Guide for generating single-cell-derived knockout clones in mammalian cell lines using the CRISPR/Cas9 system.

Genome editing has developed rapidly in various research fields for targeted genome modifications in many organisms, including cells, plants, viruses, and animals. The clustered regularly interspaced short palindromic repeats-associated protein 9 system stands as a potent tool in gene editing for generating cells and animal models with high precision. The clinical potential of clustered regularly interspaced short palindromic repeats-associated protein 9 has been extensively reported, with applications in genetic disease correction, inhibition of viral replication, and personalized or targeted therapeutics for various cancers. In this study, we provide a guide on single-guide RNA design, cloning single-guide RNA into plasmid vectors, single-cell isolation via transfection, and identification of knockout clones using next-generation sequencing. In addition, by providing the results of insertion into mammalian cell lines through next-generation sequencing, we offer useful information to those conducting research on human and animal cell lines.

Sniper2L is a high-fidelity Cas9 variant with high activity.

Although several high-fidelity SpCas9 variants have been reported, it has been observed that this increased specificity is associated with reduced on-target activity, limiting the applications of the high-fidelity variants when efficient genome editing is required. Here, we developed an improved version of Sniper-Cas9, Sniper2L, which represents an exception to this trade-off trend as it showed higher specificity with retained high activity. We evaluated Sniper2L activities at a large number of target sequences and developed DeepSniper, a deep learning model that can predict the activity of Sniper2L. We also confirmed that Sniper2L can induce highly efficient and specific editing at a large number of target sequences when it is delivered as a ribonucleoprotein complex. Mechanically, the high specificity of Sniper2L originates from its superior ability to avoid unwinding a target DNA containing even a single mismatch. We envision that Sniper2L will be useful when efficient and specific genome editing is required.

TAPE-seq is a cell-based method for predicting genome-wide off-target effects of prime editor.

Prime editors (PEs) are powerful tools that widen the possibilities for sequence modifications during genome editing. Although methods based on the analysis of Cas9 nuclease or nickase activity have been used to predict genome-wide off-target activities of PEs, no tool that directly uses PEs for this purpose has been reported yet. In this study, we present a cell-based assay, named TAgmentation of Prime Editor sequencing (TAPE-seq), that provides genome-wide off-target candidates for PEs. TAPE-seq analyses are successfully performed using many different versions of PEs. The TAPE-seq predictions are compared with results from two other off-site prediction methods, Cas9 nuclease-based GUIDE-seq and Cas9 nickase-based Digenome-seq (nDigenome-seq). TAPE-seq shows a lower miss rate, and a higher area under the receiver operating characteristic curve compared to the other methods. TAPE-seq also identified valid off-target sites that were missed by the other methods.

Development of post-disaster psychosocial evaluation and intervention for children: Results of a South Korean delphi panel survey.

OBJECTIVE: This study aimed to administer a Delphi panel survey and provide evidence for the development of a psychological intervention protocol for use after disasters in South Korea. METHOD: A three-round Delphi survey was conducted. In all rounds, respondents answered open- or closed-ended questions regarding their views on i) the concept of disaster, ii) evaluation, iii) intervention, and iv) considerations in a disaster. Data from Round 1 were subjected to content analysis. In Round 2, items with content validity ratios (CVRs) greater than 0.49 were included, and in Round 3, items with a CVR≥0.38 were accepted. RESULTS: The response rates for the Delphi survey were high: 83% (n = 15, Round 1), 80% (n = 16, Round 2), and 86% (n = 24, Round 3). The data collected during this survey showed a need for a support system for children; for preventive strategies, including disaster readiness plans; for the protection of children's safety; and for the development of post-disaster psychosocial care. CONCLUSIONS: The panel experts reached a consensus regarding the steps they considered critical in post-disaster evaluation and intervention. The findings suggest a unified model for advancing the development of the Korean version of an intervention protocol for children and adolescents exposed to traumatic events.

Korean Guidelines for the Pharmacological Treatment of Social Anxiety Disorder: Initial Treatment Strategies.

