Association between the Arylalkylamine N-Acetyltransferase (AANAT) Gene and Seasonality in Patients with Bipolar Disorder

Objective@#Bipolar disorder (BD) is complex genetic disorder. Therefore, approaches using clinical phenotypes such as biological rhythm disruption could be an alternative. In this study, we explored the relationship between melatonin pathway genes with circadian and seasonal rhythms of BD. @*Methods@#We recruited clinically stable patients with BD (n=324). We measured the seasonal variation of mood and behavior (seasonality), and circadian preference, on a lifetime basis. We analyzed 34 variants in four genes (MTNR1a, MTNR1b, AANAT, ASMT) involved in the melatonin pathway. @*Results@#Four variants were nominally associated with seasonality and circadian preference. After multiple test corrections, the rs116879618 in AANAT remained significantly associated with seasonality (corrected p=0.0151). When analyzing additional variants of AANAT through imputation, the rs117849139, rs77121614 and rs28936679 (corrected p=0.0086, 0.0154, and 0.0092) also showed a significant association with seasonality. @*Conclusion@#This is the first study reporting the relationship between variants of AANAT and seasonality in patients with BD. Since AANAT controls the level of melatonin production in accordance with light and darkness, this study suggests that melatonin may be involved in the pathogenesis of BD, which frequently shows a seasonality of behaviors and symptom manifestations.

The Mediating Effect of Psychological Distress on the Association between BDNF, 5-HTTLPR, and Tinnitus Severity

Objective@#To investigate the association between genetic polymorphisms of brain-derived neurotrophic factor (BDNF) or serotonin transporter gene-linked polymorphic region (5-HTTLPR) and tinnitus, and the mediating effects of psychological distress on this association. @*Methods@#Eighty-six patients experiencing tinnitus and 252 controls were recruited. The Tinnitus Handicap Inventory was used to assess the severity of tinnitus and the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory-II (BAI-II), and the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K) were used to assess psychological distress. We compared the association of BDNF rs6265 (Val66Met) and 5-HTTLPR variants in the two groups. The mediating effects of BDI-II, BAI-II, and BEPSI-K were examined using multiple regression analysis and validated by the Sobel test and bootstrapping. @*Results@#No significant differences were found between the groups regarding BDNF Val66Met and 5-HTTLPR, but the 5-HTTLPR variants trended toward association. Depressive symptoms appeared to act as a mediator on the relationship within the 5-HTTLPR s/s genotype and the severity of tinnitus. @*Conclusion@#Our findings provide a speculative idea on the association between the serotonergic system and tinnitus and suggest that depressive symptoms act as a mediator in tinnitus. Therefore, screening for depressive symptoms in patients with tinnitus is essential and intervention for depressive symptoms may help alleviate the severity of tinnitus.

Psychopathologic Profiles and Clusters in Tertiary Clinic Referred Patients with Adult Attention Deficit Hyperactivity Disorder: A Person-Centered Analysis

Objective@#Adult attention deficit hyperactivity disorder (ADHD) has a heterogeneous clinical presentation with patients showing very frequent emotional problems. In the present study, patients with adult ADHD were subtyped based on their psychopathology using a person-centered approach. @*Methods@#In the present chart review study, detailed findings of psychological evaluation conducted as part of routine care were utilized. A total of 77 subjects with adult ADHD were included in the analysis. Detailed ADHD symptoms, psychiatric comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses, and severity of mood and anxiety symptoms were evaluated in the person-centered analysis. @*Results@#Three clusters were generated using clustering analysis. DSM comorbid conditions did not significantly impact the clustering. Cluster 1 consisted of ADHD combined presentation (ADHD-C) with less mood symptoms, cluster 2 of ADHD predominantly inattentive presentation and cluster 3 of ADHD-C with significant mood symptoms. Patients in cluster 3 had adulthood functional impairment more frequently compared with patients in cluster 1. Patients in cluster 3 showed recurrent thoughts of death and suicidal ideation more frequently compared with patients in cluster 1. @*Conclusion@#Further studies are needed to confirm the relationships observed in the present study.

