• 제목/요약/키워드: Neuropsychiatric disorders

검색결과 128건 처리시간 0.022초

Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development

  • Adil, Keremkleroo Jym;Remonde, Chilly Gay;Gonzales, Edson Luck;Boo, Kyung-Jun;Kwon, Kyong Ja;Kim, Dong Hyun;Kim, Hee Jin;Cheong, Jae Hoon;Shin, Chan Young;Jeon, Se Jin
    • Biomolecules & Therapeutics
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    • 제30권4호
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    • pp.320-327
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    • 2022
  • Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDA-treated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.

반려견 인지기능장애증후군에 대한 한의 진단 및 한약치료 적용 가능성 고찰: 치매환자 국내한의치료기술과 비교 분석 (Potential application of herbal medicine treatment based on pattern identification for canine cognitive dysfunctional syndrome: a comparative analysis of Korea medicine therapy for patients with dementia)

  • 정경숙;조혜연;최유진;장정희
    • 대한수의학회지
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    • 제62권3호
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    • pp.25.1-25.9
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    • 2022
  • Canine cognitive dysfunction syndrome (CDS) is a neurodegenerative disease that causes cognitive and behavioral disorders and reduces the quality of life in dogs and their guardians. This study reviewed the complementary and alternative medicine (CAM) for CDS and compared the diagnosis and therapy of CAM between CDS in canines and dementia in humans. The evaluation tools for the diagnosis of CDS and dementia were similar in the neurological and neuropsychiatric examinations, daily life activity, cognitive tests, and neuroimaging, but the evaluation for dementia was further subdivided. In CAM, pattern identification is a diagnostic method for accurate, personalized treatment, such as herbal medicine. For herbal medicine treatment of cognitive impairment in canines and humans, a similar pattern identification classified as deficiency (Qi, blood, and Yin) and Excess (phlegm, Qi stagnation, and blood stasis) is being used. However, the veterinary clinical basis for verifying the efficacy and safety of CAM therapies for CDS is limited. Therefore, based on CAM evidence in dementia, it is necessary to establish CDS-targeted CAM diagnostic methods and therapeutic techniques considering the anatomical, physiological, and pathological characteristics of dogs.

Design, Synthesis, and Functional Evaluation of 1, 5-Disubstituted Tetrazoles as Monoamine Neurotransmitter Reuptake Inhibitors

  • Paudel, Suresh;Wang, Shuji;Kim, Eunae;Kundu, Dooti;Min, Xiao;Shin, Chan Young;Kim, Kyeong-Man
    • Biomolecules & Therapeutics
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    • 제30권2호
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    • pp.191-202
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    • 2022
  • Tetrazoles were designed and synthesized as potential inhibitors of triple monoamine neurotransmitters (dopamine, norepinephrine, serotonin) reuptake based on the functional and docking simulation of compound 6 which were performed in a previous study. The compound structure consisted of a tetrazole-linker (n)-piperidine/piperazine-spacer (m)-phenyl ring, with tetrazole attached to two phenyl rings (R1 and R2). Altering the carbon number in the linker (n) from 3 to 4 and in the spacer (m) from 0 to 1 increased the potency of serotonin reuptake inhibition. Depending on the nature of piperidine/piperazine, the substituents at R1 and R2 exerted various effects in determining their inhibitory effects on monoamine reuptake. Docking study showed that the selectivity of tetrazole for different transporters was determined based on multiple interactions with various residues on transporters, including hydrophobic residues on transmembrane domains 1, 3, 6, and 8. Co-expression of dopamine transporter, which lowers dopamine concentration in the biophase by uptaking dopamine into the cells, inhibited the dopamine-induced endoctytosis of dopamine D2 receptor. When tested for compound 40 and 56, compound 40 which has more potent inhibitory activity on dopamine reuptake more strongly disinhibited the inhibitory activity of dopamine transporter on the endocytosis of dopamine D2 receptor. Overall, we identified candidate inhibitors of triple monoamine neurotransmitter reuptake and provided a theoretical background for identifying such neurotransmitter modifiers for developing novel therapeutic agents of various neuropsychiatric disorders.

