Psychotropic Medications Promote Time-Dependent Reduction of Suicidal Ideation in Mood Disorder: A Prospective Cohort Study.

BACKGROUND: Despite a plethora of research on the topic, there is still no solid evidence that pharmacological treatment actually reduces the risk of suicide in patients with mental illness. In this study, we aimed to assess the effect of psychotropic medications on suicidal ideation in patients with major depressive disorder (MDD) and bipolar disorder (BPD) in two age groups: less than 25 years and 25 years and older. METHODS: We analyzed 312 patients with mood disorders with current suicidal thoughts or recent suicide attempts. We followed the participants from baseline for 6 months and assessed changes in suicidal ideation with Columbia-Suicide Severity Rating Scale (C-SSRS). The effect of psychotropic drug administration on suicidal ideation over time was analyzed using a linear mixed model. RESULTS: In patients aged 25 years and older with mood disorders, suicidal ideation was more severe when using psychotropic drugs than when not using them. However, suicidal ideation decreased rapidly over time. The time-dependent reduction in suicidal ideation was accelerated when using antidepressants and sedatives/hypnotics in adult MDD, and when using mood stabilizers in adult BPD. However, this effect was not observed in participants aged less than 25 years. CONCLUSION: Adequate psychotropic medication may reduce suicidal ideation in patients with mood disorders aged 25 years and older. Additional research on psychotropic drugs is needed to effectively reduce the risk of suicide among children and adolescents with mood disorders.

Can Pre-Transplant Psychometric Testing Predict Tacrolimus Intrapatient Variability After Living Kidney Transplantation?

OBJECTIVE: Tacrolimus intrapatient variability (Tac IPV) has been considered a marker for post-graft risk. We investigated pre-transplant psychometric testing to predict Tac IPV after living kidney transplantation. METHODS: Minnesota Multiphasic Personality Inventory-2 (MMPI-2) examined during pre-transplant evaluation by 102 recipients were analyzed. Subjects were divided into two groups, low IPV (L-IPV) and high IPV (H-IPV), by cutoffs of Tac IPV: median of 24 and value of 30. T-scores of MMPI-2 scales were used to analyze difference between L-IPV and H-IPV using independent t-tests. Stepwise multiple logistic regression was used to test whether MMPI-2 scales affected Tac IPV. Confusion matrix of logistic regression was used to explain statistical power. Cutoff values of significant scales for H-IPV were analyzed by constructing receiver operating characteristic curves. RESULTS: Hysteria (Hy) and depression (D) scale scores and Tac IPV were associated in IPV 24 (odds ratio [OR]: 1.08, p<0.01 for Hy; OR: 0.93, p<0.01 for D) and IPV 30 models (OR: 1.09, p<0.01 for Hy; OR: 0.92, p<0.01 for D). Paranoia (Pa) scale scores were associated with Tac IPV in IPV 24 model (OR=1.10, p<0.01) and were significantly higher in H-IPV 24 (p<0.01). F1 scores of confusion matrix in IPV 24 and 30 models were 0.70 and 0.71, respectively. Cutoffs of Hy, D, and Pa scales were 51, 57, and 47, respectively. CONCLUSION: MMPI-2 profile is suggested as a predictor for high Tac IPV after living kidney transplantation.

Development and external validation of a logistic and a penalized logistic model using machine-learning techniques to predict suicide attempts: A multicenter prospective cohort study in Korea.

Despite previous efforts to build statistical models for predicting the risk of suicidal behavior using machine-learning analysis, a high-accuracy model can lead to overfitting. Furthermore, internal validation cannot completely address this problem. In this study, we created models for predicting the occurrence of suicide attempts among Koreans at high risk of suicide, and we verified these models in an independent cohort. We performed logistic and penalized regression for suicide attempts within 6 months among suicidal ideators and attempters in The Korean Cohort for the Model Predicting a Suicide and Suicide-related Behavior (K-COMPASS). We then validated the models in a test cohort. Our findings indicated that several factors significantly predicted suicide attempts in the models, including young age, suicidal ideation, previous suicidal attempts, anxiety, alcohol abuse, stress, and impulsivity. The area under the curve and positive predictive values were 0.941 and 0.484 after variable selection and 0.751 and 0.084 in the test cohort. The corresponding values for the penalized regression model were 0.943 and 0.524 in the original training cohort and 0.794 and 0.115 in the test cohort. The prediction model constructed through a prospective cohort study of the suicide high-risk group showed satisfactory accuracy even in the test cohort. The accuracy with penalized regression was greater than that with the "classical" logistic model.