OBJECTIVE: The aim of the present study was to provide clinical consensus and evidence regarding initial treatment strategies for the pharmacological treatment of social anxiety disorder (SAD) in Korea. METHODS: We prepared a questionnaire to derive a consensus from clinicians regarding their preference for the pharmacological treatment of SAD in Korea. Data regarding medication regimens and psychotropic drugs used during initial treatment, the doses used, and the pharmacological treatment duration were obtained. Responses were obtained from 66 SAD experts, and their opinions were classified into three categories (first-line, second-line, third-line) using a chi-square analysis. RESULTS: Clinicians agreed upon first-line regimens for SAD involving monotherapy with selective serotonin reuptake inhibitors (SSRIs) or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, or combined therapy using antidepressants with betablockers or benzodiazepines on a standing or as-needed basis. First-line psychotropic drug choices for initial treatment included the following: escitalopram, paroxetine, sertraline, venlafaxine, and propranolol. The medication dosage used by domestic clinicians was found to be comparable with foreign guidelines. Domestic clinicians tended to make treatment decisions in a shorter amount of time and preferred a similar duration of maintenance treatment for SAD when compared with foreign clinicians. CONCLUSION: This study may provide significant information for developing SAD pharmacotherapy guidelines in Korea, especially in the early stage of treatment.

Psychiatric Symptoms in Teachers from Danwon High School after Exposure to the Sinking of the Motor Vessel Sewol.

OBJECTIVE: The goal of this study was to describe the psychiatric symptoms in the teachers from Danwon High School who were exposed to the sinking of the Motor Vessel Sewol. METHODS: Data were collected from 32 teachers who underwent psychiatric interventions by 16 volunteer psychiatrists for 3 months after the sinking of the Motor Vessel Sewol. RESULTS: The most commonly diagnosed clinical diagnosis in the teachers were normal reaction, acute stress disorder and adjustment disorder. Psychiatric symptoms including anxiety, depressed mood and sleep disturbances were also observed. CONCLUSION: In the acute aftermath of the Sewol Ferry sinking on April 16, 2014, psychiatrists volunteered to provide professional psychiatric interventions to Danwon High School teachers. These results suggest the importance of crisis intervention focused on the teachers who are exposed to disasters. The implications for future research and interventions are discussed.

Prostaglandin D2 synthase related to estrogen in the female reproductive tract.

Prostaglandin D2 synthase (PTGDS), also known as a glutathione-independent prostaglandin D synthase, catalyzes prostaglandin H2 to prostaglandin D2 that exhibits functions that include regulation of the central nervous system, contraction/relaxation of smooth muscle and inhibition of platelet aggregation. Gene profiling data based on our previous study indicated that PTGDS is significantly increased during development, differentiation and remodeling of the oviduct in chickens in response to estrogen. Therefore, the aims of the present study were to investigate expression of PTGDS in the oviduct and examine if the relationship between PTGDS and estrogen is conserved during development and remodeling of the oviduct. Results of our study indicate d that PTGDS expression is specifically localized to the luminal (LE) and glandular epithelial (GE) cells of the chicken oviduct in response to diethylstilbestrol, a synthetic estrogen. In addition, PTGDS expression increased during the regeneration phase of the oviduct in concert with increasing concentrations of estrogen in the circulation of laying hens during induced molting. Moreover, PTGDS mRNA and protein were expressed abundantly in GE of ovarian carcinoma, but not in normal ovaries. These results provide the first evidence that PTGDS is a novel estrogen-stimulated gene in oviductal epithelial cells, as well as a candidate biomarker for diagnosis of ovarian carcinoma.

Avian SERPINB12 expression in the avian oviduct is regulated by estrogen and up-regulated in epithelial cell-derived ovarian carcinomas of laying hens.

Serine protease inhibitors (SERPINs) are involved in a variety of biological processes such as blood clotting, angiogenesis, immune system, and embryogenesis. Although, of these, SERPINB12 is identified as the latest member of clade B in humans, little is known of it in chickens. Thus, in this study, we investigated SERPINB12 expression profiles in various tissues of chickens and focused on effects of steroid hormone regulation of its expression. In the chicken oviduct, SERPINB12 mRNA and protein are abundant in the luminal (LE) and glandular (GE) epithelia of the magnum in response to endogenous or exogenous estrogen. Furthermore, SERPINB12 mRNA and protein increase significantly in GE of cancerous ovaries of laying hens with epithelia-derived ovarian cancer. Collectively, these results indicate that SERPINB12 is a novel estrogen-stimulated gene that is up-regulated by estrogen in epithelial cells of the chicken oviduct and that it is a potential biomarker for early detection of ovarian carcinomas in laying hens and women.

Expression and regulation of avian cathepsin L in the oviduct during molting.

