$K^+$ channels are key components of the primary and secondary basolateral $Cl^-$ pump systems, which are important for secretion from the salivary glands. Paroxetine is a selective serotonin reuptake inhibitor (SSRI) for psychiatric disorders that can induce QT prolongation, which may lead to torsades de pointes. We studied the effects of paroxetine on a human $K^+$ channel, human ether-a-go-go-related gene (hERG), expressed in Xenopus oocytes and on action potential in guinea pig ventricular myocytes. The hERG encodes the pore-forming subunits of the rapidly-activating delayed rectifier $K^+$ channel ($I_{Kr}$) in the heart. Mutations in hERG reduce $I_{Kr}$ and cause type 2 long QT syndrome (LQT2), a disorder that predisposes individuals to life-threatening arrhythmias. Paroxetine induced concentration-dependent decreases in the current amplitude at the end of the voltage steps and hERG tail currents. The inhibition was concentration-dependent and time-dependent, but voltage-independent during each voltage pulse. In guinea pig ventricular myocytes held at $36^{\circ}C$, treatment with $0.4{\mu}M$ paroxetine for 5 min decreased the action potential duration at 90% of repolarization ($APD_{90}$) by 4.3%. Our results suggest that paroxetine is a blocker of the hERG channels, providing a molecular mechanism for the arrhythmogenic side effects of clinical administration of paroxetine.
Journal of the Korean Academy of Child and Adolescent Psychiatry
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v.14
no.1
/
pp.36-52
/
2003
Attention deficit/hyperactivity disorder is one of the most comminly treated conditions in the child psychiatric units and results in substantial impairment in peer, family and academoc functioning. For 70% to 80% of children with a diagnosis of ADHD, stimulant tratment results in successful improvement of the core ADHD symptoms. However, children with ADHD have high level of comorbidity and may respond differently from children with ADHD without comorbidity. Therefore they may need specific treatment plan. We reviewed efficacy and safety of prescribed medication for treating children with ADHD, the relationship between ADHD and the comorbid conditions and treatment algorithm projects of ADHD with/without comorbid conditions performed Korean and American child psychiatrists. Our main objective is to increase the uniformity of treatment and improve the clinical outcomes of children with comorbid ADHD.
Objectives: Prospective evaluations of the associations between depressive symptoms and suicide deaths have been mainly performed in high-risk populations, such as individuals with psychiatric disorders or histories of self-harm. The purpose of this study was to prospectively examine whether more severe depressive symptoms assessed using the Geriatric Depression Scale (GDS) were associated with a greater risk of death from suicide in a general-risk population. Methods: A total of 113 478 men from the Korean Veterans Health Study (mean age, 58.9 years) who participated in a postal survey in 2004 were followed up for suicide mortality until 2010. Results: Over 6.4 years of follow-up, 400 men died by suicide (56.7 deaths per 100 000 person-years). More severe depressive symptoms were associated with greater risk of suicide death (p for trend <0.001). The unadjusted hazard ratios (HRs) in comparison to the absence of depression were 2.18 for mild depression, 2.13 for moderate depression, 3.33 for severe depression, and 3.67 for extreme depression. After adjusting for potential confounders, men with a potential depressive disorder had an approximate 90% higher mortality from suicide (adjusted HR, 1.92; 95% confidence interval [CI], 1.38 to 2.68; p<0.001) than men without depression. Each five-point increase in the GDS score was associated with a higher risk of death by suicide (adjusted HR, 1.22; p<0.001). The value of the area under the receiver operating characteristics curve of GDS scores for suicide deaths was 0.61 (95% CI, 0.58 to 0.64). Conclusions: Depressive symptoms assessed using the GDS were found to be a strong independent predictor of future suicide. However, the estimate of relative risk was weaker than would be expected based on retrospective psychological autopsy studies.
