, and TR in the lateral orbitofrontal, superior temporal, inferior temporal, and rostral anterior cingulate area on left hemisphere in the individuals with schizophrenia. CONCLUSION: These results demonstrated GM microstructural abnormalities in the frontal, temporal, and anterior cingulate regions of individuals with schizophrenia. Furthermore, these regional GM microstructural abnormalities suggest a neuropathological basis for the working memory deficits observed clinically in individuals with schizophrenia.

Developing and Clinical Application of a Smartphone Mobile Mood Chart Application in Korean for Patients with Bipolar Disorder / 신경정신의학

OBJECTIVES: The aim of this study was to develop a Korean version of a mood chart application on an Android platform. METHODS: This application is based on the traditional mood chart. Eighteen adults with DSM-5 bipolar disorder were enrolled from November 2016 to March 2017. They were asked to rate their daily mood scores and severity of irritability and impulsivity for six months. Their clinicians rated their symptom severity monthly using the Clinical Global Impression-7 (CGI-7) scale. After six months, the participants completed an anonymous questionnaire regarding their satisfaction with the application. RESULTS: Of the 18 patients, one withdrew their consent from this study and six were males (35.3%) ; their mean age was 31.71±8.56 years. The mean follow-up duration was 159.12±49.45 days and the period of application use was 143.65±52.11 days. The mean total response rate was 59.45% and the mean response rate on the same day was 43.06%. The adherence to using the application decreased significantly declined over the duration since enrollment [odds ratio (OR)=1.008, p=0.008] but tended to increase according to age (OR=0.958, p=0.002). The application mood scores were correlated significantly with the manic (β=0.307, p=0.004) and depressive (β=−0.701, p < 0.001) subscale, and the total (β=1.026, p=0.002) of the CGI-7 (linear mixed models). The majority of subjects agreed that the application helped them manage their symptoms (92.86%), stating that the application was easy to use (78.57%). CONCLUSION: This application could be a valid and useful tool to monitor the mood symptoms of patients with bipolar disorder in Korea.

Antidepressant Prescription Patterns in Bipolar Disorder: a Nationwide, Register-based Study in Korea

BACKGROUND: The role of antidepressants (ADs) in bipolar disorder is long-standing controversial issue in psychiatry. Many clinicians have used ADs as a treatment for bipolar depression, and the selection of therapeutic agents is very diverse and inconsistent. This study aimed to examine recent AD prescription patterns for patients with bipolar disorder in Korea, using the nationwide, population-based data. METHODS: This study utilized the Korean nationwide, whole population-based registry data of the year 2010, 2011, and 2013. All prescription data of the ADs, antipsychotics, and mood stabilizers of the sampled patients diagnosed with bipolar disorder (n = 2,022 [in 2010]; 2,038 [in 2011]; 2,626 [in 2013]) were analyzed for each year. RESULTS: Annual prescription rate of ADs was 27.3%–33.6% in bipolar disorder, which was gradually increasing over the 3-year period. The combination pattern of ADs and antipsychotic drugs tended to increase over 3 years. The proportion of females and the prevalence of comorbid anxiety disorder were significantly higher in AD user group in all three years. Among individual ADs, escitalopram was prescribed most frequently, and fluoxetine and bupropion were prescribed to the next many patients. The mean duration of bipolar depressive episodes was 135.90–152.53 days, of which ADs were prescribed for 115.60–121.98 days. CONCLUSION: Our results show prescription rate of ADs in bipolar disorder was maintained at substantial level and increased in recent 3 years. More empirical data and evidence are needed to establish practical treatment consensuses.

