Differential Gene Expression in the Hippocampi of Nonhuman Primates Chronically Exposed to Methamphetamine, Cocaine, or Heroin

Objective@#Methamphetamine (MA), cocaine, and heroin cause severe public health problems as well as impairments in neural plasticity and cognitive function in the hippocampus. This study aimed to identify the genes differentially expressed in the hippocampi of cynomolgus monkeys in response to these drugs. @*Methods@#After the monkeys were chronically exposed to MA, cocaine, and heroin, we performed large-scale gene expression profiling of the hippocampus using RNA-Seq technology and functional annotation of genes differentially expressed. Some genes selected from RNA-Seq analysis data were validated with reverse transcription-quantitative polymerase chain reaction (RT-qPCR). And the expression changes of ADAM10 protein were assessed using immunohistochemistry. @*Results@#The changes in genes related to axonal guidance (PTPRP and KAL1), the cell cycle (TLK2), and the regulation of potassium ions (DPP10) in the drug-treated groups compared to the control group were confirmed using RT-qPCR. Comparative analysis of all groups showed that among genes related to synaptic long-term potentiation, CREBBP and GRIN3A were downregulated in both the MA- and heroin-treated groups compared to the control group. In particular, the mRNA and protein expression levels of ADAM10 were decreased in the MA-treated group but increased in the cocaine-treated group compared to the control group. @*Conclusion@#These results provide insights into the genes that are upregulated and downregulated in the hippocampus by the chronic administration of MA, cocaine, or heroin and basic information for developing novel drugs for the treatment of hippocampal impairments caused by drug abuse.

Phentermine and Phendimetrazine-Induced Psychotic Disorder and Bipolar Disorder: A Case Series

Objectives@#Recently, weight loss has emerged as a national concern in South Korea, and this has resulted in an increase in the frequency of use of central nervous system (CNS)-stimulating appetite suppressants. This study aimed to collect cases of psychotic disorders and bipolar disorders triggered by phentermine and phendimetrazine and explore the clinical features and courses. @*Methods@#In this retrospective study, we analyzed the electronic medical records of patients and selected eight patients who developed psychotic symptoms and manic symptoms for the first time after taking phentermine and phendimetrazine. All cases were reviewed, and their clinical features and course were summarized. @*Results@#All eight patients developed psychotic symptoms, and one had accompanying manic symptoms. The final diagnosis was appetite-suppressant-induced psychotic disorder in four patients, schizophrenia in three, and appetite-suppressant-induced bipolar disorder in one. In addition, three patients were diagnosed as having substance-use disorder. The key psychotic symptoms of these patients were hallucinations and paranoia. @*Conclusions@#These case findings suggest that phentermine and phendimetrazine can cause psychotic disorder, bipolar disorder, or substance use disorder and that medical professionals and the public should practice caution when prescribing and using these drugs.

The Effect of Stress on Compulsive Sexual Behavior Disorder: Active Coping Strategy and Self-Control as Mediators

Objective@#The aim of this study was to verify the effects of stress on compulsive sexual behavior disorder and the mediating effects of active coping strategies and self-control. @*Methods@#A self-reporting scale was administered to 300 adults aged 20 to 39, and the collected data were analyzed. The measures used for the study included a perceived stress scale, the way of coping checklist, a brief self-control scale, and an online compulsive sexual behavior disorder scale. @*Results@#The correlations between stress and active coping strategy, stress and lack of self-control, and lack of self-control and compulsive sexual behavior disorder were -0.18 (p<0.01), 0.38 (p<0.01), and 0.26 (p<0.01), respectively. @*Conclusion@#First, stress level was positively correlated with compulsive sexual behavior disorder. Second, self-control completely mediates the relationship between stress and compulsive sexual behavior disorder. Third, self-control and active coping strategies had sequential mediating effects in that order.

