1.Electroconvulsive Seizure Normalizes Motor Deficits and Induces Autophagy Signaling in the MPTP-Induced Parkinson Disease Mouse Model
Seonghoo HUH ; Hyun Sook YU ; Nuree KANG ; Yong Min AHN ; Yong Sik KIM ; Se Hyun KIM
Psychiatry Investigation 2023;20(3):273-283
Objective:
Electroconvulsive seizure (ECS) is a potent treatment modality for various neuropsychiatric diseases, including Parkinson disease (PD). Recent animal studies showed that repeated ECS activates autophagy signaling, the impairment of which is known to be involved in PD. However, the effectiveness of ECS on PD and its therapeutic mechanisms have not yet been investigated in detail.
Methods:
Systemic injection of a neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), which destroys dopaminergic neurons in the substantia nigra compacta (SNc), in mice was utilized to induce an animal model of PD. Mice were treated with ECS 3 times per week for 2 weeks. Behavioral changes were measured with a rotarod test. Molecular changes related to autophagy signaling in midbrain including SNc, striatum, and prefrontal cortex were analyzed with immunohistochemistry and immunoblot analyses.
Results:
Repeated ECS treatments normalized the motor deficits and the loss of dopamiergic neurons in SNc of the MPTP PD mouse model. In the mouse model, LC3-II, an autophagy marker, was increased in midbrain while decreased in prefrontal cortex, both of which were reversed by repeated ECS treatments. In the prefrontal cortex, ECS-induced LC3-II increase was accompanied with AMP-activated protein kinase (AMPK)-Unc-51-like kinase 1-Beclin1 pathway activation and inhibition of mamalian target of rapamycin signaling which promotes autophagy initiation.
Conclusion
The findings revealed the therapeutic effects of repeated ECS treatments on PD, which could be attributed to the neuroprotective effect of ECS mediated by AMPK-autophagy signaling.
2.An International Adult Guideline for Making Clozapine Titration Safer by Using Ancestry-Based Personalized Dosing Titrations, C-Reactive Protein and Serum Clozapine Levels: Korean Translation and Its Clinical Application Cases
Jung Su PARK ; Nuree KANG ; Yong Min AHN ; Yong Sik KIM ; Se Hyun KIM
Korean Journal of Schizophrenia Research 2023;26(2):52-60
Objectives:
During the initial clozapine titration, it is crucial to monitor for inflammatory reactions to ensure safe and effective administration. Clozapine metabolism varies by ancestry, particularly among Asians, warranting lower dosage. Recently, Dr. De Leon introduced guidelines based on ancestral differences. We aimed to provide a Korean translation, focusing on illustrating the necessity through clinical cases.
Methods:
The Korean translation of the guidelines, approved by Dr. De Leon, involved two psychiatrists who reviewed and revised each other’s work. An additional board-certified psychiatrist conducted an independent review. We examined two clinical cases from our institution’s database, where clozapine titration faced challenges due to fever and pneumonia, assessing guideline applicability.
Results:
The guidelines recommend a target clozapine dose of 175-300 mg/day for Asians with average metabolism and a slower titration rate compared to other ancestries. In both cases, CRP elevation was detected either before or simultaneously with the onset of fever, with a concentration-to-dose ratio ranging from 3.06 to 6.97.
Conclusion
The initial clozapine titration process should consider metabolic differences by ancestry and monitor for inflammation. Further research is needed to optimize the titration process for Koreans, considering metabolic rates, usage patterns, and side effects.
3.Comparative Study of the Efficacy and Side Effects of Brand-Name and Generic Clozapine for Long-Term Maintenance Treatment Among Korean Patients With Schizophrenia: A Retrospective Naturalistic Mirror-Image Study
Nuree KANG ; Hee-Soo YOON ; Se Hyun KIM ; Jae Hoon JEONG ; Minah KIM ; Jun Soo KWON
Psychiatry Investigation 2024;21(3):311-320
Objective:
Clozapine is considered the most reliable drug for treatment-resistant schizophrenia. In 2014, a generic formulation of clozapine (Clzapine) was introduced in Korea. This study was performed to provide clinical information regarding the use of clozapine and to compare efficacy and tolerability when converting from the brand-name formulation (Clozaril) to the generic formulation during longterm maintenance treatment among Korean patients with schizophrenia.
Methods:
This mirror-image study retrospectively investigated the electronic medical records of patients who had switched from Clozaril to Clzapine with a ≥1-year duration for each formulation. Clinical data were collected, including information regarding clozapine use, psychiatric hospitalization, co-medications, and blood test findings. Data before and after the switch were compared using paired t-tests.