Polygenic Risk Scores for Bipolar Disorder in Korean Populations in Comparison to European Populations / 신경정신의학

Objectives@#This study examined whether the polygenic risk score (PRS) calculated from the most recent genome-wide association study for bipolar disorder (BD) of European ancestry patients is significantly associated with BD diagnosis in the Korean population. @*Methods@#The study included 417 Korean patients with BD and 497 healthy controls. Genotyping was performed using the Korean Biobank Array. Summary statistics of the European samples from the Psychiatric Genomic Consortium were used as base data to generate the PRS for each individual. The program PRSice-2 was used to calculate the PRS. Logistic regression was conducted to determine the association between BD diagnosis and PRS for BD after adjusting for age and sex. @*Results@#PRS for BD was significantly higher in patients diagnosed with BD compared to healthy controls. The PRS at the p-value threshold of 0.01 best explained the variance of BD after adjusting for age and sex (R2 =0.0061, p=0.039). Subgroup analyses were performed for bipolar I and II subgroups. In bipolar I patients, the PRS at the p-value threshold of 0.01 best explained the diagnosis (R2 =0.0165, p=0.0055), whereas no significant result was found for bipolar II patients. @*Conclusion@#PRS for BD calculated for the Korean sample showed a significant association with the BD diagnosis. This result suggests an overlapping genetic risk for BD between the European and Korean populations.

Association between the Arylalkylamine N-Acetyltransferase (AANAT) Gene and Seasonality in Patients with Bipolar Disorder

Objective@#Bipolar disorder (BD) is complex genetic disorder. Therefore, approaches using clinical phenotypes such as biological rhythm disruption could be an alternative. In this study, we explored the relationship between melatonin pathway genes with circadian and seasonal rhythms of BD. @*Methods@#We recruited clinically stable patients with BD (n=324). We measured the seasonal variation of mood and behavior (seasonality), and circadian preference, on a lifetime basis. We analyzed 34 variants in four genes (MTNR1a, MTNR1b, AANAT, ASMT) involved in the melatonin pathway. @*Results@#Four variants were nominally associated with seasonality and circadian preference. After multiple test corrections, the rs116879618 in AANAT remained significantly associated with seasonality (corrected p=0.0151). When analyzing additional variants of AANAT through imputation, the rs117849139, rs77121614 and rs28936679 (corrected p=0.0086, 0.0154, and 0.0092) also showed a significant association with seasonality. @*Conclusion@#This is the first study reporting the relationship between variants of AANAT and seasonality in patients with BD. Since AANAT controls the level of melatonin production in accordance with light and darkness, this study suggests that melatonin may be involved in the pathogenesis of BD, which frequently shows a seasonality of behaviors and symptom manifestations.

The Mediating Effect of Psychological Distress on the Association between BDNF, 5-HTTLPR, and Tinnitus Severity

Objective@#To investigate the association between genetic polymorphisms of brain-derived neurotrophic factor (BDNF) or serotonin transporter gene-linked polymorphic region (5-HTTLPR) and tinnitus, and the mediating effects of psychological distress on this association. @*Methods@#Eighty-six patients experiencing tinnitus and 252 controls were recruited. The Tinnitus Handicap Inventory was used to assess the severity of tinnitus and the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory-II (BAI-II), and the Korean version of the Brief Encounter Psychosocial Instrument (BEPSI-K) were used to assess psychological distress. We compared the association of BDNF rs6265 (Val66Met) and 5-HTTLPR variants in the two groups. The mediating effects of BDI-II, BAI-II, and BEPSI-K were examined using multiple regression analysis and validated by the Sobel test and bootstrapping. @*Results@#No significant differences were found between the groups regarding BDNF Val66Met and 5-HTTLPR, but the 5-HTTLPR variants trended toward association. Depressive symptoms appeared to act as a mediator on the relationship within the 5-HTTLPR s/s genotype and the severity of tinnitus. @*Conclusion@#Our findings provide a speculative idea on the association between the serotonergic system and tinnitus and suggest that depressive symptoms act as a mediator in tinnitus. Therefore, screening for depressive symptoms in patients with tinnitus is essential and intervention for depressive symptoms may help alleviate the severity of tinnitus.

