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1. Integrated proteomic and genomic analysis to identify predictive biomarkers for valproate response in bipolar disorder: a 6-month follow-up study

Author

Hyunju Lee, Dohyun Han, Kyung Sue Hong, Kyooseob Ha, Hyeyoon Kim, Eun Young Cho, Woojae Myung, Sang Jin Rhee, Jayoun Kim, Tae Hyon Ha, Kang Eun Lee, Hye Won Jung, Yejin Lee, Dongbin Lee, Hyeona Yu, Daseul Lee, Yun Seong Park, Yong Min Ahn, Ji Hyun Baek, and Se Hyun Kim

Subjects
Bipolar disorder, Valproate, Genomics, Proteomics, Biomarkers, Precision medicine, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract

Abstract Background Several genetic studies have been undertaken to elucidate the intricate interplay between genetics and drug responses in bipolar disorder (BD). However, there has been notably limited research on biomarkers specifically linked to valproate, with only a few studies investigating integrated proteomic and genomic factors in response to valproate treatment. Therefore, this study aimed to identify biological markers for the therapeutic response to valproate treatment in BD. Patients with BD in remission were assessed only at baseline, whereas those experiencing acute mood episodes were evaluated at three points (baseline, 8 ± 2 weeks, and 6 ± 1 months). The response to valproate treatment was measured using the Alda scale, with individuals scoring an Alda A score ≥ 5 categorized into the acute-valproate responder (acute-VPAR) group. We analyzed 158 peptides (92 proteins) from peripheral blood samples using multiple reaction monitoring mass spectrometry, and proteomic result-guided candidate gene association analyses, with 1,627 single nucleotide variants (SNVs), were performed using the Korean chip. Results The markers of 37 peptides (27 protein) showed temporal upregulation, indicating possible association with response to valproate treatment. A total of 58 SNVs in 22 genes and 37 SNVs in 16 genes showed nominally significant associations with the Alda A continuous score and the acute-VPAR group, respectively. No SNVs reached the genome-wide significance threshold; however, three SNVs (rs115788299, rs11563197, and rs117669164) in the secreted phosphoprotein 2 gene reached a gene-based false discovery rate-corrected significance threshold with response to valproate treatment. Significant markers were associated with the pathophysiological processes of bipolar disorders, including the immune response, acute phase reaction, and coagulation cascade. These results suggest that valproate effectively suppresses mechanisms associated with disease progression. Conclusions The markers identified in this study could be valuable indicators of the underlying mechanisms associated with response to valproate treatment.

Published
2024
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2. Latent class analysis of psychotic-affective disorders with data-driven plasma proteomics

Author

Sang Jin Rhee, Dongyoon Shin, Daun Shin, Yoojin Song, Eun-Jeong Joo, Hee Yeon Jung, Sungwon Roh, Sang-Hyuk Lee, Hyeyoung Kim, Minji Bang, Kyu Young Lee, Se Hyun Kim, Minah Kim, Jihyeon Lee, Jaenyeon Kim, Yeongshin Kim, Jun Soo Kwon, Kyooseob Ha, Youngsoo Kim, and Yong Min Ahn

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Data-driven approaches to subtype transdiagnostic samples are important for understanding heterogeneity within disorders and overlap between disorders. Thus, this study was conducted to determine whether plasma proteomics-based clustering could subtype patients with transdiagnostic psychotic-affective disorder diagnoses. The study population included 504 patients with schizophrenia, bipolar disorder, and major depressive disorder and 160 healthy controls, aged 19 to 65 years. Multiple reaction monitoring was performed using plasma samples from each individual. Pathologic peptides were determined by linear regression between patients and healthy controls. Latent class analysis was conducted in patients after peptide values were stratified by sex and divided into tertile values. Significant demographic and clinical characteristics were determined for the latent clusters. The latent class analysis was repeated when healthy controls were included. Twelve peptides were significantly different between the patients and healthy controls after controlling for significant covariates. Latent class analysis based on these peptides after stratification by sex revealed two distinct classes of patients. The negative symptom factor of the Brief Psychiatric Rating Scale was significantly different between the classes (t = −2.070, p = 0.039). When healthy controls were included, two latent classes were identified, and the negative symptom factor of the Brief Psychiatric Rating Scale was still significant (t = −2.372, p = 0.018). In conclusion, negative symptoms should be considered a significant biological aspect for understanding the heterogeneity and overlap of psychotic-affective disorders.

Published
2023
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3. Using brain cell-type-specific protein interactomes to interpret neurodevelopmental genetic signals in schizophrenia

Author

Yu-Han H. Hsu, Greta Pintacuda, Ruize Liu, Eugeniu Nacu, April Kim, Kalliopi Tsafou, Natalie Petrossian, William Crotty, Jung Min Suh, Jackson Riseman, Jacqueline M. Martin, Julia C. Biagini, Daya Mena, Joshua K.T. Ching, Edyta Malolepsza, Taibo Li, Tarjinder Singh, Tian Ge, Shawn B. Egri, Benjamin Tanenbaum, Caroline R. Stanclift, Annie M. Apffel, Steven A. Carr, Monica Schenone, Jake Jaffe, Nadine Fornelos, Hailiang Huang, Kevin C. Eggan, Kasper Lage, Stephan Ripke, Benjamin M. Neale, Aiden Corvin, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Martin Begemann, Richard A. Belliveau, Jr., Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberley D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chan, Eric Y.H. Chen, Wei Cheng, Eric FC. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Franziska Degenhardt, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Srdjan Djurovic, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Ina Giegling, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Marian L. Hamshere, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Annette M. Hartmann, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, David M. Hougaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, James A. Knowles, Bettina Konte, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Patrik K.E. Magnusson, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Andrew M. McIntosh, Sandra Meier, Carin J. Meijer, Bela Melegh, Ingrid Melle, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Lili Milani, Vihra Milanova, Younes Mokrab, Derek W. Morris, Ole Mors, Kieran C. Murphy, Robin M. Murray, Inez Myin-Germeys, Bertram Müller-Myhsok, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O'Callaghan, Colm O'Dushlaine, F. Anthony O'Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Michele T. Pato, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Alan R. Sanders, Ulrich Schall, Christian R. Schubert, Thomas G. Schulze, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Jianxin Shi, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Jordan W. Smoller, Hon-Cheong So, Chris C.A. Spencer, Eli A. Stahl, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Rolf Adolfsson, Ole A. Andreassen, Douglas H.R. Blackwood, Elvira Bramon, Joseph D. Buxbaum, Anders D. Børglum, Sven Cichon, Ariel Darvasi, Enrico Domenici, Hannelore Ehrenreich, Tõnu Esko, Pablo V. Gejman, Michael Gill, Hugh Gurling, Christina M. Hultman, Nakao Iwata, Assen V. Jablensky, Erik G. Jönsson, Kenneth S. Kendler, George Kirov, Jo Knight, Todd Lencz, Douglas F. Levinson, Qingqin S. Li, Jianjun Liu, Anil K. Malhotra, Steven A. McCarroll, Andrew McQuillin, Jennifer L. Moran, Preben B. Mortensen, Bryan J. Mowry, Markus M. Nöthen, Roel A. Ophoff, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Tracey L. Petryshen, Danielle Posthuma, Marcella Rietschel, Brien P. Riley, Dan Rujescu, Pak C. Sham, Pamela Sklar, David St Clair, Daniel R. Weinberger, Jens R. Wendland, Thomas Werge, Mark J. Daly, Patrick F. Sullivan, Michael C. O'Donovan, Shengying Qin, Akira Sawa, Rene Kahn, Kyung Sue Hong, Wenzhao Shi, Ming Tsuang, Masanari Itokawa, Gang Feng, Stephen J. Glatt, Xiancang Ma, Jinsong Tang, Yunfeng Ruan, Feng Zhu, Yasue Horiuchi, Byung Dae Lee, Eun-Jeong Joo, Woojae Myung, Kyooseob Ha, Hong-Hee Won, Ji Hyung Baek, Young Chul Chung, Sung-Wan Kim, Agung Kusumawardhani, Wei J. Chen, Hai-Gwo Hwu, Akitoyo Hishimoto, Ikuo Otsuka, Ichiro Sora, Tomoko Toyota, Takeo Yoshikawa, Hiroshi Kunugi, Kotaro Hattori, Sayuri Ishiwata, Shusuke Numata, Tetsuro Ohmori, Makoto Arai, Yuji Ozeki, Kumiko Fujii, Se Joo Kim, Heon-Jeong Lee, Yong Min Ahn, Se Hyun Kim, Kazufumi Akiyama, Kazutaka Shimoda, and Makoto Kinoshita

Subjects
Molecular interaction, Developmental neuroscience, Cellular neuroscience, Proteomics, Science
Abstract

Summary: Genetics have nominated many schizophrenia risk genes and identified convergent signals between schizophrenia and neurodevelopmental disorders. However, functional interpretation of the nominated genes in the relevant brain cell types is often lacking. We executed interaction proteomics for six schizophrenia risk genes that have also been implicated in neurodevelopment in human induced cortical neurons. The resulting protein network is enriched for common variant risk of schizophrenia in Europeans and East Asians, is down-regulated in layer 5/6 cortical neurons of individuals affected by schizophrenia, and can complement fine-mapping and eQTL data to prioritize additional genes in GWAS loci. A sub-network centered on HCN1 is enriched for common variant risk and contains proteins (HCN4 and AKAP11) enriched for rare protein-truncating mutations in individuals with schizophrenia and bipolar disorder. Our findings showcase brain cell-type-specific interactomes as an organizing framework to facilitate interpretation of genetic and transcriptomic data in schizophrenia and its related disorders.

Published
2023
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4. Dissecting the genetic architecture of suicide attempt and repeated attempts in Korean patients with bipolar disorder using polygenic risk scores

Author

Dongbin Lee, Ji Hyun Baek, Kyooseob Ha, Eun-Young Cho, Yujin Choi, So-Yung Yang, Ji Sun Kim, Yunji Cho, Hong-Hee Won, and Kyung Sue Hong

Subjects
Suicide attempt, Repeated attempts, Bipolar disorder, Polygenic risk score, Obsessive–compulsive disorder, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495
Abstract

Abstract Background Bipolar disorder (BD) has the greatest suicide risk among mental and physical disorders. A recent genome-wide association study (GWAS) of European ancestry (EUR) samples revealed that the genetic etiology of suicide attempt (SA) was not only polygenic but also, in part, diagnosis-specific. The authors aimed to examine whether the polygenic risk score (PRS) for SA derived from that study is associated with SA or repeated attempts in Korean patients with BD. This study also investigated the shared heritability of SA and mental disorders which showed an increased risk of SA and a high genetic correlation with BD. Methods The study participants were 383 patients with BD. The history of SA was assessed on a lifetime basis. PRSs for reference disorders were calculated using the aforementioned GWAS data for SA and the Psychiatric Genomics Consortium data of BD, schizophrenia, major depressive disorder (MDD), and obsessive–compulsive disorder (OCD). Results The PRS for SA was significantly associated with lifetime SA in the current subjects (Nagelkerke’s R2 = 2.73%, odds ratio [OR] = 1.36, p = 0.007). Among other PRSs, only the PRS for OCD was significantly associated with lifetime SA (Nagelkerke’s R2 = 2.72%, OR = 1.36, p = 0.007). The PRS for OCD was higher in multiple attempters than in single attempters (Nagelkerke’s R2 = 4.91%, OR = 1.53, p = 0.043). Conclusion The PRS for SA derived from EUR data was generalized to SA in Korean patients with BD. The PRS for OCD seemed to affect repeated attempts. Genetic studies on suicide could benefit from focusing on specific psychiatric diagnoses and refined sub-phenotypes, as well as from utilizing multiple PRSs for related disorders.

Published
2022
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5. Alterations in blood proteins in the prodromal stage of bipolar II disorders

Author

Hyunju Lee, Dohyun Han, Sang Jin Rhee, Jayoun Kim, Yunna Lee, Eun Young Kim, Dong Yeon Park, Sungwon Roh, Myungjae Baik, Hee Yeon Jung, Junhee Lee, Tae Young Lee, Minah Kim, Hyunsuk Shin, Hyeyoon Kim, Se Hyun Kim, Jun Soo Kwon, Yong Min Ahn, and Kyooseob Ha

Subjects
Medicine, Science
Abstract

Abstract Although early intervention may help prevent the progression of bipolar disorder, there are some controversies over early pharmacological intervention. In this study, we recruited 40 subjects in the prodromal stage of BD-II (BP), according to bipolar at-risk state criteria. We compared the expression of their plasma proteins with that of 48 BD-II and 75 healthy control (HC) to identify markers that could be detected in a high-risk state. The multiple reaction monitoring method was used to measure target peptide levels with high accuracy. A total of 26 significant peptides were identified through analysis of variance with multiple comparisons, of which 19 were differentially expressed in the BP group when compared to the BD-II and HC groups. Two proteins were overexpressed in the BP group; and were related to pro-inflammation and impaired neurotransmission. The other under-expressed peptides in the BP group were related to blood coagulation, immune reactions, lipid metabolism, and the synaptic plasticity. In this study, significant markers observed in the BP group have been reported in patients with psychiatric disorders. Overall, the results suggest that the pathophysiological changes included in BD-II had already occurred with BP, thus justifying early pharmacological treatment to prevent disease progression.

