• Title/Summary/Keyword: Behavioral symptoms

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Evaluation of Therapeutic Effects of Cognitive-Behavioral Therapy in Patients with Panic Disorder using Serial $^{99m}Tc-ECD$ Brain Perfusion (공황장애 환자에서 $^{99m}Tc-ECD$ 뇌관류 SPECT를 이용한 인지행동치료 효과 평가)

  • Kim, Jung-Hee;Song, Ho-Chun;Yang, Jong-Chul;Lee, Byeong-Il;Heo, Young-Jun;Bom, Hee-Seung;Park, Tae-Jin;Min, Jung-Joon
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.6
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    • pp.302-308
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    • 2006
  • Purpose: Although several neuroanatomical models of panic disorder have been proposed, little is known regarding the neurological mechanisms underlying cognitive-behavioral therapy (CBT) in patients with panic disorder. This study was performed to identify the brain structures that show changes of regnioal cerebral blood flow (rCBF) after CBT in patients with panic disorder. Materials and Methods: Seven patients who were diagnosed as panic disorder by DSM-IV were treated with CBT for 8 weeks and twelve healthy volunteers joined in this study. Serial $^{99m}Tc-ECD$ brain perfusion SPECT images were acquisited and PDSS-SR (Self-Report version of Panic Disorder Severity Scale) and ACQ (Agoraphobic Cognitive Question) scores were measured just before and after CBT in all patients. Data were analyzed using SPM2. Results: Subjective symptoms were improved, and PDSS-SR and ACQ scores were significantly reduced ($14.9{\pm}3.9\;vs.\;7.0{\pm}1.8$, p<0.05; $30.3{\pm}8.5\;vs.\;21.6{\pm}3.4$, p<0.05, respectively) after CBT in panic patients. Before CBT, a significant increase of rCBF was found in the cingulate gylus, thalamus, midbrain, both medial frontal and temporal lobes of the panic patients compared to the normal volunteers. After CBT, we observed a significant rCBF decrease in the left parahippocamus, right insula and cingulate gyrus, both frontal and temporal lobes, and a significant rCBF increase in both the occipital lobes, left insula, both frontal and left parietal lobes. Conclusion: These data suggested that CBT is effective for panic disorder and diminish the activity of the brain areas associated with fear in panic disorder.

Comparison of Daytime Sleepiness between Normal Subjects and Patients with Sleep Disorders and Analysis of Its Clinical Implications (정상인과 수면장애 환자군 간의 주간졸림증 비교 및 임상적 의미 분석)

  • Lee, Jin-Sung;Kim, Seog-Ju;Choi, Jong-Bae;Jeong, Do-Un
    • Sleep Medicine and Psychophysiology
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    • v.9 no.2
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    • pp.106-114
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    • 2002
  • Objectives: Daytime sleepiness is a common symptom and is associated with sleep behavior, sleep deprivation, and night shift, etc. It is also one of the most important symptoms of sleep disorders like obstructive sleep apnea (OSA). According to our survey on Korean literature, a few studies have dealt with daytime sleepiness, and we have not been able to locate any study comparing normal subjects with polysomnography-proven sleep disorder patients regarding daytime sleepiness. We aimed at comparing daytime sleepiness among normal healthy daytime workers, medical students being expected to have daytime sleepiness due to chronic sleep deprivation, and patients having sleep disorders diagnosed with polysomnography. We also studied the association between subjective daytime sleepiness and objective polysomnographic findings in patients with sleep disorders. Methods: One hundred three hospital workers, 137 medical students, and patients with sleep disorders were studied. Sleep disorders included OSA, periodic limb movements in sleep (PLMS), insomnia, and narcolepsy. The degree of subjective sleepiness in each group was measured by the Korean version of Epworth sleepiness scale and compared. The relationship between polysomnographic findings reflecting severity of sleep disorder in each patient group and subjective sleepiness was analyzed. As for patients with narcolepsy, the relationship between the mean sleep latency and subjective sleepiness was studied. Results: There was a significant difference of ESS score (F=68.190, dF=5.752, p<0.001) among daytime workers, medical students, and sleep disorder patients. In OSA patient group, the degree of the sleepiness had no significant correlation either with mean O2 satuaration (p=0.062) or with RDI (p=0.807). In PLMS patient group, there was no correlation between periodic limb movement index (PLMI) and subjective sleepiness (p=0.761). In narcolepsy patient group, the subjective sleepiness had no correlation with mean sleep latency measured with MSLT (p=0.055). Conclusion: We found a significant difference of subjective sleepiness among daytime workers, medical students, and patients with sleep disorders. However, no consistent correlation was found between severity of subjective sleepiness and objective polysomnographic findings reflecting severity of each sleep disorder. This research confirms that the evaluation of subjective sleepiness is important clinically, but it cannot substitute the objective measures such as nocturnal polysomnography and MSLT.