Psychopathologic Profiles and Clusters in Tertiary Clinic Referred Patients with Adult Attention Deficit Hyperactivity Disorder: A Person-Centered Analysis

Objective@#Adult attention deficit hyperactivity disorder (ADHD) has a heterogeneous clinical presentation with patients showing very frequent emotional problems. In the present study, patients with adult ADHD were subtyped based on their psychopathology using a person-centered approach. @*Methods@#In the present chart review study, detailed findings of psychological evaluation conducted as part of routine care were utilized. A total of 77 subjects with adult ADHD were included in the analysis. Detailed ADHD symptoms, psychiatric comorbid Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnoses, and severity of mood and anxiety symptoms were evaluated in the person-centered analysis. @*Results@#Three clusters were generated using clustering analysis. DSM comorbid conditions did not significantly impact the clustering. Cluster 1 consisted of ADHD combined presentation (ADHD-C) with less mood symptoms, cluster 2 of ADHD predominantly inattentive presentation and cluster 3 of ADHD-C with significant mood symptoms. Patients in cluster 3 had adulthood functional impairment more frequently compared with patients in cluster 1. Patients in cluster 3 showed recurrent thoughts of death and suicidal ideation more frequently compared with patients in cluster 1. @*Conclusion@#Further studies are needed to confirm the relationships observed in the present study.

Polygenic Risk Scores for Bipolar Disorder in Korean Populations in Comparison to European Populations / 신경정신의학

Objectives@#This study examined whether the polygenic risk score (PRS) calculated from the most recent genome-wide association study for bipolar disorder (BD) of European ancestry patients is significantly associated with BD diagnosis in the Korean population. @*Methods@#The study included 417 Korean patients with BD and 497 healthy controls. Genotyping was performed using the Korean Biobank Array. Summary statistics of the European samples from the Psychiatric Genomic Consortium were used as base data to generate the PRS for each individual. The program PRSice-2 was used to calculate the PRS. Logistic regression was conducted to determine the association between BD diagnosis and PRS for BD after adjusting for age and sex. @*Results@#PRS for BD was significantly higher in patients diagnosed with BD compared to healthy controls. The PRS at the p-value threshold of 0.01 best explained the variance of BD after adjusting for age and sex (R2 =0.0061, p=0.039). Subgroup analyses were performed for bipolar I and II subgroups. In bipolar I patients, the PRS at the p-value threshold of 0.01 best explained the diagnosis (R2 =0.0165, p=0.0055), whereas no significant result was found for bipolar II patients. @*Conclusion@#PRS for BD calculated for the Korean sample showed a significant association with the BD diagnosis. This result suggests an overlapping genetic risk for BD between the European and Korean populations.

Comparison of Polygenic Risk for Schizophrenia between European and Korean Populations / 대한정신분열병학회지

Objectives@#This study aimed to explore whether common genetic variants that confer the risk of schizophrenia have similar effects between Korean and European ancestries using the polygenic risk score (PRS) analysis. @*Methods@#Study subjects included 713 Korean patients with schizophrenia and 497 healthy controls. The Korea Biobank array was used for genotyping. Summary statistics of the most recent genome-wide association study (GWAS) of the European population were used as baseline data to calculate PRS. Logistic regression was conducted to determine the association between calculated PRS of European patients with schizophrenia and clinical diagnosis of schizophrenia in the Korean population. @*Results@#Schizophrenia PRS was significantly higher in patients with schizophrenia than in healthy controls. The PRS at the pvalue threshold of 0.5 best explained the variance of schizophrenia (R2=0.028, p=4.4×10-6). The association was significant after adjusting for age and sex (odds ratio=1.34, 95% confidence interval=1.19-1.51, p=1.1×10−6). The pattern of the association remained similar across different p-value thresholds (0.01-1). @*Conclusion@#Schizophrenia PRS calculated using the European GWAS data showed a significant association with the clinical diagnosis of schizophrenia in the Korean population. Results suggest overlapping genetic risk variants between the two populations.