Published
2022
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6. Integrating proteomic and clinical data to discriminate major psychiatric disorders: Applications for major depressive disorder, bipolar disorder, and schizophrenia

Author

Dongyoon Shin, Sang Jin Rhee, Daun Shin, Eun‐Jeong Joo, Hee Yeon Jung, Sungwon Roh, Sang‐Hyuk Lee, Hyeyoung Kim, Minji Bang, Kyu Young Lee, Se Hyun Kim, Jihyeon Lee, Yoseop Kim, Injoon Yeo, Yeongshin Kim, Jaenyeon Kim, Jun Soo Kwon, Kyooseob Ha, Yong Min Ahn, and Youngsoo Kim

Subjects
Medicine (General), R5-920
Published
2022
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7. Comparison of serum protein profiles between major depressive disorder and bipolar disorder

Author

Sang Jin Rhee, Dohyun Han, Yunna Lee, Hyeyoung Kim, Junhee Lee, Kangeun Lee, Hyunsuk Shin, Hyeyoon Kim, Tae Young Lee, Minah Kim, Se Hyun Kim, Yong Min Ahn, Jun Soo Kwon, and Kyooseob Ha

Subjects
Major depressive disorder, Bipolar disorder, Proteomics, rab7 protein, ROCK2 protein, human, XPO7 protein, human, Psychiatry, RC435-571
Abstract

Abstract Background Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. Methods Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. Results Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10− 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10− 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10− 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. Conclusions Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.

Published
2020
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8. Plasma proteomic data in bipolar II disorders and major depressive disorders

Author

Hyunju Lee, Sang Jin Rhee, Jayoun Kim, Yunna Lee, Hyeyoung Kim, Junhee Lee, Kangeun Lee, Hyunsuk Shin, Hyeyoon Kim, Tae Young Lee, Minah Kim, Eun Young Kim, Se Hyun Kim, Yong Min Ahn, Jun Soo Kwon, Dohyun Han, and Kyooseob Ha

Subjects
Bipolar II disorder, Major depressive disorder, Liquid chromatography-tandem mass spectrometry (LC-MS), Symptom severity, Proteomics, Computer applications to medicine. Medical informatics, R858-859.7, Science (General), Q1-390
Abstract

The proteomics data included in this article supplement the research article titled “Predictive protein markers for the severity of depression in mood disorders: A preliminary trans-diagnostic approach study (manuscript ID: JPSYCHIATRES-D-20-00437).” Plasma protein was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This data article included 370 plasma protein profiles expressed in patients with bipolar II disorder (BD-II) and major depressive disorder (MDD). The tables present the comparison of protein expressions between BD-II and MDD, and the relationship between the severity of the depressive symptoms and protein expression. In addition, details of results adjusting the use of each psychotropic medication (antipsychotics, mood stabilizers, and antidepressants) for 20 proteins that showed a significant relationship with the severity of the depressive symptom were presented in the table. Results of the bioinformatics analysis of proteins, which were significantly related to the severity of depressive symptom, are presented. The blood protein profiles and the results of the analyses presented in this data article provide detailed information on the proteins associated with mood disorders, and could be used as the basis for further mass spectrometry studies in psychiatric disorders.

Published
2021
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9. The influence of poverty attribution on attitudes toward suicide and suicidal thought: A cross-national comparison between South Korean, Japanese, and American populations

Author

Hyunju Lee, C. Hyung Keun Park, Sang Jin Rhee, Bora Kim, Sang Sin Lee, Kyooseob Ha, Chang Jae Baik, and Yong Min Ahn

Subjects
Suicide, Permissive attitude, Poverty attribution, Income inequality, Structural equation model, Comparative study, Psychiatry, RC435-571
Abstract

Background: Previous studies report that income inequality is an important risk factor for depression and suicide, and an increasing income gap appears inevitable. However, little study to date has investigated associations between the attribution of poverty and suicide. Though we previously reported associations between socio-cultural factors, including income, and suicide, we tried to explore more focused associations between income, attribution of poverty (individualistic, societal), permissive attitude toward suicide, and suicidal thought using a structural equation model. Methods: A total of 2213 participants from each of three nations (South Korea, Japan, and the United States) completed an online survey. Participants without a history of psychological disorders or suicide attempts completed scales measuring attributions of poverty, attitudes toward suicide, and severity of suicidal thoughts. Results: We established a structural equation model, which exhibited a good fit for all nations, and compared significant path coefficients by country. South Korea had the highest severity of suicidal thought and societal attribution of poverty, followed by Japan and America. In all nations, a permissive attitude was positively related to the severity of suicidal thought and individualistic attribution of poverty was positively related to a permissive attitude toward suicide. Societal attribution of poverty was positively associated with a permissive attitude in Japan and the United States. Income was negatively associated with the severity of suicide in South Korea and the United States. Conclusion: Through an established structural equation model, we found the influence of poverty on suicide and identify the common and distinctive factors associated with suicide in each country.

Published
2021
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10. Study Protocol for a Prospective Longitudinal Cohort Study to Identify Proteomic Predictors of Pluripotent Risk for Mental Illness: The Seoul Pluripotent Risk for Mental Illness Study

Author

Tae Young Lee, Junhee Lee, Hyun Ju Lee, Yunna Lee, Sang Jin Rhee, Dong Yeon Park, Myung Jae Paek, Eun Young Kim, Euitae Kim, Sungwon Roh, Hee Yeon Jung, Minah Kim, Se Hyun Kim, Dohyun Han, Yong Min Ahn, Kyooseob Ha, and Jun Soo Kwon

Subjects
bipolar disorder, high-risk for mental illness, major depressive disorder, pluripotential, proteomics, schizophrenia, Psychiatry, RC435-571
Abstract

BackgroundThe Seoul Pluripotent Risk for Mental Illness (SPRIM) study was designed to identify predictors leading to mental illness in help-seeking individuals by securing sufficient statistical power through transdiagnostic approaches. The SPRIM study aims to examine the clinical characteristics of high-risk individuals for mental illness and to identify proteomic biomarkers that can predict the onset of mental illness.MethodsThis paper describes the study protocol of the SPRIM study. We aim to recruit 150 participants who meet the criteria for high risk for major mental illness, 150 patients with major psychiatric disorders (schizophrenia, bipolar disorder, and major depressive disorder), and 50 matched healthy control subjects for 2 years. Clinical evaluations, self-report measures, and proteomic analyses will be implemented. The assessment points are at baseline, 6, 12, 18, and 24 months.ConclusionsIn the present study, we introduced the study protocol of the SPRIM study, which is the first prospective cohort study of transdiagnostic high-risk concepts using proteomic biomarkers. This study has a paradigm that encompasses various diseases without aiming at predicting and preventing the development of a specific mental illness in help-seeking individuals. The transdiagnostic high-risk concept could be extended to provide a perspective for people with various psychopathological tendencies below a threshold, such that they do not meet the existing diagnostic criteria of mental illnesses, to determine what may lead them to a specific disease and help identify appropriate preventative interventions.

Published
2020
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12. Association between the Arylalkylamine N-Acetyltransferase (AANAT) Gene and Seasonality in Patients with Bipolar Disorder

Author

Taesung Park, Youngah Cho, Ji Hyun Baek, Kyung Sue Hong, So Yung Yang, Yongkang Kim, Eun Young Cho, Kyooseob Ha, and Yujin Choi

Subjects
medicine.medical_specialty, Bipolar disorder, AANAT, Biology, Melatonin, 03 medical and health sciences, 0302 clinical medicine, Melatonin pathway, Internal medicine, medicine, Circadian rhythm, Biological Psychiatry, 030304 developmental biology, 0303 health sciences, Genetic disorder, Seasonality, medicine.disease, Phenotype, Psychiatry and Mental health, Mood, Endocrinology, Original Article, 030217 neurology & neurosurgery, Imputation (genetics), medicine.drug
Abstract

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.

Published
2021

13. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author

Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. 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Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. 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P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. 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B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards 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Nyholt D.R., O'Reilly P.F., Oskarsson H., Hayward C., Heath A.C., Lewis G., Li Q.S., Madden P.A.F., Magnusson P.K., Martin N.G., McIntosh A.M., Metspalu A., Mors O., Nordentoft M., Paciga S.A., Pedersen N.L., Painter J.N., Pedersen C.B., Pedersen M.G., Peterson R.E., Peyrot W.J., Posthuma D., Quiroz J.A., Qvist P., Rice J.P., Riley B.P., Mirza S.S., Schoevers R., Schulte E.C., Shen L., Sigurdsson E., Sinnamon G.C.B., Smit J.H., Smith D.J., Stefansson H., Steinberg S., Streit F., Strohmaier J., Tansey K.E., Teismann H., Teumer A., Thompson W., Thomson P.A., Thorgeirsson T.E., Traylor M., Treutlein J., Trubetskoy V., Uitterlinden A.G., Umbricht D., der Auwera S.V., van Hemert A.M., Viktorin A., Visscher P.M., Wang Y., Webb B.T., Perlis R.H., Porteous D.J., Schaefer C., Stefansson K., Tiemeier H., Uher R., Werge T., Lewis C.M., Breen G., Borglum A.D., Sullivan P.F., O'Connell K.S., Coombes B., Qiao Z., Als T.D., Borte S., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Al Eissa M., Albani D., Alliey-Rodriguez N., Antilla V., Antoniou A., Baek J.H., Bauer M., Beins E.C., Bergen S.E., Birner A., Boen E., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Byerley W., Cairns M., Cervantes P., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Dobbyn A.L., Douzenis A., Elvsashagen T., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Gizer I.R., Gordon-Smith K., Greenwood T.A., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Holmans P.A., Huckins L., Johnson J.S., Kalman J.L., Kamatani Y., Kittel-Schneider S., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Leber M., Lee H.-J., Levy S.E., Lewis C., Lundberg M., Magnusson S.H., Maihofer A., Malaspina D., Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.

Subjects
LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

Published
2022

14. Seoul National University Bundang Hospital's Electronic System for Total Care

Author

Sooyoung Yoo, Kee Hyuck Lee, Hak Jong Lee, Kyooseob Ha, Cheong Lim, Ho Jun Chin, Jonghoar Yun, Eun-Young Cho, Eunja Chung, Rong-Min Baek, Chin Youb Chung, Won Ryang Wee, Chul Hee Lee, Hai-Seok Lee, Nam-Soo Byeon, and Hee Hwang

Subjects
hospital information systems, electronic health records, quality of health care, patient safety, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

ObjectivesSeoul National University Bundang Hospital, which is the first Stage 7 hospital outside of North America, has adopted and utilized an innovative and emerging information technology system to improve the efficiency and quality of patient care. The objective of this paper is to briefly introduce the major components of the SNUBH information system and to describe our progress toward a next-generation hospital information system (HIS).MethodsSNUBH opened in 2003 as a fully digital hospital by successfully launching a new HIS named BESTCare, "Bundang hospital Electronic System for Total Care". Subsequently, the system has been continuously improved with new applications, including close-loop medication administration (CLMA), clinical data warehouse (CDW), health information exchange (HIE), and disaster recovery (DR), which have resulted in the achievement of Stage 7 status.ResultsThe BESTCare system is an integrated system for a university hospital setting. BESTCare is mainly composed of three application domains: the core applications, an information infrastructure, and channel domains. The most critical and unique applications of the system, such as the electronic medical record (EMR), computerized physician order entry (CPOE), clinical decision support system (CDSS), CLMA, CDW, HIE, and DR applications, are described in detail.ConclusionsBeyond our achievement of Stage 7 hospital status, we are currently developing a next-generation HIS with new goals of implementing infrastructure that is flexible and innovative, implementing a patient-centered system, and strengthening the IT capability to maximize the hospital value.

Published
2012
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15. Plasma proteomic data in bipolar II disorders and major depressive disorders

Author

Se Hyun Kim, Hyeyoon Kim, Hyunsuk Shin, Yong Min Ahn, Kyooseob Ha, Minah Kim, Hyeyoung Kim, Eun Young Kim, Dohyun Han, Hyun Ju Lee, Yunna Lee, Tae Young Lee, Sang Jin Rhee, Junhee Lee, Kangeun Lee, Jun Soo Kwon, and Jayoun Kim

Subjects
Oncology, Proteomics, medicine.medical_specialty, Science (General), Computer applications to medicine. Medical informatics, R858-859.7, Major depressive disorder, Psychotropic medication, Symptom severity, Bipolar II disorder, Q1-390, Internal medicine, medicine, Depression (differential diagnoses), Data Article, Multidisciplinary, business.industry, medicine.disease, Blood proteins, Liquid chromatography-tandem mass spectrometry (LC-MS), Mood, Mood disorders, business
Abstract

The proteomics data included in this article supplement the research article titled “Predictive protein markers for the severity of depression in mood disorders: A preliminary trans-diagnostic approach study (manuscript ID: JPSYCHIATRES-D-20-00437).” Plasma protein was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This data article included 370 plasma protein profiles expressed in patients with bipolar II disorder (BD-II) and major depressive disorder (MDD). The tables present the comparison of protein expressions between BD-II and MDD, and the relationship between the severity of the depressive symptoms and protein expression. In addition, details of results adjusting the use of each psychotropic medication (antipsychotics, mood stabilizers, and antidepressants) for 20 proteins that showed a significant relationship with the severity of the depressive symptom were presented in the table. Results of the bioinformatics analysis of proteins, which were significantly related to the severity of depressive symptom, are presented. The blood protein profiles and the results of the analyses presented in this data article provide detailed information on the proteins associated with mood disorders, and could be used as the basis for further mass spectrometry studies in psychiatric disorders.