Boophone disticha attenuates five day repeated forced swim-induced stress and adult hippocampal neurogenesis impairment in male Balb/c mice

  • Nkosiphendule Khuthazelani Xhakaza;Pilani Nkomozepi;Ejekemi Felix Mbajiorgu
    • Anatomy and Cell Biology
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    • 제56권1호
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    • pp.69-85
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    • 2023
  • Depression is one of the most common neuropsychiatric disorders and is associated with dysfunction of the neuroendocrine system and alterations in specific brain proteins. Boophone disticha (BD) is an indigenous psychoactive bulb that belongs to the Amaryllidacae family, which is widely used in Southern Africa to treat depression, with scientific evidence of potent antidepressant-like effects. The present study examined the antidepressant effects of BD and its mechanisms of action by measuring some behavioural parameters in the elevated plus maze, brain content of corticosterone, brain derived neurotropic factor (BDNF), and neuroblast differentiation in the hippocampus of Balb/c mice exposed to the five day repeated forced swim stress (5d-RFSS). Male Balb/c mice were subjected to the 5d-RFSS protocol to induce depressive-like behaviour (decreased swimming, increased floating, decreased open arm entry, decreased time spent in the open arms and decreased head dips in the elevated plus maze test) and treated with distilled water, fluoxetine and BD. BD treatment (10 mg/kg/p.o for 3 weeks) significantly attenuated the 5d-RFSS-induced behavioural abnormalities and the elevated serum corticosterone levels observed in stressed mice. Additionally, 5d-RFSS exposure significantly decreased the number of neuroblasts in the hippocampus and BDNF levels in the brain of Balb/c mice, while fluoxetine and BD treatment attenuated these changes. The antidepressant effects of BD were comparable to those of fluoxetine, but unlike fluoxetine, BD did not show any anxiogenic effects, suggesting better pharmacological functions. In conclusion, our study shows that BD exerted antidepressant-like effects in 5d-RFSS mice, mediated in part by normalizing brain corticosterone and BDNF levels.

Imaging Neuroreceptors in the Living Human Brain

  • Wagner Jr Henry N.;Dannals Robert F.;Frost J. James;Wong Dean F.;Ravert Hayden T.;Wilson Alan A.;Links Jonathan M.;Burns H. Donald;Kuhar Michael J.;Snyder Solomon H.
    • 대한핵의학회지
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    • 제18권2호
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    • pp.17-23
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    • 1984
  • For nearly a century it has been known that chemical activity accompanies mental activity, but only recently has it been possible to begin to examine its exact nature. Positron-emitting radioactive tracers have made it possible to study the chemistry of the human mind in health and disease, using chiefly cyclotron-produced radionuclides, carbon-11, fluorine-18 and oxygen-15. It is now well established that measurable increases in regional cerebral blood flow, glucose and oxygen metabolism accompany the mental functions of perception, cognition, emotion and motion. On May 25, 1983 the first imaging of a neuroreceptor in the human brain was accomplished with carbon-11 methyl spiperone, a ligand that binds preferentially to dopamine-2 receptors, 80% of which are located in the caudate nucleus and putamen. Quantitative imaging of serotonin-2, opiate, benzodiazapine and muscarinic cholinergic receptors has subsequently been accomplished. In studies of normal men and women, it has been found that dopamine and serotonin receptor activity decreases dramatically with age, such a decrease being more pronounced in men than in women and greater in the case of dopamine receptors than serotonin-2 receptors. Preliminary studies in patients with neuropsychiatric disorders suggests that dopamine-2 receptor activity is diminished in the caudate nucleus of patients with Huntington's disease. Positron tomography permits quantitative assay of picomolar quantities of neuro-receptors within the living human brain. Studies of patients with Parkinson's disease, Alzheimer's disease, depression, anxiety, schizophrenia, acute and chronic pain states and drug addiction are now in progress. The growth of any scientific field is based on a paradigm or set of ideas that the community of scientists accepts. The unifying principle of nuclear medicine is the tracer principle applied to the study of human disease. Nineteen hundred and sixty-three was a landmark year in which technetium-99m and the Anger camera combined to move the field from its latent stage into a second stage characterized by exponential growth within the framework of the paradigm. The third stage, characterized by gradually declining growth, began in 1973. Faced with competing advances, such as computed tomography and ultrasonography, proponents and participants in the field of nuclear medicine began to search for greener pastures or to pursue narrow sub-specialties. Research became characterized by refinements of existing techniques. In 1983 nuclear medicine experienced what could be a profound change. A new paradigm was born when it was demonstrated that, despite their extremely low chemical concentrations, in the picomolar range, it was possible to image and quantify the distribution of receptors in the human body. Thus, nuclear medicine was able to move beyond physiology into biochemistry and pharmacology. Fundamental to the science of pharmacology is the concept that many drugs and endogenous substances, such as neurotransmitters, react with specific macromolecules that mediate their pharmacologic actions. Such receptors are usually identified in the study of excised tissues, cells or cell membranes, or in autoradiographic studies in animals. The first imaging and quantification of a neuroreceptor in a living human being was performed on May 25, 1983 and reported in the September 23, 1983 issue of SCIENCE. The study involved the development and use of carbon-11 N-methyl spiperone (NMSP), a drug with a high affinity for dopamine receptors. Since then, studies of dopamine and serotonin receptors have been carried out in over 100 normal persons or patients with various neuropsychiatric disorders. Exactly one year later, the first imaging of opitate receptors in a living human being was performed [1].

