• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.16 no.1
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• pp.15-25
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• 2005

During the recent decade, the new data about normal neurochemical system development have been accumulated very much. Based on these new data, the up-to-date theory and hypothesis have been developed. These development of this field results from the technological/methodological development which increase the sensitivity, specificity and validity of neurochemical research. Especially, molecular technological development support the recent neurochemical development. In this review article, the authors described the recent research findings in the field of normal neurochemical development of neurotransmitter system in animal and human. Most of child psychiatric disorder, especially neuropsychiatric developmental disorders (ADHD, Autism, Tourette's disorder, MR etc) seem to have underlying neurochemical developmental problems in the pathophysiological basis. So, the data on the normal ontogeny of neurotransmitter system can be the most valuable resources for the research on the etiology of the diverse child psychiatric disorders.

• Anxiety and mood
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• v.1 no.1
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• pp.7-13
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• 2005

Anxiety is one of the basic emotions which human experiences across different cultures in the world and it can be observed in mammals. Our understanding of the neurobiology of this emotion has made some advances, even though it has not been completed, with the development and advance in the investigation method including neuroimaging, neurochemical, and genetic approaches. In this article, the neuroanatomical and neurochemical basis of anxiety is reviewed. The amygdaloid complex has been known to playa key role in processing of anxiety or fear. It has extensive afferent and/or efferent connections with cortical and subcortical structures. The mesial temporal structures including hippocampus appear to be involved in acquisition of anxiety and related behaviors. The prefrontal cortical structures appear to play important roles in conscious awareness of anxiety and in modulating anxiety and related behavior. The bed nucleus of the stria terminalis (BNST) is known to playa critical role in unconditioned fear response. The central noradrenergic system and hypothalamo-pituitary-adrenal axis are known to play important roles in modulating and expressing anxiety-related responses. Anxiety has been gathering attentions from many investigators and numerous preclinical and clinical investigations of anxiety and anxiety disorders have been done. In particular, neural plasticity in critical period and the psychobiological factors related to resilience to extreme stress and anxiety are important issues in this field.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.45-46
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• 1995

Alzheimer's disease is believed to be associated with the loss of cholinergic activity in the cortex and hippocampus. In addition, it has been reported that the monoaminergic systems which also controls brain functions are disturbed in Alzheimer's patients. Based on these neurochemical background, a number of cholinesterase inhibitors including tacrine and its analogues and some monoamine oxidase inhibitors such as L-deprenyl and monoamine reuptake inhibitors have been developed for the treatment of dementia, but all of the known drugs are not truly effective. We thought that a drug that activates only one neurotransmitter system is not effective enough for the treatment of the symptoms associated with Alzheimer's disease and vascular dementia, and we conceived that an agent enhancing both central cholinergic and monoaminergic functions would be useful for the treatment of dementia

• Molecules and Cells
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• v.26 no.2
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• pp.121-130
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• 2008

Methamphetamine, a commonly used addictive drug, is a powerful addictive stimulant that dramatically affects the CNS. Repeated METH administration leads to a rewarding effect in a state of addiction that includes sensitization, dependence, and other phenomena. It is well known that susceptibility to the development of addiction is influenced by sources of reinforcement, variable neuroadaptive mechanisms, and neurochemical changes that together lead to altered homeostasis of the brain reward system. These behavioral abnormalities reflect neuroadaptive changes in signal transduction function and cellular gene expression produced by repeated drug exposure. To provide a better understanding of addiction and the mechanism of the rewarding effect, it is important to identify related genes. In the present study, we performed gene expression profiling using microarray analysis in a reward effect animal model. We also investigated gene expression in four important regions of the brain, the nucleus accumbens, striatum, hippocampus, and cingulated cortex, and analyzed the data by two clustering methods. Genes related to signaling pathways including G-protein-coupled receptor-related pathways predominated among the identified genes. The genes identified in our study may contribute to the development of a gene modeling network for methamphetamine addiction.

