Seong Hoon Jeong

Circadian Rhythm Characteristics in Mood Disorders: Comparison among Bipolar I Disorder, Bipolar II Disorder and Recurrent Major Depressive Disorder

Objective Morningness/eveningness (M/E) is a stable characteristic of individuals. Circadian rhythms are altered in episodes of mood disorder. Mood disorder patients were more evening-type than normal population. In this study, we compared the characteristics of M/E among the 257 patients with bipolar I disorder (BPD1), bipolar II disorder (BPD2) and major depressive disorder, recurrent (MDDR). Methods M/E was evaluated using the Korean version of the composite scale of morningness (CS). Factor analysis was done to extract specific elements of circadian rhythm (morning preference, morning alertness, and evening tiredness). The total score and scores for factors and individual items of CS were compared in order to evaluate differences among the three different diagnostic groups. Factor scores of CS were different among the diagnostic groups. Results BPD1 subjects had a higher score for evening tiredness than BPD2 subjects (p=0.060), and BPD1 subjects had a significantly higher score for morning alertness than subjects with MDDR (p=0.034). This difference was even more profound for the representative item scores of each factor; item 2 of CS for evening tiredness (BPD1>BPD2, p=0.007) and item 5 of CS for morning alertness (BPD1>MDDR, p=0.002). Total score of CS were not different among 3 diagnostic groups. Conclusion Circadian rhythm characteristics measured by CS were different among BPD1, BPD2, and MDDR. BPD2 showed more eveningness than BPD1. MDDR showed less morningness than BPD1. CS would be a reasonable endophenotype associated with mood disorders. More studies with large sample size of mood disorders on M/E are warranted.

Genetic Role of BDNF Val66Met and 5-HTTLPR Polymorphisms on Depressive Disorder.

Objective We investigated possible association between depressive disorders and BDNF Val66Met and 5-HTTLPR. Brain derived neurotrophic factor (BDNF) gene and serotonin transporter (SLC6A4) gene are promising candidate genes for depressive disorders. It has been suggested that BDNF promotes the survival and differentiation of serotonergic neurons and that serotonergic transmission exerts powerful control over BDNF gene expression. Methods Final analyses were performed on 186 patients with depressive disorders and 1032 controls. Val66Met polymorphism of BDNF gene and 5-HTTLPR polymorphism of serotonin transporter gene were genotyped and allele and genotypic associations on the diagnosis of depression and age at onset of depression were analyzed. Results The 5-HTTLPR was positively associated with depressive affected status in the total sample and in females (p=0.038 for allelewise, p=0.015 for genotype-wise associations), but, not in males. The BDNF Val66Met showed no association with depression. BDNF Val66Met and 5-HTTLPR alone were not associated with age at onset of depression. Additional analysis on the interaction between BDNF Val66Met and 5-HTTLPR found a significant association with age at onset of depression in the entire patient group. This association was also found in the female but not in the male patient group. None of the positive results survived Bonferroni correction for multiple testing. Conclusion This result suggested that BDNF Val66Met and 5-HTTLPR may contribute to depressive disorders in a complex way and that the genetic effect could differ by gender. Further studies with large number of patients will be necessary.

Simultaneous Comparison of Efficacy and Tolerability of Second-Generation Antipsychotics in Schizophrenia: Mixed-Treatment Comparison Analysis Based on Head-to-Head Trial Data

