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Bipolar Disorder: HELP
Articles from Miscellaneous institutions in Bethesda
Based on 44 articles published since 2010
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These are the 44 published articles about Bipolar Disorder that originated from Miscellaneous institutions in Bethesda during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review An International Society of Bipolar Disorders task force report: Precursors and prodromes of bipolar disorder. 2019

Faedda, Gianni L / Baldessarini, Ross J / Marangoni, Ciro / Bechdolf, Andreas / Berk, Michael / Birmaher, Boris / Conus, Philippe / DelBello, Melissa P / Duffy, Anne C / Hillegers, Manon H J / Pfennig, Andrea / Post, Robert M / Preisig, Martin / Ratheesh, Aswin / Salvatore, Paola / Tohen, Mauricio / Vázquez, Gustavo H / Vieta, Eduard / Yatham, Lakshmi N / Youngstrom, Eric A / Van Meter, Anna / Correll, Christoph U. ·Mood Disorders Center, New York, NY, USA. · International Consortium for Mood and Psychotic Disorders Research, McLean Hospital, Belmont, MA, USA. · Department of Psychiatry, Harvard Medical School, Mailman Research Center, McLean Hospital, Boston, MA, USA. · Department of Psychiatry-District 3, ULSS 9 Scaligera, Verona, Italy. · Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. · Department of Psychiatry, Psychotherapy and Psychosomatics, Vivantes Hospital am Urban and Vivantes Hospital im Friedrichschain, Charite Universitätsmedizin, Berlin, Germany. · IMPACT Strategic Research Centre, University Hospital Geelong, Barwon Health, Deakin University, Geelong, VIC, Australia. · Orygen, The National Center of Excellence in Youth Mental Health, Parkville, VIC, Australia. · The Florey Institute for Neuroscience and Mental Health and the Department of Psychiatry, University of Melbourne, Melbourne, VIC, Australia. · Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. · Treatment and Early Intervention in Psychosis Program (TIPP), Département de Psychiatrie CHUV, Université de Lausanne, Lausanne, Switzerland. · Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Department of Psychiatry, Student Wellness Services, Queen's University, Kingston, ON, Canada. · Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. · Department of Child and Adolescent Psychiatry, Erasmus medical Center Rotterdam, Rotterdam, The Netherlands. · Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany. · Bipolar Collaborative Network, Bethesda, MD, USA. · Department of Psychiatry, George Washington University School of Medicine, Washington, DC, USA. · Department of Psychiatry, University Hospital of Lausanne, Lausanne, Switzerland. · Psychiatry Section, Department of Neuroscience, School of Medicine, University of Parma, Parma, Italy. · Department of Psychiatry & Behavioral Sciences, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. · Psychiatry, Queen's University, Kingston, ON, Canada. · Bipolar Disorder Unit, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM, University of Barcelona, Barcelona, Spain. · Department of Psychiatry, Mood Disorders Centre, University of British Columbia, Vancouver, BD, Canada. · Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. · Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, Hempstead, NY, USA. · The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, NY, USA. · The Feinstein Institute for Medical Research, Center for Psychiatric Neuroscience, Manhasset, NY, USA. · Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany. ·Bipolar Disord · Pubmed #31479581.

ABSTRACT: OBJECTIVES: To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years. METHODS: We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies. RESULTS: Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention. CONCLUSIONS: The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.

2 Review More childhood onset bipolar disorder in the United States than Canada or Europe: Implications for treatment and prevention. 2017

Post, Robert M / Altshuler, Lori L / Kupka, Ralph / McElroy, Susan L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Keck, Paul E / Leverich, Gabriele S / Nolen, Willem A. ·Bipolar Collaborative Network, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, D.C., USA. Electronic address: robert.post@speakeasy.net. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Lindner Center of HOPE, Mason, OH, USA; Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, Mayo Clinic, Rochester, MI, USA. · Bipolar Collaborative Network, Bethesda, MD, USA. · Paracelsius Medical University, Salzburg, Austria. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; V.A. Palo Alto Health Care System, Palo Alto, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA. · University Medical Center, University of Groningen, Groningen, The Netherlands. ·Neurosci Biobehav Rev · Pubmed #28119069.

ABSTRACT: Evidence of a high or increasing incidence of childhood onset bipolar disorder in the United States (US) has been viewed skeptically. Here we review evidence that childhood onsets of bipolar disorder are more common in the US than in Europe, treatment delays are longer, and illness course is more adverse and difficult. Epidemiological data and studies of offspring at high risk also support these findings. In our cohort of outpatients with bipolar disorder, two of the major vulnerability factors for early onset - genetics and environmental adversity in childhood - were also greater in the US than in Europe. An increased familial loading for multiple psychiatric disorders was apparent in 4 generations of the family members of the patients from the US, and that familial burden was linked to early onset bipolar disorder. Since both early onset and treatment delay are risk factors for a poor outcome in adulthood, new clinical, research, and public health initiatives are needed to begin to address and ameliorate this ongoing and potentially devastating clinical situation.

3 Review Illnesses in siblings of US patients with bipolar disorder relate to multigenerational family history and patients severity of illness. 2017

Post, Robert M / Altshuler, Lori L / Kupka, Ralph / McElroy, Susan L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Keck, Paul E / Nolen, Willem A. ·Bipolar Collaborative Network, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington D.C., USA. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Lindner Center of HOPE, Mason, OH, USA; Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, Mayo Clinic, Rochester, MI, USA. · Bipolar Collaborative Network, Bethesda, MD, USA. · Department of Psychiatry and Psychotherapy, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Austria. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; V.A. Palo Alto Health Care System, Palo Alto, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA. · University Medical Center, University of Groningen, Groningen, The Netherlands. ·J Affect Disord · Pubmed #27741468.

ABSTRACT: BACKGROUND: Patients with bipolar disorder from the US have more early-onset illness and a greater familial loading for psychiatric problems than those from the Netherlands or Germany (abbreviated here as Europe). We hypothesized that these regional differences in illness burden would extend to the patients siblings. METHODS: Outpatients with bipolar disorder gave consent for participation in a treatment outcome network and for filling out detailed questionnaires. This included a family history of unipolar depression, bipolar disorder, suicide attempt, alcohol abuse/dependence, drug abuse/dependence, and "other" illness elicited for the patients' grandparents, parents, spouses, offspring, and siblings. Problems in the siblings were examined as a function of parental and grandparental problems and the patients' adverse illness characteristics or poor prognosis factors (PPFs). RESULTS: Each problem in the siblings was significantly (p<0.001) more prevalent in those from the US than in those from Europe. In the US, problems in the parents and grandparents were almost uniformly associated with the same problems in the siblings, and sibling problems were related to the number of PPFs observed in the patients. LIMITATIONS: Family history was based on patient report. CONCLUSIONS: Increased familial loading for psychiatric problems extends through 4 generations of patients with bipolar disorder from the US compared to Europe, and appears to "breed true" into the siblings of the patients. In addition to early onset, a variety of PPFs are associated with the burden of psychiatric problems in the patients' siblings and offspring. Greater attention to the multigenerational prevalence of illness in patients from the US is indicated.

