The Relationship between Plasma Oxytocin Levels and Social Anxiety Symptoms.

OBJECTIVE: The pathophysiology of social anxiety disorder (SAD) is not yet well understood, but previous research has suggested that oxytocin is associated with social behavior and may play a role in human anxiety states and anxiety-related traits. The aim of this study was to investigate the possible relationship between social anxiety symptoms and plasma oxytocin levels. METHODS: Twenty-three male patients with SAD and 28 healthy male controls participated in this study. All participants were assessed using the Mini International Neuropsychiatric Interview (MINI) and the Liebowitz Social Anxiety Scale (LSAS). Multivariate regression analysis was performed to identify associations between plasma oxytocin levels and SAD. RESULTS: In multiple regression models, after controlling for age and years of education, we found that higher oxytocin levels were significantly associated with higher total LSAS scores (R2 =0.157, coefficient=0.145, 95% CI=-0.0005-0.291, p=0.051) and fear subscale scores (R2 =0.134, coefficient=0.083, 95% CI=0.007-0.159, p=0.034) in the SAD group. CONCLUSION: In this study, increased plasma oxytocin levels were associated with higher social anxiety symptoms among SAD patients, but not among controls. This might be because among SAD patients, higher oxytocin (OT) secretion is an insufficient compensatory attempt to reduce social anxiety symptoms.

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.

Pharmacotherapy and group cognitive behavioral therapy enhance follow-up treatment duration in gambling disorder patients.

BACKGROUND: Longer treatment duration is important for the successful treatment of gambling disorder (GD). This retrospective study investigated the factors and interventions that might enhance treatment duration in GD patients in South Korea. METHODS: A total of 758 outpatients with a primary diagnosis of GD, who were treated in a clinical practice from 2002 to 2011, were assessed by retrospective chart review. We compared the treatment duration according to pharmacotherapy and group cognitive behavioral therapy (CBT). RESULTS: Pharmacotherapy contributed to a longer duration of treatment maintenance, despite the patients' gambling severity (p < 0.001). Participation in group CBT (p < 0.001) and antidepressants (p = 0.009) were associated with a longer treatment duration after adjusting for age, depression, and gambling severity. The treatment maintenance duration was the longest in those receiving combined antidepressant pharmacotherapy and group CBT (F = 35.79, p < 0.001). CONCLUSIONS: Group CBT and antidepressants seem to enhance treatment follow-up duration in GD patients. Additional studies are needed to advance GD prevention and treatment strategies.

Early Improvement in One Week Predicts the Treatment Response to Escitalopram in Patients with Social Anxiety Disorder: A Preliminary Study.

OBJECTIVE: Social anxiety disorder (SAD) shows relatively delayed responses to pharmacotherapy when compared to other anxiety disorders. Therefore, more effective early therapeutic decisions can be made if the therapeutic response is predictable as early as possible. We studied whether the therapeutic response at 12 weeks is predictable based on the early improvement with escitalopram at 1 week. METHODS: The subjects were 28 outpatients diagnosed with SAD. The subjects took 10-20 mg/day of escitalopram. The results of the Liebowitz social anxiety scale (LSAS), Hamilton anxiety rating scale, and Montgomery-Asberg depression rating scale were evaluated at 0, 1, 4, 8, and 12 weeks of treatment. Early improvement was defined as a ≥10% reduction in the LSAS total at 1 week of treatment, and endpoint response was defined as a ≥35% reduction in the LSAS total score. The correlation between clinical characteristics and therapeutic responses was analyzed by simple linear regression. The correlation between early improvement responses and endpoint responses was analyzed by multivariate logistic regression analysis and receiver operating characteristic curves. RESULTS: When we adjusted the influence of a ≥35% reduction in the LSAS total endpoint score on a ≥10% reduction of the LSAS total score at 1 week of treatment for the patients' age, the early improvement group at 1 week of treatment was expected to show stronger endpoint responses compared to the group with no early improvement. CONCLUSION: The results suggest that a ≥10% reduction in the LSAS total score in a week can predict endpoint treatment response.

Gambling disorder in financial markets: Clinical and treatment-related features.

BACKGROUND AND AIMS: To date, few studies have examined the clinical manifestation of disordered gamblers in financial markets. This study examined the differences in the clinical and treatment-related features of gambling disorder between financial markets and horse races. METHODS: Subjects who met the DSM-IV criteria for pathological gambling (PG) and who sought treatment were assessed by retrospective chart review. One hundred forty-four subjects were included in this sample, which consisted of the following groups: financial markets (n = 45; 28.6%) and horse races (n = 99; 71.4%). RESULTS: Multiple similar manifestations were found between the groups, including severity of PG, age of PG onset, amounts of gambling debts, drinking days per week, depressive mood, duration of seeking treatment after the onset of PG, and treatment follow-up duration. However, disordered gamblers who invested in the financial market were significantly more likely to be educated (p = 0.003), live with their spouses (p = 0.007), have full-time jobs (p = 0.006), and they were more likely to participate in the first type of gambling than the horse races group (p<0.001). Furthermore, the financial markets group received the anti-craving medication less often than the horse races group (p = 0.04). DISCUSSION AND CONCLUSIONS: These findings suggest that disordered gamblers in financial markets show different socio-demographic, clinical and treatment-related features compared with the horse race gamblers, despite a similar severity of gambling disorder. Understanding these differential manifestations may provide insight into prevention and treatment development for specific types of gambling.