Clinical Correlates of False Positive Assignment in Bipolar Screening Measures Across Psychiatric Diagnoses among Patients without Bipolar Disorder

Objective@#In this study, we aimed to determine clinical correlates of false positive assignment (FPA) on commonly used bipolar screening questionnaires. @*Methods@#A retrospective chart review was conducted to a total of 3885 psychiatric outpatients. After excluding patients who have bipolar spectrum illnesses, patients who were assigned as having hypomania on the mood disorder questionnaire (MDQ) or the hypomania checklist-32 (HCL-32) were identified as patients who had FPA. Psychiatric diagnoses and severity of emotional symptoms were compared between patients with and without FPA. @*Results@#Patients with FPA on the MDQ showed significant associations with presence of major depressive disorder, generalized anxiety disorder, and alcohol-use disorder, while patients with FPA on the HCL-32 showed associations with presence of panic disorder and agoraphobia. FPA on the MDQ was also associated with greater emotional symptoms and lifetime history of suicide attempts. Logistic regression analysis showed that male sex, younger age, presence of alcohol-use disorder, and severity of depression and obsessive-compulsive symptoms were significantly associated with FPA on the MDQ. @*Conclusion@#The FPA for the MDQ was associated with clinical factors linked to trait impulsivity, and the FPA for both the MDQ and the HCL-32 could be related to increased anxiety.

Public Attention to Crime of Schizophrenia and Its Correlation with Use of Mental Health Services in Patients with Schizophrenia / 대한정신분열병학회지

OBJECTIVES: This study was performed to examine the effects of the public attention to ‘crime of schizophrenia’ on the use of mental health services in patients with schizophrenia using big data analysis. METHODS: Data on the frequency of internet searches for ‘crime of schizophrenia’ and the patterns of mental health service utilization by patients with schizophrenia spectrum disorders by month were collected from Naver big data and the Health Insurance Review and Assessment Services in Korea, respectively. Their correlations in the same and following month for lagged effect were examined. RESULTS: The number of outpatients correlated negatively with public attention to ‘crime of schizophrenia’ in the same month. The lagged relationship between public attention and the number of admissions in psychiatric wards was also found. In terms of sex differences, the use of outpatient services among female patients correlated negatively with public attention in the same month while the number of male patients' admissions in both same and following month correlated positively with public attention. CONCLUSION: These findings suggested that public attention to ‘crime of schizophrenia’ could negatively affect illness behavior in patients with schizophrenia.

Effects of Renaming Schizophrenia in Korea: from “Split-Mind Disorder” to “Attunement Disorder”

OBJECTIVE: Korean Neuropsychiatric Association changed the Korean name of schizophrenia from ‘Split-mind Disorder’ to ‘Attunement Disorder’ in 2012. This study assessed attitudes towards the renaming of schizophrenia among mental health practitioners (n=440), patients with schizophrenia and their guardians (n=396), and the university students (n=140) using self-administered questionnaires. METHODS: The questionnaire included items related to participants’ perception of the renaming of the disease, the nature of informing about the disease to confirm the effect of the name change. RESULTS: It was confirmed the notification rate of disease name by mental health practitioners was increased significantly after the renaming. Among patients and their guardians, 24.9% and 15.0%, respectively, perceived their own or the family member’s illness as ‘attunement disorder’. CONCLUSION: Patients and their guardians continue to display a low awareness about the name of the disease as ‘attunement disorder.’ However, mental health practitioners were found to be able to easily use the name ‘attunement disorder’ as a result of the increased notification rate of the new disease name.