Published
2021

16. Management of bipolar depression

Author

Jae Seung Chang and Kyooseob Ha

Subjects
Anticonvulsants, antidepressants, bipolar depression, lithium, psychosocial intervention, second-generation antipsychotics, Psychiatry, RC435-571
Abstract

Patients with bipolar disorder spend more time in a depressed than manic state, even with individualized treatment. To date, bipolar depression is often misdiagnosed and ineffectively managed both for acute episodes and residual symptoms. This review attempts to summarize the current status of available treatment strategies in the treatment of bipolar depression. For acute and prophylactic treatment, a substantial body of evidence supports the antidepressive efficacy of lithium for bipolar disorders and its antisuicidal effects. Among numerous anticonvulsants with mood-stabilizing properties, valproate and lamotrigine could be first-line options for bipolar depression. Due to receptor profile, mood-stabilizing properties of second-generation antipsychotics have been explored, and up to date, quetiapine and olanzapine appear to be a reasonable option for bipolar depression. The usefulness of antidepressants in bipolar depression is still controversial. Current guidelines generally recommend the cautious antidepressant use in combination with mood stabilizers to reduce the risk of mood elevation or cycle acceleration. Results from clinical trials on psychosocial intervention are promising, especially when integrated with pharmacotherapy. Most patients with bipolar depression need individualized and combined treatment, although the published evidence on this type of treatment strategy is limited. Future studies on the utility of currently available agents and modalities including psychosocial intervention are required.

Published
2011
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17. Implementation of Medical Information Exchange System Based on EHR Standard

Author

Soon Hwa Han, Min Ho Lee, Sang Guk Kim, Jun Yong Jeong, Bi Na Lee, Myeong Seon Choi, Il Kon Kim, Woo Sung Park, Kyooseob Ha, Eunyoung Cho, Yoon Kim, and Jae Bong Bae

Subjects
electronic health record, vpn, web service security enhanced, health level 7 standard, cda r2, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

ObjectivesTo develop effective ways of sharing patients' medical information, we developed a new medical information exchange system (MIES) based on a registry server, which enabled us to exchange different types of data generated by various systems.MethodsTo assure that patient's medical information can be effectively exchanged under different system environments, we adopted the standardized data transfer methods and terminologies suggested by the Center for Interoperable Electronic Healthcare Record (CIEHR) of Korea in order to guarantee interoperability. Regarding information security, MIES followed the security guidelines suggested by the CIEHR of Korea. This study aimed to develop essential security systems for the implementation of online services, such as encryption of communication, server security, database security, protection against hacking, contents, and network security.ResultsThe registry server managed information exchange as well as the registration information of the clinical document architecture (CDA) documents, and the CDA Transfer Server was used to locate and transmit the proper CDA document from the relevant repository. The CDA viewer showed the CDA documents via connection with the information systems of related hospitals.ConclusionsThis research chooses transfer items and defines document standards that follow CDA standards, such that exchange of CDA documents between different systems became possible through ebXML. The proposed MIES was designed as an independent central registry server model in order to guarantee the essential security of patients' medical information.

Published
2010
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18. Alterations in blood proteins in the prodromal stage of bipolar II disorders

Author

Hyunju Lee, Dohyun Han, Sang Jin Rhee, Jayoun Kim, Yunna Lee, Eun Young Kim, Dong Yeon Park, Sungwon Roh, Myungjae Baik, Hee Yeon Jung, Junhee Lee, Tae Young Lee, Minah Kim, Hyunsuk Shin, Hyeyoon Kim, Se Hyun Kim, Jun Soo Kwon, Yong Min Ahn, and Kyooseob Ha

Subjects
Adult, Male, Psychiatric Status Rating Scales, Young Adult, Multidisciplinary, Bipolar Disorder, Disease Progression, Humans, Prodromal Symptoms, Female, Blood Proteins, Peptides, Biomarkers
Abstract

Although early intervention may help prevent the progression of bipolar disorder, there are some controversies over early pharmacological intervention. In this study, we recruited 40 subjects in the prodromal stage of BD-II (BP), according to bipolar at-risk state criteria. We compared the expression of their plasma proteins with that of 48 BD-II and 75 healthy control (HC) to identify markers that could be detected in a high-risk state. The multiple reaction monitoring method was used to measure target peptide levels with high accuracy. A total of 26 significant peptides were identified through analysis of variance with multiple comparisons, of which 19 were differentially expressed in the BP group when compared to the BD-II and HC groups. Two proteins were overexpressed in the BP group; and were related to pro-inflammation and impaired neurotransmission. The other under-expressed peptides in the BP group were related to blood coagulation, immune reactions, lipid metabolism, and the synaptic plasticity. In this study, significant markers observed in the BP group have been reported in patients with psychiatric disorders. Overall, the results suggest that the pathophysiological changes included in BD-II had already occurred with BP, thus justifying early pharmacological treatment to prevent disease progression.

Published
2021

19. Association between ST8SIA2 and the Risk of Schizophrenia and Bipolar I Disorder across Diagnostic Boundaries.

Author

So Yung Yang, Ik Soo Huh, Ji Hyun Baek, Eun-Young Cho, Mi Ji Choi, Seunghyong Ryu, Ji Sun Kim, Taesung Park, Kyooseob Ha, and Kyung Sue Hong

Subjects
Medicine, Science
Abstract

Findings from family studies and recent genome-wide association studies have indicated overlap in the risk genes between schizophrenia and bipolar disorder (BD). After finding a linkage between the ST8SIA2 (ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sicalyltransferase 2 gene) locus (15q26) and mixed families with schizophrenia and BD, several studies have reported a significant association between this gene and schizophrenia or BD. We investigated the genetic association between ST8SIA2 and both schizophrenia and BD in the Korean population.A total of 582 patients with schizophrenia, 339 patients with BD, and 502 healthy controls were included. Thirty-one tag single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing significant associations in previous studies were genotyped. The associations were evaluated by logistic regression analysis using additive, dominant, and recessive genetic models.Fourteen of 34 SNPs showed a nominally significant association (p < 0.05) with at least one diagnostic group. These association trends were strongest for the schizophrenia and combined schizophrenia and bipolar I disorder (BD-I) groups. The strongest association was observed in rs11637898 for schizophrenia (p = 0.0033) and BD-I (p = 0.0050) under the dominant model. The association between rs11637898 and the combined schizophrenia and BD-I group (p = 0.0006, under the dominant model) remained significant after correcting for multiple testing.We identified a possible role of ST8SIA2 in the common susceptibility of schizophrenia and BD-I. However, no association trend was observed for bipolar II disorder. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

Published
2015
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21. Dissecting the genetic architecture of suicide attempt and repeated attempts in Korean patients with bipolar disorder using polygenic risk scores

Author

Dongbin Lee, Ji Hyun Baek, Kyooseob Ha, Eun-Young Cho, Yujin Choi, So-Yung Yang, Ji Sun Kim, Yunji Cho, Hong-Hee Won, and Kyung Sue Hong

Subjects
Neurophysiology and neuropsychology, Psychiatry and Mental health, Polygenic risk score, Bipolar disorder, QP351-495, Suicide attempt, Repeated attempts, Neurosciences. Biological psychiatry. Neuropsychiatry, Obsessive–compulsive disorder, Biological Psychiatry, RC321-571
Abstract

Background Bipolar disorder (BD) has the greatest suicide risk among mental and physical disorders. A recent genome-wide association study (GWAS) of European ancestry (EUR) samples revealed that the genetic etiology of suicide attempt (SA) was not only polygenic but also, in part, diagnosis-specific. The authors aimed to examine whether the polygenic risk score (PRS) for SA derived from that study is associated with SA or repeated attempts in Korean patients with BD. This study also investigated the shared heritability of SA and mental disorders which showed an increased risk of SA and a high genetic correlation with BD. Methods The study participants were 383 patients with BD. The history of SA was assessed on a lifetime basis. PRSs for reference disorders were calculated using the aforementioned GWAS data for SA and the Psychiatric Genomics Consortium data of BD, schizophrenia, major depressive disorder (MDD), and obsessive–compulsive disorder (OCD). Results The PRS for SA was significantly associated with lifetime SA in the current subjects (Nagelkerke’s R2 = 2.73%, odds ratio [OR] = 1.36, p = 0.007). Among other PRSs, only the PRS for OCD was significantly associated with lifetime SA (Nagelkerke’s R2 = 2.72%, OR = 1.36, p = 0.007). The PRS for OCD was higher in multiple attempters than in single attempters (Nagelkerke’s R2 = 4.91%, OR = 1.53, p = 0.043). Conclusion The PRS for SA derived from EUR data was generalized to SA in Korean patients with BD. The PRS for OCD seemed to affect repeated attempts. Genetic studies on suicide could benefit from focusing on specific psychiatric diagnoses and refined sub-phenotypes, as well as from utilizing multiple PRSs for related disorders.

