Allergan’s VRAYLAR (carprazine) Receives FDA Approval For Maintenance Treatment of Schizophrenia

MedicalResearch.com Interview with:

Dr. David Nicholson PhD EVP and Chief R&D Officer Allergan

Dr. Nicholson

Dr. David Nicholson PhD
EVP and Chief R&D Officer
Allergan

Discusses Allergan’s announcement that:
New Data Shows Long-Term VRAYLAR Therapy Delayed Time to Relapse Compared to Placebo Over the Course of up to 72 Weeks and has received FDA approval for the Maintenance Treatment of Schizophrenia

MedicalResearch.com: What is the background for this FDA approval?

Response: As many clinicians know, schizophrenia is among one of the most challenging mental health disorders to manage – due to the complexity of patient symptoms, varying response to treatment and high rates of relapse. Schizophrenia requires long-term medication management, and without maintenance treatment, 60 – 70% of schizophrenia patients relapse within one year.

The approval of Vraylar (carprazine) for the maintenance treatment of schizophrenia was based upon the results of a clinical trial, which found long-term cariprazine therapy delayed time to relapse compared to placebo over the course of up to 72 weeks.

MedicalResearch.com: What does this extended indication mean for people living with schizophrenia? 

Response: Schizophrenia affects about 2.4 million American adults, and there remains serious unmet needs in the treatment of schizophrenia. The differences in how patients with schizophrenia respond to treatment underscore the importance of having more treatment options available. With its proven efficacy and well-characterized safety profile, cariprazine provides another treatment option for patients and clinicians. This study demonstrates cariprazine efficacy in the long-term (i.e., maintenance) treatment of schizophrenia.

MedicalResearch.com: What should readers take away from this announcement?

Response: As a chronic disease and disabling disorder, schizophrenia requires long-term medication management. Cariprazine is a safe and effective treatment for schizophrenia in both the short and long-term management of the illness. 

MedicalResearch.com: Is there anything else you would like to add about this FDA approval and what it means for the mental health community?

Response: On behalf of Allergan as Chief Research & Development Officer at the company, we are pleased that the FDA has recognized the benefits of cariprazine for maintenance treatment of adults with schizophrenia. This approval demonstrates our continued investment in cariprazine, as well as our commitment to developing treatments that address unmet needs facing people living with mental illness. Additionally, VRAYLAR is also approved in the U.S. in adults for the acute treatment of schizophrenia and acute treatment of manic or mixed episodes of bipolar I disorder.

David Nicholson is the Chief R&D Officer, and has served in this role since March 2015. Dr. Nicholson joined the company (then Actavis) as Senior Vice President, Global Brands R&D in August 2014. He has been in research and development in the pharmaceutical industry since 1978.

Previously, he served as Chief Technology Officer and EVP, R&D for Bayer CropScience from March 2012 to August 2014; Senior Vice President of Licensing and Knowledge Management at Merck from 2009 to December 2011; and Senior Vice President, responsible for Global Project Management and Drug Safety at Schering-Plough from 2007 to 2009. From 1988 to 2007, Dr. Nicholson held various leadership positions at Organon, where he most recently served as Executive Vice President, R&D and was a member of the company’s Executive Management Committee.

Dr. Nicholson earned his B.Sc. from the University of Manchester and his Ph.D. from the University of Wales.

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

Citation:

Allergan Receives FDA Approval For Use of VRAYLAR™ (cariprazine) in the Maintenance Treatment of Schizophrenia

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

 

 

 

 

 

Brain Imaging Patterns Moving Closer To Identifying Schizophrenia on Functional MRI

MedicalResearch.com Interview with:

Irina Rish PhD IBM T.J. Watson Research Center Yorktown Heights, NY 10598

Dr. Rish

Irina Rish PhD
IBM T.J. Watson Research Center
Yorktown Heights, NY 10598 

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

Response: Schizophrenia is a chronic and severe psychiatric disorder that affects roughly about 1% of population. Although it is not as common as other mental disorders, such as depression, anxiety, and attention deficit disorder (ADD), and so on, schizophrenia  is perhaps one of  the most debilitating psychiatric disorders,  preventing people from normal  functioning in daily life. It is characterized primarily by a range of psychotic symptoms, including hallucinations (false auditory, visual or tactile perceptions detached from reality), as well as delusions, disorganized thoughts, speech and behavior, and multiple other symptoms including difficulty showing (and recognizing) emotions, poor executive functioning, inattentiveness, problems with working memory,  and so one. Overall, schizophrenia has a devastating impact not only on patients and their families, but on the economy, as it was estimated to cost the US about 2% off  gross national product in treatment costs, missed work, etc.
Thus, taking steps towards better understanding of the disease can potentially lead to more accurate early diagnosis and better treatments.

In this work, the objective was to identify “statistical biomarkers’ of schizophrenia from brain imaging data (specifically, functional MRI), i.e. brain activity patterns that would be capable of accurately discriminating between schizophrenic patients and controls, and reproducible (stable) across multiple datasets. The focus on both predictive accuracy (generalization to previously unseen subjects) as well as on stability (reproducibility) across multiple datsets differentiates our work from majority of similar studies in neuroimaging field that tend to focus only on statistically significant differences between such patterns on a fixed dataset, and may not reliably generalize to new data.

