Association of opioid receptor gene polymorphisms with drinking severity and impulsivity related to alcohol use disorder in a Korean population

AIMS: Recent evidence suggests that the opioid system is implicated in the pathophysiology of alcohol use disorder (AUD). We aimed to examine the genetic influence of opioid receptors on susceptibility to AUD and its clinical and psychological characteristics including harmful drinking behavior and various aspects of impulsivity in AUD patients. METHODS: Three μ-opioid receptor gene (OPRM1) variants and two κ-opioid receptor gene (OPRK1) variants were examined in 314 male patients with AUD and 324 male controls. We applied the Alcohol Use Disorders Identification Test (AUDIT), Obsessive Compulsive Drinking Scale (OCDS), and Alcohol Dependence Scale. AUD patients also completed the stop-signal task, delay discounting task, balloon analogue risk task, and the Barratt Impulsiveness Scale version 11 (BIS-11). RESULTS: No significant differences in genotype distributions or haplotype frequencies were found between AUD patients and controls. However, OPRK1 SNP rs6473797 was significantly related to the severity of alcohol-related symptoms as measured by AUDIT and OCDS and a haplotype containing rs6473797 was also related to OCDS scores in AUD patients. For other psychological traits, OPRM1 SNP rs495491 was significantly associated with scores on the motor subfactor of the BIS-11. CONCLUSION: Genetic variations in opioid receptors may contribute to symptom severity and impulsivity in AUD patients.ope

Diversity in Surgical Decision Strategies for Adult Spine Deformity Treatment: The Effects of Neurosurgery or Orthopedic Training Background and Surgical Experience

OBJECTIVE: This study is aimed to investigate whether surgical strategies for adult spinal deformity (ASD) treatment differed among Korean physicians. METHODS: This study is retrospective questionnaire-based study. ASD is challenging to manage, with a broad range of clinical and radiological presentations. To investigate possible nationality- or ethnicity-related differences in the surgical strategies adopted for ASD treatment, the International Spine Study Group surveyed physicians' responses to 16 cases of ASD. We reviewed the answers to this survey from Korean physicians. Korean orthopedic surgeons (OS) and neurosurgeons (NS) received a questionnaire containing 16 cases and response forms via email. After reviewing the cases, physicians were asked to indicate whether they would treat each case with decompression or fusion. If fusion was chosen, physicians were also asked to indicate whether they would perform 3-column osteotomy. Retrospective chi-square analyses were performed to investigate whether the answers to each question differed according to training specialty or amount of surgical experience. RESULTS: Twenty-nine physicians responded to our survey, of whom 12 were OS and 17 were NS. In addition, 18 (62.1%) had more than 10 years of experience in ASD correction and were assigned to the M10 group, while 11 (37.9%) had less than 10 years of experience and were assigned to the L10 group. We found that for all cases, the surgical strategies favored did not significantly differ between OS and NS or between the M10 and L10 groups. However, for both fusion surgery and 3-column osteotomy, opinions were divided regarding the necessity of the procedures in 4 of the 16 cases. CONCLUSION: The surgical strategies favored by physicians were similar for most cases regardless of their training specialty or experience. This suggests that these factors do not affect the surgical strategies selected for ASD treatment, with patient clinical and radiological characteristics having greater importance.ope

A Validation Study of the Korean-Version of the Dimensional Obsessive-Compulsive Scale

Objectives This study was conducted to examine the reliability and validity of the Dimensional Obsessive-Compulsive Scale-Korean version (DOCS-K). Methods Fifty four individuals with obsessive-compulsive disorder (OCD) completed a battery of measures including the DOCS-K, Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Obsessive-Compulsive Inventory-Revised-Korean version (OCI-R-K), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Psychometric properties of the DOCS-K were analyzed. Results The Cronbach's α value for internal consistency of DOCS-K was in excellent range (0.91-0.95). The construct validity was analyzed on the basis of principal component analysis and 4-factor structure of the original scale was maintained. The DOCS-K total and subscale scores were more strongly correlated with those of other OC symptom-specific measures (convergent validity) than those of nonspecific depression or anxiety measures (discriminant validity). The DOCS-K total score was strongly correlated with total scores of Y-BOCS (r=0.64, p<0.01) and OCI-R-K (r=0.71, p<0.01). Correlations between the DOCS-K subscales and corresponding subscales of the OCI-R-K were stronger than correlations with the noncorresponding subscales : 1) DOCS-K Contamination and OCI-R-K Washing (r=0.69), 2) DOCS-K Responsibility and OCI-R-K Checking (r=0.54), 3) DOCS-K Unacceptable Thoughts and OCI-R-K Obsessing (r=0.73), 4) DOCS-K Symmetry and OCI-R-K Ordering (r=0.55). Conclusion This study revealed that the DOCS-K has good reliability and validity. Therefore, the DOCS-K can be used as a promising measure of dimensional OC symptoms in Korea.ope

Serum brain-derived neurotrophic factor remains elevated after long term follow-up of combat veterans with chronic post-traumatic stress disorder