4 Review Treatment of Bipolar Depression: Evolving Recommendations. 2016

Post, Robert M. ·Bipolar Collaborative Network, 5415 West Cedar Lane, Suite 201-B, Bethesda, MD 20814, USA. Electronic address: robert.post@speakeasy.net. ·Psychiatr Clin North Am · Pubmed #26876316.

ABSTRACT: Bipolar depression is the most common and difficult-to-treat phase of bipolar disorder. Antidepressants for unipolar depression are among the most widely used drugs, but recent data and meta-analyses indicate a lack of efficacy. Many of the drugs discussed here are graded provisionally for the strength of the findings in the literature, safety and tolerability, and likely utility of use in patients with bipolar disorder. Successful long-term treatment of bipolar depression is critical to preventing illness-related morbidity, disability, cognitive decline, suicide, and premature loss of years of life expectancy largely from the excess medical mortality associated with cardiovascular disorders.

5 Review More illness in offspring of bipolar patients from the U.S. compared to Europe. 2016

Post, Robert M / Altshuler, Lori L / Kupka, Ralph / McElroy, Susan L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Keck, Paul E / Leverich, Gabriele S / Nolen, Willem A. ·Bipolar Collaborative Network, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington D.C., USA. Electronic address: Robert.post@speakeasy.net. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, USA; Julia S. Gouw Professor in Mood Disorders Research, Director, UCLA Mood Disorders Research Program, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Lindner Center of HOPE, Mason, OH, USA; Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, Mayo Clinic, Rochester, MI, USA. · Bipolar Collaborative Network, Bethesda, MD, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; V.A. Palo Alto Health Care System, Palo Alto, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA. · University Medical Center, University of Groningen, Groningen, The Netherlands. ·J Affect Disord · Pubmed #26655863.

ABSTRACT: BACKGROUND: Evidence suggests that patients with bipolar disorder from the United States have an earlier age of onset and a more difficult course of illness than those from Germany and the Netherlands. These characteristics were related to a greater family burden of psychiatric illness and the experience of more psychosocial adversity in childhood. We hypothesized that this greater illness burden would extend to the offspring of the US patients. METHODS: 968 outpatients (average age 41) with bipolar illness gave informed consent for participation in a treatment outcome network and filled out a detailed questionnaire about their illness and family history of illness, including whether their offspring had a diagnosis of depression, bipolar disorder, alcohol or substance abuse, suicide attempt or "other" illness. Of those with children, 356 were from the US and 132 were from Europe. RESULTS: Compared to the Europeans, offspring of patients from the US had significantly (p<0.001) more depression, bipolar disorder, drug abuse, and "other" illnesses. The number of illnesses in the offspring was related to the bipolar parent being from the US, having had childhood adversity, more than 20 prior episodes, and more parental psychiatric illness. CONCLUSIONS: While the findings are limited by their basis on self report, the distribution of the percentages in the US offspring are similar to those of Axelson et al. (2015) who used direct interviews. The higher burden of illness in the offspring and their in direct progenitors from the US compared to Europe warrant new attempts at better treatment and prevention.

6 Review Bipolar disorder and substance misuse: pathological and therapeutic implications of their comorbidity and cross-sensitisation. 2013

Post, Robert M / Kalivas, Peter. ·MD, Head, Bipolar Collaborative Network, 5415 W. Cedar Lane, Suite 201-B, Bethesda, MD 20814, USA. robert.post@speakeasy.net ·Br J Psychiatry · Pubmed #23457180.

ABSTRACT: BACKGROUND: Bipolar disorder has a high co-occurrence with substance use disorders, but the pathophysiological mechanisms have not been adequately explored. AIMS: To review the role of stress in the onset and recurrence of affective episodes and substance misuse. METHOD: We review the mechanisms involved in sensitisation (increased responsivity) to recurrence of stressors, mood episodes and cocaine use. RESULTS: Evidence suggests that intermittent stressors, mood episodes and bouts of cocaine use not only show sensitisation to themselves, but cross-sensitisation to the others contributing to illness progression. Converseley, an understanding of the common mechanisms of sensitisation (such as regionally selective alterations in brain derived neurotrophic factor (BDNF) and hyperactivity of striatally based habit memories), could also result in single therapies (such as N-acetylcysteine) having positive effects in all three domains. CONCLUSIONS: These interacting sensitisation processes suggest the importance of early intervention in attempting to prevent increasingly severe manifestations of bipolar illness and substance misuse progression.

7 Review Acquired lithium resistance revisited: discontinuation-induced refractoriness versus tolerance. 2012

Post, Robert M. ·Bipolar Collaborative Network, 5415 W. Cedar Lane, Suite 201B, Bethesda, MD 20814, United States. robert.post@speakeasy.net ·J Affect Disord · Pubmed #22154708.

ABSTRACT: BACKGROUND: While some patients fail to respond to lithium from the outset, others are initially responsive and then develop treatment resistance. These acquired forms of lithium resistance have received relatively little clinical attention. METHODS: We review the literature on the two different forms of acquired treatment resistance lithium that occur following an initial good response to lithium-discontinuation-induced refractoriness and tolerance- and discuss the possible neurobiological mechanisms involved. RESULTS: Multiple investigators have reported cases of discontinuation-induced refractoriness, where following a good long-term response, patients discontinue lithium, suffer a major recurrence, and then do not again respond as well or at all to lithium once it is reinstituted at previously effective doses. The development of tolerance has similarly been multiply documented where lithium doses are consistently maintained, but after an extended period of excellent responsiveness, affective episodes of increasing severity, frequency, or duration begin to break through. These two forms of acquired treatment resistance appear to have different underlying neurobiological mechanisms and require differential treatment strategies. LIMITATIONS: Recognition of acquired forms of lithium resistance depends on careful case descriptions and longitudinal monitoring of patients who are usually treated naturalistically and not in controlled clinical trials. CONCLUSION: To the extent that these forms of acquired lithium resistance can be better recognized and their development slowed, prevented, or ameliorated, it could yield substantial clinical and public health benefits in avoiding the morbidity and mortality that can accompany lithium non-responsive bipolar disorder.