Objective: Neurasthenia is a disease which consists of increased fatigue or bodily weakness and exhaustion plus pantalgia, dizziness, headache and other symtoms relevant to autonomic nerve dysfunction. There are plenty of studies investigating the history of diagnostic criteria of neurasthenia, which is influenced by diverse cultural(or social) environment. The obejective of this study is to provide review of the previous studys on the changes of neurasthenia diagnoses in the context of local area to find meanings of these transition and improve health care for psychiatric patient. Methods: Literature review was conducted on studies demonstrating diagnostic criteria of neurasthenia with cultural(or social) environment. We investigated the literature reviews or observative studies which described alteration of diagnostic criteria of neurasthenia and assessed its significance. After selecting eligible studies, the authors read the articles and summarized the meaningful contents those were significant in clinical practice. Results: Transformation of Chinese Classification of Mental Disorder(CCMD) integrated with internationally utilized DSM-IV or ICD-10 is controversial about its significance in that it had limited effect on public health care due to the variables of sociocultural context, but primarily differentiated neurasthenia from other disorders. The latter one can be the directing point of the diagnostic criteria of other culture-bound diseases, which is the traits of not outstanding mood(or affect) than other neurotic disorders. Conclusion: As diagnostic criteria of neurasthenia varies, the significance of this variation is controversial, but could be the paragon of other culture-bound diseases.
Objective: This study was designed to evaluate the etiological factors of the PTSD(post traumatic stress disorder) by examining the relationship between severity of physical trauma and subsequent the severity of PTSD symptom in traffic accident related PTSD patients. Method: Subjects were 21 psychiatric inpatients with history of traffic accident related PTSD(DSM-IV criteria), the purpose of evaluation of mental disability and no evidence of organic brain leisons. The severity of physical trauma was assessed by McBride number of nonpsychiatric department and the presence / absence of loss of conciousness. The severity of PTSD symptom was assessed by Hovens' self rating inventory for PTSD. And then we evaluated the correlation between these two factors. And we also evaluated relationship between severity of PTSD symtom and clinical variables. Results : There were no significant relationship between McBride number of nonpsychiatric department severity and symptomatic severity(r= 0.17, p<0.05), the presence / absence of loss of conciousness and symptomatic severity(p>0.05). And significant relationship between symptomatic severity and clinical varibles such as sex, education level, marital status(p<0.05). Conclusions : These data did not support data of previous studies that traumatic severity was correlated with symptom severity but, suggested that other variables affecting the severity of PTSD symptom is more important indirectly. And that the 'trauma' in PTSD is psychological meaning rather than physical meaning is also suggested.
Purpose: This study was conducted to investigate the incidence and associated factors with post-traumatic stress disorders (PTSD) in patients with intensive care units (ICU) admission experience. Methods: This study is a retrospective observational study using self-reporting questionnaire. Patients who were admitted to ICU more than 72 hours and agreed to participate were enrolled in this study. PTSD were assessed by Korean version of post-traumatic diagnosis scale, and PTSD was defined as 20 points or more. Medical records of participants were reviewed to identify influencing factors of PTSD. To analyzed the data, descriptive statistics, Mann-Whitney U test, Kruskal-Wallis test and gamma regression were utilized using SPSS/WIN 23.0 program. Results: A total of 128 patients participated in the study. Mean age of participants was 58.3±11.7 years and 50 patients (39.1%) were female. Mean duration of ICU stay was 8.43±8.09 days and PTSD was diagnosed in 12 patients (9.4%). In the results of a Gamma regression analysis, Psychiatric history (B=1.09, p=.002), APACHEII score (B=.04, p=.005), CPR experience (B=1.65, p=.017) and physical restraint (B=.68, p=.049) were independently associated with PTSD occurrence. Conclusion: The results of this study suggest that a various factors influencing PTSD should be identified to prevent PTSD in patients who requires ICU care. In addition, post-ICU care programs are required to assess and reduce PTSD.
Objective : The goal of this study was to investigate the characteristics of early maladaptive schemas (EMSs), and associated neurocognitive functions as seen in visitors for military designation process. Methods : This retrospective study included 111 males aged 18 to 24 years among three groups: 41 visitors for military designation process (VMD), 21 patients with obsessive-compulsive disorder (OCD), and 49 healthy subjects. We collected the results of the Young Schema Questionnaire, Symptom Checklist-90-Revised, three neurocognitive tests as well as their clinicodemographic data. We analyzed the differences in EMSs between these three groups, and the correlations among the identified EMSs and neurocognitive performances within the VMD group. Results : Compared with both the OCD and healthy groups, the evaluation of the VMD group showed significantly higher scores in mistrust/abuse (F=6.4, p=0.002), vulnerability to harm (F=6.6, p<0.0001) and negativity/pessimism schema (F=7.3, p<0.0001), even when controlling for depression scores and levels of education. These three schemas also exhibited significant negative correlations with the score of Stroop test with r ranging from -0.34 to -0.44. Conclusion : These findings suggest that people who are likely to have difficulties adjusting to living in a military life may have psychological vulnerabilities related to certain EMSs. Further studies are warranted to test the clinical potentials of these findings, such as a treatment target and a predictor factor.