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해녀 우울장애 환자의 임상적 특징 (Clinical Characteristics of Haenyeo with Depressive Disorders)

  • 박준혁;전병선;이창인;김문두;정지운;정영은
    • 생물정신의학
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    • 제23권2호
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    • pp.63-68
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    • 2016
  • Objectives Haenyeo are Korean professional women breath-hold divers in Jeju island. The aim of this study was to investigate the clinical characteristics of depressed Haenyeo group, compared to non-Haenyeo depressed group. Methods This study included 75 Haenyeo and 340 non-Haenyeo with depressive disorders recruited from the Dementia Early Detection Program in Jeju island. Structural diagnostic interviews were performed using the Korean version of Mini International Neuropsychiatric Interview. All patients completed the questionnaires, including the Subjective Memory Complaints Questionnaire (SMCQ), the Patient Health Questionnaire-15 (PHQ-15), and the Blessed dementia scale. Depression was evaluated by the Korean version of short form the Geriatric Depression Scale (K-SGDS) and cognition was assessed by the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment packet. Results Although the mean scores of the K-SGDS were similar between Haenyeo and non-Haenyeo depressed groups, the Haenyeo group showed a higher mean score on the PSQ-15 (p < 0.001, ANCOVA adjusting for age, the K-SGDS and education). The Haenyeo group showed poorer performance on the Korean Version of Frontal Assessment Batter (p < 0.001), the Mini-Mental State Examination in the Korean version of the CERAD Assessment Packet (p < 0.018), the word fluency test (p < 0.001), and the word list memory test (p = 0.012) in ANCOVA adjusting for age and education. The mean SMCQ score was higher in the Haenyeo depressed group than in the non-Haenyeo depressed group. Conclusions The Haenyeo depressed group shows cognitive dysfunction, especially frontal lobe dysfunction, compared to the non-Haenyeo depressed group, indicating the Haenyeo depressed group may have more severe frontolimbic dysfunction due to chronic exposure to hypoxia. The Haenyeo depressed group suffers more somatic symptoms than the non-Haenyeo depressed group.

한국판 정신장애 진단 선별 질문지의 표준화 연구 (Study on Standardization of Korean Version of Psychiatric Diagnostic Screening Questionnaire(K-PDSQ))

  • 최형근;정성원;조현주;김정범;정철호
    • 대한불안의학회지
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    • 제9권1호
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    • pp.31-37
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    • 2013
  • 정신장애 진단선별 질문지(PDSQ)는 임상에서 흔하게 진단되는 DSM-IV 축 1의 장애를 평가하기위해 고안된 최초의 자기보고식 질문지이다. PDSQ는 포괄적인 평가가 가능하고, 공존질환을 평가 할 수 있으며 신뢰도와 타당도가 높은 것으로 알려져 있다. 이 연구는 K-PDSQ의 표준화를 위한 연구로서, K-PDSQ와 M.I.N.I.-Plus의 비교를 통해 K-PDSQ의 진단적 타당성과 유용성을 검증하고자 하였다. 계명대학교 동산병원 정신건강의학과를 방문한 외래와 입원환자 640명을 대상으로 K-PDSQ와 M.I.N.I.-Plus의 진단적 일치도, K-PDSQ의 시행시간, 민감도 및 특이도를 산출하였다. K-PDSQ와 M.I.N.I.-Plus의 Cohen's kappa계수는 .66로 일치도가 높게 나타났고, K-PDSQ의 시행 소요시간은 $18.2{\pm}11.80$분이었다. 타당도에 있어 국내 환자군 대상으로 산출된 절단점을 적용하였을 때 높은 수준의 민감도와 특이도를 나타냈다. 대부분의 하위척도에서 수용자 작업특성 곡선(ROC)이 대각선 위에 있었고 곡선아래 영역(AUC) 값이 .80 이상으로 선별검사로서 유용성이 입증되었다. K-PDSQ는 M.I.N.I.-Plus와 상당한 진단적 일치도를 보였고, 시행시간이 짧고, 민감도와 특이도에서 높은 수준을 보였다. 따라서 K-PDSQ는 외래 진료환경에 적용하여 임상면담 이전에 환자에 대한 진단적 평가와 공존질환을 선별해내는데 큰 도움이 될 것으로 생각된다.