Results:
Among 332 patients, the mean 1-year dosages were 233.32±149.35 mg/day for Clozaril and 217.36±136.66 mg/day for Clzapine. The mean clozapine concentration-to-dose ratios were similar before and after the switch (Clozaril, 1.33±0.68; Clzapine, 1.26±0.80). Switching from Clozaril to Clzapine resulted in no significant differences in the hospitalization rate, hospitalization duration, or laboratory findings (liver function parameters, serum cholesterol level, and serum glucose level). Equivalent doses of co-prescribed antidepressants were decreased, but concomitant medications otherwise showed no significant differences.
Conclusion
Clinical efficacy and tolerability appear comparable when switching to Clzapine during clozapine maintenance treatment. This study offers descriptive real-world clinical insights into clozapine maintenance treatment in Korea, thereby providing patients with more treatment options and contributing to the development of maintenance guidelines tailored to the Korean population.
4.Temperament and Character Associated With Resilience in Patients With Bipolar Disorder
Soo-Yeon KANG ; Bong-Jo KIM ; Cheol-Soon LEE ; So-Jin LEE ; Dongyun LEE ; Jae-Won CHOI ; Young-Ji LEE ; Eunji LIM ; Nuree KANG ; Boseok CHA
Journal of the Korean Society of Biological Therapies in Psychiatry 2023;29(3):79-86
Objectives:
The aim of this study was to investigate temperament and character associated with resilience in patients with bipolar disorder (BD).
Methods:
A total of 55 outpatients diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and 55 healthy controls matched by age and sex with the BD group were recruited.All participants completed the Connor-Davidson Resilience Scale (CD-RISC) and Temperament and Character Inventory (TCI). Multiple linear regression analysis was performed by controlling for age, length of education, age of onset, number of depressive episodes, and number of hospitalizations to determine factors related to resilience. In addition, multiple regression analysis was performed using the interaction term to investigate whether temperament and character associated with resilience differed between the two groups.
Results:
Patients with BD showed higher harm avoidance (p<0.001) and lower self-directedness (p<0.001) among the TCI dimensions compared to the control group. In multiple regression analysis, harm avoidance (β=-0.274, p=0.025) and self-directedness (β=0.431, p=0.002) were associated with resilience in patients with BD, while harm avoidance (β=-0.411, p=0.008), persistence (β=0.244, p=0.031), and cooperativeness (β=0.264, p=0.037) were associated with resilience in the control group. Self-directedness had a different relationship with resilience between the two groups (β=0.212, p=0.001).
Conclusions
The findings suggest that BD patients’ particular temperament and character are associated with resilience.Furthermore, temperament and character related to resilience differed between the BD group and the control group.
5.Association Between Suicide and Diet
Eunji LIM ; Bong-Jo KIM ; Cheol-Soon LEE ; Boseok CHA ; So-Jin LEE ; Jae-Won CHOI ; Young-Ji LEE ; Nuree KANG ; Dongyun LEE
Korean Journal of Psychosomatic Medicine 2022;30(2):73-79
Objectives:
:Suicide is a global social problem. Social burden caused by suicide is gradually increasing. Various efforts have been made to prevent suicide. Lifestyle changes to western style, especially diet changes, have increased the risk for suicide. Therefore, in this study, we discussed diet as an adjuvant treatment for suicide.
Methods:
:In this review, we summarized the biochemical mechanism of suicide, and diet as a risk factor for suicide and diet as a protective factor through a web search.
Results:
:In this study, biochemical mechanisms for suicide were reviewed and diet as a risk factor and diet as a protective factor for suicide were investigated. It was confirmed that neurotoxic effects such as oxidative stress and inflammation in the neural system could increase the risk of suicide. Based on results of previous stud-ies on the relationship between suicide and diet, it was found that heavy use of alcohol, coffee, carbonated soft drink, and fast food were risk factors for suicide. Protective factors for suicide included antioxidants such as vitamin C, carotene, and anti-inflammatory agents such as omega-3 fatty acids found in seafood in large amounts.