Kim, Seonmin;Kim, Do Gyeong;Gonzales, Edson luck;Mabunga, Darine Froy N.;Shin, Dongpil;Jeon, Se Jin;Shin, Chan Young;Ahn, TaeJin;Kwon, Kyoung Ja
Biomolecules & Therapeutics
/
v.27
no.2
/
pp.168-177
/
2019
Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.
Kim, Hee Cheol;Jeong, Seong Hoon;Ahn, Yong Min;Park, Seung Hyun;Kim, Yong Sik;Chung, In Won
Korean Journal of Biological Psychiatry
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v.27
no.2
/
pp.64-73
/
2020
Suicidality is the most serious complication of mood disorders and psychosis; effective treatment should reduce suicide rates. The Organization for Economic Cooperation and Development age-standardized suicide rate in Korea was 22.6 in 2018, much higher compared to other countries worldwide. As mental and psychiatric problems are the main reasons for suicide attempts, accounting for 31.6% in 2018, targeting such problems should be the focus of efforts to reduce suicide rates. However, the ability of current pharmacotherapeutic and psychotherapeutic interventions to reduce suicide rates is limited due to their delayed effects. Therefore, electroconvulsive therapy (ECT) has been proposed as an alternative treatment. This approach is effective for treating most mental disorders associated with high suicide rates, including severe depression, bipolar disorder, and intractable psychotic disorders; ECT is also effective for Parkinson's disease, which has the highest suicide rate among all disorders in Korea. The acute, long-term, and prophylactic effects of ECT on suicidality have been reported in the literature, and treatment guidelines outside of Korea recommend that ECT be used at an early stage for rapid reduction of suicide rates, as opposed to being applied as a treatment of last resort. However, only ~0.092 of every 10000 members of the Korean general population received ECT in 2018; this is much lower than the average rate worldwide, of 2.2 per 10000. Elimination of obstacles to the use of ECT, early crisis intervention involving administration of ECT for rapid stabilization, and maintenance ECT to prevent recurrence should reduce suicide rates.
Ara, Irfat;Kalam, Mohd Afsahul;Maqbool, Mudasir;Zehravi, Mehrukh
CELLMED
/
v.11
no.3
/
pp.14.1-14.9
/
2021
Background: Cuscuta reflexa Roxb is a member of the Cuscutaceae family, and in Unani medicine, it is known as Aftimoon. It is a parasitic plant that can be found growing abundantly on various host plants in India up to 3000 metres in altitude during the rainy season. Unani physicians have been using it for years to cure a variety of illnesses, including psychiatric illnesses like melancholia, schizophrenia, and epilepsy. It has been used to cure hepatitis, palpitations, and skin disorders, among other things. Objective of the study: To evaluate anti-anxiety effect of Cuscuta reflexa Roxb in Swiss Albino mice of either sex. Materials and Methods: A total of 24 Swiss Albino mice weighing 25-35 g were used in this study. Animals were chosen at random and held in their cages for at least 7 days in a standard setting. Group A was given regular saline as a vehicle, Group B was given a hydro alcoholic extract of the lower dose of the test drug, Group C was given a hydro alcoholic extract of the higher dose of the test drug, and Group D was given the standard drug Diazepam 5 mg/kg orally. Aftimoon as hydro alcoholic extract (200 mg/kg and 400 mg/kg body wt.) was given in single and double doses and observed for 7 days. Results: For each parameter in each category, mean and standard deviations were computed. For multiple group comparisons, a one-way ANOVA was used, followed by Turkey's post hoc test. (p<0.05) was used as the significance standard. Conclusion: These results advocate that the Aftimoon as double dose (400 mg/kg body wt.) revealed anti-anxiety effect similar to standard drug.
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