The New Mental Health and Welfare Law in Korea: Issues with Additional Diagnosis by External Psychiatrist and the Role of Admission Review Committee / 신경정신의학

The new Mental Health and Welfare Law in Korea was revised to require additional diagnosis by a psychiatrist from another public or designated hospital for involuntary admission beyond 2 weeks. In addition, it features the newly established Admission Review Committee for better protection of human rights. The provision of the additional diagnosis by an external psychiatrist resulted from misinformation about the distinction between the second opinion for medical assessment and the review of admission by independent authorities. An additional diagnosis is not required by an external doctor since it is not for review of adequacy of admission but just for second opinion for better medical assessment. Given the limited number of qualified public hospital psychiatrists, additional diagnosis by external psychiatrists does not seem practical unless private hospital doctors are required to visit neighboring hospitals. The current method of cross checking between neighboring doctors is not in accordance with the principles that review should be done by independent authorities. The Admission Review Committee also does not seem to serve the purpose since the role of the Committee is limited to document review, while the proper role of the Committee is left to individual doctors. Admission review should be performed through a thorough interview with the patient by a judicial (or quasi-judicial) authority. Law revision is urgently needed to ensure proper judicial (or quasi-judicial) review of admission, and to streamline unnecessary procedures such as the additional diagnosis by external doctors.

The United Nations Convention on the Rights of Persons with Disabilities and Compulsory Admission of Persons with Mental Illness: A Critique of Prohibition of Compulsory Admission / 신경정신의학

The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) has often been cited as the basis for the abolition of involuntary hospitalization for persons with mental illness. Although the UNCRPD itself does not refer explicitly to the abolition of involuntary hospitalization, the General Comment prohibited all compulsory admission without adequate explanation. While the disability status alone may not justify the denial of legal capacity, the existence of impaired decision-making ability can raise issues regarding whether involuntary admission can be justified in the best interest of persons with mental illness. The General Comment, however, argues that involuntary admission does not comply with the CRPD which prohibits discrimination on the basis of disabilities. This statement defies logic since the issue is whether the existence of impaired decision-making ability may be an exceptional case. It is also against the principles of beneficence to withhold treatment for persons with mental illness just for self-determination when poor outcomes are anticipated if left untreated. The concept of supported decision making suggested by the General Comment is also ambiguous, and not clearly distinguishable from substitute decision making. Another reason for the prohibition of involuntary admission relates to doubt concerning the accuracy of assessment of mental capacity, which implies adequate assessment may justify involuntary admission. In practice, it is not always complicated to assess mental capacity in order to make treatment-related decisions. The third reason concerns the argument that psychiatric treatments lack empirical evidence concerning effectiveness. Scientific evidence supporting the effectiveness of psychiatric treatment is abundant. The rights of persons with mental illness are important ethical issues. However, it is doubtful whether the blanket prohibition of compulsory admission is appropriate and ethical. Critical review of the UNCRPD and the General Comment is urgent for timely treatment and for the well-being of persons with mental illness.

A Case of needle-tract implantation of hepatocellular carcinoma in the ovary after radiofrequency ablation / 고신대학교의과대학학술지

Radiofrequency ablation (RFA), a local ablative modality, is gaining acceptance for the treatment of liver malignancies. Despite a relatively low complication rate, tumor seeding resulting from RFA in hepatocellular carcinoma (HCC) treatment can occur. A 44-year-old woman was diagnosed with HCC. Spiral computed tomography (CT) revealed a 2.3 × 2.0-cm mass in the S5 segment, which was treated with RFA on May, 2005. Follow-up imaging, performed at 6-month intervals after RFA, showed complete tumor necrosis. In October 2009, CT revealed a heterogeneous mass, 5.7 cm in diameter, in the right ovary. Since the lesion was limited to the right ovary without evidence of spread, bilateral salpingo-oophorectomy was performed. Histopathology indicated that the metastatic spread from the HCC to the ovary was positive for hepatocyte-specific antigen on immunohistochemistry. The ovary is a rare site for HCC metastasis. Moreover, needle tract implantation of HCC in the ovary is very rare.

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.

