Youl-Ri Kim

Differential methylation of the oxytocin receptor gene in patients with anorexia nervosa: a pilot study

Background and Aim Recent studies in patients with anorexia nervosa suggest that oxytocin may be involved in the pathophysiology of anorexia nervosa. We examined whether there was evidence of variation in methylation status of the oxytocin receptor (OXTR) gene in patients with anorexia nervosa that might account for these findings. Methods We analyzed the methylation status of the CpG sites in a region from the exon 1 to the MT2 regions of the OXTR gene in buccal cells from 15 patients and 36 healthy women using bisulfite sequencing. We further examined whether methylation status was associated with markers of illness severity or form. Results We identified six CpG sites with significant differences in average methylation levels between the patient and control groups. Among the six differentially methylated CpG sites, five showed higher than average methylation levels in patients than those in the control group (64.9–88.8% vs. 6.6–45.0%). The methylation levels of these five CpG sites were negatively associated with body mass index (BMI). BMI, eating disorders psychopathology, and anxiety were identified in a regression analysis as factors affecting the methylation levels of these CpG sites with more variation accounted for by BMI. Conclusions Epigenetic misregulation of the OXTR gene may be implicated in anorexia nervosa, which may either be a mechanism linking environmental adversity to risk or may be a secondary consequence of the illness.

Intranasal oxytocin attenuates attentional bias for eating and fat shape stimuli in patients with anorexia nervosa

We examined the impact of oxytocin on attentional processes for eating, shape, and weight stimuli in patients with anorexia nervosa (AN). A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with food, weight, and shape images was administered to 64 female subjects: 31 patients with AN and 33 control students. The AN group showed significant reductions in the attentional biases toward eating-related stimuli (p=0.030, d=0.516) and toward negative shape stimuli (p=0.015, d=0.498) under the influence of intranasal oxytocin. The effect of oxytocin was correlated with autistic spectrum traits in the AN group. Oxytocin had no effect on the amount of juice consumed in either group. The results of this study suggest that oxytocin attenuates the attentional vigilance to eating and fat shape stimuli in patients with AN. Further studies using oxytocin as a form of intervention for patients with AN are needed.

The Impact of Intranasal Oxytocin on Attention to Social Emotional Stimuli in Patients with Anorexia Nervosa: A Double Blind within-Subject Cross-over Experiment

Background and aim Social factors may be of importance causally and act as maintenance factors in patients with anorexia nervosa. Oxytocin is a neuromodulatory hormone involved in social emotional processing associated with attentional processes. This study aimed to examine the impact of oxytocin on attentional processes to social faces representing anger, disgust, and happiness in patients with anorexia nervosa. Method A double-blind, placebo-controlled within-subject crossover design was used. Intranasal oxytocin or placebo followed by a visual probe detection task with faces depicting anger, disgust, and happiness was administered to 64 female subjects: 31 patients with anorexia nervosa and 33 control students. Results Attentional bias to the disgust stimuli was observed in both groups under the placebo condition. The attentional bias to disgust was reduced under the oxytocin condition (a moderate effect in the patient group). Avoidance of angry faces was observed in the patient group under the placebo condition and vigilance was observed in the healthy comparison group; both of these information processing responses were moderated by oxytocin producing an increase in vigilance in the patients. Happy/smiling faces did not elicit an attentional response in controls or the patients under either the placebo or oxytocin conditions. Conclusion Oxytocin attenuated attentional vigilance to disgust in patients with anorexia nervosa and healthy controls. On the other hand, oxytocin changed the response to angry faces from avoidance to vigilance in patients but reduced vigilance to anger in healthy controls. We conclude that patients with anorexia nervosa appear to use different strategies/circuits to emotionally process anger from their healthy counterparts.