Interleukin-1β 유전자 내 -511C/T 단일염기다형성과 유방암 관련 우울증 (Interleukin-1β -511C/T Gene Polymorphism and Depression Related to Breast Cancer)

  • 김재민;강희주;장지은;김선영;김성완;신일선;박민호;윤정한;윤진상
    • 우울조울병
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    • 제9권3호
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    • pp.189-193
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    • 2011
  • Objectives : Pro-inflammatory cytokines are related to the pathophysiology of both cancer and depression, and their secretion is controlled by the transcriptional activity of particular gene polymorphisms. This study aimed to investigate whether interleukin (IL)-1β -511C/T gene polymorphism is associated with depression following mastectomy for breast cancer. Methods : A total of 309 patients with breast cancer were evaluated one week after mastectomy, and 244 (79%) were followed one year later. Depression (major+minor depressive disorders) was diagnosed according to DSM-IV criteria using the Mini International Neuropsychiatric Interview, and classified into prevalent, persistent, and incident depression. Associations of IL-1β -511C/T polymorphism with the three depressive status were estimated using logistic regression models. Results : At baseline, 74 (24%) patients were classified with prevalent depression ; and at follow up, 19 (8%) and 25 (10%) patients were classified with persistent and incident depression, respectively. The IL-1β -511T/T genotype was independently associated with prevalent and persistent depression, but not with incident depression. Conclusion : IL-1β -511T/T genotype may involve in the etiology of depression occurring in women with breast cancer who receive a mastectomy.

정신질환에 있어서의 신경펩타이드 연구 - Endorphin과 cholecystokinin을 중심으로 - (Neuropeptides in Clinical Psychiatric Research : Endorphins and Cholecystokinins)

