Neuroablative Intervention for Refractory Obsessive-Compulsive Disorder

Objective@#This review aims to investigate the progression of neuroablation, along with documented clinical efficacy and safety, in the management of treatment-resistant obsessive-compulsive disorder (OCD). @*Methods@#We searched and compiled clinical research results of neuroablation therapy reported to date. We extracted outcomes related to clinical efficacy, side effects, and surgical complications. Additionally, we summarized key claims and findings. @*Results@#Neuroablative intervention is a potential treatment approach for refractory OCD. Recent advancements, such as real-time magnetic resonance monitoring and minimally invasive techniques employing ultrasound and laser, offer distinct advantages in terms of safety and comparative efficacy when compared to conventional methods. However, the absence of randomized controlled trials and long-term outcome data underscores the need for cautious consideration when selecting neuroablation. @*Conclusion@#Neuroablative intervention shows promise for refractory OCD, but vigilant consideration is essential in both patient selection and surgical method choices due to the potential for rare yet serious complications.

Examining the Psychometric Properties and Clinical Correlates of the Korean Version of the Family Accommodation Scale-Self-Rated Version for Obsessive-Compulsive Disorder

Objective@#We aimed to develop a Korean version of the Family Accommodation Scale-Self-Rated (FAS-SR), to investigate its reliability and validity and to study the clinical correlates of family accommodation in families with obsessive compulsive disorder (OCD) patient. @*Methods@#The FAS-SR was translated into Korean under the original author’s supervision. Forty-two patients with OCD and their closest relatives participated. The internal consistency was estimated using Cronbach’s alpha and the split half method. Convergent and divergent validity were identified by measuring with other clinical variables. Test-retest reliability was also calculated. @*Results@#The reliability analyses showed that Korean version of the FAS-SR demonstrated excellent internal consistency (Cronbach’s alpha=0.91) and test-retest reliability (Intraclass correlation coefficient=0.93). It showed good convergent validity when simultaneously assessed OCD symptom severity, global functioning and relative’s psychological distress. @*Conclusion@#The findings suggest that Korean version of the FAS-SR is a reliable and valid tool for assessing family accommodation in Korean patients with OCD in both research and clinical settings.

Similarities of Aspects of Biological Rhythms between Major Depression and Bipolar II Disorder Compared to Bipolar I Disorder: A Finding from the Early-Onset Mood Disorder Cohort

OBJECTIVE: The biological rhythm is closely related to mood symptoms. The purpose of this study was to assess the differences in biological rhythms among subjects with mood disorder [bipolar I disorder (BD I), bipolar II disorder (BD II), major depressive disorder (MDD)] and healthy control subjects.METHODS: A total of 462 early-onset mood disorder subjects were recruited from nine hospitals. The controls subjects were recruited from the general population of South Korea. Subject groups and control subject were evaluated for the Korean language version of Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN) at the initial evaluation.RESULTS: The mean K-BRIAN scores were 35.59 [standard deviation (SD)=13.37] for BD I, 43.05 (SD=11.85) for BD II, 43.55 (SD=12.22) for MDD, and 29.1 (SD=8.15) for the control group. In the case of mood disorders, biological rhythm disturbances were greater than that in the control group (p<0.05). A significant difference existed between BD I and BD II (BD I <BD II, p<0.001) and between BD I and MDD (BD I<MDD, p< 0.001) but no difference was observed between BD II and MDD.CONCLUSION: BD II and MDD are similar to each other but different from BD I in biological rhythm patterns in early-onset mood disorder cases. Biological rhythm disturbances are similar for early-onset major depression and BD II.

Possible Association of the Ubiquitin-Specific Peptidase 46 Gene (USP46) with Affective Temperamental Traits in Healthy Korean Volunteers

OBJECTIVE: Ubiquitin-specific peptidase 46 gene (USP46) polymorphisms is part of ubiquitin-proteasome system, which is responsible for dynamic cellular processes such as the regulation of cell cycle. USP46 has been reported to be associated with major depressive disorder. The objective of the present study was to investigate the association of USP46 polymorphisms with affective temperamental traits in healthy subjects. METHODS: A total of 557 Korean healthy volunteers were recruited, and 545 subjects (328 male, 217 female) were included in the final analysis. The DNA of the subjects was isolated from saliva samples. Two single-nucleotide polymorphisms (SNPs) rs346005, rs2244291 in USP46 were genotyped. Affective temperaments were assessed using the Korean version of Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). RESULTS: A significant association was found between rs346005 genotypes and TEMPS-A only in male subjects. In particular, subjects with the CC genotype of rs346005 showed a more depressive temperament than subjects with AA or CA genotypes in males. For rs2244291, there were no associations between the rs2244291 genotypes and TEMPS-A scores. CONCLUSION: Some affective temperaments may serve as a genetic predisposing factors for affective disorders, such as depressive disorder, via vulnerability genes related to the ubiquitin-proteasome system.

