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July 2011
Report on Activities of "WPA Bipolar Disorder Fellowship" by Jun Chen, M.D., Ph.D.

Mentors:
Joseph R. Calabrese, M.D.,
Keming Gao, M.D., Ph.D.
Mood Disorders Program
University Hospitals Case Medical Center
Case Western Reserve University

From February 20th of 2010 to February 18th of 2011, I completed one-year WPA Bipolar Research Fellowship training in the Mood Disorders Program of the Department of Psychiatry at Case Western Reserve University. The training was focused on phenomenology and therapeutics of bipolar disorders. During the training, I was under the close supervision and mentoring of Dr. Calabrese, the Director of Mood Disorders Program and Dr. Gao, the Clinical Director of the program. Through this fellowship, I learned key elements of conducting clinical researches in mood disorders, especially in bipolar disorders, which will help me to continue clinical research in bipolar disorders in my home institution, Shanghai Mental Health Center, China. Before I report my training activities, I want to express my gratitude to the WPA for providing me this unique opportunity to advance my career. I also want to express my gratitude to my training institution, the Mood Disorders Program at Case Western Reserve University, and my mentors, Drs. Calabrese and Gao for their support. The following is a brief summary of my activities and experience during the training.

Research

My training was a state of art systematic training with a step-by-step approach. First, I studied and passed the Collaborative Institutional Training Initiative (CITI) online training course offered by the Institutional Review Board (IRB) of Case Western Reserve University to understand how to protect research participants. Second, I observed Dr. Gao how to work with research patients, including initial diagnostic evaluation, baseline history and physical examination, randomization, follow-up visit, and post-study visits, etc. Third, I started seeing research patients myself under the supervision of Dr. Gao from the third month of the fellowship. This kind of hand-on experience gave me the opportunity to understand the psychopathology and clinical presentation of bipolar disorders.

Shortly after I started seeing patients myself, I quickly mastered commonly used diagnostic instruments, like the Mini-International Neuropsychiatric Interview-Plus (M.I.N.I.), Structured Clinical Interview for DSM-IV (SCID) and symptom severity measures such as Cumulative Illness Rating Scale (CIRS), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression (CGI), Frequency, Intensity, and Burden of Side Effects Ratings/Global Rating of Side Effects Burden (FIBSR/GRSEB), Young Mania Rating Scale (YMRS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Scale (SAS).

From the beginning to the end, I had weekly meeting with Dr. Gao and monthly meeting with Dr. Calabrese. The focus with Dr. Gao’s weekly meeting was to help me to write in English, including manuscript preparation, grant application, data management, study design, and so on. The focus with Dr. Calabrese’s monthly meeting was to overall career development. In addition, I was involved in other routine clinical research meetings including biweekly research meetings, monthly program meetings, and Chinese-American Bipolar Disorder Research Initiative meetings with members of physicians, statisticians, project managers, and research assistants. Through these meetings, I learned how to execute a successful clinical study and how to become a successful clinical researcher.

Scholarship

The second component of my training was scholarship. It included but not limited to learn how to get manuscripts published in English, how to review manuscripts for journals with mentors, and how to present data in scientific meetings. So far, I published two review articles as the first author. The first one is ‘Switching to hypomania and mania: differential neurochemical, neuropsychologic, and pharmacologic triggers and their mechanisms’ published in Current Psychiatry Reports. The second one is ‘Second-generation antipsychotics in major depressive disorder: Update and clinical perspective’ published in Current Opinion in Psychiatry. I took the lead in drafting two original research articles. The first one, entitled ‘Safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania: a 12-week open-label study’, had been revised and re-submitted to Human Psychopharmacology: Clinical and Experimental. Currently, I am working on the second one entitled “different cognitive and social function impairments between unipolar treatment-resistant depression and first episode major depression”. I reviewed several articles for different journals with mentors. I also presented a poster at the 50th NCDUE Annual meeting.

Through these activities, I learned how to organize a manuscript, how to request data analyses, how to communicate with co-authors, and how to revise manuscripts. The most important lesson I learned from these activities is clarity, clarity, and clarity.