Development of a Guideline for Antipsychotic-induced Hyperprolactinemia in Korea Using the ADAPTE Process.

Objective: To develop an evidence-based guideline for the diagnosis and treatment of antipsychotic-induced hyperprolactinemia by adapting existing high-quality clinical guidelines with a view to improve the clinical symptoms and long-term quality of life of patients by providing appropriate management. Methods: This guideline was developed according to the ADAPTE methodology. The adaptation process included determining key health questions, systematically searching and screening guidelines, evaluating the quality and contents of these guidelines, deriving recommendations for key questions, and performing a peer review. The selection criteria for the guideline search were (1) evidence-based guidelines, (2) published within the last 5 years, and (3) written in English or Korean. Results: After evaluating the quality and content, we finally selected three guidelines for adaptation. The final output of the development process was 25 recommendations for 10 key questions. We adopted the Agency for Health Research Quality methodology and presented the level of evidence from levels I to IV. In addition, we defined the recommendation grades from grade A (strongly recommended) to D (no recommendation) based on the level of evidence and clinical significance of the recommendation. Conclusion: The development and dissemination of the adapted guideline is expected to increase the certainty of medical decision making and improve the quality of medical care. Further studies on the effectiveness and applicability of the developed guideline are necessary.

Effect of multimodal intervention care on cachexia in patients with advanced cancer compared to conventional management (MIRACLE): an open-label, parallel, randomized, phase 2 trial.

BACKGROUND: Cancer cachexia (CC) is a multifactorial process characterized by progressive weight loss, muscle mass, and fat tissue wasting, which adversely affects the quality of life and survival of patients with advanced stages of cancer. CC has a complex and multifactorial pathophysiology, and there is no established standard treatment. Therefore, it is often irreversible and a single treatment modality is unlikely to suppress its progression. We are conducting a randomized trial to investigate the efficacy and safety of a multimodal intervention compared to the best supportive care for patients who received palliative chemotherapy. METHODS: Patients with lung or gastrointestinal cancers undergoing palliative chemotherapy are eligible. Patients are randomized into a multimodal intervention care (MIC) arm versus a conventional palliative care (CPC) arm. MIC includes ibuprofen, omega-3-fatty acid, oral nutritional supplement, weekly physical, psychiatric assessment, nutritional counseling, and complementary and alternative medicine. CPC includes basic nutritional counseling and megestrol acetate as needed (i.e., anorexia ≥ grade 2). All interventions are performed for 12 weeks per subject. The co-primary outcomes are change (kg) in total lean body mass and handgrip strength (kg) from the baseline. A total of 112 patients will be assigned to the two arms (56 in each group). DISCUSSION: The purpose of this study is to evaluate the effect of MIC in preventing or alleviating CC in patients who underwent palliative chemotherapy. As there is no established single treatment for CC, it is expected that the results of this clinical trial will provide new insights to significantly improve the quality of life of patients with cancer. Considering the complex mechanisms of cachexia, the effect of MIC rather than a single specific drug is more promising. In this study, we did not overly restrict the type of cancer or chemotherapy. Therefore, we attempted to measure the effects of complex interventions while preserving clinical situations. Thus, it is expected that the results of this study can be applied effectively to real-world practice. TRIAL REGISTRATION: This clinical trial was registered in the Clinical Research Information Service (KCT0004967), Korean Clinical Trial Registry on April 27, 2020, and ClinicalTrial.gov (NCT04907864) on June 1, 2021.

Association between Unc-51-like autophagy activating kinase 2 gene polymorphisms and schizophrenia in the Korean population.

