OBJECTIVE: Bipolar disorder is known to have strong genetic background and cellular immune activation. Based on the hypothesis that abnormalities of normal inhibitory control of T cell immunity can contribute to the pathophysiology of bipolar disorder, we investigated the relationship between the first exon at position +49(A/G) polymorphism of cytotoxic T lymphocyte antigen 4(CTLA4) gene and bipolar disorder. METHOD: Among the Korean patients diagnosed as bipolar disorder according to DSM-IV, 90 patients without serious medical illness, neurologic illness, hormonal disorder, or concomitant mental illness were selected. The normal control group consisted of 149 age-and sex-matched subjects without current or past history of autoimmune diseases or mental disorder. DNA was extracted from whole blood and the exon 1 region of CTLA-4 gene was amplified by polymerase chain reaction. Gene typing was performed using single strand conformation polymorphism. RESULTS: There were no significant differences in genotype frequencies of G/G, G/A, and A/A between the patients with bipolar disorder and the control group(48.9% vs 46.3%, 44.4% vs 39.6%, and 6.7% vs 14.1%, respectively). There were no significant differences in allelic frequencies of G and A between the patients with bipolar disorder and the control group(71.1% vs 66.1%, and 28.9% vs 33.9%, respectively). CONCLUSION: This study did not show the association of exon 1 polymorphism of CTLA-4 gene with bipolar disorder.
Autoimmune Diseases ; Bipolar Disorder* ; Diagnostic and Statistical Manual of Mental Disorders ; DNA ; Exons ; Genotype ; Humans ; Lymphocytes ; Mental Disorders ; Polymerase Chain Reaction

OBJECT: Currently, the alteration of cytokine system has been known to play an important role in regard to depressive symptom. We focused on the relationship between immunological parameters and clinical improvement in major depressive disorder. METHOD: Data were collected on 26 patients with major depressive disorder using a 8-week prospective follow-up design. After 8-week treatment period with fluoxetine, patients were classified into a response group and a non-response group according to their psychopathological outcome as evaluated by Hamilton Depression Rating Scale. The differences of the immunological parameters between pre-treatment phase and post-treatment phase were compared among patients. The difference of those was also compared within each phase among them. The relationship between socio-demographic variables, depression, cytokine, mononuclear cells was examined by correlation analysis. Multiple regression analyses were performed to explore the predictors of clinical improvement of major depressive disorder. RESULT: Pre-treatment levels of IL-1beta in the response group were significantly higher than those in the non-response group. Pre-treatment levels of IL-1beta of all patients and in the response group were positively correlated with pre-treatment monocyte counts. Patients with subsequent remission showed significantly lower IL-6 values at baseline than those with non-response. Post-treatment values of IL-6 did not differ significantly among the patients. The correlation test showed more frequent relations among cytokines and mononuclear cells in the response group than in the non-responder group. Especially, serum level of IL-6 in pre-treatment phase was only significantly correlated with HAMD score after 8-week treatement phase, while other cytokines and mononuclear cells were not. Pretreatment level of IL-6 was of paramount importance in predicting clinical improvement of depressive symptom. CONCLUSION: The immune system of major depressive disorder patients might dichotomize the patients into subsequent responders and non-responders. Immune system might be of great influence on the clinical improvement of major depressive disorder. The mode of interaction between depression and cellular immune function and the mediators responsible for the cytokine production need to be studied further.
Cytokines ; Depression ; Depressive Disorder, Major* ; Fluoxetine ; Follow-Up Studies ; Humans ; Immune System ; Interleukin-6 ; Lymphocytes ; Monocytes ; Prospective Studies ; Tumor Necrosis Factor-alpha