The Effect of Stress on Internet Game Addiction Trends in Adults: Mindfulness and Conscientiousness as Mediators

Objective@#This study examined the mediating effect of mindfulness and consciousness among five factors on the effect of stress on Internet game addiction tendency. @*Methods@#An online survey was conducted on 400 men and women between their 20s and 40s across Korea. The scales used in the study were the Internet game addiction scale based on the DSM-5, Perceived Stress Scale, Mindfulness Scale, and Five-Factor Personality Scale. For data analysis, structural equation modeling was conducted, and Sobel verification was carried out to verify the significance of the mediating effects. @*Results@#The results of the study are as follows: Stress showed a positive correlation with Internet game addiction tendency, mindfulness mediated the effect of stress on Internet game addiction tendency. @*Conclusion@#Of the five personality factors, conscientiousness also mediated the effect of stress on Internet game addiction tendency. This study highlights the need for further research for individuals with game addiction tendency.

Reduced Volume of a Brainstem Substructure in Adolescents with Problematic Smartphone Use

Objectives@#Despite the growing concern regarding the adverse effects related to problematic smartphone use (PSU), little is known about underlying morphologic changes in the brain. The brainstem is a deep brain structure that consists of several important nuclei associated with emotions, sensations, and motor functions. In this study, we sought to examine the difference in the volume of brainstem substructures among adolescents with and without PSU. @*Methods@#A total of 87 Korean adolescents participated in this study. The PSU group (n=20, age=16.2±1.1, female:male=12:8) was designated if participants reported a total Smartphone Addiction Proneness Scale (SAPS) score of ≥42, whereas the remaining participants were assigned to the control group (n=67, age=15.3±1.7, female:male=19:48). High-resolution T1 magnetic resonance imaging was performed, and the volume of each of the four brainstem substructures [midbrain, pons, medulla, and superior cerebellar peduncle (SCP)] was measured. Analysis of covariance was conducted to reveal group differences after adjusting for effects of age, gender, whole brainstem volume, depressive symptoms, and impulsivity. @*Results@#The PSU group showed a significantly smaller volume of the SCP than the control group (F=8.273, p=0.005). The volume of the SCP and the SAPS score were negatively correlated (Pearson’s r=-0.218, p=0.047). @*Conclusion@#The present study is the first to reveal an altered volume of the brainstem substructure among adolescents with PSU. This finding suggests that the altered white matter structure in the brainstem could be one of the neurobiological mechanisms underlying behavioral changes in PSU.

Reduced Volume of a Brainstem Substructure in Adolescents with Problematic Smartphone Use

Objectives@#Despite the growing concern regarding the adverse effects related to problematic smartphone use (PSU), little is known about underlying morphologic changes in the brain. The brainstem is a deep brain structure that consists of several important nuclei associated with emotions, sensations, and motor functions. In this study, we sought to examine the difference in the volume of brainstem substructures among adolescents with and without PSU. @*Methods@#A total of 87 Korean adolescents participated in this study. The PSU group (n=20, age=16.2±1.1, female:male=12:8) was designated if participants reported a total Smartphone Addiction Proneness Scale (SAPS) score of ≥42, whereas the remaining participants were assigned to the control group (n=67, age=15.3±1.7, female:male=19:48). High-resolution T1 magnetic resonance imaging was performed, and the volume of each of the four brainstem substructures [midbrain, pons, medulla, and superior cerebellar peduncle (SCP)] was measured. Analysis of covariance was conducted to reveal group differences after adjusting for effects of age, gender, whole brainstem volume, depressive symptoms, and impulsivity. @*Results@#The PSU group showed a significantly smaller volume of the SCP than the control group (F=8.273, p=0.005). The volume of the SCP and the SAPS score were negatively correlated (Pearson’s r=-0.218, p=0.047). @*Conclusion@#The present study is the first to reveal an altered volume of the brainstem substructure among adolescents with PSU. This finding suggests that the altered white matter structure in the brainstem could be one of the neurobiological mechanisms underlying behavioral changes in PSU.