Cathepsins (CTSs) are peptidases that have biological roles in degrading extracellular matrix, catabolism of intracellular proteins, and processing of pro-hormones. Of these, cathepsin L (CTSL) is closely associated with morphological changes in reproductive organs required for proper function in mammals, including humans and mice, but little is known about CTSL in avian species. In the present study, the expression of CTSL was investigated in the oviduct of hens during regression and recrudescence in response to molting. Our results revealed that expression of CTSL mRNA increased (P<0.001) when the oviduct underwent regression during the molting period in hens. In situ hybridization and immunohistochemial analyses detected CTSL mRNA and protein predominantly in the luminal (LE) and glandular epithelia (GE) during regression of the oviduct, but not during regeneration of the oviduct. Expression of CTSL decreased in the oviduct of chicks treated with diethylstilbestrol (DES, a synthetic estrogen agonist). Furthermore, we discovered four miRNAs including miR-23b, miR-551, miR-1464 and miR-1803 that regulate expression of the CTSL gene at the post-transcriptional level, which suggests that CTSL mRNA can be regulated by specific miRNAs via 3'-UTR in chickens. Results of the present research suggest that estrogen regulates expression of CTSL during regression of the oviduct during molting and that down-regulation of CTSL is likely a prerequisite for the normal regeneration of oviductal tissues following molting in laying hens.

Avian prostatic acid phosphatase: estrogen regulation in the oviduct and epithelial cell-derived ovarian carcinomas.

Prostatic acid phosphatase (ACPP) is a glycoprotein that is mainly synthesized and secreted by glandular epithelial cells (GE) of the prostate, and it is well known as a biomarker for prostate cancer. Although ACPP was used as prognostic/diagnostic indicator and studied to elucidate regulatory mechanism(s) during several decades in humans, its role is not clearly understood. Gene profiling data using a chicken DNA microarray revealed that ACPP increased significantly during remodeling and recrudescence of the oviduct in response to estrogen. Thus, in this study, we investigated the expression and hormonal regulation of ACPP gene in the reproductive tracts of chickens. ACPP was specifically detected in the luminal cells (LE) and GE of chicken oviduct, and diethylstilbestrol (a synthetic nonsteroidal estrogen) stimulated its expression during development of the oviduct. In addition, ACPP mRNA and protein were localized to LE and GE during the regeneration phase of the oviduct of laying hens during induced molting. Furthermore, ACPP mRNA and protein were abundant in GE of ovarian carcinoma, but not in normal ovaries. Moreover, strong expression of ACPP protein was detected in epithelial cells of cancerous ovaries from women. Collectively, results of the present study are the first to show that ACPP is a novel estrogen-stimulated gene in the oviductal epithelial cells of the chicken and that its expression increases significantly in epithelial cells of ovarian carcinoma, which indicates that it may be a candidate biomarker for diagnosis of epithelia-derived ovarian cancer in women.

Hormonal regulation of beta-catenin during development of the avian oviduct and its expression in epithelial cell-derived ovarian carcinogenesis.

Beta-catenin (CTNNB1) is a dual function molecule that acts as a key component of the cadherin complex and WNT signaling pathway. It has a crucial role in embryogenesis, tumorigenesis, angiogenesis and progression of metastasis. Recently, it has been suggested that the CTNNB1 complex is a major regulator of development of the mouse oviduct and uterus. However, little is known about the CTNNB1 gene in chickens. Therefore, in this study, we focused on the CTNNB1 gene in the chicken reproductive tract and hormonal control of its expression in the chicken oviduct. CTNNB1 was localized specifically to the luminal and glandular epithelium of the four segments of chicken oviduct and DES (diethylstilbestrol, a synthetic non-steroidal estrogen) increased its expression primarily in LE of the magnum. In addition, CTNNB1 mRNA and protein were expressed abundantly in glandular epithelium of endometrioid-type ovarian carcinoma, but not in normal ovaries. Moreover, CTNNB1 expression was post-transcriptionally regulated via its 3'-UTR by binding with target miRNAs including miR-217, miR-1467, miR-1623 and miR-1697. Collectively, these results indicate that CTNNB1 is a novel gene regulated by estrogen in epithelial cells of the chicken oviduct and that it is also abundantly expressed in epithelial cells of endometrioid-type ovarian carcinoma suggesting that it could be used as a marker for diagnosis of ovarian cancer in laying hens and women.

Recrudescence mechanisms and gene expression profile of the reproductive tracts from chickens during the molting period.