ABSTRACT: Accumulating evidence indicates that the autophagy process is involved in the pathogenesis of schizophrenia. Autophagy plays a fundamental role in neuronal survival and function, and autophagy-related genes have been suggested to be associated with the pathogenesis of schizophrenia. The Unc-51-like autophagy activating kinase 2 (ULK2) gene has been implicated in autophagy regulation; therefore, we hypothesized that ULK2 polymorphisms may be associated with schizophrenia susceptibility.This study explored the association between polymorphisms of ULK2 and schizophrenia.Two single nucleotide polymorphisms (SNPs) (rs55730189 and rs150122) of ULK2 were genotyped in 279 patients with schizophrenia and 403 healthy individuals using Fluidigm SNPtype assays. We analyzed the genotype distribution of 2 SNPs and haplotypes between patients with schizophrenia and control subjects.The T allele frequency of rs55730189 showed a significant association between patients with schizophrenia and control subjects (P = .003). Genotype frequencies of rs55710189 were found to be significantly different between patients with schizophrenia and control subjects (odds ratio = 6.89, 95% confidence interval = 1.91-24.90, P < .001 in the dominant model [C/T + T/T vs C/C], OR = 6.50, 95% confidence interval = 1.83-23.01, P < .001 in the log-additive model (C/T vs T/T vs C/C)]. In haplotype analysis, the TT haplotype for these 2 SNPs was significantly associated with schizophrenia (P < .001, χ2 = 12.231).Our findings suggest that specific ULK2 polymorphisms may be associated with susceptibility to schizophrenia in the Korean population.

Identification of Brain Damage after Seizures Using an MR-Based Electrical Conductivity Imaging Method.

Previous imaging studies have shown the morphological malformation and the alterations of ionic mobility, water contents, electrical properties, or metabolites in seizure brains. Magnetic resonance electrical properties tomography (MREPT) is a recently developed technique for the measurement of electrical tissue properties with a high frequency that provides cellular information regardless of the cell membrane. In this study, we examined the possibility of MREPT as an applicable technique to detect seizure-induced functional changes in the brain of rats. Ultra-high field (9.4 T) magnetic resonance imaging (MRI) was performed, 2 h, 2 days, and 1 week after the injection of N-methyl-D-aspartate (NMDA; 75 mg/kg). The conductivity images were reconstructed from B1 phase images using a magnetic resonance conductivity imaging (MRCI) toolbox. The high-frequency conductivity was significantly decreased in the hippocampus among various brain regions of NMDA-treated rats. Nissl staining showed shrunken cell bodies and condensed cytoplasm potently at 2 h after NMDA treatment, and neuronal cell loss at all time points in the hippocampus. These results suggest that the reduced electrical conductivity may be associated with seizure-induced neuronal loss in the hippocampus. Magnetic resonance (MR)-based electrical conductivity imaging may be an applicable technique to non-invasively identify brain damage after a seizure.

Association between the promoter haplotype of RTN4 gene and schizophrenia in a Korean population.

Previous studies have suggested the involvement of Nogo-A/RTN4 in the pathogenesis of schizophrenia. We investigated an association between the promoter haplotypes of RTN4 comprised of rs1348528-rs1822618-rs2241958 and schizophrenia. A significant association between the rare TGA haplotype and schizophrenia was shown (p < 0.0001). Additionally, the promoter activity was profoundly decreased by the TGA haplotype. These results suggested that the TGA haplotype of RTN4 may contribute to the susceptibility of schizophrenia.

Economic burden of eating disorders in South Korea.

BACKGROUND: Few studies have investigated the epidemiology of eating disorders using national representative data. In this study, we investigated the treatment prevalence and economic burden of eating disorders in South Korea. METHODS: The aim of this study was to estimate the treatment prevalence and the medical expenditure of diagnosed eating disorders (ICD F50.x) in South Korea between 2010 and 2015. We also examined the economic costs of eating disorders, including the direct medical cost, direct non-medical costs, and indirect costs, in order to calculate the economic burden of such disorders. RESULTS: The total treatment prevalence of eating disorders in South Korea was 12.02 people (per 100,000) in 2010, and 13.28 in 2015. The cost of medical expenditures due to eating disorders increased from USD 1229724 in 2010 to USD 1843706 in 2015. The total economic cost of eating disorders was USD 5455626 in 2015. In 2015, the economic cost and prevalence of eating disorders was the highest in the 20-29 age group. CONCLUSIONS: The results showed the eating disorders are insufficiently managed in the medical insurance system. Further research is therefore warranted to better understand the economic burdens of each type of eating disorder.

Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner.