• Biomolecules & Therapeutics
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• v.14 no.1
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• pp.1-10
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• 2006

Drug dependence deals a heavy socioeconomic burden to the society. For adolescents, the damage from drug dependence is greater than adults considering their higher susceptibility to drug effect and increasing chance for violence leading to criminal punishment process. Habitual drug use depends on genetic and environmental factors and the complex interactions between the two. Mammalian model systems have been useful in understanding the neurochemical and cellular impacts of abused drugs on specific regions of the brain, and in identifying the molecular targets of drugs. More elucidation is required whether biological effects of drugs actually cause the habitual dependence at the cellular level. Although there is much insight available on the nature of drug abuse problems, none of the systems designed to help drug dependent individuals is efficient in screening functional ingredients of the drug, and thus resulting in the failure of helping drug dependent individuals recover from drug dependence. Alternative model systems draw the attention of researchers, such as the invertebrate model systems of nematodes (Caenorhabditis elegans) and fruit flies (Drosophila melanogaster). These models should provide new insight into the mechanisms leading to the behavior of drug users (even functional studies analyzing molecular mechanism), and screening useful components to help remove drug dependence among drug users. The relatively simple anatomy and gene expression of the invertebrate model systems should enable researchers to coordinate current knowledge on drug abuse. Furthermore, the invertebrate model systems should facilitate advance in experiments on the susceptibility of specific genetic backgrounds and the interaction between genetic factors to drug dependence.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2000.10a
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• pp.116-122
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• 2000

The molecular modification of antiepileptic drugs and direct synthesis of new drugs with the predetermined antiepileptic properties are perspective. New neurochemical attacking to solve the problem including prevention and inhibition of seizures seems to be related to ginsenosides and ginseng polypeptides. The main study based on the severity of febrile convulsions of rat pups has been done from the earlier investigations of antiepileptical action of ginsenosides between KGTRI and MSU (Chepurnov, Park et al., 1995) with different kinds of experimental models of epilepsy. From the cultured cell line DAN25 of ginseng root, the extracts of ginsenosides made in "BIOKHIMMASH" were studied by the project of preclinical anticonvulsant screening (Stables, Kupferberg, 1997). The inhibition of severity of convulsions, decrease of seizures threshold, decrease of audiogenic seizures in rats of different strains and normalization of cerebral blood flow (measured by hydrogen test) were demonstrated in rats after i.c.v., intraperitoneally and orally administration, respectively. The antiepileptical effects by the combination of compounds from ginseng; were compared with the iuluence of Rg1, Rb1, Rc and with the well known antiepileptical drugs such as carbamazepine, valproic acid. The base for the research is obtained by using the WAG/Rij strain (Luijtelaar, Coenen, Kuznetcova), an excellent genetic model for human generalized absence epilepsy. The improving action of gensinosides was effectively demonstrated on the model of electrical kindling of amygdala of WAG/Rij rats with genetically determined absences, and the influences of ginsenosides on the slow wave discharges have also been being investigated. The different characteristics of a kindling process exerted in the sex-different region of the amygdala and demonstrated that the level of sex steroids and content of neurosteroids in amygdaloid tissue can modify the development of seizures. The chemical structures of ginsenosides not only have some principal differences from well-known antiepileptical drugs but the Plant Pharmacology gives us unique possibility to develop new class of antiepileptic drugs and to improve its biological activity.

• Analytical Science and Technology
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• v.30 no.6
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• pp.355-378
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• 2017

Because neurochemicals are related to homeostasis and cognitive and behavioral functions in human body and because they enable the diagnosis of numerous neurodegenerative disorders, there has been increasing interest in the development of analytical platforms for neurochemical profiling in biological samples. In particular, mass spectrometry (MS)-based analytical methods combined with chromatographic separation have been widely used to profile neurochemicals in metabolic pathways. However, development of delicate sample preparation procedures and highly sensitive instrumental detection is necessary considering the trace levels and chemical instabilities of neurochemicals in biological samples. Therefore, in this review, analytical trends in MS-based metabolomics approaches to neurochemicals in multiple biological samples, such as urine, blood, CSF, and biological tissues, are discussed. This paper is expected to contribute to the development of an analytical platform to discover biomarkers that will aid diagnosis, prognosis, and treatment of neurodegenerative disorders.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.13 no.1
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• pp.3-14
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• 2002

