Allergan, Author Interviews, Bipolar Disorder, Mental Health Research / 23.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49298" align="alignleft" width="200"]Dr. Stephen Stahl MD PhDProfessor of Psychiatry University of California San Diego Dr. Stahl[/caption] Dr. Stephen Stahl MD PhD Professor of Psychiatry University of California San Diego  MedicalResearch.com: What is the background for this study? How does cariprazine differ from other medications for bipolar depression?  MedicalResearch.com: It is important to note that cariprazine, a dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, is approved for the treatment of schizophrenia (1.5-6 mg/d) and bipolar mania (3-6 mg/d) in adults. It is not yet approved for depressive episodes related to bipolar I disorder (bipolar depression). In these data that focus on the investigational use for the treatment of bipolar depression, cariprazine has demonstrated efficacy vs placebo (PBO) in 3 phase 2/3 studies of patients with bipolar depression (NCT01396447, NCT02670538, NCT02670551). These analyses investigated the efficacy of cariprazine in patients with bipolar depression and concurrent manic symptoms (mixed features). 
Author Interviews, Bipolar Disorder, JAMA, Schizophrenia / 11.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45151" align="alignleft" width="150"]Thomas Wolfers PhD Donders Center for Cognitive Neuroimaging Kapittelweg 29 6525EN Nijmegen  The Netherlands Dr. Wolfers[/caption] Thomas Wolfers PhD Donders Center for Cognitive Neuroimaging Kapittelweg 29 6525EN Nijmegen The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Schizophrenia and bipolar disorder are severe and complex mental disorders. Currently, the most common approach in characterizing disorders biologically is by comparing patient groups with groups of healthy individuals. We employed a fundamentally different approach and investigated how much the brains of individual patients diagnosed with schizophrenia and bipolar disorder differ from one another. For this purpose, we selected brain scans from healthy individuals to model a norm reflecting the healthy range, subsequently we compared the brain scans of patients with schizophrenia and bipolar disorder to this norm on the level of the individual. The main outcome was that individuals with schizophrenia and bipolar disorder differ substantially from one another, thus, considering only the ‘average patient’ has little to say about what might be occurring in the brain of an individual patient.
Allergan, Author Interviews, Bipolar Disorder, Depression, Mental Health Research / 05.04.2018

MedicalResearch.com Interview with: [caption id="attachment_41025" align="alignleft" width="133"]Dr. C. David Nicholson, PhD Chief R&D Officer  Allergan Dr. C. David Nicholson[/caption] Dr. C. David Nicholson, PhD Chief R&D Officer Allergan MedicalResearch.com: What is the background for this data milestone?  Response: Bipolar I depression refers to the depressive episodes of bipolar I disorder, the overarching brain and behavioral disorder. People with bipolar I disorder can have manic and depressive episodes, as well as mixed episodes that feature both manic and depressive symptoms at the same time. Bipolar I depression typically lasts at least two weeks, and can be difficult to differentiate from major depression during diagnosis. Once diagnosed, treating bipolar depression can be difficult given the few therapies available to manage these symptoms of bipolar I disorder. Additionally, patients with bipolar disorder may experience shifts from depression to mania or mania to depression as well as mixed states. More treatment options are needed so that physicians can find a therapy that will treat bipolar depression effectively, while also addressing the myriad of other symptoms that patients can experience. Cariprazine is already approved for the treatment of mania and mixed episodes. With this new data, we have the potential to also treat bipolar depression, effectively addressing the full spectrum of symptoms associated with bipolar I disorder with just one medication.
Author Interviews, Bipolar Disorder, Depression, JAMA / 01.01.2018