Catechol-O-methyltransferase Val158Met polymorphism in relation to aggressive schizophrenia in a Korean population

We examined the association between the Catechol-O-methyltransferase (COMT) Val158Met polymorphism and aggressive schizophrenia. The sample included 61 aggressive schizophrenic patients as well as 104 non-aggressive patients from psychiatric hospitals and 415 healthy volunteers in South Korea. In the case-control comparisons, there was no significant association between the aggressive schizophrenic patients and the COMT Val158Met polymorphism. Looking only at the subgroup of aggressive schizophrenic patients, however, we found a dose-dependent relationship between the Met allele and verbal aggression. In this subgroup, the Met carriers showed a higher verbal aggression score than those with the Val/Val homozygote. These findings support the hypothesized moderating role of the COMT gene in the aggressive behaviour in some schizophrenic patients, though they do not support the existence of a direct association between the COMT Val158Met polymorphism and aggressive schizophrenia case status in the Korean population.

Field trial of a putative research algorithm for diagnosing ICD-11 personality disorders in psychiatric patients: 1. Severity of personality disturbance.

This preliminary field trial examines the reliability and validity of a proposed research algorithm for diagnosing International Classification of Diseases (ICD)-11 personality disorders and its association with other psychiatric assessments for the primary classification of a single dimension of the five severity levels of personality dysfunction. In total, 137 psychiatric patients (119 with personality disorders and 18 without personality disorders) in Korea were assessed. In the first part of the study, inter-rater reliability was evaluated with an independent assessment of personality (personality assessment schedule). In the second part of the study, (1) the algorithm that identified any personality disturbance was compared with the ICD-10 and DSM-IV personality disorder diagnostic equivalents, and (ii) the four levels of severity were examined for their associations with clinical pathology and social functioning. The results showed good agreement between the algorithm and the test instruments for identifying a personality disorder. A graded increase in clinical pathology and social dysfunction was observed with increasing severity of personality disorder. These findings suggest that a simple algorithm for recording severity of a personality disturbance had both construct validity and was useful in practice, which supports severity classification as a valuable concept. These findings need to be confirmed in other cultures and ethnic groups.

Intranasal Oxytocin Lessens the Attentional Bias to Adult Negative Faces: A Double Blind within-Subject Experiment.

Objective Oxytocin is a neuropeptide that is involved in social emotional processing. A leading hypothesis is that oxytocin facilitates positive prosocial behaviors; the peptide may also play a more general role in inhibiting withdrawal-related social behaviors. The present study examined these possibilities. Methods A double-blind, placebo controlled crossover design was used with 31 healthy women. Forty-five minutes following the administration of 40 IU of intranasal oxytocin or a placebo, the participants were presented with two dot probe tests with pairs of face stimuli depicting emotional and neutral faces in adults. Results Oxytocin specifically reduced the attention bias toward the location of the faces of adults showing negative emotions, particularly in the case of disgust. Oxytocin did not enhance the attentional bias toward adult happy faces. The effect of oxytocin toward adult negative emotion was correlated with the sensitivity of the drive in the behavioral motivational system. Conclusion Oxytocin reduces attention to negative social emotions in adults, which supports oxytocin serves to inhibit withdrawal-related social behaviour.

Childhood risk factors in Korean women with anorexia nervosa: Two sets of case-control studies with retrospective comparisons

OBJECTIVE The aim of this study was to investigate the characteristics of the risk factors for anorexia nervosa (AN) in Korean women. METHOD Two sets of case-control comparisons were conducted, in which 52 women with lifetime AN from Seoul, S. Korea, were compared with 108 Korean healthy controls and also with 42 women with lifetime AN from the UK in terms of their childhood risk factors. A questionnaire designed to conduct a retrospective assessment of the childhood risk factors was administered to all participants. RESULTS The Korean AN women were more likely to report premorbid anxiety, perfectionism, and emotional undereating and were less likely to report having supportive figures in their childhood than the Korean healthy controls. There were no overall differences in the childhood risk factors between the Korean and British women with AN. DISCUSSION Premorbid anxiety, perfectionism, less social support, and emotional undereating merit attention as risk factors in Korean AN. The current results are informative, but an epidemiologically robust prospective case-control study would be needed to validate these findings.

