LATUDA Phase 3 Study Demonstrates Improvement in Pediatric and Adolescent Bipolar Depression

MedicalResearch.com Interview with:

Antony Loebel, M.D. Executive Vice President and Chief Medical Officer Sunovion, Head of Global Clinical Development Sumitomo Dainippon Pharma Group

Dr. Loebel

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).

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Gene Dosage at 22q11.2 Helps Determine Schizophrenia vs Autism Brain Differences

MedicalResearch.com Interview with:

Carrie Bearden, Ph.D. Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology Semel Institute for Neuroscience and Human Behavior University of California, Los Angeles

Dr. Bearden

Carrie Bearden, Ph.D.
Professor, Departments of Psychiatry and Biobehavioral Sciences and Psychology
Semel Institute for Neuroscience and Human Behavior
University of California, Los Angeles

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: A 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population.

Thus, we became interested in trying to understand whether there were differences in brain development that might predispose to one condition vs. the other.

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Adolescents Admitted For Self Harm At Risk For Further Self Harming Behavior

MedicalResearch.com Interview with:

Dr Annie Herbert, PhD Department of Behavioural Science and Health, Institute of Epidemiology and Healthcare University College London London  UK

Dr. Herbert

Dr Annie Herbert, PhD
Department of Behavioural Science and Health, Institute of Epidemiology and Healthcare
University College London
London  UK 

MedicalResearch.com: What is the background for this study?

Response: 1 in 25 adolescents (i.e. one in every classroom) will be admitted to hospital as an emergency with injuries related self-harm, drug or alcohol misuse, or violence. Currently, the guidelines for how these adolescents are managed differ greatly depending on the type of injury they come in with (whether through self-harm, drug or alcohol misuse, or violence).

MedicalResearch.com: What are the main findings?

Response: In our study, we found that adolescents admitted with any of these injuries were at an increased risk of suicide and of drug or alcohol related death in the ten years after leaving hospital, compared to other admitted adolescents.While the overall risk is relatively low—for example, 2–3 girls out of 1000 and 7 boys out of 1000 who are admitted as an emergency to hospital with drug or alcohol related injuries die from suicide within 10 years—the rates are 5–6 times higher than among adolescents admitted to hospital following an accident.

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Could a Strep Throat Increase Risk of OCD?

MedicalResearch.com Interview with:
Sonja Orlovska MD, PhD student

Mental Health Centre Copenhagen
Denmark

MedicalResearch.com: What is the background for this study?

Response: This Danish register-based study is the largest study so far investigating the hypothesis PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) which describes a possible link between streptococcal throat infection and the subsequent development of OCD and tic disorders in children. PANDAS is in thread with research in mental health in recent years, suggesting that infections and immune activation might increase the risk of mental disorders.

MedicalResearch.com: What are the main findings?

Response: Out of the 1,1 million individuals <18 years of age born in the study period, we found that the 349,982 individuals tested positive for a streptococcal throat infection by their GP had an increased risk of mental disorders by 18% and the risk of specifically OCD and tic disorders was increased with respectively 51% and 35%, compared to individuals who had never been tested. This seems to confirm PANDAS which speaks in favor of a specific link between strep throat and the development of OCD and tic disorders. However, we also found that non-streptococcal throat infection increased the risk of mental disorders, even though the risk of OCD and all mental disorders was larger after a strep throat. The study was performed at the Mental Health Centre Copenhagen together with Senior researcher Michael Eriksen Benros.

MedicalResearch.com: What should readers take away from your report?

Response: Our results indicate that the brain might be affected by the immunological activation caused by a streptococcal infection possibly due to streptococcal antibodies cross-reacting with brain tissue causing psychiatric symptoms which is the theory of PANDAS. However, it seems as if the immunological response caused by other types of throat infections might also have a damaging effect in some individuals. Nevertheless, it cannot be ruled out that the results to some extent might be driven by a medical care-seeking behavior in some parents bringing their child to the GP more often in spite of only few symptoms of throat infection leading to testing for strep throat and also more frequent examination and diagnosis by a psychiatrist.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Even though our study supports some elements of the PANDAS hypothesis, more research is needed to fully confirm PANDAS. The research field would benefit from larger clinical studies following children with PANDAS over a longer period of time with frequent follow-ups in order to establish if streptococcal throat infections cause and worsen neuropsychiatric symptoms of OCD and tic disorders.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Orlovska S, Vestergaard CH, Bech BH, Nordentoft M, Vestergaard M, Benros ME. Association of Streptococcal Throat Infection With Mental DisordersTesting Key Aspects of the PANDAS Hypothesis in a Nationwide Study. JAMA Psychiatry. Published online May 24, 2017. doi:10.1001/jamapsychiatry.2017.0995