Association between a Genetic Variant of CACNA1C and the Risk of Schizophrenia and Bipolar I Disorder Across Diagnostic Boundaries / 대한정신분열병학회지

OBJECTIVES: Genome-wide association studies (GWASs) and meta-analyses indicate that single-nucleotide polymorphisms (SNPs) in the a-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) gene increase the risk for schizophrenia and bipolar disorders (BDs). We investigated the association between the genetic variants on CACNA1C and schizophrenia and/or BDs in the Korean population. METHODS: A total of 582 patients with schizophrenia, 336 patients with BDs consisting of 179 bipolar I disorder (BD-I) and 157 bipolar II disorder (BD-II), and 502 healthy controls were recruited. Based on previous results from other populations, three SNPs (rs10848635, rs1006737, and rs4765905) were selected and genotype-wise association was evaluated using logistic regression analysis under additive, dominant and recessive genetic models. RESULTS: rs10848635 showed a significant association with schizophrenia (p=0.010), the combined schizophrenia and BD group (p=0.018), and the combined schizophrenia and BD-I group (p=0.011). The best fit model was dominant model for all of these phenotypes. The association remained significant after correction for multiple testing in schizophrenia and the combined schizophrenia and BD-I group. CONCLUSION: We identified a possible role of CACNA1C in the common susceptibility of schizophrenia and BD-I. However no association trend was observed for BD-II. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

The Association of the 2nd to 4th Digit Ratio with the Age of Onset and Metabolic Factors in Korean Patients with Schizophrenia

OBJECTIVES: The ratio of second to fourth digit length (2D : 4D) could be a potential epigenetic marker of sexual dimorphism reflecting prenatal testosterone exposure. Testosterone is known to affect the development of the brain through an epigenetic mechanism. The purpose of this study was to investigate the effects of exposure to fetal testosterone on the metabolic syndrome based on 2D : 4D of schizophrenia patients and the relationship with the age of onset of schizophrenia. METHODS: A total of 214 schizophrenia patients participated in this study. The participant's physical and blood tests were performed according to the American National Cholesterol Education Program's Third Amendment of the Metabolic Syndrome Diagnostic Criteria, and the 2D : 4D was measured by the method designed by McFadden. Data were statistically analyzed by t-test, Pearson's correlation analysis and multiple regression model analysis. RESULTS: 2D : 4D was significantly higher in female than male in both hands, and there was a statistically significant negative correlation between 2D : 4D and the age of onset of schizophrenia in male. However, 2D : 4D did not show statistically significant correlation with metabolic factors. CONCLUSIONS: Fetal testosterone suggests the possibility of affecting the age of onset of schizophrenia through the epigenetic mechanism, but there is no clear relationship with metabolic factors.

Prevalence of Metabolic Syndrome in Patients with Schizophrenia in Korea: A Multicenter Nationwide Cross-Sectional Study

OBJECTIVE: We designed a nationwide study with limited exclusion criteria to investigate the prevalence of metabolic syndrome (MetS) in Korea and its relationship with antipsychotic medications. METHODS: This multicenter, cross-sectional, and observational study included patients diagnosed with schizophrenia or schizoaffective disorder. Sixteen hospitals enrolled 845 patients aged 18 to 65 years prescribed any antipsychotic medication between August 2011 and August 2013. MetS was diagnosed using the criteria of the modified Adult Treatment Panel III of the National Cholesterol Education Program with the Korean abdominal obesity definition (waist circumference ≥85 cm in women, ≥90 cm in men). RESULTS: The prevalence of MetS in all patients was 36.5% and was significantly higher in men than women (men, 40.8%; women, 32.2%) and was significantly correlated with age [odds ratio (OR) 1.02] and duration of illness (OR 1.03). The prevalence of MetS across antipsychotic drugs in the major monotherapy group was as follows: 18.8% for quetiapine, 22.0% for aripiprazole, 33.3% for both amisulpride and paliperidone, 34.0% for olanzapine, 35% for risperidone, 39.4% for haloperidol, and 44.7% for clozapine. CONCLUSION: The prevalence of MetS is very high in patients with schizophrenia or schizoaffective disorder. Screening and monitoring of MetS is also strongly recommended.

