Several studies have reported on catatonia caused by the use of antipsychotic drugs and on the association between catatonia and neuroleptic malignant syndrome (NMS), but none has reported such a case in Korea. Here, we report the case of a 20-year-old woman whose catatonia and NMS appeared associated with the administration of an atypical antipsychotic drug. We discuss the association between NMS and catatonia due to neuroleptic use.
Antipsychotic Agents ; Catatonia ; Female ; Humans ; Korea ; Neuroleptic Malignant Syndrome ; Young Adult

OBJECTIVE: Benzodiazepines are from the most common drugs which are used for treatment of anxiety disorders. There are other drugs with antianxiety properties including antihistamines such as hydroxyzine, too. Body of evidence show that co-administration of two drugs which act through different mechanisms, makes the dose of each drug to be reduced, while preserving the desired effect with less adverse drug reactions. The aim of this study was to see whether co-administration of subeffective antianxiety doses of diazepam and hydroxyzine has any antianxiety effect in elevated zero-maze (EZM) in mice. METHODS: To find the highest subeffective dose of each drug, different doses of hydroxyzine from 1.5 to 24 mg/kg and diazepam in doses of 0.25, 0.5 and 1 mg/kg were injected to male mice. Thirty minutes later, the animals were placed on EZM and various parameters of anxiety were recorded by a camera to assess later. After determination of subeffective antianxiety dose of the drugs, co-administration of hydroxyzine and diazepam was done and the anxiety parameters were measured. RESULTS: In co-administration of 0.25 mg/kg of diazepam and 12 mg/kg hydroxyzine, as subeffective antianxiety doses of either drug, there were not any significant differences in main anxiety parameters, i.e., time spent in open areas and open area entries compared to control group. Hence, no anxiolytic effect was seen. CONCLUSION: It seems that subeffective doses of diazepam and hydroxyzine may not have any facilitating or synergistic effect on each other in antianxiety responses in mice.
Animals ; Anti-Anxiety Agents ; Anxiety ; Anxiety Disorders ; Benzodiazepines ; Diazepam ; Drug Toxicity ; Histamine Antagonists ; Humans ; Hydroxyzine ; Male ; Mice

OBJECTIVE: To analyze both differentially expressed genes and the Bcl-xL protein expression after acute and chronic treatment with fluoxetine in rat C6 glioma cells. METHODS: C6 glioma cells were cultured for 24 h or 72 h after treatment with 10 microM fluoxetine, and gene expression patterns were observed using microarray and qRT-PCR. Then, cells were cultured for 6 h, 24 h, 72 h or 96 h after treatment with 10 microM fluoxetine, and the expression of Bcl-xL protein was measured using western blot. RESULTS: As determined by microarray, treatment with fluoxetine for 24 h up-regulated 33 genes (including Bcl-xL and NCAM140) and down-regulated 7 genes (including cyclin G-associated kinase). Treatment with fluoxetine for 72 h up-regulated 53 genes (including Gsalpha and Bcl-xL) and down-regulated 77 genes (including Galphai2 and annexin V). Based on the qRT-PCR results, there was an increase in Gsalpha mRNA and a decrease in Galphai2 mRNA at 72 h in fluoxetine-treated cells as compared to control, a result that was consistent with microarray. We also observed an increase in Bcl-xL mRNA (both at 24 h and at 72 h) in fluoxetine-treated cells as compared to control, demonstrating a tendency to increase gradually. Bcl-xL protein expression increased as the duration of fluoxetine treatment increased. CONCLUSION: These results suggest that chronic treatment with fluoxetine not only initiates the cAMP pathway through inducing Gsalpha expression but also induces Bcl-xL expression, thus inhibiting apoptosis.
Animals ; Apoptosis ; bcl-X Protein ; Cyclins ; Fluoxetine ; Gene Expression ; Glioma ; Rats ; RNA, Messenger