Published
2021

22. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

James McKay, Frank Bellivier, Mark A. Frye, Bertram Müller-Myhsok, Fermín Mayoral, I. Nicol Ferrier, Marion Leboyer, Fabian Streit, Dan J. Stein, James L. Kennedy, Christine Søholm Hansen, Scott D. Gordon, Beata Świątkowska, Valentina Escott-Price, Michael Bauer, Lina Martinsson, Donald J. MacIntyre, Oleksandr Frei, Daniel J. Smith, Sara A. Paciga, Takeo Saito, Jennifer L. Moran, Verneri Antilla, C Pantelis, Tomas Olsson, Swapnil Awasthi, Lena Backlund, Eirini Maratou, Martin Schalling, John B. Vincent, Niamh Mullins, Sarah E. Bergen, Niamh L. O'Brien, Marco P. Boks, Carsten Bøcker Pedersen, Mikael Landén, Franziska Degenhardt, Hang Zhou, Margarita Rivera, Andrew M. McIntosh, Manuel Mattheisen, Shawn Levy, Roy H. Perlis, John P. Rice, Sigurdur H. Magnusson, Amanda Dobbyn, Michael Conlon O'Donovan, Julien Bryois, Wolfgang Maier, John-Anker Zwart, J. Raymond DePaulo, Martin Alda, Laura G. Sloofman, Friederike Sophie David, James A. Knowles, Aiden Corvin, Thomas G. Schulze, Markus M. Nöthen, Nolan Kamitaki, Nina Dalkner, Brandon J. Coombes, Gustavo Turecki, Allan H. Young, Caroline M. Nievergelt, Patricia T. Michie, Ingrid Agartz, Towfique Raj, Diego Albani, Maria Grigoroiu-Serbanescu, Bernhard T. Baune, Kyooseob Ha, Vincent Millischer, Engilbert Sigurdsson, Eva C. Beins, Nicholas G. Martin, Gulja Babadjanova, Josef Frank, Eva Z. Reininghaus, Patrick F. Sullivan, Ian R. Gizer, Guy A. Rouleau, Carmel M. Loughland, Christine Lochner, Thorsten M. Kranz, Amy Perry, Arne E. Vaaler, Mariam M. Al Eissa, Simon Xi, Claire O'Donovan, Josep Antoni Ramos-Quiroga, Ketil J. Oedegaard, Helmut Vedder, Carol A. Mathews, Panagiotis Ferentinos, Tim B. Bigdeli, Derek W. Morris, Per Hoffmann, Mark Hyman Rapaport, Peter P. Zandi, Michael John Owen, Douglas M. Ruderfer, Anders D. Børglum, Catharina Lavebratt, Thorgeir E. Thorgeirsson, Paul A. Tooney, Michiaki Kubo, Steven A. Kushner, Jan Hillert, Loes M. Olde Loohuis, Anastasia Antoniou, Murielle Brum, Chikashi Terao, Nathaniel W. McGregor, Fabio Rivas, James B. Potash, Kevin S. O’Connell, Susanne Lucae, Brian M. Schilder, Katrin Gade, Stephan Ripke, Kristina Adorjan, Kari Stefansson, Tiffany A. Greenwood, Panos Roussos, Sarah Kittel-Schneider, Steven A. McCarroll, Sergi Papiol, Heon Jeong Lee, Assen Jablensky, Liliya Abramova, Dennis Hellgren, Jonas Bybjerg-Grauholm, Martin Lundberg, Hong-Hee Won, William Byerley, Lars Alfredsson, Joel Gelernter, Andrew McQuillin, Claire Slaney, Marta Ribasés, Stephanie H. Witt, Yoichiro Kamatani, Kyung Sue Hong, Marie Bækvad-Hansen, María Soler Artigas, Julie M. Cunningham, Fanny Senner, Stacy Steinberg, Paul D. Shilling, Nakao Iwata, Eystein Stordal, Armin Birner, Sarah E. Medland, Miquel Casas, Ben Michael Brumpton, Erlend Bøen, Bryan J. Mowry, Jolanta Lissowska, Francis J. McMahon, Howard J. Edenberg, Grant W. Montgomery, John I. Nurnberger, Stéphane Jamain, Claudio Toma, Ney Alliey-Rodriguez, Ole Mors, Micha Gawlik, David Curtis, Catrin Lewis, Evangelia-Eirini Tsermpini, Georgia Panagiotaropoulou, Marcella Rietschel, Jessica Yang, Ian Jones, Eduard Vieta, Ole A. Andreassen, Richard M. Myers, Dimitris Dikeos, Melissa J. Green, Janet L. Sobell, Maria Koromina, Piotr M. Czerski, Lilijana Oruc, Sven Cichon, Udo Dannlowski, Bruno Etain, Monika Budde, Alessia Fiorentino, Naomi R. Wray, Qingqin S. Li, Murray J. Cairns, Jonathan R. I. Coleman, Jose Guzman-Parra, Andreas J. Forstner, Hannah Young, Alfredo B. Cuellar-Barboza, Julian Roth, Torbjørn Elvsåshagen, Zhen Qiao, Thomas Werge, Athanassios Douzenis, Cristiana Cruceanu, Rolf Adolfsson, Peter Holmans, Vaughan J. Carr, Thomas W. Weickert, Masashi Ikeda, Joanna M. Biernacka, Lea Sirignano, Adam X. Maihofer, Ralph W. Kupka, John Strauss, Anders M. Dale, Elliot S. Gershon, Jakob Grove, Arianna Di Florio, Helena Medeiros, Ingrid Melle, Preben Bo Mortensen, Kristi Krebs, Saskia P. Hagenaars, Liz Forty, Stanley V. Catts, David M. Hougaard, Marianne Giørtz Pedersen, Andreas Reif, Toni-Kim Clarke, Anne T. Spijker, Danielle Posthuma, Manolis Kogevinas, Michael Boehnke, Rosa Bosch, Gerome Breen, Benjamin M. Neale, Jessica S. Johnson, Katherine Gordon-Smith, Cristina Sánchez-Mora, Alexander W. Charney, Henry R. Kranzler, Digby Quested, René S. Kahn, Lili Milani, Merete Nordentoft, Nathalie Brunkhorst-Kanaan, Laura M. Huckins, James T.R. Walters, Sigrid Børte, Antonio F. Pardiñas, Kristian Hveem, Julie Garnham, Jacob Lawrence, Vassily Trubetskoy, Rodney J. Scott, Nicholas Bass, Carlos N. Pato, Andrea Pfennig, Wei Xu, Calwing Liao, Nicholas John Craddock, Thomas Damm Als, Christina M. Hultman, Fernando S. Goes, Adebayo Anjorin, Evgenia Porichi, Frans Henskens, Nelson B. Freimer, Janice M. Fullerton, Cathryn M. Lewis, Srdjan Djurovic, Roel A. Ophoff, Phil Lee, Peter McGuffin, Gunnar Morken, George P. Patrinos, Alessandro Serretti, Cynthia Shannon Weickert, Pablo Cervantes, Bendik S. Winsvold, Tatiana Foroud, Tõnu Esko, Ulrich Schall, Michele T. Pato, Ji Hyun Baek, John R. Kelsoe, Olav B. Smeland, Janos Kalman, Eva C. Schulte, Joanna Hauser, Urs Heilbronner, Magnús Haraldsson, Martin Hautzinger, Lea Zillich, Eline J. Regeer, Douglas Blackwood, Laura J. Scott, Jordan W. Smoller, Michael J. Gandal, Marquis P. Vawter, Philip B. Mitchell, Ole Kristian Drange, Peter R. Schofield, Susanne Bengesser, Stefan Herms, George Kirov, Markus Leber, Louise Frisén, Thomas W. Mühleisen, Susan L. McElroy, Irwin D. Waldman, Wade H. Berrettini, Sally I. Sharp, Minsoo Kim, Lisa Jones, Eli A. Stahl, Hreinn Stefansson, Esben Agerbo, Dolores Malaspina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), APH - Digital Health, Mullins N., Forstner A.J., O'Connell K.S., Coombes B., Coleman J.R.I., Qiao Z., Als T.D., Bigdeli T.B., Borte S., Bryois J., Charney A.W., Drange O.K., Gandal M.J., Hagenaars S.P., Ikeda M., Kamitaki N., Kim M., Krebs K., Panagiotaropoulou G., Schilder B.M., Sloofman L.G., Steinberg S., Trubetskoy V., Winsvold B.S., Won H.-H., Abramova L., Adorjan K., Agerbo E., Al Eissa M., Albani D., Alliey-Rodriguez N., Anjorin A., Antilla V., Antoniou A., Awasthi S., Baek J.H., Baekvad-Hansen M., Bass N., Bauer M., Beins E.C., Bergen S.E., Birner A., Bocker Pedersen C., Boen E., Boks M.P., Bosch R., Brum M., Brumpton B.M., Brunkhorst-Kanaan N., Budde M., Bybjerg-Grauholm J., Byerley W., Cairns M., Casas M., Cervantes P., Clarke T.-K., Cruceanu C., Cuellar-Barboza A., Cunningham J., Curtis D., Czerski P.M., Dale A.M., Dalkner N., David F.S., Degenhardt F., Djurovic S., Dobbyn A.L., Douzenis A., Elvsashagen T., Escott-Price V., Ferrier I.N., Fiorentino A., Foroud T.M., Forty L., Frank J., Frei O., Freimer N.B., Frisen L., Gade K., Garnham J., Gelernter J., Giortz Pedersen M., Gizer I.R., Gordon S.D., Gordon-Smith K., Greenwood T.A., Grove J., Guzman-Parra J., Ha K., Haraldsson M., Hautzinger M., Heilbronner U., Hellgren D., Herms S., Hoffmann P., Holmans P.A., Huckins L., Jamain S., Johnson J.S., Kalman J.L., Kamatani Y., Kennedy J.L., Kittel-Schneider S., Knowles J.A., Kogevinas M., Koromina M., Kranz T.M., Kranzler H.R., Kubo M., Kupka R., Kushner S.A., Lavebratt C., Lawrence J., Leber M., Lee H.-J., Lee P.H., Levy S.E., Lewis C., Liao C., Lucae S., Lundberg M., MacIntyre D.J., Magnusson S.H., Maier W., Maihofer A., Malaspina D., Maratou E., Martinsson L., Mattheisen M., McCarroll S.A., McGregor N.W., McGuffin P., McKay J.D., Medeiros H., Medland S.E., Millischer V., Montgomery G.W., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Potash J.B., Quested D., Raj T., Rapaport M.H., DePaulo J.R., Regeer E.J., Rice J.P., Rivas F., Rivera M., Roth J., Roussos P., Ruderfer D.M., Sanchez-Mora C., Schulte E.C., Senner F., Sharp S., Shilling P.D., Sigurdsson E., Sirignano L., Slaney C., Smeland O.B., Smith D.J., Sobell J.L., Soholm Hansen C., Soler Artigas M., Spijker A.T., Stein D.J., Strauss J.S., Swiatkowska B., Terao C., Thorgeirsson T.E., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Walters J.T.R., Witt S.H., Xi S., Xu W., Yang J.M.K., Young A.H., Young H., Zandi P.P., Zhou H., Zillich L., Adolfsson R., Agartz I., Alda M., Alfredsson L., Babadjanova G., Backlund L., Baune B.T., Bellivier F., Bengesser S., Berrettini W.H., Blackwood D.H.R., Boehnke M., Borglum A.D., Breen G., Carr V.J., Catts S., Corvin A., Craddock N., Dannlowski U., Dikeos D., Esko T., Etain B., Ferentinos P., Frye M., Fullerton J.M., Gawlik M., Gershon E.S., Goes F.S., Green M.J., Grigoroiu-Serbanescu M., Hauser J., Henskens F., Hillert J., Hong K.S., Hougaard D.M., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Jones I., Jones L.A., Kahn R.S., Kelsoe J.R., Kirov G., Landen M., Leboyer M., Lewis C.M., Li Q.S., Lissowska J., Lochner C., Loughland C., Martin N.G., Mathews C.A., Mayoral F., McElroy S.L., McIntosh A.M., McMahon F.J., Melle I., Michie P., Milani L., Mitchell P.B., Morken G., Mors O., Mortensen P.B., Mowry B., Muller-Myhsok B., Myers R.M., Neale B.M., Nievergelt C.M., Nordentoft M., Nothen M.M., O'Donovan M.C., Oedegaard K.J., Olsson T., Owen M.J., Paciga S.A., Pantelis C., Pato C., Pato M.T., Patrinos G.P., Perlis R.H., Posthuma D., Ramos-Quiroga J.A., Reif A., Reininghaus E.Z., Ribases M., Rietschel M., Ripke S., Rouleau G.A., Saito T., Schall U., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Scott R.J., Serretti A., Shannon Weickert C., Smoller J.W., Stefansson H., Stefansson K., Stordal E., Streit F., Sullivan P.F., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Waldman I.D., Weickert T.W., Werge T., Wray N.R., Zwart J.-A., Biernacka J.M., Nurnberger J.I., Cichon S., Edenberg H.J., Stahl E.A., McQuillin A., Di Florio A., Ophoff R.A., Andreassen O.A., IMRB - 'Neuropsychiatrie translationnelle' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Optimisation thérapeutique en Neuropsychopharmacologie (OPTeN (UMR_S_1144 / U1144)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etain, Bruno

Subjects
Multifactorial Inheritance, Bipolar Disorder, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Medizin, Genome-wide association study, Major Histocompatibility Complex/genetics, Major Histocompatibility Complex, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH: Bipolar Disorder, Chromosomes, Human, Spectrum disorder, Genetics, 0303 health sciences, Bipolar Disorder/genetics, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, Phenotype, Schizophrenia, Synaptic signaling, Case-Control Studie, Human, Quantitative Trait Loci, Biology, MESH: Phenotype, MESH: Chromosomes, Human, Article, 03 medical and health sciences, MESH: Major Histocompatibility Complex, SDG 3 - Good Health and Well-being, ddc:570, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, Multifactorial Inheritance/genetics, MESH: Genome, Human, 030304 developmental biology, MESH: Humans, Genome, Human, Risk Factor, Chromosomes, Human/genetics, Mental illness, medicine.disease, MESH: Quantitative Trait Loci, Human genetics, Psychologie, Case-Control Studies, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, MESH: Genome-Wide Association Study, Expression quantitative trait loci, MESH: Multifactorial Inheritance, Quantitative Trait Loci/genetics, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

International audience; Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Published
2021

23. Self-Transcendence Mediates the Relationship between Early Trauma and Fatal Methods of Suicide Attempts

Author

Kyooseob Ha, Hyun Jeong Lee, Yong Min Ahn, C. Hyung Keun Park, Hyeyoung Kim, Jaewon Lee, Sang Jin Rhee, Jeong Hun Yang, Jung-Hyun Kim, Min-Ji Kim, and Daun Shin

Subjects
Adult, Male, Character, Self-transcendence, Mediation (statistics), Personality Inventory, media_common.quotation_subject, Suicide, Attempted, Suicidal Ideation, Suicide Attempt, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Psychiatric history, Surveys and Questionnaires, Humans, Medicine, Psychiatry & Psychology, 030212 general & internal medicine, Risk factor, Temperament, Suicide Risk, media_common, Suicide attempt, business.industry, Mental Disorders, Poisoning, General Medicine, Middle Aged, Confidence interval, Suicide, Female, Original Article, Self Report, business, Clinical psychology
Abstract

Background Early trauma is known to be a risk factor of suicide-related behavior. On the other hand, people who attempt suicide using a fatal method are reported to be more likely to complete suicide. In this study, we assumed that early trauma affects an individual's temperament and character and thereby increases the risk of a fatal method of suicide attempts. Methods We analyzed 92 people with a history of previous suicide attempts. We compared the Temperament and Character Inventory-Revised scores between the groups with and without early trauma, and between the groups with and without a history of suicide attempt using fatal methods through an analysis of covariance with age, sex, and presence of a psychiatric history as covariates. A mediation analysis was conducted of the relationship between early trauma and fatal methods of suicide attempt with self-transcendence as a mediator. Results Higher self-transcendence was reported in the fatal group (27.71 ± 13.78 vs. 20.97 ± 12.27, P = 0.010) and the early trauma group (28.05 ± 14.30 vs. 19.43 ± 10.73, P = 0.001), respectively. The mediation model showed that self-transcendence mediates the relationship between early trauma and fatal methods of suicide attempt. The 95% confidence intervals for the direct and indirect effect were (−0.559, 1.390) and (0.026, 0.947), respectively. Conclusion Self-transcendence may mediate the relationship between early trauma and fatal methods of suicide attempt. Self-transcendence may be associated with unhealthy defenses and suicidal behavior for self-punishment and may constitute a marker of higher suicide risk., Graphical Abstract