8 Review Pharmacogenomics of antidepressant induced mania: a review and meta-analysis of the serotonin transporter gene (5HTTLPR) association. 2012

Biernacka, Joanna M / McElroy, Susan L / Crow, Scott / Sharp, Alexis / Benitez, Joachim / Veldic, Marin / Kung, Simon / Cunningham, Julie M / Post, Robert M / Mrazek, David / Frye, Mark A. ·Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States. Electronic address: biernacka.joanna@mayo.edu. · Lindner Center of HOPE, Mason, OH, United States; University of Cincinnati College of Medicine, Cincinnati, OH, United States; The Bipolar Collaborative Network, Bethesda, MD, United States. · Department of Psychiatry, University of Minnesota, Minneapolis, MN, United States. · Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States. · Department of Psychiatry, Austin Medical Center, Mayo Health System, Austin, MN, United States. · Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States. · The Bipolar Collaborative Network, Bethesda, MD, United States. · Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, United States; The Bipolar Collaborative Network, Bethesda, MD, United States. ·J Affect Disord · Pubmed #21680025.

ABSTRACT: BACKGROUND: Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM. METHODS: Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania. RESULTS: Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N=340 AIM+ cases, N=543 AIM- controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant. LIMITATIONS: Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling. CONCLUSIONS: There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).

9 Review Assessment of quality of life enjoyment and satisfaction questionnaire-short form responder thresholds in generalized anxiety disorder and bipolar disorder studies. 2011

Wyrwich, Kathleen W / Harnam, Neesha / Revicki, Dennis A / Locklear, Julie C / Svedsater, Henrik / Endicott, Jean. ·United BioSource Corporation, Bethesda, Maryland 20814, USA. kathy.wyrwich@unitedbiosource.com ·Int Clin Psychopharmacol · Pubmed #21164351.

ABSTRACT: Interpretation of change over time in patient-reported outcomes requires appropriate responder definitions. This study compares responder definitions for the short-form version of the Quality of Life Enjoyment and Satisfaction Questionnaire [Q-LES-Q(SF)] in populations with generalized anxiety disorder (GAD) and bipolar disorder. A review of the Q-LES-Q(SF) literature published in English from 1993 through May 2009 identified publications using the Q-LES-Q(SF) in GAD or bipolar disorder clinical trials. In six relevant articles reporting Q-LES-Q(SF) responder definitions in GAD or bipolar disorder, two methods for defining responders emerged: (i) return to a score within 10% of community norms for the Q-LES-Q(SF); and (ii) a change score at or greater than the condition-specific mean change achieved by patients with minimal improvement on the Clinical Global Impression-Improvement (CGI-I) at study endpoint or a 1-point decrease on the CGI-Severity scale between baseline and study endpoint. The magnitude of the CGI-I based responder thresholds differed across mental health conditions. Use of the Q-LES-Q(SF) community norms as a responder definition is discouraged. A responder definition needs to be investigated within each condition or disease using appropriate anchors, and may not be generalizable from one condition or disease to another.

10 Article Predictors of psychosocial outcome of bipolar disorder: data from the Stanley Foundation Bipolar Network. 2019

Bennett, Francis / Hodgetts, Sophie / Close, Andrew / Frye, Mark / Grunze, Heinz / Keck, Paul / Kupka, Ralph / McElroy, Susan / Nolen, Willem / Post, Robert / Schärer, Lars / Suppes, Trisha / Sharma, Aditya N. ·Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · School of Psychology, University of Sunderland, Sunderland, UK. · Department of Psychiatry & Psychology, Mayo Clinic, Rochester, MN, USA. · PMU Nuremberg & Psychiatrie Schwäbisch Hall, Schwäbisch Hall, Germany. · Linder Center of Hope, Mason, OH, USA. · Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands. · University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. · Bipolar Collaborative Network, Bethesda, MD, USA. · Department of Psychiatry, and Psychotherapy Medical Center, University of Freiburg, Faculty of Medicine, Freiburg im Breisgau, Germany. · School of Medicine and V.A. Palo Alto Health Care System Palo Alto, Stanford University, Palo Alto, CA, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. aditya.sharma@ncl.ac.uk. · Northumberland Tyne and Wear NHS Foundation Trust, Newcastle upon Tyne, UK. aditya.sharma@ncl.ac.uk. · Academic Psychiatry, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK. aditya.sharma@ncl.ac.uk. ·Int J Bipolar Disord · Pubmed #31840207.

ABSTRACT: BACKGROUND: Impairments in psychosocial functioning have been demonstrated in 30-60% of adults with bipolar disorder (BD). However, the majority of studies investigating the effect of comorbid mental health disorders and age at onset outcomes in BD have focused on traditional outcome measures such as mood symptoms, mortality and treatment response. Therefore, this project aimed to investigate the impact of comorbid mental health disorders and age at onset on longitudinal psychosocial outcome in participants with BD. METHOD: Mixed effects modelling was conducted using data from the Stanley Foundation Bipolar Network. Baseline factors were entered into a model, with Global Assessment of Functioning (GAF) score as the longitudinal outcome measure. Relative model fits were calculated using Akaike's Information Criterion. RESULTS: No individual comorbidities predicted lower GAF scores, however an interaction effect was demonstrated between attention deficit hyperactivity disorder (ADHD) and any anxiety disorder (t = 2.180, p = 0.030). Participants with BD I vs BD II (t = 2.023, p = 0.044) and those in the lowest vs. highest income class (t = 2.266, p = 0.024) predicted lower GAF scores. Age at onset (t = 1.672, p = 0.095) did not significantly predict GAF scores. CONCLUSIONS: This is the first study to demonstrate the negative psychosocial effects of comorbid anxiety disorders and ADHD in BD. This study adds to the growing database suggesting that comorbid mental health disorders are a significant factor hindering psychosocial recovery.

11 Article Testing a clinical staging model for bipolar disorder using longitudinal life chart data. 2019

van der Markt, Afra / Klumpers, Ursula Mh / Draisma, Stasja / Dols, Annemiek / Nolen, Willem A / Post, Robert M / Altshuler, Lori L / Frye, Mark A / Grunze, Heinz / Keck, Paul E / McElroy, Susan L / Suppes, Trisha / Beekman, Aartjan Tf / Kupka, Ralph W. ·Department of Psychiatry, Amsterdam Public Health, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. · Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. · Department of Psychiatry, University Medical Center, University of Groningen, Groningen, The Netherlands. · Bipolar Collaborative Network, Bethesda, Maryland. · Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, District of Columbia. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California. · Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, California. · Department of Psychiatry, Mayo Clinic, Rochester, Minnesota. · Klinikum am Weissenhof, Weinsberg Germany & Paracelsus Medical University, Nuremberg, Germany. · University of Cincinnati College of Medicine, Cincinnati, Ohio. · Lindner Center of HOPE, Mason, Ohio. · Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, Ohio. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California. · V.A. Palo Alto Health Care System, Palo Alto, California. ·Bipolar Disord · Pubmed #30447123.