Preliminary field trial of a putative research algorithm for diagnosing ICD‐11 personality disorders in psychiatric patients: 2. Proposed trait domains

This field trial examines the discriminant validity of five trait domains of the originally proposed research algorithm for diagnosing International Classification of Diseases (ICD)-11 personality disorders. This trial was carried out in South Korea where a total of 124 patients with personality disorder participated in the study. Participants were assessed using originally proposed monothetic trait domains of asocial-schizoid, antisocial-dissocial, anxious-dependent, emotionally unstable and anankastic-obsessional groups of the research algorithm in ICD-11. Their assessments were compared to those from the Personality Assessment Schedule interview, and the five-factor model (FFM). A total of 48.4% of patients were found to have pathology in two or more domains. In the discriminant analysis, 64.2% of the grouped cases of the originally proposed ICD-11 domains were correctly classified by the five domain categories using the Personality Assessment Schedule, with the highest accuracy in the anankastic-obsessional domain and the lowest accuracy in the emotionally unstable domain. In comparison, the asocial-schizoid, anxious-dependent and the emotionally unstable domains were moderately correlated with the FFM, whereas the anankastic-obsessional or antisocial-dissocial domains were not significantly correlated with the FFM. In this field trial, we demonstrated the limited discriminant and the convergent validities of the originally proposed trait domains of the research algorithm for diagnosing ICD-11 personality disorder. The results suggest that the anankastic, asocial and dissocial domains show good discrimination, whereas the anxious-dependent and emotionally unstable ones overlap too much and have been subsequently revised.

Impaired Set-Shifting Ability in Patients with Eating Disorders, Which Is Not Moderated by Their Catechol-O-Methyltransferase Val158Met Genotype.

The aim of this study was to examine the set-shifting ability in women with both anorexia nervosa (AN) and bulimia nervosa (BN) and to investigate whether it is contributed by the catechol-O-methyltransferase (COMT) Val158Met genotype. A total of 102 Korean participants-40 women with lifetime AN, 28 women with lifetime BN, and 34 healthy women of comparable age and intelligence quotient- were examined. A neuropsychological battery of tests was applied and blood samples were obtained for COMT Val158Met genotyping. Set-shifting impairments Trail Making Test (TMT, Part B) were found in patients with AN and BN, respectively. Furthermore, the eating disorders were also linked to deficits in attentional mechanisms (TMT, Part A) and motor skills (Finger Tapping Test). Finally, set-shifting and its link to eating disorders were not moderated by COMT Val158Met genotype.

Long-term Escitalopram Treatment in Korean Patients with Panic Disorder: A Prospective, Naturalistic, Open-label, Multicenter Trial

Objective Panic disorder is characterized by recurrent panic attacks, persistent concerns about additional attacks, and worry about the implications of the attack or significant changes in behavior related to the attacks. We examined the efficacy of 24-week naturalistic, open-label escitalopram treatment in terms of the response and remission rates and functional disability in 119 adult Korean patients with panic disorder from 6 clinical centers in South Korea. Methods Clinical severity and functional impairment were assessed at baseline and at 4, 12, and 24 weeks after the treatment using the Panic Disorder Severity Scale and Sheehan Disability Scale. Ninety-six patients (80.7%) showed a treatment response, and 87 patients (73.1%) had attained remission after 24 weeks of escitalopram treatment. Results Continuous improvement in the Panic Disorder Severity Scale and Sheehan Disability Scale scores was found over the 24 weeks of treatment. Conclusion These findings suggest that escitalopram treatment is very effective for panic disorder in terms of both response and remission rates and that long-term pharmacotherapy with escitalopram continuously improved panic symptoms and functional disability in Korean patients with panic disorder.