Published
2021

24. Genome-wide association study of over 40,000 bipolar disorder cases provides new insights into the underlying biology

Author

Niamh Mullins, Andreas J. Forstner, Kevin S. O’Connell, Brandon Coombes, Jonathan R. I. Coleman, Zhen Qiao, Thomas D. Als, Tim B. Bigdeli, Sigrid Børte, Julien Bryois, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Minsoo Kim, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Stacy Steinberg, Vassily Trubetskoy, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Esben Agerbo, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Adebayo Anjorin, Verneri Antilla, Anastasia Antoniou, Swapnil Awasthi, Ji Hyun Baek, Marie Bækvad-Hansen, Nicholas Bass, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, Rosa Bosch, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, Monika Budde, Jonas Bybjerg-Grauholm, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Toni-Kim Clarke, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Franziska Degenhardt, Srdjan Djurovic, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, Valentina Escott-Price, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Josef Frank, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Joel Gelernter, Marianne Giørtz Pedersen, Ian R. Gizer, Scott D. Gordon, Katherine Gordon-Smith, Tiffany A. Greenwood, Jakob Grove, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Stefan Herms, Per Hoffmann, Peter A. Holmans, Laura Huckins, Stéphane Jamain, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, James L. Kennedy, Sarah Kittel-Schneider, James A. Knowles, Manolis Kogevinas, Maria Koromina, Thorsten M. Kranz, Henry R. Kranzler, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Jacob Lawrence, Markus Leber, Heon-Jeong Lee, Phil H. Lee, Shawn E. Levy, Catrin Lewis, Calwing Liao, Susanne Lucae, Martin Lundberg, Donald J. MacIntyre, Sigurdur H. Magnusson, Wolfgang Maier, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Manuel Mattheisen, Steven A. McCarroll, Nathaniel W. McGregor, Peter McGuffin, James D. McKay, Helena Medeiros, Sarah E. Medland, Vincent Millischer, Grant W. Montgomery, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, James B. Potash, Digby Quested, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, John P. Rice, Fabio Rivas, Margarita Rivera, Julian Roth, Panos Roussos, Douglas M. Ruderfer, Cristina Sánchez-Mora, Eva C. Schulte, Fanny Senner, Sally Sharp, Paul D. Shilling, Engilbert Sigurdsson, Lea Sirignano, Claire Slaney, Olav B. Smeland, Daniel J. Smith, Janet L. Sobell, Christine Søholm Hansen, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, John S. Strauss, Beata Świątkowska, Chikashi Terao, Thorgeir E. Thorgeirsson, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, James T. R. Walters, Stephanie H. Witt, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, Lea Zillich, HUNT All-In Psychiatry, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Lars Alfredsson, Gulja Babadjanova, Lena Backlund, Bernhard T. Baune, Frank Bellivier, Susanne Bengesser, Wade H. Berrettini, Douglas H. R. Blackwood, Michael Boehnke, Anders D. Børglum, Gerome Breen, Vaughan J. Carr, Stanley Catts, Aiden Corvin, Nicholas Craddock, Udo Dannlowski, Dimitris Dikeos, Tõnu Esko, Bruno Etain, Panagiotis Ferentinos, Mark Frye, Janice M. Fullerton, Micha Gawlik, Elliot S. Gershon, Fernando S. Goes, Melissa J. Green, Maria Grigoroiu-Serbanescu, Joanna Hauser, Frans Henskens, Jan Hillert, Kyung Sue Hong, David M. Hougaard, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, Ian Jones, Lisa A. Jones, René S. Kahn, John R. Kelsoe, George Kirov, Mikael Landén, Marion Leboyer, Cathryn M. Lewis, Qingqin S. Li, Jolanta Lissowska, Christine Lochner, Carmel Loughland, Nicholas G. Martin, Carol A. Mathews, Fermin Mayoral, Susan L. McElroy, Andrew M. McIntosh, Francis J. McMahon, Ingrid Melle, Patricia Michie, Lili Milani, Philip B. Mitchell, Gunnar Morken, Ole Mors, Preben Bo Mortensen, Bryan Mowry, Bertram Müller-Myhsok, Richard M. Myers, Benjamin M. Neale, Caroline M. Nievergelt, Merete Nordentoft, Markus M. Nöthen, Michael C. O’Donovan, Ketil J. Oedegaard, Tomas Olsson, Michael J. Owen, Sara A. Paciga, Chris Pantelis, Carlos Pato, Michele T. Pato, George P. Patrinos, Roy H. Perlis, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Andreas Reif, Eva Z. Reininghaus, Marta Ribasés, Marcella Rietschel, Stephan Ripke, Guy A. Rouleau, Takeo Saito, Ulrich Schall, Martin Schalling, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Rodney J. Scott, Alessandro Serretti, Cynthia Shannon Weickert, Jordan W. Smoller, Hreinn Stefansson, Kari Stefansson, Eystein Stordal, Fabian Streit, Patrick F. Sullivan, Gustavo Turecki, Arne E. Vaaler, Eduard Vieta, John B. Vincent, Irwin D. Waldman, Thomas W. Weickert, Thomas Werge, Naomi R. Wray, John-Anker Zwart, Joanna M. Biernacka, John I. Nurnberger, Sven Cichon, Howard J. Edenberg, Eli A. Stahl, Andrew McQuillin, Arianna Di Florio, Roel A. Ophoff, and Ole A. Andreassen

Subjects
Genetics, 0303 health sciences, Druggability, Genome-wide association study, Biology, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Gene expression, Expression quantitative trait loci, medicine, Bipolar disorder, Synaptic signaling, Prefrontal cortex, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Bipolar disorder (BD) is a heritable mental illness with complex etiology. We performed a genome-wide association study (GWAS) of 41,917 BD cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. BD risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating eQTL data implicated 15 genes robustly linked to BD via gene expression, including druggable genes such as HTR6, MCHR1, DCLK3 and FURIN. This GWAS provides the best-powered BD polygenic scores to date, when applied in both European and diverse ancestry samples. Analyses of BD subtypes indicated high but imperfect genetic correlation between BD type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of BD, identify novel therapeutic leads and prioritize genes for functional follow-up studies.

Published
2020

25. Study Protocol for a Prospective Longitudinal Cohort Study to Identify Proteomic Predictors of Pluripotent Risk for Mental Illness: The Seoul Pluripotent Risk for Mental Illness Study

Author

Sang Jin Rhee, Jun Soo Kwon, Yunna Lee, Sungwon Roh, Kyooseob Ha, Hee-Yeon Jung, Hyun Ju Lee, Euitae Kim, Minah Kim, Se Hyun Kim, Tae Young Lee, Dong Yeon Park, Dohyun Han, Eun Young Kim, Myung Jae Paek, Yong Min Ahn, and Junhee Lee

Subjects
medicine.medical_specialty, lcsh:RC435-571, Psychological intervention, Disease, Study Protocol, 03 medical and health sciences, high-risk for mental illness, proteomics, 0302 clinical medicine, lcsh:Psychiatry, medicine, Bipolar disorder, Prospective cohort study, Psychiatry, bipolar disorder, major depressive disorder, business.industry, Mental illness, medicine.disease, 030227 psychiatry, schizophrenia, Psychiatry and Mental health, Schizophrenia, transdiagnostic, Major depressive disorder, pluripotential, business, 030217 neurology & neurosurgery, Psychopathology
Abstract

Background The Seoul Pluripotent Risk for Mental Illness (SPRIM) study was designed to identify predictors leading to mental illness in help-seeking individuals by securing sufficient statistical power through transdiagnostic approaches. The SPRIM study aims to examine the clinical characteristics of high-risk individuals for mental illness and to identify proteomic biomarkers that can predict the onset of mental illness. Methods This paper describes the study protocol of the SPRIM study. We aim to recruit 150 participants who meet the criteria for high risk for major mental illness, 150 patients with major psychiatric disorders (schizophrenia, bipolar disorder, and major depressive disorder), and 50 matched healthy control subjects for 2 years. Clinical evaluations, self-report measures, and proteomic analyses will be implemented. The assessment points are at baseline, 6, 12, 18, and 24 months. Conclusions In the present study, we introduced the study protocol of the SPRIM study, which is the first prospective cohort study of transdiagnostic high-risk concepts using proteomic biomarkers. This study has a paradigm that encompasses various diseases without aiming at predicting and preventing the development of a specific mental illness in help-seeking individuals. The transdiagnostic high-risk concept could be extended to provide a perspective for people with various psychopathological tendencies below a threshold, such that they do not meet the existing diagnostic criteria of mental illnesses, to determine what may lead them to a specific disease and help identify appropriate preventative interventions.

Published
2020

26. Comparison of serum protein profiles between major depressive disorder and bipolar disorder

Author

Dohyun Han, Minah Kim, Hyeyoon Kim, Tae Young Lee, Sang Jin Rhee, Yunna Lee, Hyunsuk Shin, Yong Min Ahn, Junhee Lee, Se Hyun Kim, Hyeyoung Kim, Jun Soo Kwon, Kangeun Lee, and Kyooseob Ha

Subjects
Adult, Male, Proteomics, 0301 basic medicine, Oncology, medicine.medical_specialty, Bipolar disorder, lcsh:RC435-571, Serum protein, Major depressive disorder, Disease, rab7 protein, 03 medical and health sciences, 0302 clinical medicine, Tandem Mass Spectrometry, lcsh:Psychiatry, Internal medicine, medicine, Humans, Protein kinase A, Depressive Disorder, Major, ROCK2 protein, human, business.industry, XPO7 protein, human, Blood Proteins, medicine.disease, Pathophysiology, Psychiatry and Mental health, 030104 developmental biology, Proteome, Female, business, Biomarkers, 030217 neurology & neurosurgery, Research Article, Chromatography, Liquid
Abstract

Background Major depressive disorder and bipolar disorder are prevalent and debilitating psychiatric disorders that are difficult to distinguish, as their diagnosis is based on behavioural observations and subjective symptoms. Quantitative protein profile analysis might help to objectively distinguish between these disorders and increase our understanding of their pathophysiology. Thus, this study was conducted to compare the peripheral protein profiles between the two disorders. Methods Serum samples were collected from 18 subjects with major depressive disorder and 15 subjects with bipolar disorder. After depleting abundant proteins, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification were performed. Data-dependent acquisition data were statistically analysed from the samples of 15 subjects with major depressive disorder and 10 subjects with bipolar disorder who were psychotropic drug-free. Two-sided t-tests were performed for pairwise comparisons of proteomes to detect differentially-expressed proteins (DEPs). Ingenuity Pathway Analysis of canonical pathways, disease and functions, and protein networks based on these DEPs was further conducted. Results Fourteen DEPs were significant between subjects with major depressive disorder and those with bipolar disorder. Ras-related protein Rab-7a (t = 5.975, p = 4.3 × 10− 6) and Rho-associated protein kinase 2 (t = 4.782, p = 8.0 × 10− 5) were significantly overexpressed in subjects with major depressive disorder and Exportin-7 (t = -4.520, p = 1.5 × 10− 4) was significantly overexpressed in subjects with bipolar disorder after considering multiple comparisons. Bioinformatics analysis showed that cellular functions and inflammation/immune pathways were significantly different. Conclusions Ras-related protein Rab-7a, Rho-associated protein kinase 2, and Exportin-7 were identified as potential peripheral protein candidates to distinguish major depressive disorder and bipolar disorder. Further large sample studies with longitudinal designs and validation processes are warranted.

Published
2020

28. TU26. POLYGENIC RISK PROFILES OF SIX FACTORS IN BIPOLAR DISORDER

Author

Ji Hyun Baek, Dongbin Lee, Kyung Sue Hong, and Kyooseob Ha

Subjects
Pharmacology, Genetics, Psychiatry and Mental health, Neurology, business.industry, Medicine, Pharmacology (medical), Polygenic risk score, Neurology (clinical), Bipolar disorder, business, medicine.disease, Biological Psychiatry
Published
2021

29. The influence of poverty attribution on attitudes toward suicide and suicidal thought: A cross-national comparison between South Korean, Japanese, and American populations

Author

C. Hyung Keun Park, Sang Sin Lee, Hyun Ju Lee, Sang Jin Rhee, Yong Min Ahn, Chang Jae Baik, Kyooseob Ha, and Bora Kim

Subjects
RC435-571, Poverty attribution, Permissive attitude, Structural equation modeling, Structural equation model, Suicidal Ideation, Individualism, Japan, Economic inequality, Republic of Korea, Humans, Income inequality, Permissive, Risk factor, Poverty, Depression (differential diagnoses), Psychiatry, United States, Suicide, Psychiatry and Mental health, Clinical Psychology, Attitude, Comparative study, Psychology, Attribution, Demography
Abstract

Background Previous studies report that income inequality is an important risk factor for depression and suicide, and an increasing income gap appears inevitable. However, little study to date has investigated associations between the attribution of poverty and suicide. Though we previously reported associations between socio-cultural factors, including income, and suicide, we tried to explore more focused associations between income, attribution of poverty (individualistic, societal), permissive attitude toward suicide, and suicidal thought using a structural equation model. Methods A total of 2213 participants from each of three nations (South Korea, Japan, and the United States) completed an online survey. Participants without a history of psychological disorders or suicide attempts completed scales measuring attributions of poverty, attitudes toward suicide, and severity of suicidal thoughts. Results We established a structural equation model, which exhibited a good fit for all nations, and compared significant path coefficients by country. South Korea had the highest severity of suicidal thought and societal attribution of poverty, followed by Japan and America. In all nations, a permissive attitude was positively related to the severity of suicidal thought and individualistic attribution of poverty was positively related to a permissive attitude toward suicide. Societal attribution of poverty was positively associated with a permissive attitude in Japan and the United States. Income was negatively associated with the severity of suicide in South Korea and the United States. Conclusion Through an established structural equation model, we found the influence of poverty on suicide and identify the common and distinctive factors associated with suicide in each country.