ABSTRACT: OBJECTIVE: Bipolar disorder has a wide range of clinical manifestations which may progress over time. The aim of this study was to test the applicability of a clinical staging model for bipolar disorder and to gain insight into the nature of the variables influencing progression through consecutive stages. METHODS: Using retrospectively reported longitudinal life chart data of 99 subjects from the Stanley Foundation Bipolar Network Naturalistic Follow-up Study, the occurrence, duration and timely sequence of stages 2-4 were determined per month. A multi-state model was used to calculate progression rates and identify determinants of illness progression. Stages 0, 1 and several other variables were added to the multi-state model to determine their influence on the progression rates. RESULTS: Five years after onset of BD (stage 2), 72% reached stage 3 (recurrent episodes) and 21% had reached stage 4 (continuous episodes), of whom 8% recovered back to stage 3. The progression from stage 2 to 3 was increased by a biphasic onset for both the depression-mania and the mania-depression course and by male sex. CONCLUSIONS: Staging is a useful model to determine illness progression in longitudinal life chart data. Variables influencing transition rates were successfully identified.

12 Article Familial abnormalities of endocannabinoid signaling in schizophrenia. 2019

Koethe, Dagmar / Pahlisch, Franziska / Hellmich, Martin / Rohleder, Cathrin / Mueller, Juliane K / Meyer-Lindenberg, Andreas / Torrey, E Fuller / Piomelli, Daniele / Leweke, F Markus. ·a Brain and Mind Centre , The University of Sydney , Sydney , Australia. · b Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim , Heidelberg University , Mannheim , Germany. · c Department of Anatomy and Neurobiology , University of California , Irvine , CA , USA. · d Institute for Medical Statistics and Computational Biology , University of Cologne , Cologne , Germany. · e The Stanley Medical Research Institute , Bethesda , MD , USA. ·World J Biol Psychiatry · Pubmed #29521179.

ABSTRACT: OBJECTIVES: Epidemiological and experimental evidence suggests that the endocannabinoid system plays a pathophysiological role in schizophrenia. This is reflected by elevated cerebrospinal levels of the endocannabinoid anandamide in schizophrenia and its initial prodromal states. METHODS: We analyzed plasma concentrations of anandamide, 2-arachidonoyl-sn-glycerol, palmitoylethanolamide and oleoylethanolamide from 25 twin pairs discordant for schizophrenia, six discordant for bipolar disorder and eight healthy twin pairs to determine hereditary traits. RESULTS: Twin pairs discordant for schizophrenia or bipolar disorder had significantly higher levels of anandamide and palmitoylethanolamide compared to healthy twins (both P < 0.002). Non-affected twins discordant for schizophrenia, who developed a psychotic disorder within 5 years follow-up showed lower anandamide (P = 0.042) and 2-arachidonoyl-sn-glycerol levels (P = 0.049) than twins who remained healthy. CONCLUSIONS: We suggest that the protective upregulation of endocannabinoid signalling reflects either a hereditary trait or mirrors a modulating response to genetically influenced cerebral function involving, e.g., other neurotransmitters or energy metabolism.

13 Article Revising Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for the bipolar disorders: Phase I of the AREDOC project. 2018

Parker, Gordon / Tavella, Gabriela / Macqueen, Glenda / Berk, Michael / Grunze, Heinz / Deckersbach, Thilo / Dunner, David L / Sajatovic, Martha / Amsterdam, Jay D / Ketter, Terence A / Yatham, Lakshmi N / Kessing, Lars Vedel / Bassett, Darryl / Zimmerman, Mark / Fountoulakis, Kostas N / Duffy, Anne / Alda, Martin / Calkin, Cynthia / Sharma, Verinder / Anand, Amit / Singh, Manpreet K / Hajek, Tomas / Boyce, Philip / Frey, Benicio N / Castle, David J / Young, Allan H / Vieta, Eduard / Rybakowski, Janusz K / Swartz, Holly A / Schaffer, Ayal / Murray, Greg / Bayes, Adam / Lam, Raymond W / Bora, Emre / Post, Robert M / Ostacher, Michael J / Lafer, Beny / Cleare, Anthony J / Burdick, Katherine E / O'Donovan, Claire / Ortiz, Abigail / Henry, Chantal / Kanba, Shigenobu / Rosenblat, Joshua D / Parikh, Sagar V / Bond, David J / Grunebaum, Michael F / Frangou, Sophia / Goldberg, Joseph F / Orum, Margo / Osser, David N / Frye, Mark A / McIntyre, Roger S / Fagiolini, Andrea / Manicavasagar, Vijaya / Carlson, Gabrielle A / Malhi, Gin S. ·1 School of Psychiatry - University of New South Wales and Black Dog Institute, Randwick, NSW, Australia. · 2 Department of Psychiatry, University of Calgary, Calgary, AB, Canada. · 3 IMPACT SRC, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia. · 4 Department of Psychiatry, Orygen, The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health and the Florey Institute for Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia. · 5 Allgemeinpsychiatrie Ost, Klinikum am Weissenhof, Weinsberg, Germany. · 6 Paracelsus Medical Private University (PMU) Nuremberg, Nuremberg, Germany. · 7 Dauten Family Center for Bipolar Treatment Innovation, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · 8 Center for Anxiety & Depression, Mercer Island, WA, USA. · 9 Department of Psychiatry & Behavioral Sciences, University of Washington, Seattle, WA, USA. · 10 School of Medicine, Case Western Reserve University, Cleveland, OH, USA. · 11 Depression Research Unit, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. · 12 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. · 13 Department of Psychiatry, The University of British Columbia, Vancouver, BC, Canada. · 14 The Copenhagen Affective Disorder Research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. · 15 Division of Psychiatry, School of Medicine, The University of Western Australia, Perth, WA, Australia. · 16 Department of Psychiatry and Human Behavior, Brown University, and Rhode Island Hospital, Providence, RI, USA. · 17 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. · 18 Department of Psychiatry, Queen's University, Kingston, ON, Canada. · 19 Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. · 20 Departments of Psychiatry and Medical Neuroscience, Dalhousie University, Halifax, NS, Canada. · 21 Department of Psychiatry, Western University, London, ON, Canada. · 22 Center for Behavioral Health, Cleveland Clinic, Cleveland, OH, USA. · 23 Discipline of Psychiatry, Westmead Clinical School, Sydney Medical School, University of Sydney, Westmead, NSW, Australia. · 24 Mood Disorders Program, Department of Psychiatry and Behavioural Neurosciences, McMaster University and Women's Health Concerns Clinic, St. Joseph's Healthcare, Hamilton, ON, Canada. · 25 The University of Melbourne and St Vincent's Hospital, Melbourne, VIC, Australia. · 26 The Centre for Affective Disorders, King's College London, London, UK. · 27 Hospital Clinic of Barcelona, Clinic Institute of Neuroscience, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain. · 28 Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. · 29 Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. · 30 Department of Psychiatry, University of Toronto, Toronto, ON, Canada. · 31 Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC, Australia. · 32 Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Carlton, VIC, Australia. · 33 Department of Psychiatry, Faculty of Medicine, Dokuz Eylül University, İzmir, Turkey. · 34 School of Medicine & Health Sciences, The George Washington University, Washington, DC, USA. · 35 Bipolar Collaborative Network, Bethesda, MD, USA. · 36 Department of Psychiatry, VA Palo Alto Health Care System, Palo Alto, CA, USA. · 37 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. · 38 Department of Psychiatry, School of Medicine, University of São Paulo, São Paulo, Brazil. · 39 Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London, London, UK. · 40 Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · 41 AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie et d'Addictologie, Université Paris-Est Créteil Val de Marne, Créteil, France. · 42 Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan. · 43 Department of Psychiatry, University of Michigan, Ann Arbor, MI, USA. · 44 Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA. · 45 New York State Psychiatric Institute, Columbia University, New York, NY, USA. · 46 Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. · 47 Open Sky Psychology, Ryde, NSW, Australia. · 48 Veterans Affairs Boston Healthcare System, Harvard Medical School, Boston, MA, USA. · 49 Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA. · 50 Department of Psychiatry, University of Toronto and Brain and Cognition Discovery Foundation, Toronto, ON, Canada. · 51 Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. · 52 Psychology Clinic, University of New South Wales, Sydney, NSW, Australia. · 53 Psychology Clinic, Black Dog Institute, Randwick, NSW, Australia. · 54 Department of Psychiatry and Behavioral Health, Stony Brook University School of Medicine, Stony Brook, NY, USA. · 55 CADE Clinic, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia. · 56 Academic Department of Psychiatry, Northern Sydney Local Health District, St Leonards, NSW, Australia. · 57 Discipline of Psychiatry, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia. ·Aust N Z J Psychiatry · Pubmed #30378461.