Association between the CLOCK gene 3111 T > C polymorphism and an irregular menstrual cycle in Korean adolescents.

The menstrual cycle is an example of a human infradian rhythm, but an altered sleep-wake cycle or a disrupted circadian rhythm can change the regularity of the menstrual cycle. In this study, we investigated whether an irregular menstrual cycle is associated with polymorphisms in the CLOCK (3111T > C) and/or PER3 (variable number tandem repeat, VNTR) genes, which are known to have an impact on the circadian rhythm. One hundred ninety-seven postmenarchal, adolescent girls from two girls' high schools in Seoul, Korea, were studied. All participants were requested to complete the Perceived Stress Scale (PSS), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Inventory (BDI) to assess the emotional distress that might cause menstrual irregularity. Every participant donated a blood sample from which DNA was extracted and genotyped for the CLOCK 3111T > C and PER3 VNTR polymorphisms. A significant association was found between the CLOCK 3111T > C genotype and irregular menstrual cycles. Subjects with the 3111T > C genotype had a high risk of an irregular menstrual cycle compared with 3111T/T homozygous subjects (odds ratio [OR] = 2.88; 95% confidence interval [CI]: 1.26-6.55). When multivariate logistic regression analysis was performed to adjust for age, PSS, STAI, BDI and BMI, subjects with the 3111T > C polymorphism showed a significantly increased OR for irregular menstrual cycles (OR = 3.09; 95% CI: 1.32-7.21). There was no significant association between the PER3 VNTR polymorphism and the irregularity of the menstrual cycle (p > 0.05). The results of this study suggest that the CLOCK 3111T > C polymorphism could be an independent risk factor for irregular menstrual cycles, irrespective of psychological distress and endocrine or metabolic conditions, and could be used as a molecular marker for gynecological studies on this aspect.

Age of pathological gambling onset: clinical and treatment-related features.

OBJECTIVES: This study examined differences in the clinical and treatment-related features of pathological gambling (PG) on the basis of the age of PG onset among pathological gamblers who sought treatment. METHODS: A total of 702 male outpatients with a primary diagnosis of PG and who were treated in a clinical practice were assessed by retrospective chart review. We selected the age of 25 years and younger as the threshold for "group 1." We then stratified the participants into 4 groups on the basis of the age of PG onset in 10-year intervals. Analysis of covariance with a covariant of age and the Pearson χ test were used for analyses. RESULTS: We found that the earlier-onset gamblers were less likely to be escape type (P < 0.05), used significantly more Internet-based gambling (P < 0.001), and were less likely to engage in nonstrategic gambling (P < 0.05) than the later-onset gamblers. In addition, the earlier-onset gamblers took anticraving medication, such as naltrexone, significantly more often (P < 0.05), and sought treatment significantly more slowly after the onset of PG than the later-onset group (P < 0.01). Regarding adherence to treatment, however, there was no significant difference among the 4 groups on the basis of the age of PG onset. CONCLUSIONS: The age of PG onset is associated with several important clinical and treatment features. More studies are needed to advance prevention and treatment strategies for each age group.

The use and perceived helpfulness of self-help interventions for depressive symptoms and sub-threshold depression: comparisons among the general population, patients with depression, and psychiatrists.

The aim of this study was to examine the patterns of use and perceived helpfulness of self-help interventions for depressive symptoms and sub-threshold depression in Korean samples drawn from the general population, patients with depression, and psychiatrists. A total of 1000 adults from the community, 114 patients with sub-threshold or mild depression, and 201 psychiatrists were asked to complete questionnaires about the use and helpfulness of 20 self-help interventions for depression chosen via the Delphi method. Psychiatrists (82.6%) and the general population (67.2%) were more likely to prefer self-help methods than were patients with depressive disorders (28.4%). Lifestyle change and psychological approaches were the preferred interventions among those with depressive disorders. Although the general population was more likely to prefer to use health supplements and dietary interventions, the perceived helpfulness of these approaches was generally lower than that of the other interventions. Although self-help strategies have been widely used, psychiatrists, patients with depression, and the general population differ with respect to their preferred intervention. Members of the general population were more likely than were psychiatrists and patients to use not consensually accepted interventions. The evidence-based use of self-help strategies for depression should be promoted by providing information about their effectiveness.

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.

Association study on pathological gambling and polymorphisms of dopamine D1, D2, D3, and D4 receptor genes in a Korean population.