Published
2021

31. Can a health information exchange save healthcare costs? Evidence from a pilot program in South Korea

Author

Yoon Kim, Eunyoung Heo, Sang-Il Lee, Hee Hwang, Kyooseob Ha, Hayoung Park, and Jeong Whun Kim

Subjects
Adult, Male, Health Information Exchange, Health information technology, Beneficiary, Pilot Projects, Health Informatics, Health Information Systems, Nursing, Dummy variable, Physicians, Republic of Korea, Health care, Humans, Medicine, Pilot program, Point of care, business.industry, Health information exchange, Health Care Costs, medicine.disease, Patient classification, Female, Medical emergency, Patient Participation, business
Abstract

Governments and institutions across the world have made efforts to adopt and diffuse the health information exchange (HIE) technology with the expectation that the technology would improve the quality and efficiency of care by allowing providers online access to healthcare information generated by other providers at the point of care. However, evidence concerning the effectiveness of the technology is limited hindering the wide adoption of a HIE. The objective of this study was to assess impacts of a HIE on healthcare utilization and costs of patient episodes at a tertiary care hospital following referrals by clinic physicians.We studied 1265 HIE and 2702 non-HIE episodes after physicians referred patients from 35 HIE and 59 non-HIE clinics to Seoul National University Bundang Hospital (SNUBH) during a 17-month period from June 2009. We examined 9 measures of healthcare utilization and the magnitude of clinical information exchanged in 4 categories. We estimated the savings resulting from HIE use through linear regression models with dummy variables for HIE participation and patient classification codes controlling the case-mix differences between HIE and non-HIE cases.The total charges incurred by the HIE group during episodes at SNUBH were approximately 13% lower (P0.001), and the charges for clinical laboratory tests, pathological diagnosis, function tests, and diagnostic imaging were 54% (P0.001), 76% (P0.001), 73% (P0.001), and 80% (P0.001) lower for the HIE group than for the non-HIE group. SNUBH physicians had access to more clinical information for HIE than for non-HIE patients.HIE technology improved physicians' access to past clinical information, which appeared to reduce diagnostic test utilization and healthcare costs. The payer was the major beneficiary of HIE cost savings whereas providers paid for the technology. Fair allocation of benefits and costs among stakeholders is needed for wide HIE adoption.

Published
2015

32. A review of factors associated with greater likelihood of suicide attempts and suicide deaths in bipolar disorder: Part II of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder

Author

Catherine Reis, Tina R. Goldstein, Anthony J. Levitt, Zoltán Rihmer, Mark Sinyor, Doris Hupfeld Moreno, Erkki Isometsä, Ayal Schaffer, Yuan-Hwa Chou, Leonardo Tondo, Carlos A. Zarate, Abraham Weizman, Annette L. Beautrais, Lars Vedel Kessing, Nancy Diazgranados, Gustavo Turecki, Frederick Cassidy, Kyooseob Ha, Lakshmi N. Yatham, and Jean-Michel Azorin

Subjects
medicine.medical_specialty, Bipolar Disorder, Advisory Committees, Poison control, Suicide, Attempted, Comorbidity, Suicide prevention, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Injury prevention, medicine, Humans, Bipolar disorder, Family history, 10. No inequality, Psychiatry, Human factors and ergonomics, General Medicine, 16. Peace & justice, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Age of onset, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Objectives: Many factors influence the likelihood of suicide attempts or deaths in persons with bipolar disorder. One key aim of the International Society for Bipolar Disorders Task Force on Suicide was to summarize the available literature on the presence and magnitude of effect of these factors. Methods: A systematic review of studies published from 1 January 1980 to 30 May 2014 identified using keywords ‘bipolar disorder’ and ‘suicide attempts or suicide’. This specific paper examined all reports on factors putatively associated with suicide attempts or suicide deaths in bipolar disorder samples. Factors were subcategorized into: (1) sociodemographics, (2) clinical characteristics of bipolar disorder, (3) comorbidities, and (4) other clinical variables. Results: We identified 141 studies that examined how 20 specific factors influenced the likelihood of suicide attempts or deaths. While the level of evidence and degree of confluence varied across factors, there was at least one study that found an effect for each of the following factors: sex, age, race, marital status, religious affiliation, age of illness onset, duration of illness, bipolar disorder subtype, polarity of first episode, polarity of current/recent episode, predominant polarity, mood episode characteristics, psychosis, psychiatric comorbidity, personality characteristics, sexual dysfunction, first-degree family history of suicide or mood disorders, past suicide attempts, early life trauma, and psychosocial precipitants. Conclusion: There is a wealth of data on factors that influence the likelihood of suicide attempts and suicide deaths in people with bipolar disorder. Given the heterogeneity of study samples and designs, further research is needed to replicate and determine the magnitude of effect of most of these factors. This approach can ultimately lead to enhanced risk stratification for patients with bipolar disorder.

Published
2015

33. International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder

Author

Doris Hupfeld Moreno, Zoltán Rihmer, Jean-Michel Azorin, Mark Sinyor, Abraham Weizman, Leonardo Tondo, Anthony J. Levitt, Nancy Diazgranados, Lars Vedel Kessing, Erkki Isometsä, Annette L. Beautrais, Kyooseob Ha, Lakshmi N. Yatham, Yuan-Hwa Chou, Ayal Schaffer, Catherine Reis, Tina R. Goldstein, Carlos A. Zarate, Gustavo Turecki, and Frederick Cassidy

Subjects
Male, Suicide Prevention, medicine.medical_specialty, Bipolar Disorder, Substance-Related Disorders, International Cooperation, Preventive Psychiatry, Poison control, Suicide, Attempted, Comorbidity, Alcohol use disorder, Personality Disorders, Risk Assessment, Suicide prevention, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, medicine, Humans, Bipolar disorder, Psychiatry, Borderline personality disorder, Societies, Medical, Biological Psychiatry, Psychiatric Status Rating Scales, Middle Aged, 16. Peace & justice, medicine.disease, Anxiety Disorders, Personality disorders, 3. Good health, 030227 psychiatry, Substance abuse, Suicide, Psychiatry and Mental health, Female, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

OBJECTIVES: Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder. METHODS: Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ≥ 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies. RESULTS: Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide. CONCLUSIONS: This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder. Language: en

Published
2014

34. Lifetime experiences of hypomanic symptoms are associated with delayed and irregular sleep–wake cycle and seasonality in non-clinical adult samples

Author

Ji Hyun Baek, Kyung Sue Hong, Kyooseob Ha, Moonoh Bae, Seunghyong Ryu, Youngah Cho, Ji Sun Kim, and Kounseok Lee

Subjects
Adult, Male, medicine.medical_specialty, Bipolar Disorder, lcsh:RC435-571, Sleep Disorders, Circadian Rhythm, lcsh:Psychiatry, medicine, Humans, Bipolar disorder, Circadian rhythm, Psychiatry, Subclinical infection, Seasonal Pattern Assessment Questionnaire, Seasonality, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Mood, Hypomania, Non clinical, Female, Seasons, medicine.symptom, Psychology, Clinical psychology
Abstract

Objectives: Disturbances of the sleep–wake cycle and seasonality have been reported in patients with bipolar disorder (BD). Considering that BD seems to be a spectrum condition in terms of clinical and biological characteristics, circadian and seasonal rhythm related to BD could be detected in non-clinical individuals with subthreshold bipolarity. The aim of this study was to screen past hypomanic symptoms in non-clinical samples and investigate their association with deviated sleep–wake cycle and seasonality. Methods: Lifetime history of hypomanic symptoms was assessed with the Hypomania Checklist-32 (HCL-32). Circadian preference, variability of sleep–wake time and seasonal changes in mood and behavior were evaluated on a lifetime-basis in non-clinical adult samples (n = 313), using the Composite Scale of Morningness (CSM), the Sleep Timing Questionnaire (STQ), and the Seasonal Pattern Assessment Questionnaire (SPAQ). Results: Two subdomains of hypomanic symptoms were identified through factor analysis of HCL-32, i.e., “active/elated” factor and “irritable/risk-taking” factor. The HCL-32 total score (p

Published
2014

35. A Prediction Model for Depression Risk

Author

Jaeyong Kim, Taesung Park, Byungju Min, Kyooseob Ha, Jae Seung Chang, Tae Hyon Ha, and Jae-Hoon Lee

Subjects
medicine.medical_specialty, Rating scale, mental disorders, Psychopathy, medicine, Bipolar disorder, medicine.disease, Psychology, Psychiatry, Degree (music), Depression (differential diagnoses), Clinical psychology
Abstract

Bipolar disorder is a psychopathy characterized by manic and major depressive episodes. It is important todetermine the degree of depression when treating patients with bipolar disorder because 8 ˘ 10% of bipolarpatients commit suicide during the periods in which they experience major depressive episodes. The Hamil-ton depression rating scale is most commonly used to estimate the degree of depression in a patient. Thispaper proposes using the Hamilton depression rating scale to estimate the effectiveness of patient treatmentbased on the linear mixed effects model and the transition model. Study subjects were recruited from theSeoul National University Bundang Hospital who scored 8 points or above in the Hamilton depression ratingscale on their first medical examination. The linear mixed effects model and the transition model were fittedusing the Hamilton depression rating scales measured at the baseline, six month, and twelve month follow-ups. Then, Hamilton depression rating scale at the twenty-four month follow-up was predicted using thesemodels. The prediction models were then evaluated by comparing the observed and predicted Hamiltondepression rating scales on the twenty-four month follow-up.Keywords: Prediction model, linear mixed effects model, transition model, bipolar disorder, Hamilton de-pression rating scale.

Published
2014

36. Assessment of implicit self-esteem in bipolar manic and euthymic patients using the implicit association test

Author

Jin Young Park, Kyooseob Ha, Hyun Sang Cho, Won Jung Choi, Ra Yeon Ha, Su Jin Lee, and Vin Ryu

Subjects
Adult, Male, medicine.medical_specialty, Bipolar Disorder, lcsh:RC435-571, behavioral disciplines and activities, Young Adult, Psychological status, lcsh:Psychiatry, mental disorders, medicine, Humans, Manic State, Bipolar disorder, Psychiatry, Implicit self-esteem, Psychiatric Status Rating Scales, Implicit-association test, social sciences, medicine.disease, Self Concept, humanities, DEPRESSED STATE, Psychiatry and Mental health, Clinical Psychology, behavior and behavior mechanisms, Female, Psychology
Abstract

Objective Although self-esteem is thought to be an important psychological factor in bipolar disorder, little is known about implicit and explicit self-esteem in manic patients. In this study, we investigated differences in implicit and explicit self-esteem among bipolar manic patients, bipolar euthymic patients, and healthy controls using the Implicit Association Test (IAT). Methods Participants included 19 manic patients, 27 euthymic patients, and 27 healthy controls. Participants completed a self-esteem scale to evaluate explicit self-esteem and performed the self-esteem IAT to evaluate implicit self-esteem. Results There were no differences among groups in explicit self-esteem. However, there were significant differences among groups in implicit self-esteem. Manic patients had higher IAT scores than euthymic patients and a trend toward higher IAT scores than healthy controls. Conclusions Our findings suggest that, on the latent level, a manic state is not simply the opposite of a depressed state. Furthermore, there may be a discontinuity of implicit self-esteem between manic and euthymic states. These unexpected results may be due to characteristics of the study participants or the methods used to assess implicit self-esteem. Nevertheless, they provide greater insights on the psychological status of manic patients.