ABSTRACT: OBJECTIVE:: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations. METHOD:: The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified. RESULTS:: Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge 'impairment' (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders. CONCLUSION:: This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.

14 Article Axis II Personality Disorders Are Linked to an Adverse Course of Bipolar Disorder. 2018

Post, Robert M / McElroy, Susan / Kupka, Ralph / Suppes, Trisha / Hellemann, Gerhard / Nolen, Willem / Frye, Mark / Keck, Paul / Grunze, Heinz / Rowe, Michael. ·Bipolar Collaborative Network, Bethesda, MD. · VU University Medical Center, Department of Psychiatry, Amsterdam, the Netherlands. · Stanford University School of Medicine and V.A. Palo Alto Health Care System, California. · UCLA Mood Disorders Research Program and VA Medical Center, Los Angeles, CA. · Universitair Medisch Centrum Groningen (UMCG), the Netherlands. · Mayo Clinic, Rochester MI. · Department of Psychiatry and Psychotherapy, Christian Doppler Klinik, Paracelsus Medical University Salzburg, Austria. ·J Nerv Ment Dis · Pubmed #29781886.

ABSTRACT: The relationship of personality disorder (PD) psychopathology to the course of bipolar disorder remains inadequately described. After giving informed consent, more than 782 outpatients with bipolar disorder rated themselves on the 99-item Personality Disorder Questionnaire, Version 4 (PDQ4) when depressed or euthymic. They also rated six poor prognosis factors (PPFs). The relationships of the PPFs to the total PDQ4 score were examined by a linear regression. Even after correcting for the higher PDQ4 scores observed when patients were suffering depression, the PDQ4 was significantly related to a history of child abuse, early age of onset, an anxiety disorder comorbidity, rapid cycling, and 20 or more previous episodes, but not substance abuse. The data suggest close relationships between the total burden of PD psychopathology and correlates of an adverse outcome of bipolar disorder. The nature of this of association and approaches to treatment of comorbid PD remain to be further explored.

15 Article Preventing the Malignant Transformation of Bipolar Disorder. 2018

Post, Robert M. ·George Washington University School of Medicine, Bethesda, Maryland. · Bipolar Collaborative Network, Bethesda, Maryland. ·JAMA · Pubmed #29507950.

ABSTRACT: -- No abstract --

16 Article Prevalence of axis II comorbidities in bipolar disorder: relationship to mood state. 2018

Post, Robert M / Leverich, Gabriele S / McElroy, Susan / Kupka, Ralph / Suppes, Trisha / Altshuler, Lori / Nolen, Willem / Frye, Mark / Keck, Paul / Grunze, Heinz / Hellemann, Gerhard. ·Bipolar Collaborative Network, Bethesda, MD, USA. · Linder Center of Hope, Mason, OH, USA. · Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, VU University Medical Center, Amsterdam,, The Netherlands. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine and V.A. Palo Alto Health Care System Palo Alto, Palo Alto, CA, USA. · UCLA Mood Disorders Research Program and West LA VA Medical Center, Los Angeles, CA, USA. · Universitair Medisch Centrum Groningen (UMCG), Groningen, The Netherlands. · Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MI, USA. · Department of Psychiatry and Neuroscience, University of Cincinnati College of Medicine Cincinnati, Mason, OH, USA. · President-CEO Lindner Center of HOPE Mason, Mason, OH, USA. · Paracelsius Medical University, Salzburg, Austria. · Biostatistician UCLA Mood Disorders Research Program and VA Medical Center, Los Angeles, CA, USA. ·Bipolar Disord · Pubmed #29369448.

ABSTRACT: OBJECTIVES: A high incidence of Axis II personality disorders is described in patients with bipolar disorder; however, their relationship to mood state remains uncertain. METHODS: A total of 966 outpatients with bipolar disorder gave informed consent and filled out the Personality Disorder Questionnaire, 4th edition (PDQ4) and a questionnaire on demographics and course of illness prior to Bipolar Treatment Outcome Network entry at average age 41 years. Patients were rated at each visit for depression on the Inventory of Depressive Symptoms-Clinician version (IDS-C) and for mania on the Young Mania Rating Scale (YMRS). In a subgroup, the PDQ4 was retaken during periods of depression and euthymia. RESULTS: Patients met criteria for most personality disorders at a much higher rate when they took the PDQ4 while depressed compared to while euthymic, and scores were significantly related to the severity of depression (IDS) and of mania (YMRS) assessed within 2 weeks of taking the PDQ. Even when euthymic, more than quarter to half of the patients met criteria for a cluster A, B or C personality disorder. CONCLUSIONS: A wide range of personality disorders occur in bipolar patients, but are highly dependent on filling out the form while depressed compared to while euthymic. How this relates to having a personality disorder assessed using a structured clinical interview remains to be tested. However, higher PDQ4 scores are related to an earlier age of onset of bipolar disorder and other factors portending a more difficult course of bipolar disorder, and the optimal treatment of these patients remains to be illuminated.

17 Article Patient preferences for important attributes of bipolar depression treatments: a discrete choice experiment. 2018

Ng-Mak, Daisy / Poon, Jiat-Ling / Roberts, Laurie / Kleinman, Leah / Revicki, Dennis A / Rajagopalan, Krithika. ·Global Health Economics and Outcomes Research, Sunovion Pharmaceuticals Inc., Marlborough, MA. · Patient-Centered Research, Evidera, Bethesda, MD, USA. ·Patient Prefer Adherence · Pubmed #29343947.

