Effect of Vortioxetine on Alcohol Intake in C57BL/6 Mice / 생물치료정신의학

Objectives@#The effectiveness of drugs currently used in medication, which is important in the treatment of alcohol use disorders, is limited. Recently, ondansetron which acts as 5-HT3 receptor antagonist, has been studied and proved possibility as new medication for alcohol use disorder. Meanwhile, there are studies supporting that 5-HT1A receptors are related to addictive behavior. Considering those studies, we expect that vortioxetine, which acts as both 5-HT3 receptor antagonist and 5-HT1A receptor agonist, may be effective in treatment of alcohol use disorder. The purpose of this study is to examine the effect of vortioxetine on alcohol intake of C57BL/6 mice. @*Methods@#In this study C57BL/6 mice were randomly assigned to normal saline group, vortioxetine 10 mg/kg group and vortioxetine 1 mg/kg group. To study effect of vortioxetine on alcohol, water, food intake and body weight of mice, we administered each medication for 14 days. @*Results@#The overall alcohol intake was different between the three groups (PGroup=0.021), and alcohol intake in vortioxetine 10 mg/kg group was significantly lower than one in placebo group. Change across time points (PTime<0.001) and the interaction between group and time (PGroup×Time =0.016) were also significant. However, there were no significant differences between the three groups in water, food intake and body weight. @*Conclusions@#These results indicated that administration of high dose vortioxetine reduced alcohol intake of mice.Therefore, it is necessary to conduct clinical studies to examine the effectiveness of vortioxetine as a new treatment for alcohol use disorder.

Capsaicin Reduces Ethanol Consumption in C57BL/6 but not DBA/2 Mice

Objective@#Capsaicin, the pungent analgesic substance of hot peppers which produces a burning sensation and pain is known to affect Substance P and central opioid activities. This experiment was designed to test the effect of capsaicin on alcohol consumption in C57BL/6 and DBA/2 mice. These two strains are known to differ in both their alcohol consumption and their endogenous opioid distribution and response to alcohol. It is hypothesized that this effect may be mediated by both increases Substance P and decreases beta-endorphin. @*Methods@#After i.p. administration of 0.01 and 0.001 mg/kg of capsaicin with a vehicle or the vehicle alone as the control for eight days in C57BL/6 and DBA/2 mice on limited access alcohol model, Capsaicin’s effects on 2-hour alcohol, 22-hours water, 24-hours food intake and body weight were studied. @*Results@#In this study, as expected, C57BL/6 mice drank significantly more alcohol than DBA/2 mice under baseline conditions. Capsaicin at both doses tested significantly reduced baseline alcohol consumption in C57BL/6 but not DBA/2 mice. These effects were selective for alcohol as capsaicin did not disrupt food or water consumption. @*Conclusion@#These results demonstrate that capsaicin differentially affects those mechanisms underlying alcohol consumption in two strains of mice known to differ in their preference for and consumption of alcohol. This effect is hypothesized to be related to differences in the response of the endogenous opioid system.

Changes in Urine Osmolal Concentration with Lithium Treatment in Children and Youth with Bipolar Disorder / 신경정신의학

Objectives@#Bipolar disorder has a high rate of recurrence, which can cause problems such as declines in cognitive and social functions. Lithium is the primary medication for preventing recurrence, but the medication compliance is poor owing to side effects that include diarrhea, tremor, polyuria, polydipsia, diabetes insipidus, increased creatinine level, and weight gain. Polyuria and polydipsia also cause voluntary discontinuation of the medication. However, no domestic and international studies have evaluated the direct correlation between lithium therapy and polydipsia in pediatric patients. Therefore, we assessed this relationship by evaluating urine osmolality changes after lithium administration in pediatric patients. @*Methods@#This study focused on patients admitted to the Department of Psychiatry, Pusan National University Yangsan Hospital. Patients had bipolar disorder types I or II and other specified bipolar disorders based on the DSM-5, criteria at discharge from December 1, 2018, to April 31, 2020. Urine osmolarity changes from admission to discharge in the patients who used lithium for the first time after admission were reviewed. @*Results@#For 47 patients, the change in osmolality was statistically significant (mean, 203.32±280.68; p<0.001) and significantly higher in those aged <14 years than in those aged ≥14 years (p=0.038). Antipsychotic use and sex-related differences did not affect urine osmolality. @*Conclusion@#The first-time users of lithium had significantly reduced urine osmolality at discharge. Considering the lithium effect on the kidneys, a prospective study to identify the relationship between lithium use and polydipsia is necessary.