Corticotropin-releasing factor(CRF) and neuropeptide Y(NPY) are known to play important roles in mediating stress responses and stress-related behavior. To elucidate the role of neuropeptides in response to the condition that had paired with traumatic event, we observed the changes of CRF and NPY by immunohistochemistry using a conditioned footshock paradigm. Male Sprague-Dawley rats were placed in a shuttle box and exposed to 20 pairings of a tone(< 70dB, 5sec) followed by a footshock(FS, 0.8mA, 1sec) over 60min. A second group was exposed to the tone-footshock pairings, returned to the homecage for 2days, and then reexposed to the test chamber and 20tones alone for 60min, prior to sacrifice. Control groups were : a) sacrificed without exposure to FS ; b) exposed to the tone-footshock pairings and then sacrificed two days later ; or c) exposed to the chamber and tones alone, returned to the homecage for 2days and then reexposed to the chamber and 20tones over 60min prior to sacrifice. CRF was increased in animals exposed to FS or the aversive condition(context and tone) that had paired to FS in bed nucleus of the stria terminalis (BNST) compared to the control. NPY was increased by FS in amygdala and PVN, but the condition previously associated with FS results in slight increase only in amygdala area. These results suggest that the BNST appears to be the mostly involved neural circuit in response to explicit cues previously paired with footshock. Moreover, this study raise the possibility that increased CRF peptide in the BNST in response to re-exposure to the aversive condition may underlie, in part, the experience of conditioned fear-related anxiety behavior.
Amygdala ; Animals ; Anxiety ; Cues ; Humans ; Immunohistochemistry ; Male ; Negotiating ; Neuropeptides* ; Rats* ; Rats, Sprague-Dawley

OBJECT: This cross-sectional study was performed in order to evaluate the prevalence of tardive dyskinesia among the hospitalized schizophrenic patients. METHODS: Four hundred nineteen hospitalized schizophrenic patients(male=263, female=156) were recruited for this study. They were treated with antipsychotics for more than 3 months. The prevalence of tardive dyskinesia was assessed by the Abnormal Involuntary Movement Scale. RESULTS: The prevalence of tardive dyskinesia was 35.6%(Male=36.9%, Female 33.3%). There were no significant differences in the prevalence of tardive dyskinesia among male and female schizophrenic patients. The prevalence of tardive dyskinesia among the patients over 30years old was much higher than those below 30years old. There were no significant correlations between the prevalence of tardive dyskinesia and the duration of hospitalization, the total amount of antipsychotics. The frequently involved parts of the body in the schizophrenic patients who have tardive dyskinesia were tongue, upper extremity, lips and perioral area, jaw, lower extremity, muscles of facial expression trunk, respectively. CONCLUSIONS: There was significant correlation between the age and the prevalence of tardive dyskinesia in the antipsychotic-treated schizophrenic patients.
Antipsychotic Agents ; Cross-Sectional Studies ; Dyskinesias ; Facial Expression ; Female ; Hospitalization ; Humans ; Jaw ; Lip ; Lower Extremity ; Male ; Movement Disorders* ; Muscles ; Prevalence* ; Schizophrenia ; Tongue ; Upper Extremity

Debates relevant to the etiology of weight gain or obesity, i.e., the dichotomous understandings about whether obesity arises from the genetic predisposition or from the environmental influences, has long existed. This is an important issue because it is related to the therapists's prejudice when treating patients with obesity. In this review, the authors first discuss the environmental and the genetic factors that cause the obesity, and in the latter part, the interactions between genetic and environmental factors will be discussed. This issue is considered and described especially in a conceptual aspect for the therapists ultimately to understand how the genetic and the environmental factors interact to arise obesity. Conclusively, obesity is best understood as a complex, multifactorial, and chronic disabled state, which cause an individual with genetic predispostion to obesity under the environmental influences. In future, in favor of the accumulated knowledge about the genetic and environmental impacts and their interactions in detail, we will be able to provide a client-specific management or prevention of obesity.
Genetic Predisposition to Disease ; Humans ; Obesity* ; Prejudice ; Weight Gain