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CLINICAL AND NEUROPSYCHOLOGICAL CHARACTERISTICS OF DSM-IV SUBTYPES OF ATTENTION DEFICIT HYPERACTIVITY DISORDER (주의력결핍 과잉행동장애의 아형별 신경심리학적 특성 비교)

  • Cheung, Seung-Deuk;Lee, Jong-Bum;Kim, Jin-Sung;Seo, Wan-Seok;Bai, Dai-Seg;Chun, Eun-Jin;Suh, Hae-Sook
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.13 no.1
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    • pp.139-152
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    • 2002
  • Objectives:This study was conducted to compare the clinical and neuropsychological characteristics by DSM-IV subtypes of attention deficit hyperactivity disorder(ADHD) patients who did not have comorbid psychiatric disorders. Methods:5-15 year old children with ADHD were recruited at psychiatric outpatient clinic of Yeungnam University hospital and the patients with comorbidity or neurological abnormalities were excluded. Finally, total 404 children with ADHD were selected for this study. There were 234 subjects of ADHD-C(57.9%), 156 subjects of ADHD-I(38.6%) and 14 subjects of ADHD-HI(3.5%), who fulfilled the DSM-IV diagnostic criteria. The mean age of the total subjects was 9.63±2.49 years old. The psychopathology, IQ, behavioral problems, neuropsychological executive function were evaluated before pharmacological treatment. The measures were Korean Personality Inventory of Child(K-PIC) for psychopathology, 4 behavioral check lists(ADDES-HV, ACTeRS, CAP, SNAP) for behavioral symptoms of ADHD, K-ABC and KEDI-WISC for IQ and Conner's CPT, WCST, SST for neuropsychological executive functions. Results:1) The prevalence of subtypes was ADHD-C, ADHD-I, ADHD-HI in decreasing order. There was no sex difference of prevalence among three subtypes. The mean age of ADHD-I was older than other subtypes. 2) There was significant differences of psychopathology among subtypes, the ADHD-C and ADHD-HI had higher than the ADHD-I in the scores of delinquent, hyperactivity and psychosis;the ADHD-C had higher than the ADHD-I in the scores of family relation and autism, the scores of ego resilience were lower than the ADHD-I. However, there was no difference in anxiety, depression and somatization scores among them. 3) The results of behavioral symptom check lists, the ADHD-C had higher the score of inattention, hyperactivity and impulsivity than the ADHD-I. Meanwhile the results of ACTeRs, which rated by the teachers, were different. 4) There were significant differences of sequential processing scale and arithmetics among subtypes in IQ using K-ABC, but there was no significant difference between the ADHD-C and the ADHD-I after excluding the ADHD-HI due to small numbers. 5) There was numerical difference among subtypes but did not reach statistical significance in three neuropsychological executive function tests. Conclusion:In conclusion, our results revealed that there was significant difference in clinical features among three subtypes but, no significant difference in executive functions.