OBJECTIVE: Smoking related cues may elicit smoking urges and psychophysiological responses in subjects with nicotine dependence. This study aimed to investigate the effect of repeated virtual cue exposure therapy using the surround-screen based projection wall system on the psychophysiological responses in nicotine dependence. METHODS: The authors developed 3-dimensional neutral and smoking-related environments using virtual reality (VR) technology. Smoking-related environment was a virtual bar, which comprised both object-related and social situation cues. Ten subjects with nicotine dependence participated in 4-week (one session per week) virtual cue exposure therapy. Psychophysiological responses [electromyography (EMG), skin conductance (SC), and heart rate] and subjective nicotine craving were acquired during each session. RESULTS: VR nicotine cue elicited greater psychophysiological responses and subjective craving for smoking than did neutral cue, and exposure to social situation cues showed greater psychophysiological responses in SC and EMG than did object-related cues. This responsiveness decreased during the course of repeated therapy. CONCLUSION: The present study found that both psychophysiological responses and subjective nicotine craving were greater to nicotine cue exposure via projection wall VR system than to neutral cues and that enhanced cue reactivity decreased gradually over the course of repeated exposure therapy. These results suggest that VR cue exposure therapy combined with psychophysiological response monitoring may be an alternative treatment modality for smoking cessation, although the current findings are preliminary.
Cues ; Heart ; Implosive Therapy ; Nicotine ; Skin ; Smoke ; Smoking ; Smoking Cessation ; Tobacco Use Disorder

OBJECTIVE: Our aim was to evaluate the changes in blood glucose control and lipid profiles after 2-months of smoking cessation in healthy males. METHODS: Smoking abstinence was evaluated through self-report and urine cotinine levels. 12 individuals who succeeded in quitting smoking were analyzed. Fasting values of glucose and insulin were used to estimate the beta-cell activity and insulin resistance was evaluated using the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: The data showed that the subjects had a significant increase in weight, body mass index and fasting plasma glucose levels after smoking cessation. The HOMA-Insulin Resistance and the HOMA beta-cell function increased significantly (p=0.005, p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In addition, the low-density lipoprotein cholesterol levels decreased significantly (p=0.028); however, changes in the high-density lipoprotein cholesterol, the triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445 respectively). CONCLUSION: During the initial stage of smoking abstinence, insulin resistance increased and insulin sensitivity decreased due to elevated body weight and fat composition. Therefore, it is important to educate individuals that stop smoking about the necessity of weight control during smoking cessation programs.
Blood Glucose ; Body Weight ; Cholesterol ; Cotinine ; Fasting ; Glucose ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Lipoproteins ; Male ; Plasma ; Smoke ; Smoking ; Smoking Cessation

OBJECTIVE: This multicenter, randomized, open-label, parallel trial aimed to provide a detailed dose-response profile for atomoxetine in Korean pediatric outpatients with attention-deficit/hyperactivity disorder (ADHD). METHODS: Male and female outpatients aged 6-18 years with ADHD meeting symptom severity criteria of 1.5 standard deviations above age and gender norms on the ADHD Rating Scale-IV-Parent: Investigator-Administered and Scored (ADHDRS-IV-Parent: Inv), and a Clinical Global Impression-ADHD-Severity score > or =4 were randomized to atomoxetine (mg/kg/day) 0.2 fixed, 0.5 fixed or 0.5 (7 days), 0.8 (7 days) then 1.2 for 28 days. The primary efficacy measure was change in ADHDRS-IV-Parent: Inv total score after 6 weeks of atomoxetine treatment. RESULTS: Of 153 randomized patients, 83.7% were male and mean age was 9.8 (SD+/-2.4) years. The completion rate was 86.9%. A graded dose response was apparent with mean change in ADHDRS-IV-Parent: Inv total scores of -9.6, -12.3 and -14.5 with atomoxetine 0.2, 0.5 and 1.2 mg/kg/day, respectively (p=0.024 - F-test). Moreover, a greater reduction in ADHD symptoms, as assessed by mean change from baseline to endpoint CGI-S and mean CGI-ADHD-Improvement at endpoint, was also observed with increasing atomoxetine dose. More patients receiving atomoxetine 1.2 mg/kg/day reported > or =1 treatment-emergent adverse event/s (58.3%) compared with 0.5 (40.7%; p=0.11) or 0.2 mg/kg/day (29.4%; p=0.005). These were generally mild to moderate. CONCLUSION: Atomoxetine was found to be safe and well tolerated at all doses administered in Korean pediatric ADHD patients, and 1.2 mg/kg/day was an efficacious dose in this population.
Aged ; Female ; Humans ; Korea ; Male ; Outpatients ; Propylamines ; Atomoxetine Hydrochloride