Clinical Application of the Korean Personality Rating Scale for Children in Attention-Deficit Hyperactivity Disorder

OBJECTIVES: The objective of this study was to compare the Korean Personality Rating Scale for Children (K-PRC) profile between children with attention-deficit hyperactivity disorder (ADHD) and typically developing children. We also aimed to investigate the association of K-PRC and ADHD symptoms. METHODS: Ninety-nine youth (age 8.3+/-2.4 years, 72 boys) with ADHD and 84 controls (age 9.2+/-2.5 years, 43 boys) were recruited from the Department of Pediatric Psychiatry of the Asan Medical Center Children's Hospital. Diagnoses of ADHD and comorbid psychiatric disorders were confirmed with the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL). The parents of the subjects completed the ADHD rating scale, and K-PRC. Independent t-tests, analysis of covariance, partial correlation analyses, and Mc Nemar test were used for analysis. RESULTS: Children and adolescents with ADHD showed higher K-PRC scores in verbal development, physical development, depression, delinquency, hyperactivity, family dysfunction and psychoticism. Delinquency and hyperactivity were significantly correlated with parent-rated ADHD rating scales and ADHD scores on K-SADS-PL. The hyperactive/impulsive and combined subtypes showed higher scores on hyperactivity and delinquency than the inattentive subtype, and the inattentive subtype showed higher scores on depression and social dysfunction of the K-PRC. CONCLUSION: Our results suggest that K-PRC could be used to comprehensively evaluate symptoms, combined psychopathologies, developmental delay and family dysfunction of children with ADHD.

Abnormal Brain Activity in Social Reward Learning in Children with Autism Spectrum Disorder: An fMRI Study

PURPOSE: We aimed to determine whether Autism Spectrum Disorder (ASD) would show neural abnormality of the social reward system using functional MRI (fMRI). MATERIALS AND METHODS: 27 ASDs and 12 typically developing controls (TDCs) participated in this study. The social reward task was developed, and all participants performed the task during fMRI scanning. RESULTS: ASDs and TDCs with a social reward learning effect were selected on the basis of behavior data. We found significant differences in brain activation between the ASDs and TDCs showing a social reward learning effect. Compared with the TDCs, the ASDs showed reduced activity in the right dorsolateral prefrontal cortex, right orbitofrontal cortex, right parietal lobe, and occipital lobe; however, they showed increased activity in the right parahippocampal gyrus and superior temporal gyrus. CONCLUSION: These findings suggest that there might be neural abnormality of the social reward learning system of ASDs. Although this study has several potential limitations, it presents novel findings in the different neural mechanisms of social reward learning in children with ASD and a possible useful biomarker of high-functioning ASDs.

New Diagnostic Criterion of Ankle Brachial Index for Peripheral Arterial Disease

BACKGROUND: The ankle brachial index (ABI) is a simple, inexpensive diagnostic test for peripheral arterial disease (PAD). However the diagnostic criterion of 0.9 has shown variable accuracy for identification of stenosis. We investigated more specific and sensitive diagnostic criterion of ABI for the diagnosis of PAD. METHODS: Among 5,379 patients who performed ABI test, 398 patients with abnormal ABI results or PAD symptoms underwent computed tomography angiography to confirm PAD. Each ABI results were compared with its sensitivity, specificity, positive and negative predictive values. ROC analysis and cross-tabulation analysis were performed to yield proper ABI criterion. RESULTS: ABI of 0.9 showed very high level of sensitivity (92.2%) and very low specificity(59.3%). ABI of 0.84 showed high level of specificity (81.4%), sensitivity (82.2%) and diagnostic correspondent rate (0.607). CONCLUSION: The ABI of 0.84 could be more accurate and useful diagnostic Criterion for identifying PAD.