The Effect of Stress on Internet Game Addiction Trends in Adults: Mindfulness and Conscientiousness as Mediators

Objective@#This study examined the mediating effect of mindfulness and consciousness among five factors on the effect of stress on Internet game addiction tendency. @*Methods@#An online survey was conducted on 400 men and women between their 20s and 40s across Korea. The scales used in the study were the Internet game addiction scale based on the DSM-5, Perceived Stress Scale, Mindfulness Scale, and Five-Factor Personality Scale. For data analysis, structural equation modeling was conducted, and Sobel verification was carried out to verify the significance of the mediating effects. @*Results@#The results of the study are as follows: Stress showed a positive correlation with Internet game addiction tendency, mindfulness mediated the effect of stress on Internet game addiction tendency. @*Conclusion@#Of the five personality factors, conscientiousness also mediated the effect of stress on Internet game addiction tendency. This study highlights the need for further research for individuals with game addiction tendency.

Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys

Objective@#The aim of this study was to investigate differentially expressed genes and their functions in the hippocampus and striatum after heroin administration in cynomolgus macaques of different ages. @*Methods@#Cynomolgus monkeys were divided by age as follows: 1 year (A1, n = 2); 3 to 4 years (A2, n = 2); 6 to 8 years (A3, n = 2); and older than 11 years (A4, n = 2). After heroin was injected intramuscularly into the monkeys (0.6 mg/kg), we performed large-scale transcriptome profiling in the hippocampus (H) and striatum (S) using RNA sequencing technology. Some genes were validated with real-time quantitative PCR. @*Results@#In the hippocampus, the gene expression of A1H was similar to that of A4H, while the gene expression of A2H was similar to that of A3H. Genes associated with the mitogen-activated protein kinase signaling pathway (STMN1, FGF14, and MAPT) and -aminobutyric acid-ergic synapses (GABBR2 and GAD1) were differentially expressed among control and heroin-treated animals. Differential gene expression between A1S and A4S was the least significant, while differential gene expression between A3S and A2S was the most significant. Genes associated with the neurotrophin signaling pathway (NTRK1 and NGFR), autophagy (ATG5), and dopaminergic synapses (AKT1) in the striatum were differentially expressed among control and heroin-treated animals. @*Conclusion@#These results suggest that even a single heroin exposure can cause differential gene expression in the hippocampus and striatum of nonhuman primates at different ages.

Dementia Research Using Healthcare Big Data

No abstract available.

Medical Big Data Is Not Yet Available: Why We Need Realism Rather than Exaggeration

Most people are now familiar with the concepts of big data, deep learning, machine learning, and artificial intelligence (AI) and have a vague expectation that AI using medical big data can be used to improve the quality of medical care. However, the expectation that big data could change the field of medicine is inconsistent with the current reality. The clinical meaningfulness of the results of research using medical big data needs to be examined. Medical staff needs to be clear about the purpose of AI that utilizes medical big data and to focus on the quality of this data, rather than the quantity. Further, medical professionals should understand the necessary precautions for using medical big data, as well as its advantages. No doubt that someday, medical big data will play an essential role in healthcare; however, at present, it seems too early to actively use it in clinical practice. The field continues to work toward developing medical big data and making it appropriate for healthcare. Researchers should continue to engage in empirical research to ensure that appropriate processes are in place to empirically evaluate the results of its use in healthcare.

The Relationship between Depression, Attention Deficit/Hyperactivity Disorder, and Internet Gaming Disorder Through Mediation Model

OBJECTIVES: Internet gaming disorder (IGD) is associated with attention deficit/hyperactivity disorder (ADHD) or depression etc. We tried to examine the mediating effects of depression in the relationship between ADHD and IGD.METHODS: This study was conducted on 2000 people who participated in on-line survey among 14–39 year-old men and women in 2017. And we clarified the relationship among IGD, ADHD, and depression and tested the mediation model. The mean and standard deviation of the main variables were calculated and correlation analysis was performed to confirm the relationship among the main variables. In order to test the mediating effect of depression on the relationship between ADHD and IGD, the structural equation model was implemented using AMOS 21 (IBM).RESULTS: There were significant correlations among the variables; IGD, ADHD and depression. Depression had a mediating effect 0.23 (95% confidence interval : 0.17–0.28) in the relationship between IGD and ADHD.CONCLUSIONS: This study showed that depression can mediate ADHD and IGD. Therefore, the evaluation and management of depression and ADHD should be included in the diagnosis and treatment of IGD.