Our prior work on neuroimaging-based analysis of schizoprenia http://journals.plos.org/plosone/article/related?id=10.1371/journal.pone.0050625, as well as other research in the field, suggest that disrupted functional connectivity can be a much more informative source of discriminative patterns than local changes in brain activations, since schizophrenia is well known to be a “network disease”, rather than a localized one.

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Schizophrenia: Impaired White Matter Linked To Deficits in Cognitive Processing Speed

MedicalResearch.com Interview with:

Peter Kochunov PhD Professor Maryland Psychiatric Research Center

Dr. Kochunov

Peter Kochunov PhD
Professor
Maryland Psychiatric Research Center 

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

Response: Schizophrenia is a debilitating disorder that strikes young people at the point of entering adulthood. In the past, we and others demonstrated that patients with schizophrenia are characterized by deficits in the white matter of the brain. White matter is the part of the brain that serves the backbone of cerebral networks transmitting information and interconnecting brain regions.

In this report, we link the impaired white matter of the brain in schizophrenia patients with the disorder-related deficits in the processing speed. We also showed that mental processing speed is a fundamental cognitive construct that partially supports other functions like working memory in patients, where processing speed acting as the intermediate between white matter deficits and reduced working memory. This interesting relationship between processing speed, working memory, and white matter is most obvious in white matter regions most vulnerable to schizophrenia. That was the main finding of the study.

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Genetic Risk of Schizophrenia May Contribute to Cognitive Dysfunction

MedicalResearch.com Interview with:

Olav B. Smeland MD PhD Postdoctoral researcher SFF NORMENT, KG Jepsen Centre for Psychosis Research, Division of Mental  Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine University of Oslo Oslo, Norway

Dr. Smeland

Olav B. Smeland MD PhD
Postdoctoral researcher
SFF NORMENT, KG Jepsen Centre for Psychosis Research, Division of Mental
Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine
University of Oslo Oslo, Norway

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

Response: Schizophrenia is a severe mental disorder associated with widespread cognitive impairments. The cognitive deficits are associated with disabilities in social, economic and occupational functioning and lower quality of life among individuals with schizophrenia. Despite this, current treatment strategies largely fail to ameliorate these cognitive impairments.

To develop more efficient treatment strategies in schizophrenia, a better understanding of the disease mechanisms underlying cognitive deficits is needed. For a long time we have known that schizophrenia is heritable, and in recent years many schizophrenia risk genes have been identified. Moreover, several studies have indicated that genetic risk of schizophrenia may contribute to cognitive dysfunction.

In this study, we aimed to identify schizophrenia risk genes that also influence cognitive function. In a large international collaboration of researchers, we combined genome-wide association studies on schizophrenia and the cognitive traits of verbal-numerical reasoning, reaction time and general cognitive function. In total, we analyzed genetic data from more than 250.000 participants. We were able to identify 21 genetic variants shared between schizophrenia and cognitive traits. For 18 of these genetic variants, schizophrenia risk was associated with poorer cognitive performance.

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Long-acting Injectable Medications Reduce Relapse and Rehospitalizations in Schizophrenia

MedicalResearch.com Interview with:

Jari Tiihonen, MD, PhD Professor, Department of Clinical Neuroscience Karolinska Institutet Stockholm, Sweden

Prof. Tiihonen

Jari Tiihonen, MD, PhD
Professor, Department of Clinical Neuroscience
Karolinska Institutet
Stockholm, Sweden 

MedicalResearch.com: What are the limitations of existing analyses of the comparative effectiveness of antipsychotics?

Response: It has remained unclear if there are clinically meaningful differences between antipsychotic treatments in relapse prevention of schizophrenia, due to the impossibility of including large unselected patient populations in randomized controlled trials, and due to residual confounding from selection biases in observational studies.

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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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Probiotics May Influence Schizophrenia Symptoms Through Yeast in Microbiome

MedicalResearch.com Interview with:
Emily G. Severance PhD
Stanley Division of Developmental Neurovirology
Department of Pediatrics
Johns Hopkins University School of Medicine
Baltimore, MD 21287

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

Response: Previously, we found that people with schizophrenia and bipolar disorder had an increased susceptibility to Candida albicans yeast infections, which was sex specific and associated with memory deficits. Also in an earlier placebo-controlled probiotic study, we found that although probiotics improved the overall bowel function of people with schizophrenia, there was no effect by this treatment on psychiatric symptoms.  Given that C. albicans infections can upset the dynamics of the human microbiome, we decided to re-evaluate the potential benefit of probiotics in the context of a patient’s C. albicans yeast status.  Not only was bowel function again enhanced following intake of probiotics, but yeast antibody levels were decreased by this treatment.

Furthermore, psychiatric symptoms were actually improved over time for men receiving probiotics who did not have elevated C. albicans antibodies. Men who were positive for C. albicans exposure, however, consistently presented with worse psychiatric symptoms irrespective of probiotic or placebo treatment.