Changes in Urine Osmolal Concentration with Lithium Treatment in Children and Youth with Bipolar Disorder / 신경정신의학

Objectives@#Bipolar disorder has a high rate of recurrence, which can cause problems such as declines in cognitive and social functions. Lithium is the primary medication for preventing recurrence, but the medication compliance is poor owing to side effects that include diarrhea, tremor, polyuria, polydipsia, diabetes insipidus, increased creatinine level, and weight gain. Polyuria and polydipsia also cause voluntary discontinuation of the medication. However, no domestic and international studies have evaluated the direct correlation between lithium therapy and polydipsia in pediatric patients. Therefore, we assessed this relationship by evaluating urine osmolality changes after lithium administration in pediatric patients. @*Methods@#This study focused on patients admitted to the Department of Psychiatry, Pusan National University Yangsan Hospital. Patients had bipolar disorder types I or II and other specified bipolar disorders based on the DSM-5, criteria at discharge from December 1, 2018, to April 31, 2020. Urine osmolarity changes from admission to discharge in the patients who used lithium for the first time after admission were reviewed. @*Results@#For 47 patients, the change in osmolality was statistically significant (mean, 203.32±280.68; p<0.001) and significantly higher in those aged <14 years than in those aged ≥14 years (p=0.038). Antipsychotic use and sex-related differences did not affect urine osmolality. @*Conclusion@#The first-time users of lithium had significantly reduced urine osmolality at discharge. Considering the lithium effect on the kidneys, a prospective study to identify the relationship between lithium use and polydipsia is necessary.

A Comparative Study on the Cognitive and Clinical Characteristics of Childhood/Adolescent- and Adult-Onset of Bipolar Disorder / 생물치료정신의학

Objectives@#：Childhood/adolescent-onset of bipolar disorder presents functional impairments on emotional, academic, and social aspects. These impairments could continue into adulthood. However, there are few studies comparing cognitive function between childhood/adolescent- and adult-onset using psychological test. This study aims to improve understanding of childhood/adolescent-onset of bipolar disorder by comparing differences in cognitive function, clinical and demographic features between the two groups. @*Methods@#：This study was conducted on 145 patients diagnosed with bipolar disorder type I, II, and other specified bipolar disorder by DSM 5 at the time of discharge from 2016 to 2019 at the Department of Psychiatry, Pusan National University Yangsan Hospital. Demographic information, clinical data, and results of psychological tests (K-WISC-IV, K-WAIS-IV) were collected and reviewed. @*Results@#：Childhood/adolescent-onset group was significantly low in total potential IQ and in language understanding than adult-onset group (p=0.008 and p=0.013). The childhood/adolescent group had significantly more psychiatric comorbidities than the adult group (p<0.001). The average number of prescribed antipsychotic agents was 1.18 (SD= ±0.64) in the childhood/adolescent group, and 1.78 (SD=±0.82) in the adult group. The difference was statistically significant (p<0.001). @*Conclusion@#：Patients with childhood/adolescent-onset bipolar disorder have lower total potential IQ and language understanding comparing patients with adult-onset bipolar disorder. This highlights the importance of conducting a well-designed prospective study to find out more about the characteristics of childhood/adolescent-onset bipolar disorder.

Difference in Cognitive Function by First Onset Age of Alcohol Induced Blackout and Its Duration

OBJECTIVE: Alcohol-induced blackout (blackout) is a typical early symptom of cognitive impairment caused by drinking. However, the first onset age of blackout or the duration after onset of blackout has not been directly compared in previous studies. The purpose of this study was to investigate the differences in cognitive function to the first start age of blackouts and their duration. METHODS: Thirty-one male subjects were included in this study. Their age at the first blackout and the duration after the onset of blackout were investigated. Neuropsychological tests were conducted to determine their attention, memory, and executive function. Subjects were divided into three groups according to their age of the first onset blackout (group O1, 40 years). Subjects were also divided into three groups by duration after the onset of blackout (P1, 30 years). We then examined differences in neurocognitive function among these groups. RESULTS: O1 tended to have a lower memory score than O2 (F = 3.28, p = 0.053). Significant differences were observed in attention and executive function between groups P1 and P3 (Digit Span_backward: F = 6.07, p < 0.05; visual span_forward: F = 4.19, p < 0.05; executive intelligence quotient: F = 3.55, p < 0.05). CONCLUSION: Greater memory impairment was detected in subjects having an earlier age of the first blackout. The longer the duration after the onset of blackout, the more impaired their attention and executive function skills.