Published
2014

37. Neuropsychological and Behavioral Profiles in Attention-Deficit Hyperactivity Disorder Children of Parents with a History of Mood Disorders: A Pilot Study

Author

Mira Park, Eun Jin Park, Je-Wook Kang, Hee Jeong Yoo, Young Hui Yang, Kyooseob Ha, Kang-E M Hong, and Subin Park

Subjects
medicine.medical_specialty, High-risk, Mood disorder, CBCL, medicine.disease, behavioral disciplines and activities, Attention deficit hyperactivity disorder, Psychiatry and Mental health, Endophenotype, Offspring, Mood, Wisconsin Card Sorting Test, Mood disorders, Neuropsychology, mental disorders, medicine, Original Article, Psychology, Child Behavior Checklist, Psychiatry, Neurocognitive, Biological Psychiatry, Clinical psychology, Stroop effect
Abstract

ObjectiveaaWe aimed to investigate the neurocognitive and behavioral endophenotypes of premorbid mood disorder. We compared intelligence, neuropsychological functioning, and behavioral problems among three groups: 1) a high-risk group [attention-deficit hyperac tivity disorder (ADHD) children of parents with a history of a mood disorder], 2) a low-risk group (ADHD children of parents without a history of a mood disorder), and 3) normal comparison subjects. MethodsaaWe used the Korean Educational Development Institute Wechsler Intelligence Scale for Children-Revised (KEDI-WISC-R), the Stroop Color Word Interference Test (Stroop), the Wisconsin Card Sorting Test (WCST), and the Rey-Osterrieth Complex Figure Test (RCFT) as neurocognitive measures, and we used the Child Behavior Checklist (CBCL) as a behavioral measure. Performance on these neuropsychological tests and score on the CBCL of 18 high-risk children were compared to those of 20 low-risk children and 24 healthy children. We also assessed the children’s current mood state and familial functioning to control for the confounding effects of these variables. ResultsaaCompared to low-risk and healthy children, high-risk children were impaired on the Picture Completion and Stroop Word subtest and showed higher scores on the CBCL subscales representing internalizing symptoms. These significant group differences per sisted even after adjustment for the children’s current mood state and familial functioning. ConclusionaaNeuropsychological deficits in the offspring of parents with a mood disorder may be associated with the current mood state rather than with innate characteristics, while their internalizing symptoms may partially stem from innate characteristics that are endophenotypes of a premorbid mood disorder. Psychiatry Investig 2014;11:65-75 Key Wordsaa Mood disorder, Attention deficit hyperactivity disorder, Neuropsychology, Endophenotype, High-risk, Offspring.

Published
2014

38. Egr1 regulates lithium-induced transcription of the Period 2 (PER2) gene

Author

Yong Min Ahn, Kyooseob Ha, Yong Sik Kim, Young Han Lee, Hong Geun Park, Soon Young Shin, Hyun Yu, and Se Hyun Kim

Subjects
Male, MAPK/ERK pathway, Transcription, Genetic, Fluorescent Antibody Technique, Electrophoretic Mobility Shift Assay, Mice, Neuroblastoma, Transcription (biology), Tumor Cells, Cultured, RNA, Small Interfering, Luciferases, Promoter Regions, Genetic, Mice, Knockout, Regulation of gene expression, Mitogen-Activated Protein Kinase 3, Reverse Transcriptase Polymerase Chain Reaction, Per2, Period Circadian Proteins, Mood stabilizer, Cell biology, Egr1, Molecular Medicine, Transcriptional Activation, Chromatin Immunoprecipitation, endocrine system, Bipolar disorder, Blotting, Western, Molecular Sequence Data, EGR1, Lithium, Biology, Real-Time Polymerase Chain Reaction, ELK1, Animals, Humans, Electrophoretic mobility shift assay, RNA, Messenger, Molecular Biology, Early Growth Response Protein 1, ets-Domain Protein Elk-1, Binding Sites, Base Sequence, Blotting, Northern, Mice, Inbred C57BL, Gene Expression Regulation, Circadian gene, Mutation, Mutagenesis, Site-Directed, Cancer research, Ectopic expression, Chromatin immunoprecipitation
Abstract

A growing body of evidence suggests that the circadian molecular system is involved in the pathogenic and therapeutic mechanisms underlying bipolar disorders. Lithium, a representative mood stabilizer, has been reported to induce the Period2 (PER2) gene; however, the underlying molecular mechanisms require further study. We found that lithium upregulated PER2 expression at the transcriptional level in neuronally differentiated SH-SY5Y human neuroblastoma cells. Promoter reporter analyses using serial deletions of the PER2 promoter revealed that two early growth response 1 (Egr1)-binding sites (EBS) between positions −180 and −100 are required for maximal activation of the PER2 promoter by lithium. Ectopic expression of Egr1 enhanced lithium-induced PER2 promoter activity, while a point mutation in EBS abolished it. Electrophoretic mobility shift assays and chromatin immunoprecipitation indicated that Egr1 bound directly to the PER2 promoter. Stimulation of the extracellular-signal regulated kinase (ERK)1/2/Elk1 pathway by lithium was functionally linked to PER2 expression through Egr1 induction, and lithium-induced PER2 expression was strongly attenuated by depletion of Egr1 by siRNA. Lithium also upregulated the expression of Per2 and Egr1 in mouse frontal cortex. Induction of Per2 by lithium was attenuated in Egr1−/− mice. In conclusion, lithium stimulates PER2 transcription through the ERK/Elk1/Egr1 pathway in neuronal cells, indicating a connection between the ERK-Egr1 pathway and a circadian gene system in the mechanism of action of lithium.

Published
2013

39. Behavioral and Electrophysiological Alterations for Reinforcement Learning in Manic and Euthymic Patients with Bipolar Disorder

Author

Ra Yeon Ha, Su Jin Lee, Hyun Sang Cho, Kyooseob Ha, and Vin Ryu

Subjects
Adult, Male, medicine.medical_specialty, Bipolar I disorder, Bipolar Disorder, Dysfunctional family, Stimulus (physiology), Audiology, 03 medical and health sciences, 0302 clinical medicine, Bias, Physiology (medical), mental disorders, medicine, Reinforcement learning, Humans, Pharmacology (medical), In patient, Bipolar disorder, Psychiatry, Evoked Potentials, Probability, Pharmacology, Psychiatric Status Rating Scales, Analysis of Variance, Biofeedback, Psychology, Electroencephalography, Original Articles, Middle Aged, Response bias, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Electrophysiology, Female, Psychology, Reinforcement, Psychology, 030217 neurology & neurosurgery, psychological phenomena and processes
Abstract

SummaryAims Bipolar disorder is characterized by behavioral changes such as risk-taking and increasing goal-directed activities, which may result from altered reward processing. Patients with bipolar disorder show impaired reward learning in situations that require the integration of reinforced feedback over time. In this study, we examined the behavioral and electrophysiological characteristics of reward learning in manic and euthymic patients with bipolar disorder using a probabilistic reward task. Methods Twenty-four manic and 20 euthymic patients with bipolar I disorder and 24 healthy control subjects performed the probabilistic reward task. We assessed response bias (RB) as a preference for the stimulus paired with the more frequent reward and feedback-related negativity (FRN) to correct identification of the rich stimulus. Results Both manic and euthymic patients showed significantly lower RB scores in the early learning stage (block 1) in comparison with the late learning stage (block 2 or block 3) of the task, as well as significantly lower RB scores in the early stage compared to healthy subjects. Relatively more negative FRN amplitude is elicited by no presentation of an expected reward, compared to that elicited by presentation of expected feedback. The FRN became significantly more negative from the early (block 1) to the later stages (blocks 2 and 3) in both manic and euthymic patients, but not in healthy subjects. Changes in RB scores and FRN amplitudes between blocks 2 and 3 and block 1 correlated positively in healthy controls, but correlated negatively in manic and euthymic patients. The severity of manic symptoms correlated positively with reward learning scores and negatively with the FRN. Conclusions These findings suggest that patients with bipolar disorder during euthymic or manic states have behavioral and electrophysiological alterations in reward learning compared to healthy subjects. This dysfunctional reward processing may be related to the abnormal decision-making or altered goal-directed activities frequently seen in patients with bipolar disorder.

Published
2016

40. Randomised, double-blind, placebo-controlled study of olanzapine in patients with bipolar I depression

Author

Mauricio Tohen, Juan Carlos Gomez, Shigenobu Kanba, Michael Case, Yi Ru Fang, David McDonnell, Kyooseob Ha, and Hideaki Katagiri

Subjects
Olanzapine, medicine.medical_specialty, Placebo-controlled study, Hamilton Rating Scale for Depression, Young Mania Rating Scale, Placebo, 030227 psychiatry, law.invention, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Clinical Global Impression, 030212 general & internal medicine, Psychology, Psychiatry, Depression (differential diagnoses), medicine.drug
Abstract

BackgroundAtypical antipsychotics are widely used in bipolar mania. However, the efficacy of atypical antipsychotics in bipolar depression has not been comprehensively explored.AimsTo evaluate olanzapine monotherapy in patients with bipolar depression.MethodPatients with bipolar depression received olanzapine (5–20mg/day, n = 343) or placebo (n = l71) for 6 weeks. The primary outcome was change from baseline to end-point in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Secondary outcomes included: Clinical Global impression - Bipolar Version (CGI-BP) scale, 17-item Hamilton Rating Scale for Depression (HRSD-17) and Young Mania Rating Scale (YMRS) scores, and the rate of response (≥50% reduction in MADRS at end-point), recovery (MADRS ≤12 for ≥4 weeks plus treatment completion) and remission (MADRS ≤8). The trial was registered with ClinicalTrials.gov (NCT00510146).ResultsOlanzapine demonstrated: significantly greater (Pv. -11.67), HRSD-17 and YMRS total scores and all CGI-BP subscale scores v. placebo; significantly (P≤0.05) more response and remission, but not recovery; significantly (PPConclusionsOlanzapine monotherapy appears to be efficacious in bipolar depression. Additional long-term studies are warranted to confirm these results. Safety findings were consistent with the known safety profile of olanzapine.

Published
2012

41. Physicians' Perceptions and Use of a Health Information Exchange: A Pilot Program in South Korea

Author

Kyooseob Ha, Hayoung Park, Hee Hwang, Sang Il Lee, Yoon Kim, Jeong Whun Kim, and Eun Young Cho

Subjects
Adult, Male, Program evaluation, Telemedicine, medicine.medical_specialty, Attitude of Health Personnel, Health information technology, Pilot Projects, Health Informatics, Health informatics, Health Information Systems, Health Information Management, Physicians, Republic of Korea, medicine, Humans, Information flow (information theory), Original Research, Descriptive statistics, Attitude to Computers, business.industry, Health information exchange, General Medicine, Variance (accounting), Middle Aged, Health Care Surveys, Family medicine, Female, Perception, Medical Record Linkage, business, Delivery of Health Care, Program Evaluation
Abstract

Objective: We examined physicians' perceived needs, benefits, and concerns regarding health information exchange (HIE) technology prior to experiencing it and their actual usage of exchanged information in care processes during an HIE pilot program in South Korea. Materials and Methods: We conducted a survey through a structured questionnaire to collect data on physician perceptions about an HIE prior to implementation. We analyzed responses using descriptive statistics and one-way analyses of variance. We also conducted a post-implementation survey through a computerized tool designed to collect data on physician assessment of HIE item usefulness. We defined two indices to measure the volume of information flow and usefulness for individual HIE items and analyzed the indices with Fisher's exact test. Results: Physicians' overall perceptions about the need for an HIE and benefits of the technology were positive despite their concerns about information safety and security, system costs, and disputes between care providers in cases of malpractice. We found that physician practice settings significantly influenced the details of their perceptions. In the both pre- and post-implementation studies, the most needed and valued information were pathology and lab results, diagnostic imaging, medication, and working diagnosis. Physicians most agreed with the benefit potentials in the quality domain, least agreed with those in time and cost savings of healthcare delivery, and least worried about the decrease in revenues resulting from the technology. Conclusions: The overall physician acceptance of the HIE technology in South Korea is promising, but the adoption and diffusion strategy needs to be tailored to the type of physician practice. Concerted efforts may be needed to realize the much-anticipated potential of healthcare cost savings.

Published
2012

42. Prodromes and coping types in bipolar patients with nonpsychotic or psychotic mania

Author

Vin Ryu, Hyun Sang Cho, Ra Yeon Ha, Dong-Ho Song, and Kyooseob Ha

Subjects
Adult, Male, Prodromal Period, Psychosis, medicine.medical_specialty, Coping (psychology), Bipolar Disorder, Hallucinations, lcsh:RC435-571, Prodromal Symptoms, Denial, Psychological, Manic Psychosis, Relapse prevention, Severity of Illness Index, lcsh:Psychiatry, Adaptation, Psychological, Severity of illness, medicine, Humans, Bipolar disorder, Psychiatry, Middle Aged, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Psychotic Disorders, Female, medicine.symptom, Psychology, Mania, Clinical psychology
Abstract

Background Bipolar disorder is a recurrent and cyclical illness frequently accompanied by psychotic symptoms. Detecting prodromes and enhancing coping skills for prodromal symptoms in bipolar patients are very important for relapse prevention. Psychotic features in bipolar patients are related to poor prognosis. We aimed to investigate the differences in prodromal symptoms and coping styles in psychotic and nonpsychotic bipolar patients. Methods Eighty-three euthymic bipolar patients with or without a history of manic psychosis were interviewed about their demographic, diagnostic, and clinical information and completed a 40-item checklist for prodromal symptoms. After the interview, they completed the Coping Inventory for Prodromes of Mania. Results The differences between the psychotic patients and the nonpsychotic patients were found in the prodromal durations, and a few prodromal symptoms such as afraid of going crazy ( P = .03), energetic-very active ( P = .01), and hearing hallucination ( P = .02). The psychotic patients showed a higher score of denial or blame than the nonpsychotic ones (1.92 ± 0.73 in nonpsychosis, 2.32 ± 0.84 in psychosis; P = .03). Logistic regression revealed that the duration of prodromes ( P = .02) and hearing hallucination ( P = .01) were related to the presence of psychotic features. Conclusion Psychotic patients had a tendency to use denial or blame coping strategy and to experience attenuated psychotic symptoms a little more during the prodromal period. Timely psychosocial approaches for detecting signs and enhancing coping strategies would improve the outcomes.