ABSTRACT: Purpose: The purpose of this study was to assess patient preferences regarding pharmacological treatment attributes for bipolar depression using a discrete choice experiment (DCE). Methods: Adult members of an Internet survey panel with a self-reported diagnosis of bipolar depression were invited via e-mail to participate in a web-based DCE survey. Participants were asked to choose between hypothetical medication alternatives defined by attributes and levels that were varied systematically. The six treatment attributes included in the DCE were time to improvement, risk of becoming manic, weight gain, risk of sedation, increased blood sugar, and increased cholesterol. Attributes were supported by literature review, expert input, and results of focus groups with patients. Sawtooth CBC System for Choice-Based Conjoint Analysis was used to estimate the part-worth utilities for the DCE analyses. Results: The analytical sample included 185 participants (50.8% females) from a total of 200 participants. The DCE analyses found weight gain to be the most important treatment attribute (relative importance =49.6%), followed by risk of sedation (20.2%), risk of mania (13.0%), increased blood sugar (8.3%), increased cholesterol (5.2%), and time to improvement (3.7%). Conclusion: Results from this DCE suggest that adults with bipolar depression considered risks of weight gain and sedation associated with pharmacotherapy as the most important attributes for the treatment of bipolar depression. Incorporating patient preferences in the treatment decision-making process may potentially have an impact on treatment adherence and satisfaction and, ultimately, patient outcomes.

18 Article The relationship between self-reported borderline personality features and prospective illness course in bipolar disorder. 2017

Riemann, Georg / Weisscher, Nadine / Post, Robert M / Altshuler, Lori / McElroy, Susan / Frye, Marc A / Keck, Paul E / Leverich, Gabriele S / Suppes, Trisha / Grunze, Heinz / Nolen, Willem A / Kupka, Ralph W. ·Saxion, University of Applied Science, Handelskade 75, 7417 DH, Deventer, The Netherlands. g.riemann@saxion.nl. · Dimence Mental Health, Center for Bipolar Disorders, Deventer, The Netherlands. g.riemann@saxion.nl. · GGZ Centraal, Center for Mental Health, Hilversum, The Netherlands. · Bipolar Collaborative Network, 5415 W. Cedar Ln, Suite 201-B, Bethesda, MD, 20814, USA. · Psychiatry and Behavioral Sciences, George Washington University, Washington, DC, USA. · Former Head UCLA Mood Disorders Research Program, VA Medical Center, Los Angeles, CA, USA. · Lindner Center of HOPE, Mason, OH, USA. · Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Psychiatry, Mayo Clinic, Rochester, MI, USA. · Psychiatry & Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA. · Paracelsus Medical University, Salzburg, Austria. · University Medical Center, University of Groningen, Groningen, The Netherlands. · Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands. · GGZ inGeest, Center for Mental Health Care, Amsterdam, The Netherlands. · Altrecht Institute for Mental Health Care, Utrecht, The Netherlands. ·Int J Bipolar Disord · Pubmed #28944443.

ABSTRACT: BACKGROUND: Although bipolar disorder (BD) and borderline personality disorder (BPD) share clinical characteristics and frequently co-occur, their interrelationship is controversial. Especially, the differentiation of rapid cycling BD and BPD can be troublesome. This study investigates the relationship between borderline personality features (BPF) and prospective illness course in patients with BD, and explores the effects of current mood state on self-reported BPF profiles. METHODS: The study included 375 patients who participated in the former Stanley Foundation Bipolar Network. All patients met DSM-IV criteria for bipolar-I disorder (n = 294), bipolar-II disorder (n = 72) or bipolar disorder NOS (n = 9). BPF were assessed with the self-rated Personality Diagnostic Questionnaire. Illness course was based on 1-year clinician rated prospective daily mood ratings with the life chart methodology. Regression analyses were used to estimate the relationships among these variables. RESULTS: Although correlations were weak, results showed that having more BPF at baseline is associated with a higher episode frequency during subsequent 1-year follow-up. Of the nine BPF, affective instability, impulsivity, and self-mutilation/suicidality showed a relationship to full-duration as well as brief episode frequency. In contrast all other BPF were not related to episode frequency. CONCLUSIONS: Having more BPF was associated with an unfavorable illness course of BD. Affective instability, impulsivity, and self-mutilation/suicidality are associated with both rapid cycling BD and BPD. Still, many core features of BPD show no relationship to rapid cycling BD and can help in the differential diagnosis.

19 Article A Multisymptomatic Child With Bipolar Disorder: How to Track and Sequence Treatment. 2017

Post, Robert M / Rowe, Michael / Kaplan, Dana / Findling, Robert L. ·Bipolar Collaborative Network, 5415 W Cedar Ln, Ste 201-B, Bethesda, MD 20814. robert.post@speakeasy.net. · Department of Psychiatry and Behavioral Sciences, George Washington University School of Medicine, Washington, DC, USA. · Bipolar Collaborative Network, Bethesda, Maryland, USA. · Division of Child and Adolescent Psychiatry, Johns Hopkins Hospital/Bloomberg Children's Center, Baltimore, Maryland, USA. ·Prim Care Companion CNS Disord · Pubmed #28906604.

ABSTRACT: Treatment sequences for the multisymptomatic child with bipolar disorder are not adequately described or based on a systematic clinical trial database, and systems for longitudinal tracking of symptoms are rarely utilized. We present a patient whose symptoms of depression, anxiety, attention-deficit/hyperactivity disorder, oppositional behavior, and mania are rated by a parent and plotted on a weekly basis in the Child Network under a Johns Hopkins Institutional Review Board-approved protocol. This 9-year-old girl remained inadequately responsive to lithium or risperidone. We describe a range of other treatment options and a possible sequence for their introduction. We encourage the use of systematic longitudinal ratings to help better visualize course of symptom fluctuations and response of the child to treatment. Given the highly fluctuating course of many symptoms in very young children as illustrated here, prospective monitoring appears essential. The current case also highlights the great unmet need for comparative effectiveness data in children less than 10 years of age to better guide clinical therapeutics.

20 Article Homer1a protein expression in schizophrenia, bipolar disorder, and major depression. 2017

Leber, Stefan L / Llenos, Ida C / Miller, Christine L / Dulay, Jeannette R / Haybaeck, Johannes / Weis, Serge. ·Department of Neuropathology, Institute of Pathology, Medical University of Graz, Graz, Austria. · Department of Pediatrics, Johns Hopkins University, Baltimore, MD, USA. · Laboratory of Brain Research and Neuropathology, The Stanley Medical Research Institute, Bethesda, USA. · Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. · Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. · Department of Pathology, Paracelsus Medical University, Salzburg, Austria. · Department of Pathology, Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany. · Laboratory of Brain Research and Neuropathology, The Stanley Medical Research Institute, Bethesda, USA. serge.weis@kepleruniklinikum.at. · Division of Neuropathology, Department of Pathology and Neuropathology, Neuromed Campus, Kepler University Hospital, School of Medicine, Johannes Kepler University, Wagner-Jauregg-Weg 15, 4020, Linz, Austria. serge.weis@kepleruniklinikum.at. ·J Neural Transm (Vienna) · Pubmed #28815330.