Grant Submission

In addition to participating in all ongoing clinical studies in the Mood Disorders Program, I initiated my own study. Since, misdiagnosis of bipolar disorders is still common and problematic, self-reported questionnaires on manic/hypomanic symptoms might help clinicians to reduce the risk for misdiagnosis in patients with bipolar disorders. Mood Disorder Questionnaire (MDQ) is helpful for screening patients with bipolar I disorder, but not those with bipolar II disorder. European data has shown that Hypomania/Mania Symptom Checklist (HCL-32) is more sensitive for screening patients with bipolar II disorder. UP to now, there were some studies validated MDQ and HCL-32 in detecting mania/hypomania in different clinic populations with mood disorders, but their application in treatment-resistant depression has never been studied.

To address this issue, I initiated a study to use MDQ and HCL-32 to screen all research patients in the Mood Disorders Program at the initial assessment through revising the screening protocol of the program. At the same time, I proposed to conduct a similar study in Shanghai Mental Health Center to the Shanghai Health Bureau, Shanghai, China during my training. Despite this challenging process, the knowledge and experience I gained will allow me to write more effective grants in the future.

Education

From the beginning of this fellowship, I joined the weekly psychiatry department grand rounds and monthly mood disorders program journal club. These grand rounds gave me opportunities to learn from other professionals from different psychiatric research areas. Close to the end of my research fellowship, I spent one week to observe the Intensive Outpatient Program (IOP) of the department of psychiatry. I also observed electroconvulsive therapy (ECT) and Dr. Gao’s clinical practice in inpatients department. I spent one half-day to visit the free clinic, a community mental health center of Cuyahoga County of Ohio. Through these activities, I learned the differences in mental health services between U.S. and China, especially the IOP model. I am planning to establish a similar high efficient IOP in my institution.

Another important part of my education was to attend national meetings. With the help of my mentors, I successfully submitted and presented a poster presentation on the 2010 NCDEU Annual Meeting. The NCDEU meeting, which was organized annually by the National Institute of Mental Health, is one of the most important academic meetings in the psychiatric clinical research, especially in clinical trials. My presentation topic was ‘Comparison of Cognitive Function in Patients with Treatment Resistant Depression, Fist Episode Depression, and Healthy Control’. I received very positive feedbacks on my findings and my presentation, which gave me encouragement to conduct world class clinical studies in China. During this meeting, I learned the state of art in clinical studies, like how to conduct an international multi-center research, how to develop clinical research instruments, how to protect patients’ privilege and prevent suicide during the study, and how to use neuroimaging findings for clinical practice.
Another important academic meeting I attended was the ‘Building Harmony: Enhancing Human Subject Protections through Coordinated Regulatory Oversight’, hosted by Case Western Reserve University. During this meeting, I learned newly updated ethical related issues and how to protect research patients.

Other Activities

During my research fellowship, I was involved in peer-reviewing for journals. Working with my mentors, I peer-reviewed four manuscripts for different journals, including American Journal of Psychiatry, Indian Journal of Pharmacology, Primary Psychiatry, and Neuropsychopharmacology. This process enriched me the knowledge in how to evaluate a successful academic paper and give an academic feedback as well. A unique experience for me was that I was interviewed by the biggest local newspaper – The Cleveland Plain Dealer. During the interview, I introduced the WPA research fellowships program, as well as my original institution (Shanghai Mental Health Center) to the American public.

Post-Fellowship Activities in China

This training also enriched me to be more competitive and successful in my country. After I came back to China, I was assigned as the director of the Depressive Disorders Program in the Division of Mood Disorders of Shanghai Mental Health Center. The goal of this newly established program is to become the best mood disorder research program in China, especially in the area of treatment-resistant depression and bipolar disorders. At the same time, I was selected as an administrator for the Division of Psychiatry and Neurology of the National Natural Science Foundation of China by my home institution in the March of this year. The main responsibility for the administrator is to review and score grants submitted to the National Natural Science Foundation and to decide which grant should be funded. The foundation manages over 20 billion RMB each year and covers a variety of scientific areas. The term for each administrator is full-time for 6 months. Although this position is very demanding, it is an honor and a privilege as an administrator for foundation since each year, only one person from a handful of large institutions with strong research background is requested by the Chinese government to work for the foundation. I believe that my one year WAP fellowship training played a major role for me being selected. In addition, the Asian Federation of Psychiatric Associations (AFPA) is planning to establish an Asian Young Psychiatrist Association (AYPA) at the 3rd World Congress of Asian Psychiatry at Melbourne Australia in August, 2011. I was appointed as one of the Steering Committee members of the AYPA and have worked closely with the AFPA.