Objective Second-generation antipsychotics have been repeatedly shown to be superior to placebo. However, the comparative efficacy among these drugs has not been systematically evaluated. In this study, we used Mixed Treatment Comparison (MTC) procedures to elucidate the comparative efficacy and tolerability of second-generation antipsychotics. Methods Seven antipsychotics were selected based on the availability of the relevant data. Data were gathered from a series of review article published by the Cochrane Collaboration. Six outcome measures were analyzed: 1) percentage of no clinically important response as defined by the original authors, 2) PANSS total score change from baseline to endpoint, 3) percentage of akathisia, 4) percentage of antiparkinson medication use, 5) percentage of total body weight increase more than 7%, and 6) percentage of drop-out due to any reasons. Results All the second-generation antipsychotics included in this study showed fairly similar efficacy but widely different tolerability. In terms of efficacy, amisulpride, clozapine and olanzapine were ranked higher than aripiprazole, quetiapine and ziprasidone. Clozapine and olanzapine were superior in terms of akathisia and extrapyramidal symptom risk, but, far more prone to induce clinically important weight gain. Conclusion Using MTC methodology, we could line up the second generation antipsychotics according to their hierarchical superiority in terms of efficacy and tolerability. Though the wide overlap among the confidence intervals and the inconsistency between the direct and indirect comparison results may limit the validity of these results, it may still allow the important insights into the relative merits of the available drugs.

Altered cardiorespiratory coupling in young male adults with excessive online gaming.

INTRODUCTION This study aimed to investigate changes in heart rate variability and cardiorespiratory coupling in male college students with problematic Internet use (PIU) excessive gaming type during action video game play to assess the relationship between PIU tendency and central autonomic regulation. METHOD Electrocardiograms and respiration were simultaneously recorded from 22 male participants with excessive online gaming and 22 controls during action video game play. Sample entropy (SampEn) was computed to assess autonomic regularity, and cross-SampEn was calculated to quantify autonomic coordination. RESULTS During video game play, reduced cardiorespiratory coupling (CRC) was observed in individuals with PIU excessive gaming type compared with controls, implicating central autonomic dysregulation. The PIU tendency was associated with the severity of autonomic dysregulation. CONCLUSION These findings indicate impaired CRC in PIU excessive gaming type, which may reflect alterations of central inhibitory control over autonomic responses to pleasurable online stimuli.

Electroconvulsive Seizure Alters the Expression and Daily Oscillation of Circadian Genes in the Rat Frontal Cortex

Objective Electroconvulsive therapy (ECT) is the most effective treatment for mood disorders. Accumulating evidence has suggested the important role of circadian genes in mood disorders. However, the effects of ECT on circadian genes have not been systemically investigated. Methods We examined the expression and daily oscillation of major circadian genes in the rat frontal cortex after electroconvulsive seizure (ECS). Results Firstly, mRNA and protein level were investigated at 24 hr after single ECS (E1X) and repeated ECS treatements for 10 days (E10X), which showed more remarkable changes after E10X than E1X. mRNA expression of Rorα, Bmal1, Clock, Per1, and Cry1 was decreased, while Rev-erbα expression was increased at 24 hr after E10X compared to sham. The proteins showed similar pattern of changes. Next, the effects on oscillation and rhythm properties (mesor, amplitude, and acrophase) were examined, which also showed more prominent changes after E10X than E1X. After E10X, mesor of Rorα, Bmal1, and Cry1 was reduced, and that of Rev-erbα was increased. Five genes, Rev-erbα, Bmal1, Per1, Per2, and Cry2, showed earlier acrophase after E10X. Conclusion The findings suggest that repeated ECS induces reduced expression and phase advance of major circadian genes in the in vivo rat frontal cortex.

T224. THE FUNCTIONAL CONNECTIVITY DERIVED WITH BIVARIATE ANALYSIS, COHERENCE AND PHASE LOCKING VALUE IN PATIENTS WITH SCHIZOPHRENIA UNDER CLOZAPINE