Recent studies have reported that changes in gut microbiota composition could induce neuropsychiatric problems. In this study, we investigated alterations in gut microbiota induced by early-life stress (ELS) in rats subjected to maternal separation (MS; 6 h a day, postnatal days (PNDs) 1-21), along with changes in inflammatory cytokines and tryptophan-kynurenine (TRP-KYN) metabolism, and assessed the differences between sexes. High-throughput sequencing of the bacterial 16S rRNA gene showed that the relative abundance of the Bacteroides genus was increased and that of the Lachnospiraceae family was decreased in the feces of MS rats of both sexes (PND 56). By comparison, MS increased the relative abundance of the Streptococcus genus and decreased that of the Staphylococcus genus only in males, whereas the abundance of the Sporobacter genus was enhanced and that of the Mucispirillum genus was reduced by MS only in females. In addition, the levels of proinflammatory cytokines were increased in the colons (IFN-γ and IL-6) and sera (IL-1ß) of the male MS rats, together with the elevation of the KYN/TRP ratio in the sera, but not in females. In the hippocampus, MS elevated the level of IL-1ß and the KYN/TRP ratio in both male and female rats. These results indicate that MS induces peripheral and central inflammation and TRP-KYN metabolism in a sex-dependent manner, together with sex-specific changes in gut microbes.

Depression, Anxiety, Related Risk Factors and Cognitive Distortion in Korean Patients with Inflammatory Bowel Disease.

OBJECTIVE: To evaluate the severity of depression, anxiety, associated risk factors, and cognitive distortion in Korean patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS: This study included 369 patients with inflammatory bowel disease. The severity of depression and anxiety was examined using Patient Health Questionnaire-9 and Hospital Anxiety and Depression Scale. The Anxious Thoughts and Tendencies scale was used to measure catastrophizing tendency. Multivariate regression analyses were performed. RESULTS: The predictors of depression were marital status, anti-tumor necrosis factor-α (TNF-α) agent use, age, and body mass index in UC patients and marital status, disease activity, alcohol use, and employment status in CD patients. For anxiety, sex and marital status were the associated factors in UC patients, whereas steroid use was the only significant predictor in CD patients. Comparing the cognitive distortion level, there were no significant differences between UC and CD patients although there was an increasing tendency according to the severity of depression or anxiety. CONCLUSION: If patients are accompanied by high levels of depression or anxiety and their associated risk factors including TNF-α agent or steroid use, it is recommended that not only symptoms are treated but also cognitive approach and evaluation be performed.

Association of the Promoter Haplotype of IFN-γ-Inducible Protein 16 Gene with Schizophrenia in a Korean Population.

OBJECTIVE: Viral infections play an important role in the development of schizophrenia, inducing the faulty immunological responses and aberrant inflammation. IFN-γ-inducible protein 16 (IFI16) is an immunological DNA sensor against viral infections, triggering the inflammatory responses. In this study, we investigated an association between putative promoter single nucleotide polymorphisms (SNPs) and haplotypes of IFI16 and schizophrenia. METHODS: A total of 280 schizophrenia patients and 427 control subjects were recruited in this study. We genotyped three promoter SNPs (rs1465175, rs3754464, rs1417806) using direct sequencing. Associations of SNPs and haplotypes of IFI16 with schizophrenia were analyzed. The promoter activities on the haplotypes of IFI16 were measured. RESULTS: The T allele of rs1465175 and the C allele of rs1417806 were protectively associated with schizophrenia (p=0.021 on rs1465175; p=0.016 on rs1417806), whereas the G allele of rs3754464 was associated with an increased risk of schizophrenia (p=0.019). In haplotype analysis, a significant association between the GGA haplotype and schizophrenia was shown (p=0.013). Moreover, we found that the GGA haplotype elevated the promoter activity compared to the GAA haplotype, whereas the TAC haplotype reduced that. CONCLUSION: The promoter SNPs and haplotypes of IFI16 may contribute to the susceptibility of schizophrenia, affecting the promoter activity of IFI16.

Differences in Personality, Defense Styles, and Coping Strategies in Individuals with Depressive Disorder According to Age Groups Across the Lifespan.

OBJECTIVE: This study aimed to examine the differences in personality, defense style, and coping styles among patients with depression according to age groups. METHODS: A total of 211 participants ranging from 19 to 81 years old were recruited for the study. To assess participants' five dimensions of personality, the Neuroticism-Extraversion-Openness Personality Inventory-Revised (NEO-PI-R) was administered. In addition, the Korean-Defense Style Questionnaire and the Korean version of the coping checklist were administered to examine the defense and coping style. RESULTS: In the analysis of NEO-PI-R, the mean value of Agreeableness, Conscientiousness, and Neuroticism showed significant differences between the young adult age group (20-34 years) and the late middle age group (50-64 years) (p<0.05). The young age group used more immature defense styles and made less use of problem-focused coping strategy than the old age patients (65 years and older) (p<0.05). CONCLUSION: In the young age group associations with lower Agreeableness and Conscientiousness, as well as higher Neuroticism than the late middle age group were observed. Moreover, the young age group had a higher usage of immature defense style, and restricted use of problem-focused coping style than other age groups.