Smartphone Addiction in Japanese College Students: Usefulness of the Japanese Version of the Smartphone Addiction Scale as a Screening Tool for a New Form of Internet Addiction

OBJECTIVE@#Smartphone use is pervasive among youth in Japan, as with many other countries, and is associated with spending time online and on social media anywhere at any time. This study aimed to test a Japanese version of the Smartphone Addiction Scale-Short Version (SAS-SV) among Japanese college students.@*METHODS@#The subjects of this study were 602 college students in Japan. The study questionnaire consisted of questions about demographics (age, gender etc.), possession of a smartphone, internet use [length of internet use on weekdays and weekend, favorite social networking service (SNS) etc.], Young’s Internet Addiction Test (IAT), and the Smartphone Addiction Scale-Short Version (SAS-SV) translated into Japanese.@*RESULTS@#There was a total of 573 respondents (180 male, 393 female) who completed the questionnaire (mean 19.3±1.3 years). LINE was the most popular social media platform (52.0%) followed by Twitter (36.3%). The overall Internet Addiction Test (IAT) score was 45.3±13.2, with 4.5% classified as having severe addiction (IAT ≥70). The mean SAS-SV scores were 24.4±10.0 for males and 26.8±9.9 for females. Based on proposed cutoff scores, 22.8% of males and 28.0% of females screened positive for smartphone addiction. The total scores of the SAS-SV and the IAT was correlated significantly.@*CONCLUSION@#As the number of smartphone users becomes higher, problems related to smartphone use also become more serious. Our results suggest that the Japanese version of SAS-SV may assist in early detection of problematic use of smartphones.

Transitions in Problematic Internet Use: A One-Year Longitudinal Study of Boys

OBJECTIVE: Longitudinal studies may help elucidate the factors associated with Problematic Internet Use (PIU); however, little prospective research has been conducted on the subject. The aim of the current study was to prospectively examine PIU in children/adolescents and identify the possible risk factors associated with transitions in PIU severity. METHODS: 650 middle-school boys were surveyed at two points one year apart and assessed for PIU using the Internet Addiction Proneness Scale for Youth (KS-II) and on other psychological characteristics. RESULTS: We found that 15.3% at baseline and 12.4% at one year met the criteria for at-risk/high-risk PIU (ARHRPIU). Both the persistent-ARHRPIU and emerging-ARHRPIU groups revealed greater depressive, motor impulsive, and smart-phone-addiction tendencies than the remitting-ARHRPIU group or the persistent low-risk group. In addition, we found that individuals exhibiting higher hyperkinetic attention-deficit/hyperactivity disorder (ADHD) scores were less likely to remit from ARHRPIU, and that individuals exhibiting more ADHD-related cognitive dysfunction and reporting fewer Internet-game-free days were more likely to demonstrate an emergence of ARHRPIU. CONCLUSION: The present findings support previous studies in that specific negative-health features are linked to transitions in ARHRPIU. Furthermore, these findings suggest that intervention is needed and may be best targeted at specific groups of youths.

Altered Plasma Levels of Glial Cell Line-Derived Neurotrophic Factor in Patients with Internet Gaming Disorder: A Case-Control, Pilot Study

Glial cell line-derived neurotrophic factor (GDNF) has been reported to be involved in negatively regulating the effects of addictive disorders. The objective of this study was to investigate alterations in the levels of GDNF in patients with Internet gaming disorder (IGD) and to assess the relationship between GDNF levels and the severity of IGD indices. Nineteen male patients with IGD and 19 sexmatched control subjects were evaluated for alteration of plasma GDNF levels and for relationship between GDNF levels and clinical characteristics of Internet gaming, including the Young's Internet Addiction Test (Y-IAT). The GDNF levels were found to be significantly low in patients with IGD (103.2±62.0 pg/mL) compared with the levels of controls (245.2±101.6 pg/mL, p<0.001). GDNF levels were negatively correlated with Y-IAT scores (Spearman's rho=-0.645, p=<0.001) and this negative correlation remained even after controlling for multiple variables (r=-0.370, p=0.048). These findings support the assumed role of GDNF in the regulation of IGD.