ABSTRACT: In recent years, there was growing interest in postsynaptic density proteins in the central nervous system. Of the most important candidates of this specialized region are proteins belonging to the Homer protein family. This family of scaffolding proteins is suspected to participate in the pathogenesis of a variety of diseases. The present study aims to compare Homer1a expression in the hippocampus and cingulate gyrus of patients with major psychiatric disorders including schizophrenia, bipolar disorder and major depression. Immunohistochemistry was used to analyze changes of Homer1a protein expression in the hippocampal formation and the cingulate gyrus from the respective disease groups. Glial cells of the cingulate gyrus gray matter showed decreased Homer1a levels in bipolar disorder when compared to controls. The same results were seen when comparing cingulate gyrus gray matter glial cells in bipolar disorder with major depression. Stratum oriens glial cells of the hippocampus showed decreased Homer1a levels in bipolar disorder when compared to controls and major depression. Stratum lacunosum glial cells showed decreased Homer1a levels in bipolar disorder when compared to major depression. In stratum oriens interneurons Homer1a levels were increased in all disease groups when compared to controls. Stratum lucidum axons showed decreased Homer1a levels in bipolar disorder when compared to controls. Our data demonstrate altered Homer1a levels in specific brain regions and cell types of patients suffering from schizophrenia, bipolar disorder and major depression. These findings support the role of Homer proteins as interesting candidates in neuropsychiatric pathophysiology and treatment.

21 Article The Child Network for Parents to Track Their Child's Mood and Behavior. 2017

Post, Robert M / Rowe, Michael / Kaplan, Dana / Findling, Robert. ·1 Department of Psychiatry, George Washington University School of Medicine , Washington, DC. · 2 Bipolar Collaborative Network , Bethesda, Maryland. · 3 Division of Child and Adolescent Psychiatry, Johns Hopkins Hospital/Bloomberg Children's Center , Baltimore, Maryland. ·J Child Adolesc Psychopharmacol · Pubmed #28441041.

ABSTRACT: INTRODUCTION: A wide range of psychiatric disorders are common in young children, especially in those at high risk because of a parent with a unipolar or bipolar mood disorder in the United States. Yet in part because most children are seen in primary care, these illnesses are often not recognized or treated in a timely fashion. To begin to address this problem, we started the Child Network. METHODS: The Child Network is for parents of children age 2-12 with mood or behavioral symptoms or at high risk for them. The parents rate the severity of symptoms of depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), oppositional behavior, and mania on a once a week basis on a secure website under a Johns Hopkins Intramural Review Board (IRB)-approved protocol. These ratings can then be printed out along with any treatments given to aide in visualization of symptom course. A demographics form, which includes diagnoses given to the child in the community, and a symptom checklist are filled out upon Network entry. We report on the retrospective diagnoses and prospective treatment of the first 65 parents to join the Network. RESULTS: The most common diagnoses were anxiety disorders and ADHD followed by disruptive behavioral disorders and bipolar spectrum disorders. Prospective ratings of two or more consecutive weeks of moderate to severe rating in any of the five symptom domains paralleled these diagnoses given in the community. Atypical antipsychotics, anticonvulsant mood stabilizers, and medications for ADHD were among the most widely used drugs. An illustrated example of symptom course is presented. DISCUSSION: Many children continued to show substantial symptom severity despite treatment with an average of 2.2 medications. The Child Network provides a useful longitudinal approach to visualize the course of symptoms, which should help lead to earlier and more effective treatment.

22 Article Dosing patterns and medication adherence in bipolar disorder patients treated with lurasidone: a US retrospective claims database analysis. 2016

Sajatovic, Martha / Ng-Mak, Daisy / Solem, Caitlyn T / Lin, Fang-Ju / Rajagopalan, Krithika / Loebel, Antony. ·Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, Cleveland, OH, USA. · Sunovion Pharmaceuticals Inc., Global Health Economics & Health Outcomes Research, 84 Waterford Drive, Marlborough, MA 01752, USA. · Pharmerit International, Bethesda, MD, USA. · Sunovion Pharmaceuticals Inc., Marlborough, MA, USA. · Sunovion Pharmaceuticals Inc., Fort Lee, NJ, USA. ·Ther Adv Psychopharmacol · Pubmed #28008349.

ABSTRACT: BACKGROUND: The aim of this study was to describe dosing patterns and medication adherence among bipolar patients who initiated lurasidone in a real-world setting. METHODS: Adult bipolar patients who initiated lurasidone between 1 November 2010 and 31 December 2012 (index period) with 6-month pre- and post-index continuous enrollment were identified from the IMS RWD Adjudicated Claims US database. Patients were grouped by starting lurasidone daily dose: 20 mg (7.1%), 40 mg (62.2%), 60-80 mg (28.7%), and 120-160 mg (2.1%). Patient characteristics were compared across doses using Cochran-Armitage trend tests. Multivariable ordinal logistic regression assessed the association between initial lurasidone dose and patient characteristics. Medication adherence was measured using medication possession ratio (MPR). RESULTS: Of 1114 adult bipolar patients (mean age 40.6 years, 70.6% female), 90% initiated lurasidone at 40 mg or 80 mg/day (mean 51.9 mg/day). Of these, 16.2% initiated lurasidone as monotherapy. Mean lurasidone maintenance dose was 55.2 mg/day and mean MPR was 0.53 [standard deviation (SD) = 0.34] over the 6-month follow up. Substance use, hyperglycemia, obesity, and prior antipsychotic use were associated with higher initial lurasidone doses ( CONCLUSIONS: This real-world analysis of bipolar patients indicated that 40 mg or 80 mg/day were the most common starting doses of lurasidone. A majority of patients used concomitant psychiatric medications (polypharmacy). Higher doses of lurasidone were prescribed to patients with comorbidities or prior antipsychotic use. Adherence to lurasidone was comparable to or better than antipsychotic adherence reported in bipolar disorder literature.