Schizophrenics suffer not only psychotic symptoms but also cognitive deficits such as an attentional difficulty, memory impairment, poor abstraction, etc. These cognitive abnormalities have been reported to be significantly related to the social and occupational outcome in schizophrenia. Thus, it is important to explore the cause and pathophysiology for the cognitive abnormalities in patients with schizophrenia. In this regard, hippocampus is one of the most promising brain areas to search for the clue because it is closely involved in memory related function. In fact, during the past several decades, there have been extensive studies supporting hippocampal abnormalities as a cause of schizophrenia in both clinical and preclinical field. In this review, basic anatomical knowledge about hippocampus and major findings of preclinical and clinical studies which investigated the correlation between schizophrenia and hippocampus were highlighted. The contents are 1) anatomical structure of hippocampus, 2) neuronal pathway and receptor distribution in hippocampus, 3) function of hippocampus, 4) hippocampal animal model for schizophrenia, 5) hippocampus-related studies on antipsychotic drugs, and 6) clinical studies in hippocampus in patients with schizophrenia.
Antipsychotic Agents ; Brain ; Hippocampus* ; Humans ; Memory ; Models, Animal ; Neurons ; Schizophrenia*

The use of atypical antipsychotics is limited by occurrence of adverse reactions such as weight gain, despite of their benefits. This article provides a comprehensive review and discussion of the most significant findings regarding obesity-related pathways and integrates these with the known mechanism of atypical antipsychotic action. The focus of this article is primarily on the genetics of obesity related pathways that may be disrupted by atypical antipsychotics. This review also discussed weight gain, hyperglycemia or occurrence of diabetes while being treated with atypical antipsychotics from the point of view of pharmacogenetics. Pharmacogenetic research seeks to uncover genetic factors that will help clinicians identify the best treatment strategies for their patients. It will aid clinically in the prediction of response and side effects, such as antipsychotic-induced weight gain, and minimize the current "trial and error" approach to prescribing in the near future. This article also presents the genetics of both central and peripheral pathways putatively involved in antipsychotic-induced weight gain while providing a comprehensive review of the obesity literature. This article also review obesity related candidate molecules which may be disrupted during atypical antipsychotic drug treatment.
Antipsychotic Agents ; Genetics ; Humans ; Hyperglycemia ; Obesity ; Pharmacogenetics* ; Weight Gain*

BACKGROUND & PURPOSE: Neuropsychological disorders after traumatic brain injury(TBI) are poorly correlated with structural lesions detected by structural neuroimaging techniques such as computed tomography(CT) scan or magnetic resonance imaging(MRI). It is well known that patients with TBI have cognitive and behavioral disorders even in the absence of structural lesions of the brain. This study investigated whether there are abnormalities of regional cerebral blood flow(rCBF) in TBI patients without structural abnormality on MRI, using technetium 99m ethyl cysteinate dimer(Tc-99m-ECD) single photon emission computed tomography(SPECT) scans. MATERIALS AND METHODS: Twenty-eight TBI patients without structural abnormality on MRI(mild, n=13/moderate, n=9/severe, n=6) and fifteen normal controls were scanned by SPECT. A voxel-based analysis using statistical parametric mapping(SPM) was performed to compare the patients with the normal controls. RESULTS: rCBF was reduced in the right uncus and the right lateral orbitofrontal gyrus in the TBI patients. However, no increase of rCBF was noted in the patients in comparison to the normal controls. CONCLUSIONS: These results suggest that the TBI patients, even in the absence of structural lesion of the brain, may have dysfunction of the brain, particularly of the orbitofrontal and anterior pole of the temporal cortex. They also suggest that SPECT can be a useful method to identify brain dysfunctions in combination with structural brain imaging and neuropsychological tests.
Brain ; Brain Injuries* ; Evaluation Studies as Topic* ; Humans ; Magnetic Resonance Imaging* ; Neuroimaging ; Neuropsychological Tests ; Technetium ; Tomography, Emission-Computed, Single-Photon*