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A Study on the Utilization Level of Traditional Medicine by Residents - On the basis of Use of Folk Medical Techniques - (주민(住民)의 전통의술(傳統醫術) 이용도(利用度) 조사연구(調査硏究) - 민속요법(民俗療法) 이용(利用)을 중심(中心) 으로 -)

  • Kim, Jin-Soon
    • Journal of agricultural medicine and community health
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    • v.13 no.1
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    • pp.3-18
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    • 1988
  • The general objective of this research is to study behavioral pattern of health care utilization and to measure the level of utilization of the traditional medicine. The specific objective is to study utilization pattern and content of folk medicine which is the indegenous medical technology recognized part of traditional medicine. This research was under taken to generate valid information that will provide basis data for formulating general direction for health education activities and for designing service package for general population. A social survey method was employed to obtain required information for the research activities, The survey field team consisted of 20 surveyors who all participated is an intensive 2 day training course. A total of 3091 households were visited and interviewed by the field team during the period 7 September to 6 October 1987. The major findings obtained from the information collected by the field survey are as follows ; 1) General characteristics of the study households 2562 households out of 3091 households visited were selected for final data process, 80.2 of the selected households were nuclear families ; 17.4%, extended families ; others 2.4%. Only 4.3 percent of the study population in the urban households indicated "no schooling" whereas 14.2% of the rural household members falls within this category. Study population in the urban areas are more protected against diseases by the national medical insurance system than those in rural areas. In their self appraisal of living standard, those who responded with low group are 39.6% and 50.3% respectively by urban and rural households. 2) Morbidity status Period prevalence rate for all diseases during the preceding 15 days before the date of the household interview v as 243,0 per 1,000 study population. For cases with the illness duration of within 15 days, the initial points of medical entry were diversied ; 56.9%, drug stores ; 30.9%, clinics and hospitals ; 4.6% folk medicine ; 1.7% clinics of Korean oriental medicine. Among the chronic case; with illness duration of over 90 days, 34.6% of these people utilized clinics and hospitals of modern medicine ; 31.6%, drug stores ; 18.6% clinics of Korean oriental medicine ; 6.8% folk medical techniques. Noticeable is the almost ten fold increase from the mere 0.9% in the utilization of Korean oriental medicine, whereas in the utilization of folk medicine, it is short of two-fold increase. 3) Folk medicine and its utilization Households that use folk medicine for relief and care of signs and symptoms commonly encountered in daily life, number 1969 households, which accounts for 76.9% of all the study households. This rather high level use of folk medicine is not different from rural to urban areas. The order of frequency of utilizing folk medicine among the study people are : the highest 14.3% for the relief of indigestion ; 8.6% for burns ; 5.1% for common cold ; 4.7% for hiccough ; and 4.2% for hordeolum. A present various procedures of folk medicine is being used to relieve all kinds of symptoms. 192 symptoms are identified at present. The most frequently used procedures of folk medicine appear to be based either on principles of the Korean oriental medicine or of scientific knowledge. Based on these survey findings, proposals for utilizing folk medicine are as follows First, this survey's findings will be feed back to both on the job training and on the spot guidance of community health practitioners, public health nurses and other peripheral work force in the health field, who are in daily contacts with community. This feed back will assure that the health personnel carry out their health education and information activities that are based on the utilization pattern of folk medicine as found in the survey result. Second, studies will be soon implemented that are designed to measure the efficiency and potency of these procedures and to improve these procedures of folk medicine were most frequently used by the community. Third, studies will continue to systematize medicinal plants and skills of Korean oriental medicine that are easily available at minimal cost in daily life for the prevention of diseases and management of emergency cases.

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Experimental Models of Schizophrenia (정신분열병의 실험적 모델)