Long-Term Treatment Response to Lithium and Valproate in Patients with Bipolar 1 Disorder Treated More Than 2 Years : A Retrospective Study

OBJECTIVES: Treatment response of bipolar disorders (BDs) to long-term mood stabilizers maintenance has not been well explored because of complicated clinical and treatment courses. This study aims at investigating long-term clinical response of BDs to lithium and/or valproate in a naturalistic setting of a tertiary-care university-affiliated hospital. METHODS: Subjects were 65 patients with bipolar I (BD-I) disorders who had been treated with lithium and/or valproate for more than two years at single bipolar disorder clinic. Long-term response to the best treatment based on treatment algorithms and the current clinical standard of care was retrospectively evaluated using the Alda Scale and the Clinical Global Impression Scale for use in bipolar illness (CGI-BP). Patients were classified into full responder and partial/non responder groups based on the total score of the Alda Scale with the cut-off score generated from the frequentist mixture analysis of the authors' previous study. RESULTS: The mean duration of treatment with the index medication was 69.2 months. Baseline demographic and clinical characteristics were not different among three mood stabilizer groups (valproate, lithium, and combination groups). Twenty-one subjects were classified into full responder group (32.3%). Treatment response assessed by the Alda Scale and CGI-BP scores was not different between lithium and valproate groups. The Alda Scale scores were well correlated with the CGI-BP scores (p < 0.05). CONCLUSIONS: One third of the patients showed a full response to the long-term lithium and/or valproate treatment in BD-I. The degree of response was similar between lithium and valproate groups.

Linkage and Association Analyses of Schizophrenia with Genetic Variations on Chromosome 22q11 in Koreans

OBJECTIVE: Chromosome 22q11 has been implicated as a susceptibility locus of schizophrenia. It also contains various candidate genes for which evidence of association with schizophrenia has been reported. To determine whether genetic variations in chromosome 22q11 are associated with schizophrenia in Koreans, we performed a linkage analysis and case-control association study. METHODS: Three microsatellite markers within a region of 4.35 Mb on 22q11 were genotyped for 47 multiplex schizophrenia families, and a non-parametric linkage analysis was applied. The association analysis was done with 227 unrelated patients and 292 normal controls. For 39 single nucleotide polymorphisms (SNPs) spanning a 1.4 Mb region (33 kb interval) containing four candidate schizophrenia genes (DGCR, COMT, PRODH and ZDHHC8), allele frequencies were estimated in pooled DNA samples. RESULTS: No significant linkage was found at any of the three microsatellite markers in single and multi-point analyses. Five SNPs showed suggestive evidence of association (p<0.05) and two more SNPs showed a trend for association (p<0.1) in pooled DNA association analysis. Individual genotyping was performed for those seven SNPs and four more intragenic SNPs. In this second analysis, all of the 11 SNPs individually genotyped did not show significant association. CONCLUSION: The present study suggests that genetic variations on chromosome 22q11 may not play a major role in Korean schizophrenia patients. Inadequate sample size, densities of genetic markers and differences between location of genetic markers of linkage and association can contribute to an explanation of the negative results of this study.