Abnormal Activation of the Social Brain Network in Children with Autism Spectrum Disorder: An fMRI Study

OBJECTIVE: The aim of this study is to investigate abnormal findings of social brain network in Korean children with autism spectrum disorder (ASD) compared with typically developing children (TDC). METHODS: Functional magnetic resonance imaging (fMRI) was performed to examine brain activations during the processing of emotional faces (happy, fearful, and neutral) in 17 children with ASD, 24 TDC. RESULTS: When emotional face stimuli were given to children with ASD, various areas of the social brain relevant to social cognition showed reduced activation. Specifically, ASD children exhibited less activation in the right amygdala (AMY), right superior temporal sulcus (STS) and right inferior frontal gyrus (IFG) than TDC group when fearful faces were shown. Activation of left insular cortex and right IFG in response to happy faces was less in the ASD group. Similar findings were also found in left superior insular gyrus and right insula in case of neutral stimulation. CONCLUSION: These findings suggest that children with ASD have different processing of social and emotional experience at the neural level. In other words, the deficit of social cognition in ASD could be explained by the deterioration of the capacity for visual analysis of emotional faces, the subsequent inner imitation through mirror neuron system (MNS), and the ability to transmit it to the limbic system and to process the transmitted emotion.

The Analysis of Treatment of Aggressive Fibromatosis Using Oral Methotrexate Chemotherapy

BACKGROUND: Aggressive fibromatosis is a rare but invasive tumor infiltrating widely between fascia and muscle fibers. It has a high tendency to be locally recurrent despite complete resection. Effectiveness of adjuvant treatment for aggressive fibromatosis including radiotherapy, pharmacological agents, hormonal treatments, and chemotherapy have been previously reported. The purpose of this article was to collect and analyze all information regarding the effectiveness and side effects of oral methotrexate in aggressive fibromatosis. METHODS: From 2005 to 2011, eleven patients with aggressive fibromatosis treated with oral methotrexate at our institution were analyzed in this study. Oral methotrexate was administered once per week at 10 mg per week. Authors collected information about effectiveness concerning cases of local recurrence and metastasis. RESULTS: Eleven patients had remission, two patients had local recurrence. Fatal complications or toxicity were not observed. CONCLUSIONS: Oral methotrexate given at this dose and schedule was considered as a useful treatment in primary inoperable fibromatosis and recurrent fibromatosis.

Sprengel Deformity with Bilateral Huge Omovertebra / 대한정형외과학회잡지

Sprengel's deformity is characterized by the congenital migration of the scapula superiorly in relation to the thoracic cage. Other congenital anomalies, such as Klippel-Feil syndrome, may occur in combination with Sprengel's deformity. We report on a case of Sprengel's deformity with a huge bilateral omovertebrae, which was combined with the clinical features of Klippel-Feil syndrome, including cervical fusion, short neck, low posterior hairline, and limitation of neck motion. However, no other deformities or functional defects were observed.

An fMRI Study Regarding the 'Theory of Mind' in Korean Schizophrenic Patients Using a First Order False Belief Task / 신경정신의학

OBJECTIVES: The aim of this study was to investigate brain activation during a Korean language-based 'theory of mind (TOM)' task and fMRI in Korean schizophrenic patients. METHODS: Fourteen Korean schizophrenic patients and 15 normal controls participated in this study. For all participants, several clinical states and psychosocial functions were evaluated. The subjects were then scanned while performing Korean language-based fMRI tasks. The tasks were comprised of conditions-first order false belief (TOM task), physical causality, and unrelated situations. Imaging data were analyzed using SPM2 software (uncorrected p<0.005, extent threshold kappa=10). RESULTS: 1) Compared with the control group, the patient group showed significantly poorer performance on the TOM task, and no significant correlation between TOM and empathic abilitiesy. 2) In the patient group, there were no significantly activated brain regions associated with the TOM task as compared to the physical causality task. With respect to between-group differences, the patient group showed significantly less activation of the left medial frontal region (primarily BA 8) and signifcantly different activation of the left precuneus (BA 7) associated with the TOM task. CONCLUSION: These results suggest that Korean schizophreniac patients show different brain activity associated with TOM functions, especially with respect to the Korean language-based first order false belief tasks.