In terms of grant submission after I came back to China, I am happy to inform you that my proposal to use MDQ and HCL-32 to screen bipolar disorders in patients with treatment-resistant depression and atypical depression was approved by the Shanghai Health Bureau in May 2011 with a total of award of 300,000 RMB. In the next 3 years, I will collect data in the Chinese population. Afterwards, I will compare and combine the data from the Mood Disorders Program at Case Western Reserve University. In addition, I also sent an application to the Science and Technology Commission of Shanghai Municipality. The application was focus on studying cognitive function impairments and neuroimaging changes in patients with bipolar I disorder. It had passed the first-round peer-review and now is pending for the final decision.

In summary, this one-year research fellowship gave me a very precious opportunity to closely observe and learn from the world famous bipolar disorder researchers. The gains from this fellowship will help me to grow and to become a top Chinese researcher in mood disorders, especially in bipolar disorders. I will continue working diligently to achieve my goals in research, scholarship, grant submission, and teaching in my home institution. I will work closely with the WPA, the Mood Disorders Program at Case Western Reserve University, and Shanghai Mental Health center to promote bipolar disorder research in China and other parts of the world.

Paper Published:
[1] CHEN, J., GAO, K. & KEMP, D. E. (2010) Second-generation antipsychotics in major depressive disorder: update and clinical perspective. Curr Opin Psychiatry, 24, 10-7.
[2] CHEN, J., FANG, Y., KEMP, D. E., CALABRESE, J. R. & GAO, K. (2010) Switching to hypomania and mania: differential neurochemical, neuropsychological, and pharmacologic triggers and their mechanisms. Curr Psychiatry Rep, 12, 512-21.

Manuscript Revised and Re-submitted:
[1] CHEN, J., MUZINA, D. J., KEMP, D. E., CONROY, C., CHAN, P., SERRANO, M. B., GANOCY, S. J., FANG, Y., CALABRESE, J. R. & GAO, K. Safety and Efficacy of Olanzapine Monotherapy in Treatment-Resistant Bipolar Disorder Mania: A 12-week Open-Label Study. Hum Psychopharmacol.

Manuscript Under Preparation:
[1] CHEN, J., CALABRESE, J. R., GAO, K., Fang, Y. et al. Differences of Cognitive and Social Function Impairments between Unipolar Treatment-Resistant Depression and First Episode Major Depression: An 8-week Open-Label Healthy-Controlled Study in Chinese Han Population.

Poster presentation:
[1] Comparison of Cognitive Function in Patients with Treatment Resistant Depression, First Episode Depression, and Healthy Control. 2010 NCDEU, Boca Raton, Florida, U.S.

Meeting attended:
[1] 2010 New Research Approaches for Mental Health Interventions. Boca Raton, Florida, U.S..
[2] Building Harmony: Enhancing Human Subject Protections through Coordinated Regulatory Oversight. Cleveland, Ohio, U.S..

Post-Fellowship Grant Application:
[1] Using structural instruments to screen bipolar disorder in patients with treatment-resistant depression and atypical depression. Shanghai Health Bureau, China. (300,000 RMB).
[2] Cognitive function impairments and neuroimaging changes in patients with bipolar I disorder

Post-Fellowship Appointment:
[1] Director, Depressive Disorders Program, Division of Mood Disorders, Shanghai Mental Health Center.
[2] Short-term Administrator, Division of Psychiatry and Neurology, Department of Medicine, National Natural Science Foundation of China.
[3] Steering Committee member, Asian Young Psychiatrist Association (AYPA) of the Asian Federation of Psychiatric Associations.

>> Please click here to read the PDF version of the report.