  • Cheon, Jin-Sook
    • Korean Journal of Biological Psychiatry
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    • v.6 no.2
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    • pp.153-160
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    • 1999
  • Animal models can provide a useful tool for the study of some aspects of psychiatric disorders and their treatment. The four criteria for the evaluation of animal models of psychiatric disorders are as following : 1) similarity of inducing conditions 2) similarity of behavioral state 3) common underlying neurobiological mechanisms 4) reversal by clinically effective treatment techniques. Several animal models have been proposed for schizophrenia : phenylethylamine model, L-dopa model, hallucinogen model, cocaine model, amphetamine model, phencyclidine model, noradrenergic reward system lesion model, reticular stimulation model, social isolation model, conditioned avoidance reaction, catalepsy test, paw test, self-stimulation paradigms, latent inhibition paradigms, blocking paradigms, prepulse inhibition of the startle reflex, rodent interaction, social behavior in monkeys, hippocampal damage, high ambient pressure, and models using selective breeding. Among them, animals with bilateral lesion of the hippocampus may provide an adequate animal model for several symptoms of schizophrenia, and ketamine model can reproduce negative symptoms and cognitive deficits as well as positive symptoms of schizophrenia. In conclusion, no model of schizophrenia is entirely representative of the disease, and findings gleaned from model systems must be cautiously interpreted. Furthermore, the process of developing and validating animal models must work in concert with the process to identify reliable measures of human phenomenology.

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A Case of Childhood Obstructive Sleep Apnea Syndrome with Co-morbid Attention Deficit Hyperactivity Disorder Treated with Continuous Positive Airway Pressure Treatment (지속적(持續的) 상기도(上氣道) 양압술(陽壓術)을 시행(施行)하여 치료효과(治療效果)를 본 주의력(注意力) 결핍(缺乏).과잉(過剩) 운동장애(運動障碍)를 동반(同伴)한 소아기(小兒基) 폐쇄성(閉鎖性) 수면무호흡증(睡眠無呼吸症) 1례(例))

  • Sohn, Chang-Ho;Shin, Min-Sup;Hong, Kang-E;Jeong, Do-Un
    • Sleep Medicine and Psychophysiology
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    • v.3 no.1
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    • pp.85-95
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    • 1996
  • Obstructive sleep apnea syndrome(OSAS) in childhood is unique and different n-om that in adulthood in several aspects, including pathophysiology, clinical features, diagnostic criteria, complications, management, and prognosis. Characteristic features of childhood OSAS in comparison with the adult form are the variety of severe complications such as developmental delay, more prominent behavioral and cognitive impairments, vivid cardiovascular symptoms, and increased death risk, warranting a special attention to the possible diagnosis of OSAS in children who snore. However, the childhood OSAS is often neglected and unrecognized. We, therefore, report a case of very severe OSAS in a 5-year-old boy who was sucessfully treated with continuous positive airway pressure(CPAP) treatment. Interestingly, the patient was comor-bid with the attention deficit hyperactivity disorder. Prior to the initial visit to us, adenotonsillectomy had been done at the age of 4 with no significant improvement of apneic symptoms and heavy snoring. On the initial diagnostic procedures, marked degree of snoring was audible even in the daytime wake state and the patient was observed to be very hyperactive. Increased pulmonary vascularity with borderline cardiomegaly was noted on chest X-ray. The baseline polysomnography revealed that the patient was very sleep-apneic and snored very heavily, with the respiratory disturbance index(RDI) of 46.9 per hour of sleep, the mean SaO2 of 78.8%, and the lowest SaO2 of 40.0%(the lowest detectable oxygen level by the applied oxymeter). The second night polysomnography was done for CPAP titration and the optimal pressure turned out to be $8.0\;cmH_2O$. The applied CPAP treatment was well tolerated by the patient and was found to be very effective in alleviating heavy snoring and severe repetitive sleep apneas. After 18 months of the CPAP treatment, the patient was followed up with nocturnal polysomnography(baseline and CPAP nights) and clinical examination. Sleep apneas were still present without CPAP on the baseline night. However, the severity of OSAS was significantly decreased(RDI of 15.7, mean SaO2 of 96.2%, and the lowest SaO2 of 83.0%), compared to the initial polysomnographic findings before initiation of long-term CPAP treatment. Wechsler intelligence tests done before and after the CPAP treatment were compared with each other and surprising improvement of intelligence(total 9 points, performance 16 points) was noted. Clinically he was found to be markedly improved in his attention deficit hyperactive behavior after CPAP treatment, but with minimal change of TOVA(test of variables of attention) scores except conversion of reaction time score into normal range. On the chest X-ray taken after 18 months of CPAP application, the initial cardiopulmonary abnormalities were not found at all. We found that the CPAP treatment in a young child is very effective, safe, and well-tolerated and also improves the co-morbid attention deficit hyperactive symptoms. Overall, the growth and development of the child has been facilitated with the long-term use of CPAP. Cardiovascular complications induced by OSAS have been also normalized with CPAP treatment. We suggest that early diagnosis and active treatment intervention of OSAS in children are crucial in preventing and ameliorating possible serious complications caused by repetitive sleep apneas and consequent hypoxic damage during sleep.