The reproductive system of chickens undergoes dynamic morphological and functional tissue remodeling during the molting period. The present study identified global gene expression profiles following oviductal tissue regression and regeneration in laying hens in which molting was induced by feeding high levels of zinc in the diet. During the molting and recrudescence processes, progressive morphological and physiological changes included regression and re-growth of reproductive organs and fluctuations in concentrations of testosterone, progesterone, estradiol and corticosterone in blood. The cDNA microarray analysis of oviductal tissues revealed the biological significance of gene expression-based modulation in oviductal tissue during its remodeling. Based on the gene expression profiles, expression patterns of selected genes such as, TF, ANGPTL3, p20K, PTN, AvBD11 and SERPINB3 exhibited similar patterns in expression with gradual decreases during regression of the oviduct and sequential increases during resurrection of the functional oviduct. Also, miR-1689* inhibited expression of Sp1, while miR-17-3p, miR-22* and miR-1764 inhibited expression of STAT1. Similarly, chicken miR-1562 and miR-138 reduced the expression of ANGPTL3 and p20K, respectively. These results suggest that these differentially regulated genes are closely correlated with the molecular mechanism(s) for development and tissue remodeling of the avian female reproductive tract, and that miRNA-mediated regulation of key genes likely contributes to remodeling of the avian reproductive tract by controlling expression of those genes post-transcriptionally. The discovered global gene profiles provide new molecular candidates responsible for regulating morphological and functional recrudescence of the avian reproductive tract, and provide novel insights into understanding the remodeling process at the genomic and epigenomic levels.

The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells.

Resistance to cisplatin-based therapy is a major cause of treatment failure in human ovarian cancer. A better understanding of the mechanisms of cisplatin resistance will offer new insights for novel therapeutic strategies for this deadly disease. Akt and p53 are determinants of cisplatin sensitivity. Rictor is a component of mTOR protein kinase complex 2, which is required for Akt phosphorylation (Ser473) and full activation. However, the precise role of rictor and the relationship between rictor and p53 in cisplatin resistance remains poorly understood. Here, using sensitive wild-type p53 (OV2008 and A2780s), resistant wild-type p53 (C13* and OVCAR433), and p53 compromised (A2780cp, OCC1, and SKOV-3) ovarian cancer cells, we have demonstrated that (i) rictor is a determinant of cisplatin resistance in chemosensitive human ovarian cancer cells; (ii) cisplatin down-regulates rictor content by caspase-3 cleavage and proteasomal degradation; (iii) rictor down-regulation sensitizes chemo-resistant ovarian cancer cells to cisplatin-induced apoptosis in a p53-dependent manner; (iv) rictor suppresses cisplatin-induced apoptosis and confers resistance by activating and stabilizing Akt. These findings extend current knowledge on the molecular and cellular basis of cisplatin resistance and provide a rationale basis for rictor as a potential therapeutic target for chemoresistant ovarian cancer.

Sex-specific expression of CTNNB1 in the gonadal morphogenesis of the chicken.

BACKGROUND: Beta-catenin (CTNNB1), as a key transcriptional regulator in the WNT signal transduction cascade, plays a pivotal role in multiple biological functions such as embryonic development and homeostasis in adults. Although it has been suggested that CTNNB1 is required for gonad development and maintenance of ovarian function in mice, little is known about the expression and functional role of CTNNB1 in gonadal development and differentiation in the chicken reproductive system. METHODS: To examine sex-specific, cell-specific and temporal expression of CTNNB1 mRNA and protein during gonadal development to maturation of reproductive organs, we collected left and right gonads apart from mesonephric kidney of chicken embryos on embryonic day (E) 6, E9, E14, E18, as well as testes, oviduct and ovaries from 12-week-old and adult chickens and performed quantitative PCR, in situ hybridization, and immunohistochemical analyses. In addition, localization of Sertoli cell markers such as anti-Müllerian hormone (AMH), estrogen receptor alpha (ESR1), cyclin D1 (CCND1) and N-cadherin (CDH2) during testicular development was evaluated. RESULTS: Results of the present study showed that CTNNB1 mRNA and protein are expressed predominantly in the seminiferous cords on E6 to E14 in the male embryonic gonad, and are mainly localized to the medullary region of female embryonic gonads from E6 to E9. In addition, CTNNB1 mRNA and protein are abundant in the Sertoli cells in the testes and expressed predominantly in luminal epithelial cells of the oviduct, but not in the ovaries from 12-week-old and adult chickens. Concomitant with CTNNB1, AMH, ESR1, CCND1 and CDH2 were detected predominantly in the seminiferous cord of the medullary region of male gonads at E9 (after sex determination) and then maintained or decreased until hatching. Interestingly, AMH, ESR1, CCND1 and CDH2 were located in seminiferous tubules of the testes from 12-weeks-old chickens and ESR1, CCND1 and CDH2 were expressed predominantly in the Sertoli cells within seminiferous tubules of adult testes. CONCLUSIONS: Collectively, these results revealed that CTNNB1 is present in gonads of both sexes during embryonic development and it may play essential roles in differentiation of Sertoli cells during formation of seminiferous tubules during development of the testes.