Mentors:
Joseph R. Calabrese, M.D.,
Keming Gao, M.D., Ph.D.
Mood Disorders Program
University Hospitals Case Medical Center
Case Western Reserve University

From February 20th of 2010 to February 18th of 2011, I completed one-year WPA Bipolar Research Fellowship training in the Mood Disorders Program of the Department of Psychiatry at Case Western Reserve University. The training was focused on phenomenology and therapeutics of bipolar disorders. During the training, I was under the close supervision and mentoring of Dr. Calabrese, the Director of Mood Disorders Program and Dr. Gao, the Clinical Director of the program. Through this fellowship, I learned key elements of conducting clinical researches in mood disorders, especially in bipolar disorders, which will help me to continue clinical research in bipolar disorders in my home institution, Shanghai Mental Health Center, China. Before I report my training activities, I want to express my gratitude to the WPA for providing me this unique opportunity to advance my career. I also want to express my gratitude to my training institution, the Mood Disorders Program at Case Western Reserve University, and my mentors, Drs. Calabrese and Gao for their support. The following is a brief summary of my activities and experience during the training.

Research

My training was a state of art systematic training with a step-by-step approach. First, I studied and passed the Collaborative Institutional Training Initiative (CITI) online training course offered by the Institutional Review Board (IRB) of Case Western Reserve University to understand how to protect research participants. Second, I observed Dr. Gao how to work with research patients, including initial diagnostic evaluation, baseline history and physical examination, randomization, follow-up visit, and post-study visits, etc. Third, I started seeing research patients myself under the supervision of Dr. Gao from the third month of the fellowship. This kind of hand-on experience gave me the opportunity to understand the psychopathology and clinical presentation of bipolar disorders.

Shortly after I started seeing patients myself, I quickly mastered commonly used diagnostic instruments, like the Mini-International Neuropsychiatric Interview-Plus (M.I.N.I.), Structured Clinical Interview for DSM-IV (SCID) and symptom severity measures such as Cumulative Illness Rating Scale (CIRS), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Hamilton Anxiety Rating Scale (HAM-A), Clinical Global Impression (CGI), Frequency, Intensity, and Burden of Side Effects Ratings/Global Rating of Side Effects Burden (FIBSR/GRSEB), Young Mania Rating Scale (YMRS), Barnes Akathisia Rating Scale (BARS), and Simpson-Angus Scale (SAS).

From the beginning to the end, I had weekly meeting with Dr. Gao and monthly meeting with Dr. Calabrese. The focus with Dr. Gao’s weekly meeting was to help me to write in English, including manuscript preparation, grant application, data management, study design, and so on. The focus with Dr. Calabrese’s monthly meeting was to overall career development. In addition, I was involved in other routine clinical research meetings including biweekly research meetings, monthly program meetings, and Chinese-American Bipolar Disorder Research Initiative meetings with members of physicians, statisticians, project managers, and research assistants. Through these meetings, I learned how to execute a successful clinical study and how to become a successful clinical researcher.

Scholarship

The second component of my training was scholarship. It included but not limited to learn how to get manuscripts published in English, how to review manuscripts for journals with mentors, and how to present data in scientific meetings. So far, I published two review articles as the first author. The first one is ‘Switching to hypomania and mania: differential neurochemical, neuropsychologic, and pharmacologic triggers and their mechanisms’ published in Current Psychiatry Reports. The second one is ‘Second-generation antipsychotics in major depressive disorder: Update and clinical perspective’ published in Current Opinion in Psychiatry. I took the lead in drafting two original research articles. The first one, entitled ‘Safety and efficacy of olanzapine monotherapy in treatment-resistant bipolar mania: a 12-week open-label study’, had been revised and re-submitted to Human Psychopharmacology: Clinical and Experimental. Currently, I am working on the second one entitled “different cognitive and social function impairments between unipolar treatment-resistant depression and first episode major depression”. I reviewed several articles for different journals with mentors. I also presented a poster at the 50th NCDUE Annual meeting.

Through these activities, I learned how to organize a manuscript, how to request data analyses, how to communicate with co-authors, and how to revise manuscripts. The most important lesson I learned from these activities is clarity, clarity, and clarity.