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Modified Hospital Elder Life Program Reduces Post-Op Delirium and Length of Stay

MedicalResearch.com Interview with:
Cheryl Chia-Hui Chen, RN, DNSc

Vice Dean for Student Affairs
Professor of Nursing
National Taiwan University
Nurse Supervisor at National Taiwan University Hospital
Taipei, Taiwan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Older patients undergoing abdominal surgery often experience preventable delirium, which greatly influences their postoperative recovery and hospital length of stay. The modified Hospital Elder Life Program (mHELP) utilizes nurses to reduce postoperative delirium and LOS among older patients undergoing abdominal surgery for resection of malignant tumor. The mHELP consisted of 3 protocols: oral and nutritional assistance, early mobilization, and orienting communication, researchers say.

Researchers at the National Taiwan University Hospital randomly assigned 377 patients undergoing abdominal surgery for a malignant tumor to an intervention (n = 197) or usual care (n = 180).

Postoperative delirium occurred in 6.6 percent of mHELP participants vs 15.1 percent of control individuals (odds of delirium reduced by 56 percent). Intervention group participants received the mHELP for a median of 7 days, and they had a median LOS that was two days shorter (12 vs 14 days).

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Metformin Reverses Some Autism Symptoms In Animal Model

MedicalResearch.com Interview with:
Ilse Gantois, PhD

Research Associate
Dr. Nahum Sonenberg’s laboratory
Department of Biochemistry
McGill University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by cognitive impairment and affects 1 in 4000 males and 1 in 6000 females. About 60% of persons with Fragile X also have autism spectrum disorder. FXS is caused by absence of Fragile X protein (FMRP), which results in hyperactivation of ERK (extracellular signal-regulated kinase) and mTORC1 (mechanistic target of rapamycin complex 1) signaling. We show that treatment with metformin, the most widely used FDA-approved antidiabetic drug, suppresses translation by inhibiting the ERK pathway, and alleviates a variety of behavioural deficits, including impaired social interaction and excessive grooming. In addition, metformin also reversed defects in dendritic spine morphogenesis and synaptic transmission.
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Familial History Improves Predictive Value of TOMM40 Gene in Alzheimer’s Disease

MedicalResearch.com Interview with:

Auriel Willette, M.S., Ph.D. Assistant Professor Departments of Food Science and Human Nutrition and Psychology Iowa State University

Dr. Willette

Auriel Willette, M.S., Ph.D.
Assistant Professor
Departments of Food Science and Human Nutrition and Psychology
Iowa State University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is a gene that regulates the width of the outer mitochondrial pore, facilitating the transport of ribosomal pre-proteins into the inner mitochondrial matrix for translational modification into functional proteins. In 2010, Dr. Allen Roses, who discovered the Apolipoprotein E (APOE) gene, Dr. Michael Lutz, and other colleagues found that a variation in poly-T length at locus rs10524523 (‘523) within intron 6 predicted Alzheimer’s disease onset. Specifically, a “long” versus “short” poly-T length was related to earlier age of onset by 8 years.

However, several multi-cohort studies either failed to replicate the findings or found the opposite relationship, where a “long” or “very long” poly-T length was related to later age of onset. The literature has remained mixed to this day.

We were interested in testing factors that might change the relationship between TOMM40 and both cognitive decline and risk for having Alzheimer’s disease. It is known that a family history (FH) of Alzheimer’s disease has been associated with mitochondrial dysfunction. We reasoned, then, that FH may interact with TOMM40 to modulate how it was related to our outcomes of interest. We investigated this hypothesis in two separate cohorts: the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a late middle-aged cohort, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a well-characterized sample of aged participants from across the Alzheimer’s spectrum.

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How and Where Does the Brain Encode Fearful Memories

MedicalResearch.com Interview with:

Jun-Hyeong Cho, M.D., Ph.D. Assistant Professor Department of Cell Biology & Neuroscience University of California, Riverside Riverside, CA 92521

Dr. Jun-Hyeong Cho

Jun-Hyeong Cho, M.D., Ph.D.
Assistant Professor
Department of Cell Biology & Neuroscience
University of California, Riverside
Riverside, CA 92521

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In order to survive in a dynamic environment, animals develop adaptive fear responses to dangerous situations, which requires coordinated neural activity in the hippocampus, medial prefrontal cortex (mPFC), and amygdala. Dysregulation of this process leads to maladaptive generalized fear in post-traumatic stress disorder (PTSD), which affects 7 percent of the U.S. population.