MedicalResearch.com Interview with: [caption id="attachment_39118" align="alignleft" width="300"]Yokoi and Sumiyoshi. 2015 tDCS administration at National Center of Neurology and Psychiatry Hospital. A subject (front) sits on a sofa relaxed, and a researcher (behind) controls the tDCS device (a). In this picture, anodal (b) and cathodal (c) electrodes with 35-cm2 size are put on F3 and right supraorbital region, respectively. We use a head strap (d) for convenience and reproducibility, and also use a rubber band (e) for reducing resistance tDCS administration at National Center of Neurology and Psychiatry Hospital. A subject (front) sits on a sofa relaxed, and a researcher (behind) controls the tDCS device (a). In this picture, anodal (b) and cathodal (c) electrodes with 35-cm2 size are put on F3 and right supraorbital region, respectively. We use a head strap (d) for convenience and reproducibility, and also use a rubber band (e) for reducing resistance
Wikipedia file[/caption] Andre Russowsky Brunoni, MD, PhD Coordinator, Service of Interdisciplinary Neuromodulation, Laboratory of Neurosciences  Department and Institute of Psychiatry Coordinator, Interdisciplinary Center for Applied Neuromodulation, University Hospital University of São Paulo São Paulo, Brasil  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In this study, our aim was to evaluate the safety and efficacy of transcranial direct current stimulation (tDCS) as an add-on treatment for patients with bipolar depression. There are a only few treatment alternatives for bipolar depression, which often have important side effects. Thus, we wanted to evaluate the efficacy of this non-pharmacological treatment. We found that active vs. sham tDCS effected greater response and remission for patients with bipolar depression. The frequency of adverse effects was similar, including treatment-emergent affective switches. However, higher rates of skin redness were observed in the active group.
Allergan, Author Interviews, Bipolar Disorder, Brigham & Women's - Harvard / 20.12.2017

MedicalResearch.com Interview with: allerganGary Sachs, MD Associate Clinical Professor of Psychiatry Harvard Medical School  MedicalResearch.com: What is the background for this data milestone? Response: Bipolar disorder affects about 5.7 million adults in the United States.  It is a common, often disabling condition in which abnormal mood states impair a person’s ability to carry out everyday tasks. Bipolar disorder touches nearly every family and community in America, because periods of illness, a patient’s symptoms often impact their family, their friends, and their community. There are a limited number of products approved to treat bipolar depression and even fewer products that have been studied and approved to treat the full spectrum of bipolar disorder, from mania through depression. Having another product proven to treat the full range of bipolar disorder would be a welcome addition to the treatment options currently available to the psychiatry community and patients.
Author Interviews, Bipolar Disorder, Depression, Pediatrics / 27.05.2017

MedicalResearch.com Interview with: [caption id="attachment_34902" align="alignleft" width="133"]Antony Loebel, M.D. Executive Vice President and Chief Medical Officer Sunovion, Head of Global Clinical Development Sumitomo Dainippon Pharma Group Dr. Loebel[/caption] Antony Loebel, M.D. Executive Vice President and Chief Medical Officer Sunovion, Head of Global Clinical Development Sumitomo Dainippon Pharma Group MedicalResearch.com: What is the background for this study? What are the main findings? In the six-week, randomized, double-blind, placebo-controlled study, 347 children and adolescents (10 to 17 years of age) with bipolar depression received once-daily LATUDA flexibly dosed (20-80 mg/day) or placebo.The Phase 3 clinical study met its primary endpoint, showing statistically significant and clinically meaningful improvement in symptoms compared to placebo. LATUDA was generally well tolerated, with minimal effects on weight and metabolic parameters. The primary efficacy endpoint was change from baseline to week 6 on the Children Depression Rating Scale, Revised (CDRS-R) total score. LATUDA was associated with statistically significant and clinically meaningful improvement in bipolar depression symptoms compared to placebo, based on CDRS-R total score (-21.0 vs. -15.3; effect size = 0.45; p<0.0001) and CGI-BP-S score for depression (-1.49 vs. -1.05; effect size = 0.44; p<0.001). LATUDA also demonstrated statistically significant improvement on secondary efficacy endpoints. The most common treatment-emergent adverse events reported for LATUDA compared to placebo were nausea (16% vs. 5.8%), somnolence (9.1% vs. 4.7%), weight gain (6.9% vs. 1.7%), vomiting (6.3% vs. 3.5%), dizziness (5.7% vs. 4.7%) and insomnia (5.1% vs. 2.3%). LATUDA was associated with no increases in fasting glucose or lipids, and minimal increase in mean weight vs. placebo (+0.74 kg vs. +0.44 kg).
Author Interviews, Bipolar Disorder, Mental Health Research, Pediatrics, Schizophrenia / 21.10.2016