Conclusions
:The only treatment for suicide is prevention. In this context, effectiveness, accessibility, and safety are important for preventing for suicide. Antioxidants and anti-inflammatory agents that are relatively safe and readily available to the public could be effective adjuvant treatments to decrease the risk of suicide. In addition, it is necessary to educate the public on reducing diets that could increase the risk of suicide
6.Dietary Carotene Intake and Suicidal Ideation in Korean Females: Analysis of Data From the Korea National Health and Nutrition Examination Survey (2012, 2013, and 2015)
Eunji LIM ; Bong-Jo KIM ; Cheol-Soon LEE ; Boseok CHA ; So-Jin LEE ; Ji-Yeong SEO ; Jae-Won CHOI ; Young-Ji LEE ; Nuree KANG ; Seung Chan KIM ; Dongyun LEE
Psychiatry Investigation 2023;20(10):897-903
Objective:
The suicide rate in Korea was the highest among countries in the Organisation for Economic Co-operation and Development in 2019. In a previous study, higher intake of vegetables and fruits was associated with a lower risk of suicidal ideation, and carotene-rich fruits and vegetables lowered the risk of depression. This study aimed to examine the direct relationship between carotene intake and suicidal ideation, adjusting for the effect on depression.
Methods:
This study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2012, 2013, and 2015. Carotene intake was assessed through a food intake frequency survey with a 24-hour recall. Suicidal ideation and depression were assessed using the mental health section of the KNHANES. We applied logistic regression to assess the relationship between carotene intake and suicidal ideation, adjusting for potential confounders.
Results:
A total of 5,480 females aged 19–64 years were included in this study. Carotene intake was significantly lower in the suicidal ideation group (3,034.5±1,756.4 μg/day) than in the nonsuicidal ideation group (3,225.4±1,795.1 μg/day) (p=0.015). We found a significant inverse association between carotene intake and the risk of suicidal ideation after adjusting for potential confounders (odds ratio=0.934, 95% confidence interval=0.873–0.999).
Conclusion
These results suggest that carotene intake may be inversely associated with the risk of suicidal ideation. Our findings may inform the development of new nutritional interventions to prevent increases in the risk of suicide worldwide.
7.Association Between Depressed Mood Changes and Physical Activity Among Adolescents Post COVID-19 Pandemic
Jina JANG ; Bong-Jo KIM ; Cheol-Soon LEE ; Boseok CHA ; So-Jin LEE ; Dongyun LEE ; Young-Ji LEE ; Eunji LIM ; Nuree KANG ; Jae-Won CHOI
Journal of the Korean Academy of Child and Adolescent Psychiatry 2023;34(4):242-249
Objectives:
Following the coronavirus disease 2019 (COVID-19) pandemic, adolescents have experienced decreased physical activity and a decline in mental health. This study analyzed the association between changes in depressed mood after the COVID-19 pandemic and physical activity among adolescents.
Methods:
The analysis was based on the results of the 17th Youth Health Behavior Online Survey conducted in 2021, which included 54848 middle and high school students in South Korea. Information on physical activity included low-intensity physical activity lasting >60 min/day, high-intensity physical activity, and strength training exercises. A logistic regression analysis was performed to evaluate the association between physical activity and changes in depression after the COVID-19 pandemic.
Results:
After adjusting for sociodemographic characteristics and previous depression, adolescents who performed strength training exercises more than once per week had a 0.95-fold lower risk (odds ratio [OR]=0.948, 95% confidence interval [CI]=0.905–0.994, p= 0.027) of increasing depression after the COVID-19 pandemic, while the risk of decreasing depression increased by 1.22-fold (OR=1.215, 95% CI=1.131–1.305, p<0.001). The results were not significant for low-intensity physical activity for >60 min/day and high-intensity physical activity.
Conclusion
Strength-training exercises are significantly associated with the prevention of depression among adolescents following the COVID-19 pandemic.
8.Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial
Se Hyun KIM ; Do-Un JUNG ; Do Hoon KIM ; Jung Sik LEE ; Kyoung-Uk LEE ; Seunghee WON ; Bong Ju LEE ; Sung-Gon KIM ; Sungwon ROH ; Jong-Ik PARK ; Minah KIM ; Sung Won JUNG ; Hong Seok OH ; Han-yong JUNG ; Sang Hoon KIM ; Hyun Seung CHEE ; Jong-Woo PAIK ; Kyu Young LEE ; Soo In KIM ; Seung-Hwan LEE ; Eun-Jin CHEON ; Hye-Geum KIM ; Heon-Jeong LEE ; In Won CHUNG ; Joonho CHOI ; Min-Hyuk KIM ; Seong-Jin CHO ; HyunChul YOUN ; Jhin-Goo CHANG ; Hoo Rim SONG ; Euitae KIM ; Won-Hyoung KIM ; Chul Eung KIM ; Doo-Heum PARK ; Byung-Ook LEE ; Jungsun LEE ; Seung-Yup LEE ; Nuree KANG ; Hee Yeon JUNG
Psychiatry Investigation 2024;21(7):762-771
Objective:
This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia.
Methods:
Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed.
Results:
Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea.
Conclusion
Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.