In this study, we found that a population of hippocampal neurons project to both amygdala and medical prefrontal cortex (mPFC). We also found neural mechanisms how these double-projecting neurons efficiently convey contextual information to the amygdala and mPFC to encode and retrieve fear memory for a context associated with an aversive event.

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Fear of Uncertain Future Linked To Brain Region Associated With OCD

MedicalResearch.com Interview with:
Justin M. Kim, Ph.D

Dartmouth College
Advisor: Paul J. Whalen

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Anxiety (and its co-conspirator ‘worry’) is an active, energy consuming process. You haven’t given up – you are still fighting back, trying to anticipate what might happen tomorrow. The problem of course is that there are an infinite number of ‘what if…’ scenarios you can come up with. For some individuals, the uncertainty of what ‘might happen’ tomorrow, is actually worse than the negative event itself actually happening. These individuals are intolerant of uncertainty.

We were interested in how uncertainty and ambiguity of potential future threat contribute to the generation of anxiety and how they might be represented in our brain. In the psychology literature, how we deal with an uncertain future can be quantified as intolerance of uncertainty (IU). As is the case with any other personality characteristic, we all have varying degrees of IU. For example, individuals high in IU display difficulty accepting the possibility of potential negative events in the future. Importantly, psychiatric disorders such as generalized anxiety disorder (GAD) or obsessive-compulsive disorder (OCD), whose symptoms are marked with worrying/obsessing, are commonly associated elevated IU. We noticed that while much of the neuroimaging research on IU has been primarily focused on brain function, brain structural correlates of IU have received little attention so far. As such, we believed that it was an important endeavor to assess the relationship between IU and the structural properties of the brain, which can be done through the use of magnetic resonance imaging (MRI) techniques.

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Salivary Biomarker May Lead To Spit Test For Early Diagnosis of Alzheimer’s Disease

MedicalResearch.com Interview with:

Ali Yilmaz, PhD Beaumont Research Institute Beaumont Health, Royal Oak, MI

Dr. Yilmaz

Ali Yilmaz, PhD
Beaumont Research Institute
Beaumont Health, Royal Oak, MI

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by the accumulation of β-amyloid plaques and tau tangles. Mild cognitive impairment (MCI) is progressive degree of impairment that is greater than might be attributed to normal age-related cognitive decline, but is not so severe as to merit a diagnosis of dementia. MCI is thought to be a transitional state between normal aging and AD sufferers phenotypically converting to AD at a rate of 10% per year. Currently there is no cure and few reliable diagnostic biomarkers for AD. As we live longer there is an ever increasing demand for valid and reliable biomarkers of Alzheimer’s disease; not only because it will help clinicians recognize the disease in its earliest symptomatic stages but will also be important for developing novel treatment of AD. Using 1D H NMR metabolomics, we biochemically profiled saliva samples collected from healthy-controls (n = 12), mild cognitive impairment (MCI) sufferers (n = 8), and Alzheimer’s disease (AD) patients (n = 9). We accurately identified significant concentration changes in 22 metabolites in the saliva of MCI and AD patients compared to controls.

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Depressive Symptoms Not Found To Increase Risk of Dementia

MedicalResearch.com Interview with:

Archana Singh-Manoux, PhD Research Professor (Directeur de Recherche) Epidemiology of ageing & age-related diseases INSERM U1018, France Honorary Professor University College London, UK

Dr. Archana Singh-Manoux

Archana Singh-Manoux, PhD
Research Professor (Directeur de Recherche)
Epidemiology of ageing & age-related diseases
INSERM  France
Honorary Professor
University College London, UK 

MedicalResearch.com: What is the background for this study?

Response: Depressive symptoms are common in dementia patients. Previous studies, based on older adults, show depressive symptoms in late life to be associated with an increased risk of dementia. These studies do not allow conclusions to be drawn on the causal nature of the association between depressive symptoms and dementia.

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Genetic Links Indicate Anorexia Has Both Psychiatric and Metabolic Roots

MedicalResearch.com Interview with:

Cynthia Bulik, PhD

Cynthia Bulik, PhD

Cynthia Bulik, PhD, FAED
Founding director of the UNC Center of Excellence for Eating Disorders and
Professor at Karolinska Institutet in Stockholm, Sweden.

MedicalResearch.com: What is the background for this study?

Response: Researchers and clinicians from around the world came together to create the most powerful genome-wide association study of anorexia nervosa to date. Via this global collaboration, we were able to identify the first significant locus that influences risk for anorexia nervosa. We have known that anorexia is heritable for over a decade, but now we are actually identifying which genes are implicated. This is the first one identified!

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