Attempts to correlate blood levels of brain-derived neurotrophic factor (BDNF) with post-traumatic stress disorder (PTSD) have provided conflicting results. Some studies found a positive association between BDNF and PTSD diagnosis and symptom severity, while others found the association to be negative. The present study investigated whether serum levels of BDNF are different cross-sectionally between combat trauma-exposed veterans with and without PTSD, as well as whether longitudinal changes in serum BDNF differ as a function of PTSD diagnosis over time. We analyzed data of 270 combat trauma-exposed veterans (230 males, 40 females, average age: 33.29 ± 8.28 years) and found that, at the initial cross-sectional assessment (T0), which averaged 6 years after the initial exposure to combat trauma (SD=2.83 years), the PTSD positive group had significantly higher serum BDNF levels than the PTSD negative controls [31.03 vs. 26.95 ng/mL, t(268) = 3.921, p < 0.001]. This difference remained significant after excluding individuals with comorbid major depressive disorder, antidepressant users and controlling for age, gender, race, BMI, and time since trauma. Fifty-nine of the male veterans who participated at the first timepoint (T0) were re-assessed at follow-up evaluation (T1), approximately 3 years (SD=0.88 years) after T0. A one-way ANOVA comparing PTSD positive, "subthreshold PTSD" and control groups revealed that serum BDNF remained significantly higher in the PTSD positive group than the control group at T1 [30.05 vs 24.66 ng/mL, F(2, 56)= 3.420, p = 0.040]. Serum BDNF levels did not correlate with PTSD symptom severity at either time point within the PTSD group [r(128) = 0.062, p = 0.481 and r(28) = 0.157, p = 0.407]. Serum BDNF did not significantly change over time within subjects [t(56) = 1.269, p = 0.210] nor did the change of serum BDNF from T0 to T1 correlate with change in PTSD symptom severity within those who were diagnosed with PTSD at T0 [r(27) = -0.250, p = 0.192]. Our longitudinal data are the first to be reported in combat PTSD and suggest that higher serum BDNF levels may be a stable biological characteristic of chronic combat PTSD independent of symptom severity.ope

Comparison of Cervical Alignment and Clinical Outcomes in Patients with Os Odontoideum versus Non-Os Odontoideum after Atlantoaxial Fixation

Objective: The purpose of this study was to compare the effect of atlantoaxial fixation on cervical alignment and clinical outcomes in patients with os odontoideum (OO) versus non-os odontoideum (non-OO). Methods: A total of 119 patients who underwent atlantoaxial fixation for instability were identified between January 1998 and January 2014. Inclusion criteria included age more than 21 years and diagnosis of OO and non-OO. There were 22 OO patients, and 20 non-OO patients. Measuring the Oc-C1 Cobb angle, C1-2 Cobb angle, C2-7 Cobb angle, and C2-7 sagittal vertical axis (SVA) was assessed. Clinical outcome was assessment of suboccipital pain was determined using a visual analogue scale (VAS), and Japanese Orthopedic Association (JOA) scores were obtained in all patients pre- and postoperatively. Results: The preoperative C1-2 angle in the OO group (26.02°±10.53°) was significantly higher than the non-OO group (p=0.04). After C1-2 fixation, the OO group had significantly higher kyphotic change in the C1-2 angle (ΔC1-2) (3.2°±7.3° [OO] vs. -1.46°±7.21° [non-OO]) (p=0.04), and higher decrease in postoperative C2-7 SVA (ΔC2-7 SVA) (5.64±11.56 mm [OO] vs. -0.51± 6.57 mm [non-OO]) (p=0.04). Both groups showed improvements in the health related quality of life (HRQOL) after surgery based on the VAS and JOA score (p<0.001). Conclusion: After fixation, kyphotic angular change in atlantoaxial joint and decrease C2-7 SVA were marked in the OO group. Both the OO and non-OO groups improved in neurological function and outcome after surgery.ope

Discovery of Depression-Associated Factors From a Nationwide Population-Based Survey: Epidemiological Study Using Machine Learning and Network Analysis

Background: In epidemiological studies, finding the best subset of factors is challenging when the number of explanatory variables is large. Objective: Our study had two aims. First, we aimed to identify essential depression-associated factors using the extreme gradient boosting (XGBoost) machine learning algorithm from big survey data (the Korea National Health and Nutrition Examination Survey, 2012-2016). Second, we aimed to achieve a comprehensive understanding of multifactorial features in depression using network analysis. Methods: An XGBoost model was trained and tested to classify "current depression" and "no lifetime depression" for a data set of 120 variables for 12,596 cases. The optimal XGBoost hyperparameters were set by an automated machine learning tool (TPOT), and a high-performance sparse model was obtained by feature selection using the feature importance value of XGBoost. We performed statistical tests on the model and nonmodel factors using survey-weighted multiple logistic regression and drew a correlation network among factors. We also adopted statistical tests for the confounder or interaction effect of selected risk factors when it was suspected on the network. Results: The XGBoost-derived depression model consisted of 18 factors with an area under the weighted receiver operating characteristic curve of 0.86. Two nonmodel factors could be found using the model factors, and the factors were classified into direct (P<.05) and indirect (P≥.05), according to the statistical significance of the association with depression. Perceived stress and asthma were the most remarkable risk factors, and urine specific gravity was a novel protective factor. The depression-factor network showed clusters of socioeconomic status and quality of life factors and suggested that educational level and sex might be predisposing factors. Indirect factors (eg, diabetes, hypercholesterolemia, and smoking) were involved in confounding or interaction effects of direct factors. Triglyceride level was a confounder of hypercholesterolemia and diabetes, smoking had a significant risk in females, and weight gain was associated with depression involving diabetes. Conclusions: XGBoost and network analysis were useful to discover depression-related factors and their relationships and can be applied to epidemiological studies using big survey data.ope