OBJECTIVE: This study was conducted to confirm the results of the authors' previous research on schizophrenia manifesting high serum homocysteine and low folate levels. This study is anchored on a theory that a high serum homocysteine concentration affects schizophrenia by virtue of a neurotoxic mechanism, and on a report that some schizophrenia patients with high homocysteine levels benefited from high folate ingestion. METHODS: The serum homocysteine, folate, and vitamin B12 levels of 236 normal-control-group subjects and 234 schizophrenia subjects who met the diagnostic criteria based on DSM-IV-TR were compared. The homocysteine levels were measured via fluorescence polarization immunoassay, and the folate and vitamin B12 levels were determined via radioimmunoassay. RESULTS: The homocysteine levels of the patient group were significantly higher than those of the normal control group. The homocysteine level was more negatively correlated with the folate level in the schizophrenia group than in the control group. The percentages of female and male schizophrenia subjects manifesting high homocysteine levels were 33.8 and 51.5%, respectively. The percentage of schizophrenia subjects with low folate levels was 66.2%. In the low- and normal-folate-level groups, the patient group showed significantly higher homocysteine levels than the normal control group. The low-folate-level patient group particularly showed significantly higher homocysteine levels than the low-folate-level normal control group. CONCLUSION: Some schizophrenia patients with high serum homocysteine levels may have the genetic defect of having low folate serum levels. In such cases, folate ingestion may be a good management modality for clinical improvement.
Eating ; Female ; Fluorescence Polarization Immunoassay ; Folic Acid ; Homocysteine ; Humans ; Male ; Schizophrenia ; Virtues ; Vitamin B 12

OBJECTIVE: Psychiatric disorders such as depression, anxiety and alcohol dependence are associated with serotonin metabolism. We assessed the methylation level of the serotonin transporter (5-HTT) promoter region in control and alcohol dependent patients. METHODS: Twenty seven male patients who met the Diagnostic and Statistical Manual of Mental Disorder IV (DSM-IV) criteria for alcohol dependence were compared with fifteen controls. Polymerase chain reaction (PCR) assays of bisulfate-modified DNA were designed to amplify a part of the CpG island in the 5HTT gene. Pyrosequencing was performed and the methylation level at seven CpG island sites was measured. RESULTS: We found no differences in the methylation patterns of the serotonin transporter linked promoter region (5-HTTLPR) between alcohol-dependent and control subjects. CONCLUSION: Our negative finding may be because 5-HTT epigenetic variation may not affect the expression for 5-HTT or there may be other methylation site critical for its expression. To find out more conclusive result, repeating the study in more methylation sites with a larger number of samples in a well-controlled setting is needed.
Alcoholism ; Anxiety ; CpG Islands ; Depression ; DNA ; Epigenomics ; Humans ; Male ; Mental Disorders ; Methylation ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; Serotonin ; Serotonin Plasma Membrane Transport Proteins