Avian WNT4 in the female reproductive tracts: potential role of oviduct development and ovarian carcinogenesis.

The wingless-type MMTV integration site family of proteins (WNTs) is highly conserved secreted lipid-modified signaling molecules that play a variety of pivotal roles in developmental events such as embryogenesis, tissue homeostasis and cell polarity. Although, of these proteins, WNT4 is known to be involved in genital development in fetuses of mammalian species, its role is unknown in avian species. Therefore, in this study, we investigated expression profiles, as well as hormonal and post-transcriptional regulation of WNT4 expression in the reproductive tract of female chickens. Results of this study demonstrated that WNT4 is most abundant in the stromal and luminal epithelial cells of the isthmus and shell gland of the oviduct, respectively. WNT4 is also most abundant in the glandular epithelium of the shell gland of the oviduct of laying hens at 3 h post-ovulation during the laying cycle. In addition, treatment of young chicks with diethylstilbestrol (DES, a synthetic estrogen agonist) stimulated WNT4 only in the glandular epithelial cells of the isthmus and shell gland of the oviduct. Moreover, results of our study demonstrated that miR-1786 influences WNT4 expression via specific binding sites in its 3'-UTR. On the other hand, our results also indicate that WNT4 is expressed predominantly in the glandular epithelium of cancerous ovaries, but not in normal ovaries of hens. Collectively, these results indicate cell-specific expression of WNT4 in the reproductive tract of chickens and that it likely has crucial roles in development and function of oviduct as well as initiation of ovarian carcinogenesis in laying hens.

Hypermethylation and post-transcriptional regulation of DNA methyltransferases in the ovarian carcinomas of the laying hen.

DNA methyltransferases (DNMTs) are key regulators of DNA methylation and have crucial roles in carcinogenesis, embryogenesis and epigenetic modification. In general, DNMT1 has enzymatic activity affecting maintenance of DNA methylation, whereas DNMT3A and DNMT3B are involved in de novo methylation events. Although DNMT genes are well known in mammals including humans and mice, they are not well studied in avian species, especially the laying hen which is recognized as an excellent animal model for research on human ovarian carcinogenesis. Results of the present study demonstrated that expression of DNMT1, DNMT3A and DNMT3B genes was significantly increased, particularly in the glandular epithelia (GE) of cancerous ovaries, but not normal ovaries. Consistent with this result, immunoreactive 5-methylcytosine protein was predominantly abundant in nuclei of stromal and GE cells of cancerous ovaries, but it was also found that, to a lesser extent, in nuclei of stromal cells of normal ovaries. Methylation-specific PCR analysis detected hypermethylation of the promoter regions of the tumor suppressor genes in the initiation and development of chicken ovarian cancer. Further, several microRNAs, specifically miR-1741, miR-16c, and miR-222, and miR-1632 were discovered to influence expression of DNMT3A and DNMT3B, respectively, via their 3'-UTR which suggests post-transcriptional regulation of their expression in laying hens. Collectively, results of the present study demonstrated increased expression of DNMT genes in cancerous ovaries of laying hens and post-transcriptional regulation of those genes by specific microRNAs, as well as control of hypermethylation of the promoters of tumor suppressor genes.

Risk factors for suicidal ideation of the general population.

The aim of this study was to investigate risk factors of suicide ideation in general population. A total of 1,116 adults were sampled with randomization in an urban area. After excluding 116 participants due to incomplete answer, 1,000 participants (500 males; mean age 39.6 ± 11.6) completed self-report questionnaire including the Center for Epidemiologic Study Depression Scale (CES-D), the Beck Scale for Suicide Ideation (BSI), the Spielberger State-Trait Anger Expression Inventory (STAXI), the Barratt Impulsiveness Scale (BIS), and questions on weekday sleep duration. Results showed higher scores on the BSI were related with higher scores on the STAXI, CES-D, a family history of psychiatric illness, and short or long sleep duration (≤ 5 or ≥ 10 hr) (adjusted R (2) = 0.151, P < 0.001, P < 0.001, P = 0.001, and P = 0.008, respectively). The predictive power of the STAXI scores, the presence of psychiatric family history and short or long sleep duration was stronger in the high CES-D group with scores of 16 or higher (adjusted R (2) = 0.275, P < 0.001, P < 0.001, and P < 0.001, respectively). These findings suggest that suicide idea in general population may be related with the presence of family history for psychiatric illness, depressive mood, high anger and short or long sleep duration.