The Bodily Panic Symptoms and Predisposing Stressors in Korean Patients with Panic Disorder / 신경정신의학

OBJECTIVES@#The purpose of this study was to investigate the distinctive features of bodily panic symptoms and the predisposing conditions in Korean patients with panic disorder.@*METHODS@#This was a retrospective chart review study and the data were collected from twelve university-affiliated hospitals in Korea. The patients selected met the diagnostic criteria for panic disorder, were older than 20 years of age, and had initially visited a psychiatry department. The assessments included the chief complaints related to bodily panic symptoms, recent stressors, recent history of alcohol and sleep problems, and time to visit an outpatient clinic.@*RESULTS@#A total of 814 participants were included in the study. The most commonly experienced symptoms were cardiovascular and respiratory symptoms, which were observed in 63.9% and 55.4% of participants, respectively. Just before the onset of a panic attack, 25.6% of participants experienced sleep-related problems. Episodic binge drinking was also frequently observed (13.2%) and was more prevalent in men than in women (22.6% vs. 4.9%, p<0.001). About 75% of participants experienced stressful life events just before panic onset. Work-related issues were more prevalent in men than in women (22.0% vs. 13.4%, p=0.001). Family-related issues (4.8% vs. 14.1%, p<0.001) and conflict with a spouse or partner (4.0% vs.11.7%, p<0.001) were more prominent in women than in men.@*CONCLUSION@#Our results suggest that cardiovascular symptoms are the most common bodily panic symptoms in Korean patients. Our results suggest that a substantial portion of the Korean patients experienced stressful life events, sleep problems, and/or episodic binge drinking just before the onset of panic disorder.

Pharmacological Treatment Strategies for Acute Bipolar Depression / 신경정신의학

Of the different phases of bipolar disorder, bipolar depression is more prevailing and is more difficult to treat. However, there is a deficit in systemic research on the pharmacological treatment of acute bipolar depression. Therefore, consensuses on the pharmacological treatment strategies of acute bipolar depression has yet to be made. Currently, there are only three drugs approved by the Food and Drug Administration for acute bipolar depression : quetiapine, olanzapine-fluoxetine complex, and lurasidone. In clinical practice, other drugs such as mood stabilizers (lamotrigine, lithium, valproate) and/or the other atypical antipsychotics (aripiprazole, risperidone, ziprasidone) are frequently prescribed. There remains controversy on the use of antidepressants in bipolar depression. Here, we summarized the evidence of current pharmacological treatment options and reviewed treatment guidelines of acute bipolar depression from recently published studies.

The Potential Usefulness of Magnetic Resonance Guided Focused Ultrasound for Obsessive Compulsive Disorders

Obsessive compulsive disorder is a debilitating condition characterized by recurrent obsessive thoughts and compulsive reactions. A great portion of the obsessive compulsive disorder (OCD) patients are managed successfully with psychiatric treatment such as selective serotonin-reuptake inhibitor and cognitive behavioral psychotherapy, but more than 10% of patients are remained as non-responder who needs neurosurgical treatments. These patients are potential candidates for the neurosurgical management. There had been various kind of operation, lesioning such as leucotomy or cingulotomy or capsulotomy or limbic leucotomy, and with advent of stereotaxic approach and technical advances, deep brain stimulation was more chosen by neurosurgeon due to its characteristic of reversibility and adjustability. Gamma knife radiosurgery are also applied to make lesion targeting based on magnetic resonance (MR) imaging, but the complication of adverse radiation effect is not predictable. In the neurosurgical field, MR guided focused ultrasound has advantage of less invasiveness, real-time monitored procedure which is now growing to attempt to apply for various brain disorder. In this review, the neurosurgical treatment modalities for the treatment of OCD will be briefly reviewed and the current state of MR guided focused ultrasound for OCD will be suggested.

The Potential Usefulness of Magnetic Resonance Guided Focused Ultrasound for Obsessive Compulsive Disorders

Obsessive compulsive disorder is a debilitating condition characterized by recurrent obsessive thoughts and compulsive reactions. A great portion of the obsessive compulsive disorder (OCD) patients are managed successfully with psychiatric treatment such as selective serotonin-reuptake inhibitor and cognitive behavioral psychotherapy, but more than 10% of patients are remained as non-responder who needs neurosurgical treatments. These patients are potential candidates for the neurosurgical management. There had been various kind of operation, lesioning such as leucotomy or cingulotomy or capsulotomy or limbic leucotomy, and with advent of stereotaxic approach and technical advances, deep brain stimulation was more chosen by neurosurgeon due to its characteristic of reversibility and adjustability. Gamma knife radiosurgery are also applied to make lesion targeting based on magnetic resonance (MR) imaging, but the complication of adverse radiation effect is not predictable. In the neurosurgical field, MR guided focused ultrasound has advantage of less invasiveness, real-time monitored procedure which is now growing to attempt to apply for various brain disorder. In this review, the neurosurgical treatment modalities for the treatment of OCD will be briefly reviewed and the current state of MR guided focused ultrasound for OCD will be suggested.