Published
2012

43. Seoul National University Bundang Hospital's Electronic System for Total Care

Author

Hai Seok Lee, Kee Hyuck Lee, Hak Jong Lee, Cheong Lim, Nam Soo Byeon, Won Ryang Wee, Hee Hwang, Jonghoar Yun, Eunja Chung, Sooyoung Yoo, Ho Jun Chin, Chul Hee Lee, Kyooseob Ha, Eun Young Cho, Rong Min Baek, and Chin Youb Chung

Subjects
Hospital information system, business.industry, Application, Computer applications to medicine. Medical informatics, R858-859.7, Biomedical Engineering, Information technology, Health Informatics, medicine.disease, Data science, Patient care, Patient safety, Health Information Management, Health care, medicine, Information system, Hospital Information Systems, Total care, Electronic Health Records, Medical emergency, Patient Safety, business, Electronic systems, Quality of Health Care
Abstract

Objectives Seoul National University Bundang Hospital, which is the first Stage 7 hospital outside of North America, has adopted and utilized an innovative and emerging information technology system to improve the efficiency and quality of patient care. The objective of this paper is to briefly introduce the major components of the SNUBH information system and to describe our progress toward a next-generation hospital information system (HIS). Methods SNUBH opened in 2003 as a fully digital hospital by successfully launching a new HIS named BESTCare, "Bundang hospital Electronic System for Total Care". Subsequently, the system has been continuously improved with new applications, including close-loop medication administration (CLMA), clinical data warehouse (CDW), health information exchange (HIE), and disaster recovery (DR), which have resulted in the achievement of Stage 7 status. Results The BESTCare system is an integrated system for a university hospital setting. BESTCare is mainly composed of three application domains: the core applications, an information infrastructure, and channel domains. The most critical and unique applications of the system, such as the electronic medical record (EMR), computerized physician order entry (CPOE), clinical decision support system (CDSS), CLMA, CDW, HIE, and DR applications, are described in detail. Conclusions Beyond our achievement of Stage 7 hospital status, we are currently developing a next-generation HIS with new goals of implementing infrastructure that is flexible and innovative, implementing a patient-centered system, and strengthening the IT capability to maximize the hospital value.

Published
2012

44. Management of bipolar depression

Author

Kyooseob Ha and Jae Seung Chang

Subjects
Olanzapine, medicine.medical_specialty, Lithium (medication), RC435-571, Review Article, Lamotrigine, psychosocial intervention, mental disorders, medicine, Bipolar disorder, Psychiatry, Depression (differential diagnoses), bipolar depression, second-generation antipsychotics, medicine.disease, Clinical Psychology, Psychiatry and Mental health, Mood, lithium, antidepressants, Antidepressant, Quetiapine, Anticonvulsants, Psychology, medicine.drug
Abstract

Patients with bipolar disorder spend more time in a depressed than manic state, even with individualized treatment. To date, bipolar depression is often misdiagnosed and ineffectively managed both for acute episodes and residual symptoms. This review attempts to summarize the current status of available treatment strategies in the treatment of bipolar depression. For acute and prophylactic treatment, a substantial body of evidence supports the antidepressive efficacy of lithium for bipolar disorders and its antisuicidal effects. Among numerous anticonvulsants with mood-stabilizing properties, valproate and lamotrigine could be first-line options for bipolar depression. Due to receptor profile, mood-stabilizing properties of second-generation antipsychotics have been explored, and up to date, quetiapine and olanzapine appear to be a reasonable option for bipolar depression. The usefulness of antidepressants in bipolar depression is still controversial. Current guidelines generally recommend the cautious antidepressant use in combination with mood stabilizers to reduce the risk of mood elevation or cycle acceleration. Results from clinical trials on psychosocial intervention are promising, especially when integrated with pharmacotherapy. Most patients with bipolar depression need individualized and combined treatment, although the published evidence on this type of treatment strategy is limited. Future studies on the utility of currently available agents and modalities including psychosocial intervention are required.

Published
2011

45. Implementation of Medical Information Exchange System Based on EHR Standard

Author

Woo Sung Park, Bi Na Lee, Soon Hwa Han, Myeong Seon Choi, Kyooseob Ha, Jun Yong Jeong, Sang Guk Kim, Il Kon Kim, Jae Bong Bae, Yoon Kim, Eun Young Cho, and Min Ho Lee

Subjects
CDA R2, Computer science, Network security, business.industry, Interoperability, Computer applications to medicine. Medical informatics, Web Service Security Enhanced, Biomedical Engineering, R858-859.7, Health Informatics, computer.file_format, Information security, Clinical Document Architecture, VPN, World Wide Web, Health Information Management, ebXML, Information system, Health Level 7 Standard, Original Article, Electronic Health Record, Database security, business, computer, Information exchange
Abstract

Objectives: To develop effective ways of sharing patients' medical information, we developed a new medical information exchange system (MIES) based on a registry server, which enabled us to exchange different types of data generated by various systems. Methods: To assure that patient's medical information can be effectively exchanged under different system environments, we adopted the standardized data transfer methods and terminologies suggested by the Center for Interoperable Electronic Healthcare Record (CIEHR) of Korea in order to guarantee interoperability. Regarding information security, MIES followed the security guidelines suggested by the CIEHR of Korea. This study aimed to develop essential security systems for the implementation of online services, such as encryption of communication, server security, database security, protection against hacking, contents, and network security. Results: The registry server managed information exchange as well as the registration information of the clinical document architecture (CDA) documents, and the CDA Transfer Server was used to locate and transmit the proper CDA document from the relevant repository. The CDA viewer showed the CDA documents via connection with the information systems of related hospitals. Conclusions: This research chooses transfer items and defines document standards that follow CDA standards, such that exchange of CDA documents between different systems became possible through ebXML. The proposed MIES was designed as an independent central registry server model in order to guarantee the essential security of patients' medical information.

Published
2010

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

Author

Ji Hyun Baek, Kyung Sue Hong, Kyooseob Ha, So Yung Yang, Eun Young Cho, Yu Sang Lee, Bora Lee, and Yoojin Choi

Subjects
medicine.medical_specialty, Bipolar I disorder, Schizophrenia, business.industry, medicine, Genetic variants, Single-nucleotide polymorphism, Bipolar disorder, medicine.disease, Association (psychology), Psychiatry, business
Published
2018

47. Validity and reliability of the Korean version of the Mood Disorder Questionnaire

Author

Duk-In Jon, Han Yong Jung, Narei Hong, Kyooseob Ha, Won-Myong Bahk, Bo-Hyun Yoon, and Young Chul Shin

Subjects
Adult, Male, Predictive validity, medicine.medical_specialty, Psychometrics, lcsh:RC435-571, Validity, Test validity, Psychiatric history, Asian People, Cronbach's alpha, Surveys and Questionnaires, lcsh:Psychiatry, Confidence Intervals, medicine, Humans, Translations, Bipolar disorder, Psychiatry, Mood Disorders, Mood Disorder Questionnaire, medicine.disease, Psychiatry and Mental health, Clinical Psychology, Female, Factor Analysis, Statistical, Psychology
Abstract

Backgrounds: This study aimed to elucidate the validity and reliability of the Korean version of the Mood Disorder Questionnaire (K-MDQ), which is a screening instrument developed for bipolar disorders. Methods: This study translated the MDQ into Korean to produce the K-MDQ. The K-MDQ was applied to 126 outpatients with bipolar disorder clinically diagnosed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and 112 controls without a psychiatric history. The long-term test-retest reliability with a 10-month interval was investigated in 30 bipolar outpatients. Results: The internal consistency (Cronbach α) of the K-MDQ was .88. The correlations between each item and the total score ranged from 0.43 to 0.76 and were all statistically significant (P < .001). Factor analysis revealed 3 factors that explained 59.5% of the total variance. The mean total score was higher in patients (8.48) than in controls (4.51) (P < .001). A total K-MDQ score of at least 7 was chosen as the optimal cutoff, with the 2 parts of the questionnaire on symptoms clustering and functional problems being excluded, since this provided good sensitivity (0.75) and specificity (0.69). The Pearson correlation coefficient for the total test-retest score was 0.63 (P < .001), and the intraclass correlation coefficient was 0.77 (P < .001; 95% confidence interval, 0.52-0.89). Conclusions: These findings demonstrated the adequate validity and reliability of the K-MDQ, suggesting that this instrument is useful for screening bipolar disorders in Korea. However, we recommend that the original criteria be modified to improve the sensitivity.

Published
2009

48. Epidemiology, neurobiology and pharmacological interventions related to suicide deaths and suicide attempts in bipolar disorder: Part I of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder

Author

Gustavo Turecki, Erkki Isometsä, Frederick Cassidy, Ayal Schaffer, Kyooseob Ha, Jean-Michel Azorin, Lars Vedel Kessing, Doris Hupfeld Moreno, Anthony J. Levitt, Yuan-Hwa Chou, Zoltán Rihmer, Leonardo Tondo, Catherine Reis, Mark Sinyor, Abraham Weizman, Tina R. Goldstein, Lakshmi N. Yatham, Carlos A. Zarate, Nancy Diazgranados, and Annette L. Beautrais

Subjects
Male, medicine.medical_specialty, Bipolar Disorder, Advisory Committees, Poison control, Neuroimaging, Suicide, Attempted, Suicide prevention, Occupational safety and health, Article, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Antimanic Agents, Risk Factors, Epidemiology, Injury prevention, medicine, Humans, Bipolar disorder, Psychiatry, Incidence (epidemiology), Human factors and ergonomics, Brain, General Medicine, Protective Factors, 16. Peace & justice, medicine.disease, 030227 psychiatry, 3. Good health, Psychiatry and Mental health, Suicide, Lithium Compounds, Anticonvulsants, Female, Psychology, Neuroscience, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Objectives: Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. Methods: Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. Results: The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval = [5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4–14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23–26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. Conclusion: This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder.

Published
2015

49. Association between ST8SIA2 and the Risk of Schizophrenia and Bipolar I Disorder across Diagnostic Boundaries

Author

Kyung Sue Hong, Iksoo Huh, Taesung Park, So Yung Yang, Ji Hyun Baek, Kyooseob Ha, Ji Sun Kim, Mi Ji Choi, Seunghyong Ryu, and Eun Young Cho

Subjects
Adult, Bipolar I disorder, Bipolar Disorder, Genotype, lcsh:Medicine, Genome-wide association study, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Bipolar II disorder, Young Adult, Gene Frequency, Risk Factors, Genetic model, mental disorders, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, lcsh:Science, Psychiatric genetics, Alleles, Genetic association, Genetics, Multidisciplinary, lcsh:R, Middle Aged, medicine.disease, Sialyltransferases, Logistic Models, Phenotype, Schizophrenia, lcsh:Q, Research Article
Abstract

Background Findings from family studies and recent genome-wide association studies have indicated overlap in the risk genes between schizophrenia and bipolar disorder (BD). After finding a linkage between the ST8SIA2 (ST8 alpha-N-acetyl-neuraminide alpha-2, 8-sicalyltransferase 2 gene) locus (15q26) and mixed families with schizophrenia and BD, several studies have reported a significant association between this gene and schizophrenia or BD. We investigated the genetic association between ST8SIA2 and both schizophrenia and BD in the Korean population. Methods A total of 582 patients with schizophrenia, 339 patients with BD, and 502 healthy controls were included. Thirty-one tag single nucleotide polymorphisms (SNPs) across the ST8SIA2 region and three other SNPs showing significant associations in previous studies were genotyped. The associations were evaluated by logistic regression analysis using additive, dominant, and recessive genetic models. Results Fourteen of 34 SNPs showed a nominally significant association (p < 0.05) with at least one diagnostic group. These association trends were strongest for the schizophrenia and combined schizophrenia and bipolar I disorder (BD-I) groups. The strongest association was observed in rs11637898 for schizophrenia (p = 0.0033) and BD-I (p = 0.0050) under the dominant model. The association between rs11637898 and the combined schizophrenia and BD-I group (p = 0.0006, under the dominant model) remained significant after correcting for multiple testing. Discussion We identified a possible role of ST8SIA2 in the common susceptibility of schizophrenia and BD-I. However, no association trend was observed for bipolar II disorder. Further efforts are needed to identify a specific phenotype associated with this gene crossing the current diagnostic categories.

Published
2015

50. PS66. The protective effects of hypomanic symptoms in a major depressive episode on suicide attempt in bipolar disorder

Author

Tea Hyon Ha, Teawon Chung, Doran Park, Hyun Jean Jeong, Kyooseob Ha, Eun-Ju Kim, Yoon Seong Park, Lee, Jeong Eun Ryu, and Jongha Lee

Subjects
Pharmacology, medicine.medical_specialty, Suicide attempt, business.industry, Sunday Abstracts, medicine.disease, Psychiatry and Mental health, Abstracts, Medicine, Pharmacology (medical), Bipolar disorder, medicine.symptom, business, Psychiatry, Major depressive episode
Published
2016

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