Grant Submission

In addition to participating in all ongoing clinical studies in the Mood Disorders Program, I initiated my own study. Since, misdiagnosis of bipolar disorders is still common and problematic, self-reported questionnaires on manic/hypomanic symptoms might help clinicians to reduce the risk for misdiagnosis in patients with bipolar disorders. Mood Disorder Questionnaire (MDQ) is helpful for screening patients with bipolar I disorder, but not those with bipolar II disorder. European data has shown that Hypomania/Mania Symptom Checklist (HCL-32) is more sensitive for screening patients with bipolar II disorder. UP to now, there were some studies validated MDQ and HCL-32 in detecting mania/hypomania in different clinic populations with mood disorders, but their application in treatment-resistant depression has never been studied.

To address this issue, I initiated a study to use MDQ and HCL-32 to screen all research patients in the Mood Disorders Program at the initial assessment through revising the screening protocol of the program. At the same time, I proposed to conduct a similar study in Shanghai Mental Health Center to the Shanghai Health Bureau, Shanghai, China during my training. Despite this challenging process, the knowledge and experience I gained will allow me to write more effective grants in the future.

Education

From the beginning of this fellowship, I joined the weekly psychiatry department grand rounds and monthly mood disorders program journal club. These grand rounds gave me opportunities to learn from other professionals from different psychiatric research areas. Close to the end of my research fellowship, I spent one week to observe the Intensive Outpatient Program (IOP) of the department of psychiatry. I also observed electroconvulsive therapy (ECT) and Dr. Gao’s clinical practice in inpatients department. I spent one half-day to visit the free clinic, a community mental health center of Cuyahoga County of Ohio. Through these activities, I learned the differences in mental health services between U.S. and China, especially the IOP model. I am planning to establish a similar high efficient IOP in my institution.

Another important part of my education was to attend national meetings. With the help of my mentors, I successfully submitted and presented a poster presentation on the 2010 NCDEU Annual Meeting. The NCDEU meeting, which was organized annually by the National Institute of Mental Health, is one of the most important academic meetings in the psychiatric clinical research, especially in clinical trials. My presentation topic was ‘Comparison of Cognitive Function in Patients with Treatment Resistant Depression, Fist Episode Depression, and Healthy Control’. I received very positive feedbacks on my findings and my presentation, which gave me encouragement to conduct world class clinical studies in China. During this meeting, I learned the state of art in clinical studies, like how to conduct an international multi-center research, how to develop clinical research instruments, how to protect patients’ privilege and prevent suicide during the study, and how to use neuroimaging findings for clinical practice.
Another important academic meeting I attended was the ‘Building Harmony: Enhancing Human Subject Protections through Coordinated Regulatory Oversight’, hosted by Case Western Reserve University. During this meeting, I learned newly updated ethical related issues and how to protect research patients.

Other Activities

During my research fellowship, I was involved in peer-reviewing for journals. Working with my mentors, I peer-reviewed four manuscripts for different journals, including American Journal of Psychiatry, Indian Journal of Pharmacology, Primary Psychiatry, and Neuropsychopharmacology. This process enriched me the knowledge in how to evaluate a successful academic paper and give an academic feedback as well. A unique experience for me was that I was interviewed by the biggest local newspaper – The Cleveland Plain Dealer. During the interview, I introduced the WPA research fellowships program, as well as my original institution (Shanghai Mental Health Center) to the American public.

Post-Fellowship Activities in China

This training also enriched me to be more competitive and successful in my country. After I came back to China, I was assigned as the director of the Depressive Disorders Program in the Division of Mood Disorders of Shanghai Mental Health Center. The goal of this newly established program is to become the best mood disorder research program in China, especially in the area of treatment-resistant depression and bipolar disorders. At the same time, I was selected as an administrator for the Division of Psychiatry and Neurology of the National Natural Science Foundation of China by my home institution in the March of this year. The main responsibility for the administrator is to review and score grants submitted to the National Natural Science Foundation and to decide which grant should be funded. The foundation manages over 20 billion RMB each year and covers a variety of scientific areas. The term for each administrator is full-time for 6 months. Although this position is very demanding, it is an honor and a privilege as an administrator for foundation since each year, only one person from a handful of large institutions with strong research background is requested by the Chinese government to work for the foundation. I believe that my one year WAP fellowship training played a major role for me being selected. In addition, the Asian Federation of Psychiatric Associations (AFPA) is planning to establish an Asian Young Psychiatrist Association (AYPA) at the 3rd World Congress of Asian Psychiatry at Melbourne Australia in August, 2011. I was appointed as one of the Steering Committee members of the AYPA and have worked closely with the AFPA.