Due to co-morbidities and treatment resistant nature of pervasive developmental disorder (PDD), diverse combinations of regimens have been tried. This retrospective study aimed to explore adjunctive use of aripiprazole in children with PDD. Changes in illness severity were measured by Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I) in 14 aripiprazole-treated patients with PDD. Improvement of illness severity was observed after aripiprazole add-on (5.8+/-0.8 to 4.9+/-1.0, Z=-2.75, p=0.001). Mean dosage was 7.7 mg/day [standard deviation (SD) 3.3, range 5-15]. A higher mean dosage was observed in group with improvement in symptoms (t=-2.33, df =12, p=0.004). The target symptoms most effectively improved after using aripiprazole were positive psychotic symptoms (mean CGI-I: 2.0+/-1.4, 3 responders/4 patients, 75% response) followed by aggressive behavior (2.5+/-1.7, 3/4, 75%), self-injurious behavior (2.0+/-1.0, 2/3, 67%), stereotypic behavior (2.7+/-1.2, 2/3, 67%), tic (2.8+/-1.0, 2/4, 50%), irritability (3.5+/-2.1, 1/2, 50%), obsessive behavior (2.5+/-2.1, 1/3, 33%), hyperactivity (3.4+/-1.6, 3/7, 43%) and mood fluctuation (3, 0/1, no response). Five patients (35%) discontinued aripiprazole due to treatment-emergent adverse effects (akathisia, insomnia, withdrawal). The results of this study suggest that aripiprazole augmentation may be used safely in maladaptive behaviors of some populations of PDD. However, future studies are required to con-firm these preliminary findings.
Autistic Disorder ; Child ; Humans ; Obsessive Behavior ; Piperazines ; Quinolones ; Retrospective Studies ; Self-Injurious Behavior ; Sleep Initiation and Maintenance Disorders ; Tics ; Aripiprazole

OBJECTIVE: Panic disorder (PD) is a common and often chronic psychiatric illness, and serotonin-specific reuptake inhibitors (SSRIs) are the drugs of choice for the treatment of PD. Previous studies suggested the cerebral cortex and limbic brain structures played a major role in the development of PD, but the therapeutic effect of SSRIs on specific brain structures remains unclear in PD. We examined the changes in PD patients' glucose metabolism using the [18F] Fluorodeoxy-glucose-positron emission tomography (FDG-PET) before and after 12 weeks of paroxetine treatment. METHODS: We assessed the brain glucose metabolism of 5 PD patients, using the [18F]FDG-PET, and treated them with paroxetine (12.5-37.5 mg/day) for 12 weeks. Then, we compared before and after treatment PET images of the patients, using voxel-based statistical analysis and a post hoc regions of interest analysis. Furthermore, we measured the patients' clinical variables, including information from the Panic Disorder Severity Scale (PDSS), Clinical Global Impression for Severity (CGI-S), and Hamilton Anxiety Rating Scale (HAMA). RESULTS: After 12 weeks of paroxetine treatment, the patients showed significant clinical improvement in terms of PDSS, CGI-S and HAMA scores (12.8+/-1.8 vs. 3.8+/-2.3, 4.6+/-0.5 vs. 2.0+/-1.4, and 15.2+/-4.0 vs. 5.0+/-1.2, respectively; all p values<0.05). After treatment, patients' glucose metabolism increased significantly in global brain areas: the right precentral gyrus, right middle frontal gyrus, right amygdala, right caudate body, right putamen, left middle frontal gyrus, left precentral gyrus, left insula, left parahippocampal gyrus, and left inferior frontal gyrus (All areas were significant at uncorrected p<0.001 and cluster level corrected p<0.05). CONCLUSION: In these PD patients, cerebral cortex and limbic brain functions changed after short-term treatment with paroxetine. The therapeutic action of paroxetine may be related to altered glucose metabolism at both the cerebral cortex and limbic brain areas.
Amygdala ; Anxiety ; Brain ; Cerebral Cortex ; Glucose ; Humans ; Neuroimaging ; Panic ; Panic Disorder ; Parahippocampal Gyrus ; Paroxetine ; Pilot Projects ; Positron-Emission Tomography ; Putamen