The Effect of Oral Administration of Black Sticky Rice with Giant Embryo on Brain GABA Concentrations

OBJECTIVE: Black sticky rice with giant embryo (BSRGE) contains high GABA content and affects alcohol-related indices among social drinkers, and alcohol intake and anxiety-related behavior of mice. However, it is unknown whether the intake of BSRGE affects GABAergic activity of brain directly. The purpose of this study is to elucidate the effect of oral administration of BSRGE on brain GABA concentrations compared with commercially available GABA compound and regular feeds. METHODS: Twenty-one male C57BL/6 mice were assigned to BSRGE, a regular feed (AIN-76) lacking GABA, and a regular feed containing GABA compound. After feeding freely for 48 h, the cortex and striatum were separated from the brain. An enzyme-linked immunosorbent assay was conducted to measure GABA and glutamate concentrations in mouse brain. RESULTS: The GABA concentration of the BSRGE group was higher than that of regular feed and GABA compound group (p<0.001). However, the GABA compound group showed no significant difference from the regular feed group (p=0.50). CONCLUSION: Intake of BSRGE containing high GABA content increased GABA concentrations in mouse brain compared with regular feed unlike GABA compound. The results of this study constitute an important basis for further investigations into the clinical applications of BSRGE.

Psychophysiological Characteristics of Insomnia Patients Measured by Biofeedback System / 수면정신생리

BACKGROUND AND OBJECTIVES: Insomnia is the most prevalent sleep disorder in the general population and is considered to be a disorder of hyperarousal. The aim of this study was to measure the psychophysiological responses in insomnia patients using a biofeedback system, and to compare them with results from normal healthy subjects. MATERIALS AND MATHODS: Eighty patients with primary insomnia (35 males and 45 females, average age 49.71 +/- 12.91 years) and 101 normal healthy controls (64 males and 37 females, average age 27.65 +/- 2.77) participated in this study. Electromyography (EMG), heart rate (HR), skin conductance (SC), skin temperature (ST), and respiratory rate (RR) were recorded using a biofeedback system during 5 phases (baseline, stress 1, recovery 1, stress 2, recovery 2) of a stress reactivity test, and average values were calculated. Difference in values between the two groups in each corresponding phase was analyzed with independent t-test, and change in values across phases of the stress reactivity test was analyzed with paired t-test (all two-tailed, p<0.05). RESULTS: Compared to normal controls, insomnia patients had higher EMG in all 5 phases (baseline : 7.72 +/- 3.88 microV vs. 4.89 +/- 1.73 microV, t = -6.06, p<0.001 ; stress 1 : 10.29 +/- 5.16 microV vs. 6.63 +/- 2.48 microV, t = -5.84, p<0.001 ; recovery 1 : 7.87 +/- 3.86 microV vs. 5.17 +/- 2.17 microV, t = -5.61, p<0.001 ; stress 2 : 10.22 +/- 6.07 microV vs. 6.98 +/- 2.98 microV, t = -4.37, p<0.001 ; recovery 2 : 7.88 +/- 4.25 microV vs. 5.17 +/- 1.99 microV, t = -5.27, p<0.001). Change in heart rate across phases of the stress reactivity test were higher in normal controls than in insomnia patients (stress 1-baseline : 6.48 +/- 0.59 vs. 3.77 +/- 0.59, t = 3.22, p = 0.002 ; recovery 1- stress 1 : -5.36 +/- 0.0.59 vs. -3.16 +/- 0.47, t = 2.91, p = 0.004 ; stress 2-recovery 1 : 8.45 +/- 0.61 vs. 4.03 +/- 0.47, t = 5.72, p<0.001 ; recovery 2-stress 2 : -8.56 +/- 0.65 vs. 4.02 +/- 0.51, t = -5.31, p<0.001). CONCLUSION: Psychophysiological profiles of insomnia patients in a stress reactivity test were different from those of normal healthy controls. These results suggest that the sympathetic nervous system is more highly activated in insomnia patients.