Abstract Background Coherence (COH) and Phase Locking Value (PLV) may have considerable potentials for investigating anomalies of functional connectivity in schizophrenia but results are still conflicting. This study is aimed to investigate relationships between plasma levels of clozapine (p-CZP) and norclozapine (p-NCZP), and total and cognitive factor scores of Positive and Negative Syndrome Scale (PANSS-T, -C), and functional connectivity by COH and PLV. Methods Fifty-eight patients who were diagnosed as schizophrenia with DSM-5 criteria and under CZP were recruited (duration of illness, 15.5 ± 8.0 years; duration of CZP, 6.8 ± 4.6 years; mean daily dose of CZP, 233.6 ± 88.4 mg). COH and PLV were calculated with Neurophysiological Biomarker Toolbox from qEEG and were averaged from the signals of electrodes in the designated brain regions, frontal (F), temporal (T), central (C) and occipitoparietal (OP). For interhemispheric connectivity, electrodes except all midline channels were combined into Odd (O) and Even (E). The results were presented at ≥0.30 of Spearman correlation. Results 1) Correlation coefficient between p-CZP and p-NCZP was 0.84, and those of CZP dose with p-CZP and p-NCZP were 0.38 and 0.53, respectively. 2) p-CZP showed correlations with OCEC in delta and alpha, OTEC in delta, OCEOP in theta, OTEF in alpha, and OOPEF in gamma band in COH, and OOPEOP in beta band in PLV. 3) p-NCZP showed correlations with ETEOP in delta, theta, and gamma, OCEC in delta and alpha, OFOC and OCEOP in delta, OFET and OTET in alpha, OCEF in beta, OOPEC in gamma band in COH, and with ETEOP in delta, theta, and beta, OTET and OCEC in alpha, OCEF in beta band in PLV. 4) CZP dose showed correlations with ETEC in beta and gamma, ETEOP in theta, OCEF in alpha, OTET in beta, OOPEF and OOPET in gamma band in COH, and with OTET in alpha and beta, ETEOP in theta, OTEOP in alpha, ETEC in beta, OFOC in gamma band in PLV. 5) PANSS-T showed correlations with OFEOP and EFEOP in alpha, OCEOP in beta, OTOC and OTEF in gamma band in COH, and with OTEF in beta and gamma, OFET in delta, OOPEF in beta, OTOC and OCEOP in gamma band in PLV. 6) PANSS-C showed correlations with EFEOP in delta, theta, alpha, and beta, OOPEOP in delta, alpha, and beta, OFET and OTEF both in alpha and beta, OOPEF in delta, OFEOP in alpha, OFEC and OCEOP in beta, OTOC in gamma band in COH, and with EFEOP in theta, alpha, and beta, OFEOP and OOPEOP both in alpha and beta, OFET in delta and beta, OTOC, OOPEF, OOPEOP in beta, OTOC and OCEOP in PLV. 7) PANSS-T and -C showed no correlations with p-CZP, p-NCZP and CZP dose. 8) However, the clinical and drug variables showed significant simultaneous correlation with certain functional connectivity, but sometimes the direction correlation was opposite. Discussion The relationship between functional connectivity and clozapine parameters seems to demonstrate inter- and intra-hemispheric connections in brain regions. However, there were same and/or opposite directions of correlations between COH and PLV dependent EEG band frequencies and clinical and drug variables. Taken together, investigating the functional connectivity with COH and PLV could give the information about p-CZP and p-NCZP before the laboratory reports, the degree of psychopathology in patients with schizophrenia under CZP, and the differentiations of surface symptoms whether derived from pathophysiology of schizophrenia or from clozapine effects.

Combination of Electroconvulsive Therapy and Clozapine in Treatment-Resistant Schizophrenia

Objective This study aimed to investigate the effectiveness and tolerability of the combination of electroconvulsive therapy (ECT) in patients with clozapine-treated schizophrenia. Methods Patients with clozapine-treated schizophrenia during five years of pre-determined period were recruited from Electronic Medical Record. Clinical effects of acute ECT on psychotic symptoms were investigated. We also tried to identify predictive variables requiring maintenance treatment of ECT. Results Fourteen patients received ECT and clozapine and sixteen were treated with clozapine alone. In the ECT group, which could be refined as clozapine-resistance, PANSS total score was significantly reduced by 19.0±9.9 points, corresponding to a reduction rate of 18.5±8.3%. The clinical remission defined as 20% PANSS reduction criteria was achieved at 42.9%. The subscale factors were significantly reduced, among which the negative symptom was the least. There was no difference in demographic and clinical information between patients receiving and not receiving maintenance ECT, and not all patients seemed to need maintenance ECT if clozapine is continued. Conclusion Combination of ECT and clozapine in patients with clozapine-resistant schizophrenia resulted in a rapid and substantial reduction of psychotic symptoms. Further studies are needed to improve the effectiveness and tolerability of ECT.