Several studies have reported that some dopaminergic receptor polymorphisms are associated with pathological gambling (PG). Considering that there are major race and ethnic group difference in dopaminergic polymorphisms, the result of genetic association studies should be confirmed in more homogeneous population to avoid problems of population stratification. The present study aimed to investigate whether selected polymorphisms in the dopamine receptors genes (DRD1, DRD2, DRD3, and DRD4) are associated with PG in Korean population which is consisted of only Korean ancestry. Subjects were 104 men with a diagnosis of PG and 114 unrelated age-matched normal control men. Genotyping was performed for the DRD1 gene -48 A/G, DRD2 gene TaqI A, DRD3 gene Ser9Gly, and DRD4 gene exon III variable number tandem repeat polymorphisms. The method of multifactor dimensionality reduction (MDR) was used to analyze gene-gene interactions. There were no differences in the frequencies of any studied polymorphisms between patients with PG and normal controls. MDR analysis did not show a significant effect of the 4 dopamine receptor gene polymorphisms on susceptibility to PG (P > 0.05). The present study suggests that the analyzed polymorphisms of the dopamine receptor genes might not be associated with PG in a Korean population.

Comparison of anxiety-related traits between generalized and nongeneralized subtypes of social anxiety disorder.

This study aimed to investigate the possible difference in anxiety-related traits between the generalized and nongeneralized subtypes of social anxiety disorder (SAD). Two hundred seventy-three SAD Korean outpatients completed the Anxiety Sensitivity Index (ASI), the Trait Form of the State-Trait Anxiety Inventory (STAI-T), Retrospective Self-Report of Inhibition (RSRI), and the Liebowitz Social Anxiety Scale (LSAS) as part of their assessments. The unadjusted total scores of the ASI, STAI-T, RSRI, and LSAS differed between the two subtypes, according to an independent t-test. However, this result was not significant (ASI: F = 2.363, p = 0.127; STAI-T: F = 0.004, p = 0.949; RSRI: F = 1.518, p = 0.220) after adjusting for LSAS total score. The comparison of anxiety-related traits did not show any difference between the subtypes after adjusting for illness severity. These results may suggest that the two SAD subtypes are on a continuum of the same illness, differentiated only by symptom severity.

Lack of Association between Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphisms and Generalized Social Anxiety Disorder in Korean Population.

OBJECTIVE: Several lines of evidence suggest that brain-derived neurotrophic factor (BDNF) plays a role in the pathophysiology of anxiety. We analyzed the association of the BDNF gene polymorphism, G196A (val66met), in the coding region of exon XIIIA in chromosome 11p13, and generalized social anxiety disorder (GSAD). METHODS: Patients with GSAD (n=73) and age-matched control subjects (n=152) were tested for the BDNF (val66met) polymorphism. A clinical interview and a Mini-International Neuropsychiatric Interview were conducted by trained psychiatrists in order to diagnose GSAD. The symptomatic characteristics of the GSAD patients were assessed with the Hamilton Anxiety Rating Scale, the Beck Anxiety Inventory, the Retrospective Self Report of Inhibition, the Spielberger State-Trait Anxiety Inventory, and the Liebowitz Social Anxiety Scale. RESULTS: There were no significant differences in the frequencies of the genotypes (χ(2)=0.961, degree of freedom [df]=2, p=0.619), alleles (χ(2)=0.415, df=1, p=0.519), or allele (methionine) carriers (χ(2)=0.019, df=1, p=0.889) between the patients and controls. In addition, when we compared the severity of social anxiety symptom as determined by the clinical scales with the genotypes of the BDNF gene, we could not find any significant differences between the genotypes or allele carriers. CONCLUSION: These results do not support the hypothesis that the BDNF gene might be a candidate gene for susceptibility or severity of GSAD in the Korean population in this study.

Associations between the serotonin-1A receptor C(-1019)G polymorphism and disordered eating symptoms in female adolescents.

The purpose of this study was to examine the relationship between the C(-1019)G polymorphism of the serotonin-1A receptor gene and eating behavior in female adolescents. A total of 204 post-menarche, adolescent women, aged 16-17 years, were recruited from two neighboring high schools in Seoul. Polymerase chain reaction (PCR) was used to isolate and examine the C(-1019)G polymorphism in the serotonin-1A receptor genes (rs6295) of all participants. The Bulimia Investigatory Test, Edinburgh (BITE) and the Eating Attitude Test-26 (EAT-26) were administered to all participants. The total score of the EAT-26 differed significantly among the three genotype groups [CC, CG, GG (F = 4.844, p = 0.009)]. Both the EAT-26 (F = 9.69, p = 0.002) and the BITE (F = 5.22, p = 0.023) scores were higher in the participants who were G allele carriers than in the non-carrier group. The dieting subscale of the EAT-26 was higher among the G allele carriers (F = 12.941, p < 0.001), and these results were maintained even after adjusting for depression and anxiety. These findings suggest that the C(-1019)G polymorphism in the 5-HT1A receptor gene is associated with disordered eating symptoms in Korean female adolescents.