The Development of Evidence-Based Guideline for Diagnosis and Management of Headache in Korea.

OBJECTIVE: We aimed to develop the clinical guideline for headache by the systematic review and synthesis of existing evidence-based guidelines. The purpose of developing the guideline was to improve the appropriateness of diagnosis and treatment of headache disorder, and consequently, to improve patients' pain control and quality of life. The guideline broadly covers the differential diagnosis and treatment of tension-type headache, migraine, cluster headache, and medication-overuse headache. METHODS: This is a methodological study based on the ADAPTE methodology, including a systematic review of the literature, quality assessment of the guidelines using the Appraisal of Clinical Guidelines for REsearch & Evaluation II (AGREE II) Instrument, as well as an external review using a Delphi technique. The inclusion criteria for systematic search were as follows: topic-relevant, up-to-date guidelines including evidence from within 5 years, evidence-based guidelines, guidelines written in English or Korean, and guidelines issued by academic institutions or government agencies. RESULTS: We selected five guidelines and conducted their quality assessment using the AGREE II Instrument. As a result, one guideline was found to be eligible for adaptation. For 13 key questions, a total of 39 recommendations were proposed with the grading system and revised using the nominal group technique. CONCLUSION: Recommendations should be applied to actual clinical sites to achieve the ultimate goal of this guideline; therefore, follow-up activities, such as monitoring of guideline usage and assessment of applicability of the recommendations, should be performed in the future. Further assessment of the effectiveness of the guideline in Korea is needed.

Altered resting-state functional connectivity in depressive disorder patients with suicidal attempts.

In this study, we attempted to examine the resting state functional connectivity (resting state FC) and its correlation with clinical features in depressed disorder patients with suicidal attempts (SA). A total of 32 individuals participated in this study: 12 depressive disorder patients with SA and 20 healthy controls were included. Resting state FC was investigated between the two groups by region of interest (ROI) to ROI analysis. Then seed to voxel analysis was performed using significant ROIs as a seed. The correlations of significant resting state FC with clinical data were analyzed. The connectivity of anterior division of right parahippocampus-posterior division of left parahippocampus (pPaHCl) and temporooccipital part of right inferior temporal gyrus-right frontal eye field of dorsal attention network (FEFrDAN) were significantly increased, while connectivity of medial frontal cortex (MedFC)-right supplementary motor cortex (SMAr) was significantly decreased in the patients (p-FDR [false discovery rate] <0.05). The patient group showed a stronger connectivity between the pPaHCl and a cluster of voxels in the right uncus as well as FEFrDAN and a cluster of voxels in the right fusiform gyrus (p-FDR <0.05). MedFC and SMAr connectivity showed a negative correlation to suicidal ideation (p-FDR = 0.018). These findings suggest a possible role of altered resting state FC among brain regions in neurobiology of depressive disorder and suicidal ideation.

Psychological impact of the 2015 MERS outbreak on hospital workers and quarantined hemodialysis patients.

OBJECTIVES: This study aimed to assess the immediate stress and psychological impact experienced by quarantined patients undergoing hemodialysis and university hospital workers who treated patients Middle East respiratory syndrome (MERS) during its outbreak. DESIGN: The group of subjects consisted of 1800 hospital practitioners and 73 quarantined patients undergoing hemodialysis. The Impact of Events Scale-Revised (IES-R) was administered to the practitioners twice, once during the hospital shutdown and again one month after the shutdown. The Mini International Neuropsychiatric Interview and Hospital Anxiety and Depression Scale were administered to patients undergoing hemodialysis. RESULTS: During the initial stages of the MERS outbreak, healthcare workers who performed MERS-related tasks scored significantly higher on the total IES-R and its subscales. In the second assessment of the high-risk group, the sleep and numbness subscale scores from the IES-R differed depending on the implementation of home quarantine, and the intrusion subscale scores differed depending on the performance of MERS-related tasks. CONCLUSION: Medical staff that performed MERS-related tasks showed the highest risk for post-traumatic stress disorder symptoms even after time had elapsed. The risk increased even after home quarantine. Prompt and continuous psychiatric intervention is needed in high mortality infectious disease outbreaks.