Gender-Specific Association between Alcohol Consumption and Stress Perception, Depressed Mood, and Suicidal Ideation: The 2010–2015 KNHANES

OBJECTIVE: Alcohol drinking can cause various psychiatric and medical diseases. Although women generally consume less alcohol than men, they may be at a greater risk for alcohol-related psychological distress. The aim of the current study is to evaluate whether the association between alcohol consumption and psychological distress, including stress, depressed mood, and suicidal ideation and the risks of psychological distress differ based on gender. METHODS: The cross-sectional study included 31,657 participants (17,915 women and 13,742 men) from the 2010–2013 and 2015 Korea National Health and Nutrition Examination Survey. Alcohol drinking and Alcohol Use Disorders Identification Test (AUDIT) levels were assessed for evaluating the amount of alcohol intake and alcohol-related problems. Self-perception of stress, depressed mood, and suicidal ideation were assessed for evaluating psychological distress. Odds ratio and 95% confidence intervals for psychological distress were calculated using multiple logistic regression models. RESULTS: The risks of psychological distress were not significantly associated with drinking level in both sexes. However, the risks of psychological distress were associated with an increase in AUDIT levels, and there were gender differences in the psychological consequences of alcohol-related problems. The association was more drastic in women, and women showed a significant association even though the severity of drinking problem was low with the exception of stress perception. CONCLUSION: The risks of psychological distress were associated with the severity of alcohol-related problems and women were more likely to be susceptible. Therefore, it is recommended that women even at low-risk for problematic drinking should be screened for psychological distress.

Prevalence Risk of Metabolic Syndrome Associated with Alcohol Use Behavior in Korean Women

OBJECTIVE: Considerable research has been conducted on the relationship between alcohol consumption and metabolic syndrome. Although various standards for the amount and frequency of alcohol consumption have been suggested, a tool to measure individual alcohol use behavior against a consistent standard is required. Moreover, the association of alcohol use behavior with health should be examined on the basis of such a standard. In this study, we examined the relationships between alcohol use behavior according to the Alcohol Use Disorders Identification Test (AUDIT) and metabolic syndrome and its components in Korean women. METHODS: This study utilized data from the fifth Korean National Health and Nutrition Examination Survey, which was administered from 2010 through 2012. We investigated the relationships between alcohol use behavior and metabolic syndrome and its components in a sample of 2,906 women by using analysis of covariance and logistic regression analysis. RESULTS: After adjusting for confounding variables, alcohol use behavior was significantly associated with metabolic syndrome [odds ratio (OR) 2.877; 95% confidence interval (CI) 1.523–5.435 in the problem use group]. AUDIT score also was significantly related to abdominal obesity (OR 2.263; 95% CI 1.704–4.459 in the problem use group), hypertension (OR 3.377; 95% CI 1.871–6.095 in the problem use group), hypertriglyceridemia (OR 3.204; 95% CI 1.800–5.702 in the problem use group), and impaired fasting glucose (OR 3.034; 95% CI 1.721–5.348 in the problem use group). CONCLUSION: In this study, positive associations were observed between AUDIT score and risk of metabolic syndrome and its components.