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Current Status of Korean Ginseng Research (한국인삼론(韓國人蔘論))

  • Han, Byung-Hoon
    • Korean Journal of Pharmacognosy
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    • v.3 no.3
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    • pp.151-160
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    • 1972
  • Recent achievements of scientific research on the pharmacologic activities and the chemical problems of dammalene glycosides, which are considered to be effective principles of Korean ginseng, are reviewed and analyzed in view of structure-activity relationship. 1) S. Shibata and his co-workers detected 12 glycoside spots of dammalene series on the two dimensional T.L.C. of total glycoside fraction from Japanese ginseng, and designated them Ginsenoside Rx(x=a, b, c, g, h, etc.) in the order of increasing Rf-value. The aglycones of those glycosides were characterized to be protopanaxadiol for the Ginsenoside $Rx(x=a,\;b_{1},\;b_{2},\;c,\;d,\;e,\;f)$ and protopanaxatriol for the Ginsenoside $Rx(x=g_{1},\;g_{2},\;g_{3},\;h_{1}\;'h_{2})$. Using Korean ginseng as the material for our study, the author and his coworkers isolated a new dammalene glycoside(Panax Saponin C), which comes under the category of protopanaxadiol glycosides based on the classification of S. Shibata et al., and characterized this saponin to be the glycoside of protopanaxatriol series. Furthermore, Panax Saponin C dissociated into $two\;components(C_{1}\;and\;C_{2}-acetate)$ by acetylation, both of which returned to original Panax Saponin C by deacetylation. Based on this result, more than 13 glycoside components of dammalene series will be expected in the Korean ginseng. 2) The structures of protopanaxadiol and protopanaxatriol, the genuine aglycones of dammalene glycosides, are fully established to be structural analogues by S. Shibata and his co-workers, therefore antagonistic and/or analogical activities will be expected for the pharmacologic activities of these glycoside series of structural analogues. K. Takaki and his co-workers found central nervous system (CNS) stimmulant activity from the glycosides of protopanaxatriol series and CNS-depressant activity from the glycosides of protopanaxadiol series. On the other hand, the author and his co-workers found stimmulating activity on the protein synthesis from both the series of dammalene glycosides with delayed and long-lasting characteristics. This delayed and long-lasting characteristics were also observed in the anti-inflammatory activity of glycosides of protopanaxatriol series on their time course tendency. For the convenience's sake of argument, pluralistic pharmacologic activities of dammalene glycosides, which were observed by many workers at various pharmacologic site, may be classified into two main categories; one is pan-cellular activity and the other is organ specific activity to the certain tissue which is a mass of cells differentiated to a certain direction for their special functions in the body. Based on the data of K. Takaki and those of the authors, following assumption will be probable; Pharmacologic activities of both series of glycosides of protopanaxadiol and protopanaxatriol aglycones may be antagonistic on their tissue-specific activities and analogic on their pan-cellular activities. Therefore, the mixture of these two series of glycosides in an appropriate ratio, as the case of total extract of Korean ginseng, will be probably beneficial to the host by increasing the synthesis of some functional proteins, due to the additive action of pan-cellular activity, and with the disappearance of any significant behavioral symptoms due to the antagonism of tissue specific activity. This fact will probably be the main reason why classical trials of pharmacologists failed in re-discovering the efficacy of Korean ginseng with their behavioral test. 3) The author and his co-workers achieved the synthesis of $C^{14}-labelled\;Panax\;Saponin\;A\;on\;C_{25}-C_{27}\;position\;of\;aglycone$ in the interest of tracer studies in vivo. The method will be applicable to other dammalene glycosides regardless of their chemical structure. 4) The author and his co-workers converted chemically betulafolienetriol, a triterpene component of Betula platyphylla, to the protopanaxadiol, one of genuine aglycone of dammalene glycosides.