OBJECT AND METHOD: Minor physical anomalies(MPAs) are frequently seen in patients with schizophrenia. MPAs are considered to arise from the anomalous development of ectoderm-originated tissues in the developing fetus. Since the central nervous system originates from ectoderm, MPAs can be regarded as externally observable and objective indicators of the aberrant development which might have taken place in the central nervous system. To investigate whether MPAs are more frequent in schizophrenic patients, the frequencies of MPAs were compared between schizophrenic patients and normal controls. Total 245 schizophrenic patients diagnosed with DSM-IV(male : 158, female : 87), and 418 normal control subjects(male : 216, female : 202) were included in this study. The MPAs were measured using the modified Waldrop scale with fifteen items in six bodily regions; head, eye, ear, mouth, hand, and foot. RESULT: The total scores of Waldrop scale were 4.40+/-1.93(mean+/-standard deviation) in patients and 3.43+/- 1.68 in controls for females, and for males, 4.58+/-1.75 in patients and 4.28+/-1.59 in controls. For females, the excess of MPAs in schizophrenic patients was statistically significant(t-test : p<0.001). For males, schizophrenic patients also showed more MPAs than normal controls, but this tendency did not reach statistical significance (t-test : p=0.094). When the modified Waldrop total scores excluding head circumference were compared, the total scores in schizophrenic patients were significantly higher for both male and female subjects(t-test : male p<0.001, female p=0.001). The individual anomaly items included in Waldrop scale were also investigated. The items of epicanthus, hypertelorism, malformed ears, syndactylia were significantly more frequent in schizophrenic patients. In contrast, the items of adherent ear lobes, asymmetric ears, furrowed tongue, curved fifth finger, single palmar crease and big gap between toes did not show any differences in frequency between schizophrenic patients and normal controls. Since a lot of statistical analyses showed different results between male and female subjects, it seems to be necessary to consider gender as an important controlling variable for the analysis, however only the item of head circumference showed statistically significant gender-related difference according to log-linear analysis. CONCLUSION: With a relatively large sample size, the frequencies of MPAs enlisted in Waldrop scale were compared between schizophrenic patients and normal controls in this study. MPAs were more frequently seen in schizophrenic patients and, especially, several specific items in the Waldrop scale showed prominent excess in schizophrenic patients. Although definite conclusions cannot be drawn due to the inherent limitation of the study using Waldrop scale, these results seem to support the possibility that aberrant neurodevelopmental process might be involved in the pathogenesis of schizophrenia in some of the patients.
Central Nervous System ; Ear ; Ectoderm ; Female ; Fetus ; Fingers ; Foot ; Hand ; Head ; Humans ; Hypertelorism ; Male ; Mouth ; Sample Size ; Schizophrenia* ; Syndactyly ; Toes ; Tongue, Fissured

OBJECTIVE: This study was performed to investigate the prescribing patterns of antimanic agents in the treatment of acute bipolar disorder inpatients in Korea from 1990 through 2000. The results will serve as the basic data for the practice guideline for the pharmacotherapy of bipolar disorder patients in Korea. METHOD: Retrospective chart review of bipolar disorder inpatients of Soonchunhyang Medical Center in Seoul and Chun-An was conducted for each of the year 1990, 1995, and 2000. The following data are collected ; 1) demographic data, 2) history of bipolar disorder, 3) length of hospital stay, 4) detailed drug titration records of antimanic agents and antipsychotic agents. RESULTS: During the last decade, the frequency of lithium monotherapy was decreased obviously. Instead, more than half of the patients in 2000 were on combination therapy of lithium and anticonvulsants. Lithiumvalproate combination was the preferred strategy and the use rate of carbamazepine has been decreased. In addition, most of the patients were given antipsychotic agents during the last 10 years. And recently, atypical antipsychotics were increasingly prescribed. These changes in the field of pharmacology of bipolar disorder have resulted neither in shorter hospital stays nor lower dosages of concurrent neuroleptics. CONCLUSIONS: The results indicate the trends in the prescribing of antimanic agents for the treatment of bipolar disorder in Korea across the past 10 years. Mostly, the change seems to correspond to the international practice guideline. More systematic research is needed to find out the clinical benefits of the anticonvulsants in the real practice of treatment of bipolar disorder.
Anticonvulsants ; Antimanic Agents* ; Antipsychotic Agents ; Bipolar Disorder ; Carbamazepine ; Drug Therapy ; Humans ; Inpatients* ; Korea ; Length of Stay ; Lithium ; Pharmacology ; Retrospective Studies ; Seoul