An Effects of Hemostatic Materials on Cranial Bone Osteogenesis in Rabbit

The influence of hemostatic materials in split thickness calvarial bone defects was evaluated in 24 white rabbit models. The rabbits were divided in 4 groups. In the group A, Surgicel(R) was inserted into the 2x2cm sized left calvarial defects. In the group B, Gelfoam(R) was inserted and in group C, Bonewax(R) was inserted and in group D, Collagen bloc was inserted. The contralateral side underwent sham operation as the control group. After 4 and 8 weeks, radiological findings, histopathological findings and immunohistopathological findings were studied to find development of trabeculae, appearance of osteoblast, calcification and increased expression of TGF-beta. As a result, osteoid and osteoblast were richly found in Surgicel(R), Gelfoam(R), Collagen bloc inserted groups. In Bonewax(R) inserted group, bone regeneration was delayed and foreign body reaction was seen in 4 weeks and it reduced in 8 weeks. The TGF-beta was darkly stained in periosteum, connective tissue and periphery of bone defect. From this result it would be concluded as follows. Surgicel(R), Gelfoam(R) and Collagen bloc effects positively on bone healing with marked increasing of osteoid, osteoblasts and rapid bone remodeling. Bonewax(R) prolongs bone healing with increasing foreign body reaction. Bone regeneration was confirmed with increased expression of TGF-beta in Surgicel(R), Gelform(R) and Collagen bloc applied groups especially in periosteum and ends of bone defects. It suggests that bone regeneration was originated from these areas.

Functional MRI Study on Perceiving Orthographic Structure and Simplified Semantic Pictures

The different perceiving patterns of each picture, alphabetic words and Chinese characters, were widely investigated psychophysically. The more precise localisation can be done in terms of brain activity using functional image technique such as PET and fMRI recently. Until now, there was no fMRI study to make direct comparison between perception of single Chinese character and simplified pictures (pictograph). We have made direct comparison of these two components using modern magnetic resonance techniques. We cannot confirm the right hemispheric dominance for perception of single Chinese character and pictographs. These two kinds of perceiving pattern can be underlying different mechanism.

The Effects of an Aldosterone Synthase (CYP11B2) Gene Polymorphism on the Risk of Myocardial Infarction

BACKGROUND AND OBJECTIVES: Several polymorphisms of the renin-angiotensin-aldosterone system have been found to have pleiotropic effects on cardiovascular diseases. Polymorphism of the aldosterone synthase gene (CYP11B2), which may influence plasma aldosterone levels, has been reported to cause systemic hypertension, influence the left ventricular diameter and mass, and decrease baroreflex sensitivity of the cardiovascular system. Through these mechanisms, it is thought to increase the risk of myocardial infarction (MI). Our study was designed to elucidate whether polymorphism of CYP11B2 increased the risk of MI. SUBJECTS AND METHODS: We analyzed the genotypes of CYP11B2 and the classic risk factors of MI in 188 MI patients and 320 control subjects without history of MI. RESULTS: There was no significant difference in the distribution of genotypes between the patient and control groups. Adjusting for the classical risk factors, multiple logistic regression analysis showed no significant effect of CYP11B2 gene polymorphism on the development of MI. However, the presence of the -344C allele is associated with a markedly increased MI risk conferred by classic risk factors including hypertension, smoking, and male sex. In particular, hypertension was not a significant risk factor as compared with non-hypertensive patients in subjects without -344C, but the relative risk was increased to 2.40 (95% CI:1.05-5.51, p<0.05) with - 344C. The relative risks of smoking and male sex were also increased with the presence of the - 344C allele. CONCLUSION: CYP11B2 polymorphism is not an independent risk factor of MI, although hypertension, smoking, and male sex are more potent risk factors for MI in Koreans who possess the - 344C allele.

Subtemporal Approach vs. Pterional Approach in Basilar Bifurcation Aneurysms: 2 Case Reports

Two patients with basilar bifurcation aneurysm were treated by different approach, low lying posteriorly projecting aneurysm was clipped with subtemporal approach and high bifurcated basilar bifurcation aneurysm with multiplicity approached through pterional method. The author reviewed literature concerning the approaches of basilar bifurcation aneurysm.