23 Article Age at Onset of Bipolar Disorder Related to Parental and Grandparental Illness Burden. 2016

Post, Robert M / Altshuler, Lori L / Kupka, Ralph / McElroy, Susan L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Keck, Paul E / Leverich, Gabriele S / Nolen, Willem A. ·Bipolar Collaborative Network, 5415 West Cedar Ln, Ste 201B, Bethesda, MD 20814. robert.post@speakeasy.net. · Bipolar Collaborative Network, Bethesda, Maryland, USA. · Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, DC, USA. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, California, USA. · Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, California, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. · Lindner Center of HOPE, Mason, Ohio, USA. · Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, Ohio, USA. · Department of Psychiatry, Mayo Clinic, Rochester, Michigan, USA. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA. · VA Palo Alto Health Care System, Palo Alto, California, USA. · University Medical Center, University of Groningen, the Netherlands. ·J Clin Psychiatry · Pubmed #27631141.

ABSTRACT: OBJECTIVE: The age at onset of bipolar disorder varies greatly in different countries and continents. The association between load of family history of psychiatric illness and age at onset has not been adequately explored. METHODS: 979 outpatients with bipolar disorder (from 4 sites in the United States and 3 in the Netherlands and Germany) gave informed consent and completed a questionnaire about their demographics, age at onset of illness, and family history of unipolar and bipolar disorder, alcohol and substance abuse comorbidity, suicide attempts, and "other" illnesses in their parents, 4 grandparents, and any offspring. We examined how the parental and grandparental burden of these illnesses related to the age at onset of the patients' bipolar disorder. RESULTS: The burden of family psychiatric history was strongly related to an earlier age at onset of illness in both US and European patients (F₃,₉₀₆ = 35.42, P < .0001). However, compared to the Europeans, patients in the United States had both more family history of most difficulties and notably earlier age at onset. Earlier age at onset was associated with a greater illness burden in the patient's offspring (t₅₆₈ = 4.1, P < .0001). CONCLUSIONS: More parental and grandparental psychiatric illness was associated with an earlier age at onset of bipolar disorder, which is earlier in the United States compared with Europe and is strongly related to a poor long-term prognosis. This apparent polygenic contribution to early onset deserves further study and therapeutic attempts at ameliorating the transgenerational impact.

24 Article Age of onset of bipolar disorder: Combined effect of childhood adversity and familial loading of psychiatric disorders. 2016

Post, Robert M / Altshuler, Lori L / Kupka, Ralph / McElroy, Susan L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Keck, Paul E / Leverich, Gabriele S / Nolen, Willem A. ·Bipolar Collaborative Network, Bethesda, MD, USA; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington D.C., USA. Electronic address: Robert.post@speakeasy.net. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, Los Angeles, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA. · Lindner Center of HOPE, Mason, OH, USA; Biological Psychiatry Program, University of Cincinnati Medical College, Cincinnati, OH, USA. · Department of Psychiatry, Mayo Clinic, Rochester, MI, USA. · Bipolar Collaborative Network, Bethesda, MD, USA. · Paracelsus Medical University, Salzburg, Austria. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA; V.A. Palo Alto Health Care System, Palo Alto, CA, USA. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH, USA; Lindner Center of HOPE, Mason, OH, USA. · University Medical Center, University of Groningen, Groningen, The Netherlands. ·J Psychiatr Res · Pubmed #27392070.

ABSTRACT: BACKGROUND: Family history and adversity in childhood are two replicated risk factors for early onset bipolar disorder. However, their combined impact has not been adequately studied. METHODS: Based on questionnaire data from 968 outpatients with bipolar disorder who gave informed consent, the relationship and interaction of: 1) parental and grandparental total burden of psychiatric illness; and 2) the degree of adversity the patient experienced in childhood on their age of onset of bipolar disorder was examined with multiple regression and illustrated with a heat map. RESULTS: The familial loading and child adversity vulnerability factors were significantly related to age of onset of bipolar and their combined effect was even larger. A heat map showed that at the extremes (none of each factor vs high amounts of both) the average age of onset differed by almost 20 years (mean = 25.8 vs 5.9 years of age). LIMITATIONS: The data were not based on interviews of family members and came from unverified answers on a patient questionnaire. CONCLUSIONS: Family loading for psychiatric illness and adversity in childhood combine to have a very large influence on age of onset of bipolar disorder. These variables should be considered in assessment of risk for illness onset in different populations, the need for early intervention, and in the design of studies of primary and secondary prevention.

25 Article Further Evidence of a Cohort Effect in Bipolar Disorder: More Early Onsets and Family History of Psychiatric Illness in More Recent Epochs. 2016

Post, Robert M / Kupka, Ralph / Keck, Paul E / McElroy, Susan L / Altshuler, Lori L / Frye, Mark A / Rowe, Michael / Grunze, Heinz / Suppes, Trisha / Leverich, Gabriele S / Nolen, Willem A. ·5415 W Cedar Ln, Ste 201-B, Bethesda, MD 20814. robert.post@speakeasy.net. · Bipolar Collaborative Network, Bethesda, Maryland, USA. · Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, DC. · Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands. · Department of Psychiatry & Behavioral Neuroscience, University of Cincinnati College of Medicine, Ohio, USA. · Lindner Center of HOPE, Mason, Ohio, USA. · Biological Psychiatry Program, University of Cincinnati Medical College, Ohio, USA. · Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles. · Department of Psychiatry, VA Greater Los Angeles Healthcare System, West Los Angeles Healthcare Center, California, USA. · Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota, USA. · Newcastle University, Institute of Neuroscience & Campus of Aging and Vitality, Wolfson Research Centre, Newcastle upon Tyne, United Kingdom. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California, USA. · VA Palo Alto Health Care System, Palo Alto, California, USA. · University of Groningen, University Medical Center Groningen, the Netherlands. ·J Clin Psychiatry · Pubmed #27379705.

ABSTRACT: OBJECTIVE: Given that a cohort effect is rarely mentioned as one of the possible contributors to the increased incidence of childhood-onset bipolar disorder in the United States, we reexamined evidence for the phenomenon within our outpatient Bipolar Collaborative Network. METHODS: 968 outpatients (mean age, 41 years) with DSM bipolar disorder from 1995 to 2002 from 4 sites in the United States and 3 in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic, illness, and family history information on a patient questionnaire. Family history of bipolar disorder, depression, suicide attempt, alcohol abuse, substance abuse, and "other" illness was collected for each parent and the 4 grandparents. Age at onset and family history of illness burden were then assessed as a function of the age of the patient at network entry. RESULTS: Data for patients aged 35 years or older (n = 613) were included in the first analysis. Compared to older patients, those who were younger when they entered the network had an earlier age at onset of their bipolar disorder (r = 0.33, P < .001). Similarly, the youngest patients at entry (representing the most recent cohorts) had parents and grandparents with more psychiatric illness than patients born in earlier cohorts (n = 968). CONCLUSIONS: These preliminary data, taken with the substantial literature, suggest a cohort effect for earlier age at onset of bipolar disorder and greater burden of psychiatric disorders in 2 generations of direct progenitors of our patients. The resulting likely increase in severity of bipolar illness in future generations based on this earlier age at onset and increased familial loading, particularly in the United States, deserves focused clinical and public health attention and attempts at amelioration.

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