Clinical differences between early- and late-onset social anxiety disorders.

AIM: The aim of this study was to elucidate the clinical differences between early- and late-onset social anxiety disorder (SAD) in the Korean population. METHODS: Three hundred and eighty-seven outpatients diagnosed with SAD participated in this study. Confirmation of SAD diagnosis was based on the Mini International Neuropsychiatric Interview. All subjects completed the Liebowitz Social Anxiety Scale and anxiety-trait-related scales such as the Anxiety Sensitivity Index, Retrospective Self-Report of Inhibition, Trait Form of the State-Trait Anxiety Inventory, and Beck Depression Inventory. RESULTS: The early-onset group (n = 209) consisted of subjects aged up to 18 years at the time of onset, whereas the late-onset group (n = 178) consisted of subjects older than 18 years at the time of onset. Early-onset SAD patients were more likely to have the generalized subtype and to visit clinics with chief complaints other than social anxiety symptoms. They exhibited more severe symptoms and higher behavioural inhibitions. After adjusting for age and symptom severity, behavioural inhibition was the only significant difference between the two groups. The degree of behavioural inhibitions was associated with earlier onset age. CONCLUSION: Symptom severity and behavioural inhibitions, especially in social/school situations, were clinical characteristics that differentiated between early- and late-onset SAD.

Altered risk-aversion and risk-taking behaviour in patients with Alzheimer's disease.

AIM: Normal individuals are risk averse for decisions framed as gains but risk taking for decisions framed as losses. This framing effect is supposed to be attenuated in Alzheimer's disease (AD) patients. We investigated the effects of highlighting rewards versus highlighting punishments on the risky decision-making of AD patients. METHOD: Fourteen mild to moderate AD patients (Mini-Mental Status Examination score, 11-23; Clinical Dementia Rating, 1-2) and 16 healthy volunteers were recruited for the study. Subjects completed a computerized task on risky decision-making in which mathematically equivalent dilemmas were presented in terms of opportunities to gain monetary rewards ('positive frame') or avoid suffering losses ('negative frame'). RESULTS: As expected, AD patients chose more risky options under the positive frame than the negative frame, contrary to the control group (Z =-2.671, P= 0.007). The normal difference in the distribution of risky choices between positively and negatively framed dilemmas was significantly reduced in the AD group after we adjusted for years of education, mean age and depression (F= 5.321, P= 0.030). Deliberation time did not differ significantly between the two groups. CONCLUSION: These results suggest that AD patients making high-risk choices is associated with attenuated sensitivity to the emotional frames that highlight rewards or punishments, possibly reflecting altered evaluations of prospective gains and losses.

Comparison of treatment adherence between selective serotonin reuptake inhibitors and moclobemide in patients with social anxiety disorder.

OBJECTIVE: With respect to the pharmacotherapy of social anxiety disorder (SAD), it has been suggested that treatment duration is an important factor that can significantly predict responses. The present study aimed to compare the treatment adherence of SAD patients who were taking either SSRIs or reversible inhibitors of MAO-A (moclobemide) by measuring treatment duration and all-cause discontinuation rates of pharmacotherapy in a natural clinical setting. METHODS: We retrospectively analysed the data of 172 patients diagnosed with SAD. Depending on their medication, we divided the patients into two groups, SSRI (n=54) or moclobemide (n=118). The expected number of all-cause discontinuation every 2 weeks after starting treatment was calculated by life table survival methods. A multi-variable Cox proportional hazard regression was used to analyze the potential influence of explanatory variables. RESULTS: Treatment duration was significantly longer in the SSRI group [46.41±56.96, median=12.0 (weeks)] than in the moclobemide group [25.53±34.74, median=12.0 (weeks), Z=2.352, p=0.019]. Overall, all-cause discontinuation rates were significantly lower with SSRIs (81%) than moclobemide (96%, χ²=4.532, p=0.033). CONCLUSION: The SSRI group had a longer treatment duration and lower all-cause discontinuation rate than moclobemide. Further, only the type of medication had a significant effect on all-cause discontinuation rates and therefore, we could predict better treatment adherence with the SSRIs in the treatment of SAD.