In terms of grant submission after I came back to China, I am happy to inform you that my proposal to use MDQ and HCL-32 to screen bipolar disorders in patients with treatment-resistant depression and atypical depression was approved by the Shanghai Health Bureau in May 2011 with a total of award of 300,000 RMB. In the next 3 years, I will collect data in the Chinese population. Afterwards, I will compare and combine the data from the Mood Disorders Program at Case Western Reserve University. In addition, I also sent an application to the Science and Technology Commission of Shanghai Municipality. The application was focus on studying cognitive function impairments and neuroimaging changes in patients with bipolar I disorder. It had passed the first-round peer-review and now is pending for the final decision.

In summary, this one-year research fellowship gave me a very precious opportunity to closely observe and learn from the world famous bipolar disorder researchers. The gains from this fellowship will help me to grow and to become a top Chinese researcher in mood disorders, especially in bipolar disorders. I will continue working diligently to achieve my goals in research, scholarship, grant submission, and teaching in my home institution. I will work closely with the WPA, the Mood Disorders Program at Case Western Reserve University, and Shanghai Mental Health center to promote bipolar disorder research in China and other parts of the world.

Paper Published:
[1] CHEN, J., GAO, K. & KEMP, D. E. (2010) Second-generation antipsychotics in major depressive disorder: update and clinical perspective. Curr Opin Psychiatry, 24, 10-7.
[2] CHEN, J., FANG, Y., KEMP, D. E., CALABRESE, J. R. & GAO, K. (2010) Switching to hypomania and mania: differential neurochemical, neuropsychological, and pharmacologic triggers and their mechanisms. Curr Psychiatry Rep, 12, 512-21.

Manuscript Revised and Re-submitted:
[1] CHEN, J., MUZINA, D. J., KEMP, D. E., CONROY, C., CHAN, P., SERRANO, M. B., GANOCY, S. J., FANG, Y., CALABRESE, J. R. & GAO, K. Safety and Efficacy of Olanzapine Monotherapy in Treatment-Resistant Bipolar Disorder Mania: A 12-week Open-Label Study. Hum Psychopharmacol.

Manuscript Under Preparation:
[1] CHEN, J., CALABRESE, J. R., GAO, K., Fang, Y. et al. Differences of Cognitive and Social Function Impairments between Unipolar Treatment-Resistant Depression and First Episode Major Depression: An 8-week Open-Label Healthy-Controlled Study in Chinese Han Population.

Poster presentation:
[1] Comparison of Cognitive Function in Patients with Treatment Resistant Depression, First Episode Depression, and Healthy Control. 2010 NCDEU, Boca Raton, Florida, U.S.

Meeting attended:
[1] 2010 New Research Approaches for Mental Health Interventions. Boca Raton, Florida, U.S..
[2] Building Harmony: Enhancing Human Subject Protections through Coordinated Regulatory Oversight. Cleveland, Ohio, U.S..

Post-Fellowship Grant Application:
[1] Using structural instruments to screen bipolar disorder in patients with treatment-resistant depression and atypical depression. Shanghai Health Bureau, China. (300,000 RMB).
[2] Cognitive function impairments and neuroimaging changes in patients with bipolar I disorder

Post-Fellowship Appointment:
[1] Director, Depressive Disorders Program, Division of Mood Disorders, Shanghai Mental Health Center.
[2] Short-term Administrator, Division of Psychiatry and Neurology, Department of Medicine, National Natural Science Foundation of China.
[3] Steering Committee member, Asian Young Psychiatrist Association (AYPA) of the Asian Federation of Psychiatric Associations.

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