MedicalResearch.com Interview with: Merete Nordentoft DrMSc Professor, chief Psychiatrist University of Copenhagen Mental Health Centre Copenhagen MedicalResearch.com: What is the background for this study? Response: We knew that children born to parents with mental illness had an increased risk for developing a mental disorder them selves, either the same disorder as their parent or another menal disorder. We also knew that some of these children would have pootrt motor function and other difficulties in functioning. However previous studies were smaller, they were not based on a representative sample, and children were at different age. That is the background for The Danish High Risk and Resilience Study-VIA 7, in which a large group of 522 children and their families were thoroughly assessed. The children were seven year old, and 202 had a parent who had schizophrenia, 120 had a parent with bipolar disorder and 200 had parent with neither of these disorders.
Author Interviews, Bipolar Disorder, JAMA, Schizophrenia / 06.07.2016

MedicalResearch.com Interview with: [caption id="attachment_25894" align="alignleft" width="200"]Thomas M. Lancaster, PhD Neuroscience and Mental Health Research Institute Cardiff University Brain Imaging Research Centre Cardiff University, Cardiff, United Kingdom  Dr. Thomas Lancaster[/caption] Thomas M. Lancaster, PhD Neuroscience and Mental Health Research Institute Cardiff University Brain Imaging Research Centre Cardiff University, Cardiff, United Kingdom   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psychotic disorders such as schizophrenia and bipolar disorders are heritable. Part of this genetic risk may be conferred by the combined effects of common risk alleles identified via genome wide association studies. Individuals with psychosis are also more likely to experience alterations in the ventral striatum (VS); a key node in the brain’s reward processing network. We hypothesized that common genetic risk for psychosis may confer risk via alterations in the VS. Using functional magnetic resonance imaging (fMRI) data from an adolescent sample (the IMAGEN cohort), we showed that increased psychosis risk was associated with increased BOLD (blood oxygen level dependency) in the VS, during reward processing.
Author Interviews, Bipolar Disorder, Infections, Johns Hopkins, Mental Health Research, Microbiome, Schizophrenia / 05.05.2016

MedicalResearch.com Interview with: [caption id="attachment_24088" align="alignleft" width="120"]Emily G. Severance, Ph.D Stanley Division of Developmental Neurovirology Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, MD Dr. Emily Severance[/caption] Emily G. Severance, Ph.D Stanley Division of Developmental Neurovirology Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, MD  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Severance: This research stems in part from anecdotal dialogues that we had with people with psychiatric disorders and their families, and repeatedly the issue of yeast infections came up. We found that Candida overgrowth was more prevalent in people with mental illness compared to those without psychiatric disorders and the patterns that we observed occurred in a surprisingly sex-specific manner.  The levels of IgG antibodies directed against the Candida albicans were elevated in males with schizophrenia and bipolar disorder compared to controls. In females, there were no differences in antibody levels between these groups, but in women with mental illness who had high amounts of these antibodies, we found significant memory deficits compared to those without evidence of past infection.
Author Interviews, Bipolar Disorder, Kidney Disease, Lancet, Mental Health Research, Pharmacology / 24.10.2015