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A Case of Paraneoplastic Limbic Encephalitis Associated with Small Cell Lung Cancer

  • Ryu, Ja Young;Lee, Seung Hyeun;Lee, Eun Joo;Min, Kyung Hoon;Hur, Gyu Young;Lee, Sung Yong;Kim, Je Hyeong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.73 no.5
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    • pp.273-277
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    • 2012
  • Paraneoplastic limbic encephalitis (PLE) is a rare syndrome characterized by memory impairment, affective and behavioral disturbances and seizures. Among many different neoplasms known to cause PLE, small cell lung cancer (SCLC) is the most frequently reported. The pathogenesis is not fully understood but is believed to be autoimmune-related. We experienced a patient with typical clinical features of PLE. A 67-year-old man presented with seizure and disorientation. Brain magnetic resonance imaging demonstrated high signal intensity in the bilateral amygdala and hippocampus in flair and T2-weighted images suggestive of limbic encephalitis. Cerebrospinal fluid tapping revealed no evidence of malignant cells or infection. Positron emission tomography/computed tomography showed a lung mass with pleural effusion and a consequent biopsy confirmed the diagnosis of PLE associated with SCLC. The patient was subsequently treated with chemotherapy and neurologic symptoms gradually improved.

A Comparison Study of Clinical Characteristics in Adolescents with Autism Spectrum Disorder without and with Attention-Deficit Hyperactivity Disorder (자폐 스펙트럼 장애 청소년에서 주의력결핍 과잉행동장애 유무에 따른 임상적 특성 : 자폐증상, 정서문제, 부모·자녀관계를 중심으로)

  • Song, Jae-Won;Bahn, Geon-Ho;Cho, In-Hee;Cho, Soo-Churl;Kim, Bung-Nyun;Shin, Min-Sup;Kim, Jae-Won;Park, Subin;Hong, Soon-Beom;Yoo, Hee-Jeong
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.24 no.4
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    • pp.213-219
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    • 2013
  • Objectives : It is known that adolescents with autism spectrum disorder (ASD) often concurrently exhibit attention-deficit hyperactivity disorder (ADHD). The objective of this study is to investigate how ADHD symptoms modify clinical characteristics in adolescents with ASD. Methods : Subjects were recruited from the Program for the Education Enrichment of Relational Skills program, which is a program for adolescents with ASD to promote and train social skills. The study participants and their parents completed the study questionnaires, such as the ADHD rating scale, Autism Diagnostic Observation Schedule, and Korean version of Child Behavior Checklist. Results : Adolescents with ASD and ADHD (N=19) were found to have more impaired sociality, less open communication with their parents, and more behavioral and emotional problems compared with adolescents with ASD, and without ADHD (N=28). Conclusion : Although further research is needed, the results of our study suggest that adolescents with ASD present different clinical characteristics when comorbid with ADHD.

Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates Aβ1-42 Oligomer-Induced Memory Impairment in Mice

  • Ko, Sang Yoon;Lee, Hyung Eun;Park, Se Jin;Jeon, Se Jin;Kim, Boseong;Gao, Qingtao;Jang, Dae Sik;Ryu, Jong Hoon
    • Biomolecules & Therapeutics
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    • v.23 no.2
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    • pp.156-164
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    • 2015
  • Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-${\beta}_{1-42}$ oligomer ($A{\beta}O$) in mice. Memory impairment was induced by intracerebroventricular injection of $A{\beta}O$ ($50{\mu}M$) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated $A{\beta}O$-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through $A{\beta}O$, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after $A{\beta}O$ injection. In addition, spinosin rescued the $A{\beta}O$-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through $A{\beta}O$, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid ${\beta}$ protein-induced cognitive dysfunction observed in AD patients.