Tardive Dyskinesia and Tardive Dystonia with Second-Generation Antipsychotics in Bipolar Disorder Patients Unexposed to First-Generation Antipsychotics

OBJECTIVES: Second-generation antipsychotics (SGAs) are frequently used in the treatment of bipolar disorder. However, there is still no consensus on their risk of tardive movement syndromes especially for first-generation antipsychotics (FGAs)-naive patients. This study aimed to investigate the prevalence and associated factors of SGAs-related tardive dyskinesia and tardive dystonia in patients with bipolar disorder, in a naturalistic out-patient clinical setting. METHODS: The authors assessed 78 non-elderly patients with bipolar (n = 71) or schizoaffective disorder (n = 7) who received SGAs with a combined use of mood stabilizers for more than three months without previous exposure to FGAs. Multiple direct assessments were performed and hospital records longer than one recent year describing any observed tardive movement symptoms were also reviewed. RESULTS: The prevalence rates of tardive dyskinesia and tardive dystonia were 7.7% and 6.4%, respectively. These patients were being treated with ziprasidone, risperidone, olanzapine, quetiapine, or paliperidone at the time of the onset of the movement symptoms. Tardive dyskinesia was mostly observed in the orolingual area, and tardive dystonia was most frequently detected in oromandibular area. A past history of acute dystonia was significantly associated with presence of both tardive movement syndromes. CONCLUSIONS: Our findings suggest that SGAs-related tardive movement syndromes occur in a substantial portion of bipolar disorder patients. Acute dystonia, a reported risk factor of tardive movement syndromes in the era of FGAs is confirmed as a risk factor of both tardive dyskinesia and tardive dystonia that were induced-by SGAs.

Association Study of ANK3 Polymorphism and Risk of Schizophrenia

OBJECTIVES: Previous genome-wide association studies have indicated the association between ankyrin 3 (ANK3) and the vulnerability of schizophrenia. We investigated the association between single nucleotide polymorphisms (SNPs) covering the whole ANK3 locus and schizophrenia in the Korean population. METHODS: The study subjects were 582 patients with schizophrenia and 502 healthy controls. Thirty-eight tag SNPs on ANK3 and five additional SNPs showing significant association with schizophrenia in previous studies were genotyped. RESULTS: Three (rs10994181, rs16914791, rs1938526) of 43 SNPs showed a nominally significant association (p < 0.05) with at least one genotype model. But none of these associations remained significant after adjusting for multiple testing errors with Bonferroni's correction. CONCLUSIONS: We could not identify a significant association between ANK3 and schizophrenia in the Korean population. However, three SNPs showing an association signal with nominal significance need to be investigated in future studies with higher statistical power and more specific phenotype crossing the current diagnostic categories.

Correlation of Lifetime Symptom Dimensions with Cognitive Function and Other Clinical Characteristics in Schizophrenia Patients / 대한정신분열병학회지

OBJECTIVES: Considering large diversity of clinical presentation of schizophrenia, it is important to identify valid clinical subtypes or dimensions that might have homogeneous biological underpinning. The current study aimed to explore lifetime symptom-based dimensional phenotypes in patients with chronic schizophrenia, and to investigate their correlation with cognitive functions and other clinical characteristics. METHODS: Lifetime-based symptoms and additional clinical variables were measured using the Diagnostic Interview for Genetic Studies and the Schedule for the Deficit Syndrome in 315 clinically stable patients with chronic schizophrenia. Through principal components factor analysis, eight dimensional phenotypes were obtained. Comprehensive neuropsychological tests were administered for 103 out of 315 patients, and domain scores were calculated for cognitive domains defined in the MATRICS consensus battery. RESULTS: 'Non-paranoid delusion factor' including delusions of grandiose or religious nature, showed significant negative correlation with processing speed, working memory, attention/vigilance, and general cognitive ability, and positive correlation with intra-individual variability. 'Negative symptom factor' showed significant negative correlation only with general cognitive ability. Those two factors were also negatively correlated with function levels measured by Global Assessment Scale (GAS), and associated with poor treatment responses. CONCLUSION: Symptom-based dimensional phenotypes of schizophrenia measured on a lifetime basis showed discriminative correlation with cognitive function domains, global functioning level, and overall treatment responses, indicating their possibility as valid phenotype axes of schizophrenia having homogeneous biologic basis.