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

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

Design and Methods of the Mood Disorder Cohort Research Consortium (MDCRC) Study

The Mood Disorder Cohort Research Consortium (MDCRC) study is designed as a naturalistic observational prospective cohort study for early-onset mood disorders (major depressive disorders, bipolar disorders type 1 and 2) in South Korea. The study subjects consist of two populations: 1) patients with mood disorders under 25 years old and 2) patients with mood disorders within 2 years of treatment under 35 years old. After successful screening, the subjects are evaluated using baseline assessments and serial follow-up assessments at 3-month intervals. Between the follow-up assessments, subjects are dictated to check their own daily mood status before bedtime using the eMood chart application or a paper mood diary. At the regular visits every 3 months, inter-visit assessments are evaluated based on daily mood charts and interviews with patients. In addition to the daily mood chart, sleep quality, inter-visit major and minor mood episodes, stressful life events, and medical usage pattern with medical expenses are also assessed. Genomic DNA from blood is obtained for genomic analyses. From the MDCRC study, the clinical course, prognosis, and related factors of early-onset mood disorders can be clarified. The MDCRC is also able to facilitate translational research for mood disorders and provide a resource for the convergence study of mood disorders.

Association between the Catechol-O-Methyltransferase (COMT) Val(158)Met Polymorphism and Alexithymia in Patients with Obsessive-Compulsive Disorder

PURPOSE: Alexithymia, defined as a deficit in the ability to recognize and describe one's own feelings, may be related to the development and maintenance of obsessive-compulsive symptoms. The aim of this study was to evaluate the association between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and alexithymia in patients with obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: We recruited 244 patients with OCD (169 males, 75 females). Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20), and genotyping of the COMT Val(158)Met polymorphism was evaluated. RESULTS: Patients with the COMT Val/Val genotype had significantly higher total and "difficulty identifying feelings" (DIF) subdimension scores than those with the Val/Met or Met/Met genotypes. Patients with the COMT Val/Val genotype had significantly higher "difficulty describing feelings" (DDF) subdimension scores than those with the COMT Val/Met genotype. However, there were no differences in the scores for the "externally oriented thinking" (EOT) subdimension among the three genotypes. CONCLUSION: These results indicate that the high-activity Val allele of the COMT Val(158)Met polymorphism is associated with increased alexithymic traits in patients with OCD. The present finding suggests that alexithymia is an endophenotype of OCD that is mediated by the COMT Val(158)Met polymorphism.

Review of Cohort Studies for Mood Disorders

This paper aimed to review currently available cohort studies of subjects with mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD). Using the PubMed and KoreaMed databases, we reviewed eight major cohort studies. Most studies recruited participants with MDD and BD separately, so direct comparison of factors associated with diagnostic changes was difficult. Regular and frequent follow-up evaluations utilizing objective mood ratings and standardized evaluation methods in a naturalistic fashion are necessary to determine detailed clinical courses of mood disorders. Further, biological samples should also be collected to incorporate clinical findings in the development of new diagnostic and therapeutic approaches. An innovative cohort study that can serve as a platform for translational research for treatment and prevention of mood disorders is critical in determining clinical, psychosocial, neurobiological and genetic factors associated with long-term courses and consequences of mood disorders in Korean patients.

The Relationship between Risk Taking, Impulsivity and Intolerance of Uncertainty

OBJECTIVES: Risk taking has been implicated in the development of various psychiatric disorders. Previous studies have indicated that risk taking behavior is associated with high levels of impulsiveness. Risk taking entail uncertain situation that outcome probability is unknown. This study tested impulsivity, intolerance of uncertainty and risk taking behavior. METHODS: A total of 73 participants completed a test battery comprised of the UPPS-P scale as a psychometric measurement of five dimensions of impulsivity, Intolerance of Uncertainty Scale, and Balloon Analog Risk Task (BART) as a behavioral measure of risk taking. The Pearson correlation analysis was used. RESULTS: The sensation seeking factor was positively correlated with BART measure (r = 0.27, p = 0.02). Specifically, the relationship between sensation seeking and BART was significant in females. CONCLUSIONS: Among the five factors of UPPS-P, only the sensation seeking factor predicts risk taking propensity.