Association of CCL11 promoter polymorphisms with schizophrenia in a Korean population.

BACKGROUND: Immunological alterations and dysregulation of the inflammatory response have been suggested to play a crucial role in schizophrenia pathophysiology. Growing evidence supports the involvement of chemokines in brain development, thus many chemokines have been studied in relation with schizophrenia. The C-C motif chemokine ligand 11 (CCL11) has been shown to be related with synaptic plasticity and neurogenesis. Moreover, altered levels of CCL11 have been observed in schizophrenia patients. Therefore, we examined whether single nucleotide polymorphisms (SNPs) of the CCL11 in the promoter region contribute to susceptibility to schizophrenia. METHODS: Four promoter SNPs [rs17809012 (-384T>C), rs16969415 (-426C>T), rs17735961 (-488C>A), and rs4795896 (576G>A)] were genotyped in 254 schizophrenia patients and 405 control subjects using Fluidigm SNPtype assays. RESULTS: The genotype frequency of CCL11 rs4795896 (-576G>A) showed significant association with schizophrenia in a recessive model (AA vs. GG/AG, p < 0.0001) and in a log-additive model (AG vs. AA vs. GG, p < 0.0001). The allele frequency of rs4795896 also showed a significant association with schizophrenia (p < 0.0001). Furthermore, haplotype analysis revealed that GCT, ACT, and GCC haplotypes containing rs4795896, rs17735961 and rs17809012 were significantly associated with schizophrenia (p = 0.0044, p < 0.0001, and p < 0.0001, respectively). CONCLUSION: Our results suggest that CCL11 promotor polymorphism is associated with increased risk for the development of schizophrenia in a Korean population.

Gray Matter Volume Reductions Were Associated with TPH1 Polymorphisms in Depressive Disorder Patients with Suicidal Attempts.

OBJECTIVE: Structural changes of brain areas have been reported in depressive disorder and suicidal behavior (SB), in which TPH1 also has been known as a promising candidate gene. We investigated gray matter volume (GMV) differences, TPH1 rs1800532 and rs1799913 polymorphisms previously found to be associated with depressive disorder and SB, and the relationship between the two markers. METHODS: Thirteen depressive disorder patients with suicidal attempts (SA) and twenty healthy controls were included. We examined GMV differences using a voxel-based morphometry and regions of interest analysis. Direct sequencing was used for genotyping. RESULTS: The patients showed significant GMV reduction in left cerebral region including middle frontal gyrus, inferior frontal gyrus, and anterior cingulate cortex; in right middle temporal gyrus; in left cerebellar tonsil; and in right cerebral region including precentral gyrus and postcentral gyrus (corrected p<0.005). The right precentral and postcentral gyri GMV values of AA and CA genotypes patients were significantly decreased compared to those of CC genotype subjects (corrected p=0.040). CONCLUSION: These findings show the possibility that both GMV reductions and TPH1 rs1800532/rs1799913 A allele may be involved in the pathogenesis of depressive disorder patients with SA.

BBOX1 is down-regulated in maternal immune-activated mice and implicated in genetic susceptibility to human schizophrenia.

Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorders such as bipolar disorder, autism, and schizophrenia in later life. Gamma-butyrobetaine hydroxylase (BBOX 1) is an enzyme responsible for the biosynthesis of l-carnitine, a key molecule in fatty acid metabolism. This cytosolic dimeric protein belongs to the dioxygenase family. In this study, we investigated whether BBOX 1 expression was related to psychiatric disorder in an animal model. We also conducted a case-control study using 284 schizophrenia patients and 409 controls with single-nucleotide polymorphisms (SNPs) in the 5'-near region of BBOX 1. BBOX 1 expression was increased in the medial frontal cortex of a mouse model of schizophrenia induced by maternal immune activation. Furthermore, the genotype and allele frequencies of two SNPs (rs7939644 and rs10767592) were significantly associated with schizophrenia susceptibility. Our results suggest that BBOX 1 might be associated with maternal immune activation and schizophrenia susceptibility. Therefore, it might be involved in the pathophysiology of schizophrenia.