  • 김영훈;심주철
    • 생물정신의학
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    • 제5권1호
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    • pp.34-45
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    • 1998
  • 단가아민 신경전달물질과 신경펩타이드의 가장 큰 차이점은 합성과정에 있다. 시냅스에서의 활동과 비활성화 과정에서도 양자의 차이는 뚜렷하다. 단가아민 신경전달물질의 작용은 매우 단시간 내에 일어나며, 대개는 재흡수기전을 통해 활동이 정지되고, 일부가 효소반응에 의해 비활성물질로 대사된다. 또한 이들은 단가아민 신경전달물질들과 마찬가지로 presynaptic peptidergic receptor를 갖는다는 사실이 알려져 있으며, 신경펩타이드 분비를 조절하는 자가수용체도 갖고 있다. 신경펩타이드의 시냅스전 세포로의 재흡수기전에 대해서는 아직 밝혀져 있지 않다. 신경펩타이드들도 시냅스 후막의 수용체로 확산되어 이차전령, 삼차전령을 통해 생물학적 반응을 일으킨다는 것은 단가아민 신경전달 물질과 동일하다. 본래 신경세포는 자극에 의해 glycoproteins, enzymes, inorganic ions, metal ions, phospholipids, purines, amines, peptides 등의 물질들을 함께 분비한다. 이들 중에는 신경전달물질의 기준에 부합되는 것도 있으나, 대다수는 기능이 없다. 때로는 수 종류의 신경전달물질들과 신경신경펩타이드들이 한가지 신경전달물질의 분비에 관여하기도 한다. 저자들은 현재 임상연구에서 괄목할 만한 진전을 보이고 있는 두가지 신경펩타이드들에 대해 그 신경생물학적 측면과 임상적 측면을 고찰하였다. 알코올의 신경생리에 있어 가장 흥미있는 것은 아마 강화기전일 것이다. 내인성 opioid계 물질들이 알코올의 강화효과와 관계가 있다는 근거들은 많다. Naltrexone은 수용체 차단을 통해 이러한 강화기전을 차단함으로서 음주욕을 감소시키는 것으로 해석된다. Opioid reinforcement는 변연계의 도파민 활성화를 통해 이루어진다. 이는 알코올의 강화에 도파민이 관여한다는 사실과도 관계된다. 이를 도파민-알코올 강화 가설이라 한다. 기타 세로토닌도 알코올의 강화를 중재하는 신경전달물질로 생각되고 있다. 선택적 세로토닌 재흡수 차단제를 장기간 사용하거나, $5-HT_3$ 수용체 길항제를 사용하면 음주욕이 감소된다고 알려져 있다. 신경전달물질계간에는 중요한 상호작용이 있다. 알코올이 측중격핵에서 도파민의 분비를 촉진시키는 기전에도 여러 신경전달계의 상호작용이 관여된다. 이의 기전에 생리적 수준에서 관여되는 대표적인 물질로는 (1) opiates, (2) serotonin, (3) amino acids, (4) 기타 neuropeptide들을 들 수 있다. Opiate 수용체 길항제들은 측중격핵에서 도파민 분비를 차단하고, $5-HT_3$ 수용체 효현제는 이를 자극한다. 이들을 총체적으로 종합하면, 도파민, 세로토닌, opiate 수용체들을 조절하면 알콜리즘을 치료할 수 있다는 것이다. CCK는 흥분성 신경전달물질로 밝혀지고 있으며, 진통 및 morphine에 대한 내성형성, 포만, 기억 등의 정신병리에 일부 관여하나, 역시 최근 가장 주목을 받는 것은 CCK계가 불안의 병리에 관여한다는 소견이다. 이 분야의 연구에 기폭제가 된 것은 CCK-4가 공황발작을 유발한다는 임상 연구결과로부터 비롯된다. 이에 의한 불안반응은 자연유발된 공황발작과 거의 같으며, 정상인과 공황장애 환자를 구별하는 민감도를 갖고 있다. 이 CCK-4에 의해 유발된 공황발작은 $CCK_B$ 길항제들에 의해 차단된다. 즉 공황불안의 기전에 $CCK_B$ 수용체가 관여할 가능성이 있다. 따라서 공황발작이 $CCK_B$ 수용체의 민감도 결함으로 추정될 수 있다. 또한 이 반응은 imipramine과 benzodiazepine계 약물들에 의해 차단됨이 알려져 있다. 이 공황 불안의 형성 기전에 다른 신경전달계와의 상호작용이 있다. 본고에서는 특히 benzodiazepine계와의 상호작용 및 5-HT계와의 상호작용을 거론하였다. 향후 CCK 길항제들이 항불안제로 개발될 전망이다. 이들은 내성형성, 금단증상, 진정작용 등의 문제가 없으므로 새로운 항불안제로 기대된다.

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산후우울증에서 위험인자로서의 가족응집성-적응력 평가 : 예비적 연구 (Evaluation of Family Adaptability and Cohesion as Risk Factor of Postpartum Depression : Preliminary Study)

  • 김보라;서신영;장성운;이상혁;최태규;김용우;조성준;육근영;류미;김묘정;김근향;육기환
    • 정신신체의학
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    • 제17권1호
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    • pp.15-22
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    • 2009
  • 연구목적 : 산후 우울증은 10~15%의 산모가 경험하는 흔한 질환이다. 본 예비적 연구의 목적은 산후 우울증과 산전 위험요인으로 가족 적응력 및 응집성과의 관계를 알아보기 위함이다. 방법 : 24명의 산모를 대상으로 출산 전후의 시기에 전향적으로 연구하였다. 임신 36~40주에 산전 위험요인에 대한 질문지, Edinburgh 산후 우울증 척도(EPDS), 가족 적응력-응집성 평가 척도(FACES), Beck 불안 척도(BAI) 등을 시행하였다. 출산 후 4~6주에 구조적 면담으로 미니 국제신경정신인터뷰를 시행하여 산후 우울증을 진단하였으며 산후 위험요인에 대한 질문지, EPDS, BAI 등을 시행하였다. 결과 : 산후 우울증 군과 비 산후 우울증 군을 비교한 결과, 여러 v위험 요인 중 가족 적응력 및 응집성, 산전 우울증상 및 임신 중 기분 변화가 유의한 차이를 보였다. 로지스틱 회귀분석 상 임신 중 기분변화, 낮은 가족 적응력-응집성 평가 척도 총점 및 각 하위 척도 점수가 산후 우울증의 유의한 연관 요인으로 나타났다. 결론 : 본 연구의 결과는 산후 우울증에 있어 낮은 가족 적응력 및 응집성이 유의한 연관성을 가진 요인일 수 있음을 시사한다. 그러나 본 연구는 예비적 연구로 연구 대상 수가 적어 상기 결과가 지지되기 위해서는 대규모 연구가 필요하다.

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