Psychological factors associated with COVID-19 related anxiety and depression in young adults during the COVID-19 pandemic

Background: The coronavirus disease 2019 (COVID-19) pandemic and the corresponding lockdown have drastically changed our lives and led to high psychological distress and mental health problems. This study examined whether psychological factors such as loneliness, perfectionism, and health anxiety are associated with COVID-19 related anxiety and depression during the pandemic in young Korean adults, after controlling for various socio-demographic factors and early life stress. Methods: A total of 189 participants (58.2% women) completed a cross-sectional online survey including the Fear of COVID-19 Scale, Center for Epidemiologic Studies Depression Scale, 3-item Revised UCLA Loneliness Scale, Frost Multidimensional Perfectionism Scale, and Whiteley Index-6. Hierarchical linear regression analyses with three blocks were employed to identify the factors that contributed to COVID-19 related anxiety and depressive symptoms. Results: Hierarchical regression analyses showed that higher health anxiety was significantly associated with more severe COVID-19 related anxiety (standardized regression coefficient, β = 0.599, p < 0.001). Additionally, higher levels of loneliness (β = 0.482, p < 0.001), perfectionism (β = 0.124, p = 0.035), and health anxiety (β = 0.228, p < 0.001) were significantly associated with higher depression scores. The three psychological factors explained 32.8% of the total variance in depressive symptom scores, after taking all covariates into account. Conclusion: The results showed that health anxiety was a risk factor for both COVID-19 related anxiety and depression in young adults. Loneliness was the strongest predictor of depressive symptoms during the COVID-19 pandemic. These findings highlight the importance of identifying vulnerable individuals and encouraging psychological counselling and social connections to reduce the burden of psychiatric disorders during the pandemic. Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ope

Clinical Efficacy of Repetitive Transcranial Magnetic Stimulation for Treatment of Depression and Latest Trends in TMS Techniques

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique which can change cortical excitability in targeted area by producing magnetic field pulses with an electromagnetic coil. rTMS treatment has been used to treat various neuropsychiatric disorders including depression. In this review, we evaluate the literature on rTMS for depression by assessing its efficacy on different subtypes of depression and different technical parameters. In particular, we focus on the results of randomized clinical trials and meta-analyses for depression after the US Food and Drug Administration approval in 2008, which acknowledged its efficacy and acceptability. We also review the new forms of rTMS therapy including deep TMS, theta-burst stimulation, and magnetic seizure therapy (MST) that have been under recent investigation. High frequency rTMS over left dorsolateral prefrontal cortex (DLPFC), low frequency rTMS over right DLPFC, or bilateral rTMS is shown to be effective and acceptable in treatment for patients with non-psychotic, unipolar depression either as monotherapy or adjuvant. Deep TMS, theta-burst stimulation and MST are promising new TMS techniques which warrant further research.ope

A Prospective, Multi-Center, Double-Blind, Randomized Study to Evaluate the Efficacy and Safety of the Synthetic Bone Graft Material DBM Gel with rhBMP-2 versus DBM Gel Used during the TLIF Procedure in Patients with Lumbar Disc Disease

Objective: This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). Methods: This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. Results: The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. Conclusion: This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.ope

Association of PPM1G methylation with risk-taking in alcohol use disorder

Alcohol use disorder (AUD) is a chronic and relapsing disease with a substantial genetic influence. Given the recent discovery of the association of PPM1G methylation with alcohol use disorder (AUD) from a genome-wide methylation study, we sought to verify and extend the previous work of AUD-related impulsivity in a Korean population with AUD. A total of 244 men with AUD were assessed for psychological characteristics and behavioral impulsivity using stop signal task (response inhibition) and Balloon Analog Risk Task (risk-taking). Leukocyte DNA methylation at PPM1G was quantified using pyrosequencing. The effects of PPM1G methylation on severity of problematic drinking measured by Alcohol Use Disorder Identification Test (AUDIT) and multidimensional impulsivity were tested using linear regression analyses. Hypermethylation of PPM1G was significantly associated with risk-taking propensity among men with AUD. No significant association of PPM1G methylation was found to be associated with AUDIT scores and response inhibition. Our findings indicate that altered methylation of PPM1G may influence the impulsive choice of risk-taking in AUD. Further research is required in order to determine the role of PPM1G in the pathophysiology of AUD and multidimensional impulsivity.ope