Childhood psychic trauma appears to be a crucial factor in the development of serious disorders both in childhood and in adulthood. Traumatized children show strong tendency to revisualize or re-feel a traumatic events. Play and behavioral reenactments are frequent manifestations of both the single blow and the long-standing traumas in childhood. Those children who suffer the results of single, intense terror appear to exhibit detailed memory, retrospective reworkings and misperceptions. In long-standing or repetitive trauma, children would show psychic numbing, self-hypnosis, dissociation and rage. Child's brain is undergoing critical and sensitive periods of differentiation. During this time, developing central nervous system is exquisitely sensitive to stress. Stressor-activated neurotransmitters and hormones can play major roles in neurogenesis, migration, synaptogenesis, and neurochemical differentiation. Internal opiate system operates in some trauma and causes the victim to fail to respond, to avoid, to shut off feelings. Evidence is also accumulating in traumatology that dysfuntion of locus coeruleus and ventral tegmental neucleus system leads to catecholamine receptors hypersensitivity. This change result in hypervigilance, increased startle, affective lability, and increased autonomic nervous system hyperreactivity. Another site of action of trauma on the brain is hypothalamic-pituitary-adrenal axis. Individuals with PTSD do not have enough cortisol to halt the alarm reaction. When children are exposed to long-standing extreme events, massive attempts to protect the psyche and to preserve the self are put into gear. These developmental traumas mobilize various kinds of defense mechanisms. Massive denial, dissociation, self anesthesia, identification with aggressor and aggression turned against the self often lead to profound character changes in the youngsters.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.18 no.2
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• pp.123-129
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• 2007

Objectives: Autism is a complex neurodevelopmental spectrum disorder with a strong genetic component. Previous neurochemical and genetic studies have suggested the possible involvement of the serotonin system in autism. Tryptophan 2,3-dioxygenase(TDO2) is the rate-limiting enzyme in the catabolism of tryptophan, which is the precursor of serotonin synthesis. The aim of this study was to investigate the association between the TDO2 gene and autism spectrum disorders(ASD) in a Korean population. Methods: The patients were diagnosed with ASD on the basis of the DSM-IV diagnostic classification outlined in the Korean version of the Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule. The present study included the detection of four single nucleotide polymorphisms(SNPs) in the TDO2 gene(rs2292536, rs6856558, rs6830072, rs6830800) and the family-based association analysis of the single nucleotide polymorphisms in Korean ASD trios using a transmission disequilibrium test(TDT) and haplotype analysis. The family trios of 136 probands were included in analysis. 87.5% were male and 86.0% were diagnosed with autism. The mean age of the probands was $78.5{\pm}35.8$ months(range: 26-264 months). Results: Two SNPs showed no polymorphism, and there was no significant difference in transmission in the other two SNPs. We also could not find any significant transmission in the haplotype analysis(p>.05). Conclusion: We could not find any significant statistical association between the transmission of SNPs in the TDO2 gene and ASD in a Korean population. This result may not support the possible involvement of the TDO2 gene in the development of ASD, and further exploration might be needed to investigate other plausible SNP sites.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.34-45
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• 1998

We provide the reader with a brief introduction to the neurobiology of neuropeptides. Several comprehensive reviews of the distribution and neurochemical, neurophysiological, neuropharmacological and behavioral effects of the major neuropeptides have recently appeared. In reviews of the large number of neuropeptides in brain and their occurance in brain regions thought to be involved in the pathogenesis of major psychiatric disorders, investigators have sought to determine whether alternations in neuropeptide systems are associated with schizophrenia, mood disorders, anxiety disorders, alcoholism and neurodegenerative disease. There is no longer any doubt that neuropeptide-containing neurons are altered in several neuropsychiatric disorders. One of the factors that has hindered neuropeptide research to a considerable extent is the lack of pharmacological agents that specifically alter the synaptic availability of neuropeptides. With the exception of naloxone and naltrexone, the opiate-receptor antagonists, there are few available neuropeptide- receptor antagonists. Two independent classes of neuropeptide-receptor antagonists has been expected to be clinically useful. Naltrexone, a potent ${\mu}$-receptor antagonist, has been used successfully to reduce the need for alcohol consumption. And cholecycstokinin antagonists are now in development as a new class of anxiolytics, which would be expected to be free from tolerance and physical dependence and lack of sedation. In this review, we deal with these two kinds of neuropeptide system, the opioid system and cholesystokinins in the brain. The role of opioid systems in the reinforcement after alcohol consumtion and that of cholesystokinins in the pathogenesis of anxiety will be discussed briefly. As we know, the future for neuropeptides in psychiatry remains bright indeed.