Decreased Serum Glutamate Levels in Male Adults with Internet Gaming Disorder: A Pilot Study

OBJECTIVE: Alteration in glutamatergic neurotransmission and dopaminergic dysfunction has been implicated in both the initiation and expression of addiction related behaviors. This pilot study was aimed to investigate the serum levels of glutamate and dopamine in adults with internet gaming disorder (IGD). METHODS: We measured serum levels of glutamate and dopamine in male participants with IGD (n=26) and age-matched healthy controls (n=25). Clinical interviews were performed to identify IGD and to rule out psychiatric comorbidities. Serum levels of glutamate and dopamine were examined by enzyme immunoassays using ELISA Kits. RESULTS: Serum levels of glutamate were lower among IGD than control (IGD: 24.184±12.303 μg/ml; control: 33.676±12.413μg/ml; t=2.742, p=0.008), while levels of dopamine did not differ between. Serum glutamate and dopamine levels did not correlate with gaming hours and exposure to game in the IGD group. But serum glutamate levels were positively correlated with the dopamine levels (r=0.360, p=0.013). CONCLUSION: Our results suggest that altered glutamatergic neurotransmission may contribute to the pathophysiology of IGD.

Effect of Stress and Serotonin-Transporter-Linked Polymorphic Region Variants on Internet Gaming Disorder in Korean Adults

OBJECTIVES: Internet gaming disorder (IGD) is known to be related to stress and the serotonin-transporter-linked polymorphic region (5-HTTLPR) that is known to be associated with stress and has been studied to affect various psychiatric illness outbreaks. We tried to examine the relationship between stress, 5-HTTLPR and IGD. METHODS: A total of 59 participants with IGD, diagnosed according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria and 67 normal controls (NC) were enrolled. The IGD group and the NC were compared using chisquare test and independent sample t-test, and logistic regression analysis was used to examine the relationship between stress, the 5-HTTLPR, and IGD. RESULTS: The mean scores for anxiety, impulsivity and stress were significantly higher in the IGD group than in the NC. In addition, there was a significant association between stress and IGD [odds ratio (OR) = 1.172, 95% confidence interval (CI) = 1.008–1.362]. CONCLUSIONS: This study showed that stress would affect IGD. Therefore, the evaluation and management of stress should be included in the diagnosis and treatment of IGD.

Reliability and Validity of the Korean Version of the General-Food Craving Questionnaire-Trait for Children

OBJECTIVE: The General-Food Craving Questionnaire-Trait (G-FCQ-T) is a validated, assessment scale for food craving. The aim of this study was to measure its reliability and validity for Korean children. METHODS: A total of 172 children (94 boys and 78 girls) were selected to fill out a set of questionnaires, including the G-FCQ-T, the Children's version of the Dutch Eating Behavior Questionnaire (DEBQ-C), and the Three-Factor Eating Questionnaire (TFEQ) in the Korean language. RESULTS: The internal consistency (Cronbach's alpha=0.933) and test-retest reliability (r=0.653) were satisfactory. The G-FCQ-T showed a significantly positive correlation with the DEBQ-C (r=0.560) and the TFEQ (r=0.397). The optimum cutoff score of the G-FCQ-T set by Receiver Operating Characteristics analysis was 51, with sensitivity and specificity of 0.833 and 0.825, respectively, for children. CONCLUSION: The G-FCQ-T showed good reliability and validity for assessing food craving for children and could become a practial instrument in clinical and research settings.

The OAuth 2.0 Web Authorization Protocol for the Internet Addiction Bioinformatics (IABio) Database

Internet addiction (IA) has become a widespread and problematic phenomenon as smart devices pervade society. Moreover, internet gaming disorder leads to increases in social expenditures for both individuals and nations alike. Although the prevention and treatment of IA are getting more important, the diagnosis of IA remains problematic. Understanding the neurobiological mechanism of behavioral addictions is essential for the development of specific and effective treatments. Although there are many databases related to other addictions, a database for IA has not been developed yet. In addition, bioinformatics databases, especially genetic databases, require a high level of security and should be designed based on medical information standards. In this respect, our study proposes the OAuth standard protocol for database access authorization. The proposed IA Bioinformatics (IABio) database system is based on internet user authentication, which is a guideline for medical information standards, and uses OAuth 2.0 for access control technology. This study designed and developed the system requirements and configuration. The OAuth 2.0 protocol is expected to establish the security of personal medical information and be applied to genomic research on IA.