MedicalResearch.com Interview with: Dr. Stefan Clos MSc Applied Health Statistics Psychiatrist Murray Royal Hospital Scotland UK Medical Research: What is the background for this study? Dr. Clos: For more than 40 years there has been a debate about the long-term effect of lithium maintenance therapy on renal function. There is a lack of good quality data from randomized clinical trials and two previous meta-analyses from 2010 and 2012 suggest that little evidence exists for a clinically significant reduction in renal function in most patients who are on lithium therapy. However, the two publications point out the poor quality of available study data, emphasising the need for large scale epidemiological studies that control for confounders. Several population-based studies have since attempted to address this problem, but had insufficient ability to adjust for confounders or had limitations because of inappropriate cross-sectional study design or did not include an appropriate comparator group. 
Author Interviews, Bipolar Disorder, Depression, JAMA / 18.05.2015

MedicalResearch.com Interview with: Maaike M. M. Rive Program for mood disorders AMC/De Meren, Department of Psychiatry PA3.221 Amsterdam  The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: For clinicians, it can be difficult to distinguish whether a depressed patient suffers from major depressive disorder (characterized by depressive episodes only) or bipolar disorder (characterized by both depressive and (hypo)manic episodes). Differentiation between the two disorders is important because e.g. the treatment approaches are different. Although we know that both types of mood disorders are characterized by emotion regulation disturbances, little is known about differences in emotion regulation between the two disorders. Better insight in these differences would be helpful for differentiation between uni- and bipolar disorder. However, previous studies comparing these disorders often allowed medication use, and this may have influenced results. Furthermore, much is unknown about the effect of mood state on emotion regulation differences. We therefore investigated emotion regulation by showing happy, sad and fearful pictures to patients and healthy controls. Participants were instructed to either passively view the pictures, or to distance themselves from their feelings, by thoughts like: ‘this is only a picture’, ‘this will never happen to me’, etc. Emotion regulation success was measured by the difference between subjective ratings of emotional intensity after passive viewing versus distancing. Brain activity was measured with fMRI. The results of our study indicate that emotion regulation does indeed differ between medication-free major depressive or bipolar patients, and that specific differences depend on mood state. During remission, bipolar patients showed impaired emotion regulation across different types of emotions. In contrast, patients with major depressive disorder did not how such impairments during remission. During depression, patients differed regarding happy and sad emotion regulation: bipolar patients showed impaired sad, but unexpectedly normal happy emotion regulation, whereas in major depressive disorder, both sad and happy emotion regulation were compromised. These emotion regulation difficulties were associated with differences in brain activity in the dorsolateral prefrontal cortex (involved in effortful emotion regulation) and the rostral anterior cingulate cortex (connecting emotional and cognitive brain areas).
Author Interviews, Bipolar Disorder, JAMA, Schizophrenia / 23.10.2014

Glenn T. Konopaske, MD McLean Hospital, Belmont, Massachusetts Department of Psychiatry, Harvard Medical School Boston, MassachusettsMedicalResearch.com Interview with: Glenn T. Konopaske, MD McLean Hospital, Belmont, Massachusetts Department of Psychiatry, Harvard Medical School Boston, Massachusetts Medical Research: What are the main findings of the study? Dr. Konopaske: Using postmortem human brain tissue this study did reconstructions of basilar dendrites localized to pyramidal cells in the deep layer III of the dorsolateral prefrontal cortex. Tissue from individuals with schizophrenia, bipolar disorder or controls was examined. Dendritic spine density (number of spines per μm dendrite) was significantly reduced in bipolar disorder and also reduced in schizophrenia at a trend level. The number of dendritic spines per dendrite and dendrite length were significantly reduced in subjects with schizophrenia and bipolar disorder.
Author Interviews, Bipolar Disorder, Genetic Research, Nature / 21.10.2014