Comparison of clinician-rated and self-report insight in Korean patients with schizophrenia using VAGUS insight scale

This study was aimed to explore self-report auditory verbal hallucinations to provide unique and valuable information in addition to clinician-rated assessment in patients with schizophrenia. The VAGUS (http://www.vagusonline.com) is a recently developed insight scale that includes both clinician-rated (CR) and self-report (SR) versions. Insight measures obtained by the two versions of the VAGUS from the clinicians and the patients, respectively, in forty-one patients diagnosed with schizophrenia by DSM-IV-TR criteria were compared. Correlation coefficients for inter-scale convergence and 3-D biplots for multivariate relationship were derived from the subscales of the VAGUS. For external validation, correlation analyses with abridged version of Scale to Assess Unawareness in Mental Disorder (SUMD-A) and PANSS G12 item were conducted. Total scores of VAGUS-CR and -SR were 5.2 ± 2.6 and 4.9 ± 2.2, respectively. There was a strong correlation between them along with moderate pairwise correlations among the subscales. The 3-D biplots demonstrated that most subscales were clustered as a single factor apart from self-report Symptom Attribution separated as an independent factor. The VAGUS-CR, not -SR correlated significantly with the SUMD-A and PANSS G12. The utility of the VAGUS in reaching more overall understanding of the elusive phenomenon of insight in patients with schizophrenia is discussed.

Association between the 5-HTTLPR Genotype and Childhood Characteristics in Mood Disorders.

Objective The features of childhood attention deficit hyperactivity disorder (ADHD) are significantly associated with adult mood disorders. Some genetic factors may be common to both ADHD and mood disorders underlie the association between these two phenotypes. The present study aimed to determine whether a genetic role may be played by the serotonin transporter-linked polymorphic region (5-HTTLPR) in the childhood ADHD features of adult patients with mood disorders. Methods The present study included 232 patients with major depressive disorder (MDD), 154 patients with bipolar disorder (BPD), and 1,288 normal controls. Childhood ADHD features were assessed with the Korean version of the Wender Utah Rating Scale (WURS-K). The total score and the scores of three factors (impulsivity, inattention, and mood instability) from the WURS-K were analyzed to determine whether they were associated with the 5-HTTLPR genotype. Results In the BPD type II group, the 5-HTTLPR genotype was significantly associated with the total score (p=0.029) and the impulsivity factor (p=0.004) on the WURS-K. However, the inattention and mood instability factors were not associated with the 5-HTTLPR genotype. BPD type I, MDD and normal control groups did not exhibit any significant associations between the WURS-K scores and the 5-HTTLPR genotype. Conclusion The findings suggest that the 5-HTTLPR genotype may play a role in the impulsivity component of childhood ADHD in patients with BPD type II. Because of a small sample size and a single candidate gene, further studies investigating other candidate genes using a larger sample are warranted to determine any common genetic links.

Higher Immersive Tendency in Male University Students with Excessive Online Gaming

Although problems with online game use are gaining concerns, high-risk traits associated with excessive online gaming are not yet understood. Immersive tendency was suggested as the personality trait to behave playfully and to become involved in continuous stimuli. Because immersive tendency can be assessed through everyday activities, it may be used to find a risk group for excessive online gaming. We investigated the difference in immersive tendency, problematic online gaming, and problematic Internet use between 21 male university students with excessive online gaming and 21 matched controls. Higher immersive tendency was observed in participants with excessive online gaming. The immersive tendency can reflect an individual’s susceptibility to excessive online gaming.