Relationships between Chronotypes and Temperament and Character Dimensions in Healthy Young Adults

OBJECTIVES: Circadian rhythms have been known to have associations with psychiatric disorders and personality traits. The present study investigated the relationships between circadian typology and temperaments/characters in a non-clinical Korean population. METHODS: Two hundred six healthy Korean college students (male 109, female 97) participated in this study. The subjects completed the Composite Scale of Morningness for circadian typology and 140-item Temperament and Character Inventory-Revised-Short version (TCI-RS). RESULTS: Multivariate analyses of covariance showed a significant association between chronotypes and temperamental dimensions of the TCI-RS. Morning types were significantly associated with lower harm avoidance and higher persistence and self-directedness dimensions, compared to evening types and intermediate types. No interaction effects between sex and chronotypes were shown for temperamental dimensions. CONCLUSIONS: The present findings suggest that high persistence and self-directedness characters are related to morning types and high harm avoidance temperament is more related to evening types.

Is the GABA System Related to the Social Competence Improvement Effect of Aripiprazole? An 18F-Fluoroflumazenil PET Study

OBJECTIVE: Patients with schizophrenia who are treated with aripiprazole experience some benefits including an improvement of social competence, but the underlying mechanism of this improvement has not been investigated yet. This study aimed to provide preliminary evidence that the GABA system may be involved in the effect of aripiprazole on social competence. METHODS: Seventeen outpatients with schizophrenia (9 taking aripiprazole and 8 taking risperidone) and 18 healthy controls underwent 18F-fluoroflumazenil PET, and GABAA receptor binding potential was compared between the three groups. RESULTS: Voxelwise one-way ANOVA showed that GABAA receptor binding potentials in the right medial prefrontal cortex (p=0.04) and right dorsolateral prefrontal cortex (p=0.02) were significantly lower in the aripiprazole group than the risperidone group, and those in the left frontopolar cortex (p=0.03) and right premotor cortex (p=0.02) were significantly lower in the aripiprazole group than the risperidone and control groups. CONCLUSION: Our results suggest that aripiprazole administration results in increased GABA transmission in the prefrontal regions, and that these increases may be a neural basis of aripiprazole's clinical benefits on an improvement of social competence.

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

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

Association of the Brain-derived Neurotrophic Factor Gene and Clinical Features of Bipolar Disorder in Korea

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) plays an important role in cell survival, differentiation, and cell death as well as in neural plasticity. Recent studies have suggested that BDNF is involved in the pathogenesis of bipolar disorder. The aim of this study was to investigate the association of the genetic variations of the BDNF gene with bipolar disorder in Korea. We also studied the possible association of these genetic variants with clinical features. METHODS: The allelic and genotypic distributions of Val66Met polymorphism of the BDNF gene were analyzed using a polymerase chain reaction-based method in 184 bipolar patients and 214 controls. Analysis was performed to investigate an association of the Val66Met polymorphism of the BDNF gene and the clinical features in bipolar patients. RESULTS: No significant difference was found between bipolar patients and controls in the genotype and allele frequencies for the investigated BDNF polymorphism. However, the age of onset of bipolar disorder among the Val/Val (25.57), Val/Met (30.42) and Met/Met (32.45) genotype groups were significantly different (p=0.037). CONCLUSION: This study suggests that Val66Met polymorphisms are unlikely to contribution to the genetic predisposition to bipolar disorder as a whole. But Val66Met polymorphism may be associated with age of onset of the disorder, further studies designed to investigate the relationship in a larger population may be warranted.

Clinical Case Conference / 신경정신의학

No abstract available.

Genome-Wide Association Study in Psychiatric Disorders / 신경정신의학

Most psychiatric disorders are some kinds of complex genetic traits. Identifying the causal genes of psychiatric disorders has been challenging. Through recent revolutionary advances, such as the HapMap Project and the development of high-throughput genotyping chips, the genome-wide association study (GWAS) has recently become possible and is now in the spotlight in psychiatric genetics. In this article, we reviewed the concepts, rationale, designs and general steps of GWAS, and also introduced a few previous GWAS of several psychiatric disorders.

Genome-Wide Association Study in Psychiatric Disorders / 신경정신의학

Most psychiatric disorders are some kinds of complex genetic traits. Identifying the causal genes of psychiatric disorders has been challenging. Through recent revolutionary advances, such as the HapMap Project and the development of high-throughput genotyping chips, the genome-wide association study (GWAS) has recently become possible and is now in the spotlight in psychiatric genetics. In this article, we reviewed the concepts, rationale, designs and general steps of GWAS, and also introduced a few previous GWAS of several psychiatric disorders.