Edward I. Ginns, MD, PhD, Director Program in Medical Genetics and Lysosomal Disorders Treatment and Research Program University of Massachusetts Medical School Reed Rose Gordon Building, Room 137 Shrewsbury, MA 01545MedicalResearch.com: Interview with: Edward I. Ginns, MD, PhD, Director Program in Medical Genetics and Lysosomal Disorders Treatment and Research Program University of Massachusetts Medical School Reed Rose Gordon Building, Room 137 Shrewsbury, MA 01545 Medical Research: What are the main findings of the study? Dr. Ginns: Our study identified that sonic hedgehog signaling, an important brain pathway, is involved in bipolar affective disorder. This finding shows a mechanism and provides new targets for drug development. It suggests that sonic hedgehog signaling can be modulated to help manage bipolar symptoms in adults by using drugs already being studied in clinical trials for other medical conditions. The new findings were uncovered by decades of translational research in the Old Order Amish families of Pennsylvania, where in a few special families in the Amish Study there is a high incidence of both bipolar disorder and a rare genetic dwarfism, Ellis van‐Creveld (EvC) syndrome. No person with EvC had bipolar disorder despite forty years of documented research across multiple generations, suggesting that the genetic cause of this rare dwarfism was protective of bipolar affective disorder.
Author Interviews, Bipolar Disorder, JAMA, Stanford / 27.08.2014

MedicalResearch.com Interview with: Manpreet K. Singh, MD MS Assistant Professor of Psychiatry and Behavioral Sciences Akiko Yamazaki and Jerry Yang Faculty Scholar in Pediatric Translational Medicine Stanford University School of Medicine Medical Research: What are the main findings of the study? Dr. Singh: Our research team used a monetary incentive delay paradigm to measure fronto-limbic activity and connectivity associated with anticipation and receipt of reward and loss in healthy offspring of parents with bipolar I disorder. We found that compared to youth offspring without any family history of psychopathology, high-risk offspring had aberrant prefrontal and cingulate activations and connectivity during reward processing. Further, greater striatal, amygdalar, and insula activations while anticipating and receiving rewards and losses were associated with greater novelty-seeking and impulsivity traits in high-risk youth.
Author Interviews, Bipolar Disorder, JAMA / 19.04.2014

John I. Nurnberger, Jr., M.D., Ph.D. Professor of Psychiatry Joyce and Iver Small Professor of PsychiatryMedicalResearch.com Interview with: John I. Nurnberger, Jr., M.D., Ph.D. Professor of Psychiatry Joyce and Iver Small Professor of Psychiatry Indiana University School of Medicine   MedicalResearch.com: What are the main findings of this study? Dr. Nurnberger: The main findings of the study are the biological pathways identified to be associated with bipolar disorder, including those involved in hormonal regulation, calcium channels, second messenger systems, and glutamate signaling. Gene expression studies implicated neuronal development pathways as well. These findings highlight the role of certain neurobiological processes that have been considered in prior hypotheses of bipolar disorder. They underline a role for calcium signaling, which has only been clearly implicated in the genetics of bipolar disorder in recent years. They also feature hormonal processes such as the hypothalamic-pituitary-adrenal axis, which has been known to be involved in stress responses, but has not been prominent in many recent theories of the pathogenesis of bipolar disorder.
Author Interviews, Bipolar Disorder, Flu - Influenza / 23.02.2014

MedicalResearch.com Interview with: Alan S. Brown, M.D., M.P.H. Professor of Clinical Psychiatry and Clinical Epidemiology College of Physicians and Surgeons of Columbia University Director Unit in Birth Cohort Studies Division of Epidemiology New York State Psychiatric Institute New York, NY 10032Alan S. Brown, M.D., M.P.H. Professor of Clinical Psychiatry and Clinical Epidemiology College of Physicians and Surgeons of Columbia University Director Unit in Birth Cohort Studies Division of Epidemiology New York State Psychiatric Institute New York, NY MedicalResearch.com: What are the main findings of the study? Dr. Brown: We found that a mother's exposure to influenza during pregnancy, documented by antibodies in her serum, increased the risk of bipolar disorder with psychotic symptoms in her offspring.  We did not show a relationship between influenza and bipolar disorder not accompanied by psychosis.