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No Increased Health Consequences After Chinese Famine Except Schizophrenia

MedicalResearch.com Interview with:

L. H. Lumey, MD, PhD Professor of Epidemiology Mailman School of Public Health Columbia University

Dr. Lumey

L. H. Lumey, MD, PhD
Professor of Epidemiology
Mailman School of Public Health
Columbia University

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

Response: The Chinese Great Leap Forward Famine in 1959-1961 is the largest famine in human history. Earlier studies have reported that overweight, type 2 diabetes, hyperglycemia, the metabolic syndrome and schizophrenia were more common among adults who were exposed to the famine. Our re-analysis of all previous studies shows no increases in diabetes, high blood pressure and other chronic conditions among famine births except for schizophrenia.

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Our ‘Motor Signature’ Is a Window Into Mental Health

MedicalResearch.com Interview with:

Dr. Piotr Słowiński</strong> Department of Mathematics College of Engineering Mathematics and Physical Sciences, Research Fellow University of Exeter

Dr. Piotr Słowiński

Dr. Piotr Słowiński
Department of Mathematics
College of Engineering
Mathematics and Physical Sciences,
Research Fellow
University of Exeter

MedicalResearch.com: What are the main findings?

Response: In an earlier study, we have found that every person has an individual style of moving (its own individual motor signature) and that people who have similar motor signatures are better in coordinating with each other (http://rsif.royalsocietypublishing.org/content/13/116/20151093). In the current study, we show that both these characteristics, own motor signature, and quality of interaction with others, have potential to give and insight into person’s mental health condition.

Assessment of motor symptoms is already a part of a clinical interview during a neurological evaluation by an expert psychiatrist. Our method, if confirmed in clinical trials, would speed up such examination and would allow for better allocation of the valuable time of medical professionals (for example, for more advanced tests in cases of diagnostic uncertainty). Additionally, it could allow for monitoring and personalization of treatment.

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Elevated Fasting Glucose and Insulin Resistance Seen Early in Schizophrenia

MedicalResearch.com Interview with:

Dr Toby Pillinger MA(Oxon) BM BCh MRCP Institute of Psychiatry, Psychology and Neuroscience King's College London

Dr. Toby Pillinger

Dr Toby Pillinger MA(Oxon) BM BCh MRCP
Institute of Psychiatry, Psychology and Neuroscience
King’s College London

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

Response: Our meta-analysis has provided strong evidence that compared with healthy controls, individuals with early schizophrenia are at increased risk of developing type 2 diabetes mellitus, even when the effects of antipsychotic drugs, diet and exercise are taken out of the equation.

Schizophrenia is associated with a dramatically reduced life expectancy, with individuals dying up to 30 years earlier than the general population. Approximately 60% of this excess mortality is due to physical health disorders such as heart attack or stroke, for which diabetes is a major risk factor.

People with long-term schizophrenia are 3 times more likely than the general population to have diabetes, something that has previously been blamed on poor diet and exercise habits, as well as the use of antipsychotic medication. However, the link between schizophrenia and diabetes was first made back in the 19th century, long before the use of antipsychotics, and in an era where diets were less likely to cause diabetes. This could suggest that there is a causative link between schizophrenia and diabetes.

Our meta-analysis examined whether diabetes risk is already raised in people at the onset of schizophrenia, before antipsychotics have been prescribed and before a prolonged period of illness that may be associated with poor diet and sedentary behaviour. We pooled data from 16 studies comprising 731 patients and 614 individuals from the general population. We collated blood data examining fasting blood glucose levels, blood glucose levels following the oral glucose tolerance test, fasting insulin levels and degree of insulin resistance.

We demonstrated that compared with healthy controls, individuals with early schizophrenia had raised fasting glucose, raised levels of glucose following the oral glucose tolerance test, raised fasting insulin and elevated insulin resistance. Furthermore, these results remained statistically significant even when we restricted our analyses to studies where individuals with schizophrenia were matched to healthy controls with regards their diet, the amount of exercise they engaged in and their ethnic background.

This suggests that our results were not wholly driven by differences in lifestyle factors or ethnicity between the two groups, and may therefore point towards a direct role for schizophrenia in increasing risk of diabetes.

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Schizophrenia: SynCav1 As Potential Target To Restore Neuron Function

MedicalResearch.com Interview with:

Brian P. Head, MS, PhD Associate Professor, UCSD Research Scientist, VASDHS Department of Anesthesiology VA San Diego Healthcare System San Diego, CA 92161-9125

Dr. Brian Head

Brian P. Head, MS, PhD
Associate Professor, UCSD
Research Scientist, VASDHS
Department of Anesthesiology
VA San Diego Healthcare System
San Diego, CA 92161-9125

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

Response: DISC1 is a schizophrenia associated gene originally identified in a Scottish family. DISC1 protein is highly expressed in the developing brain and in the dentate gyrus of the adult hippocampus, and is involved in neuritogenesis and neuronal signaling. DISC1 is located in multiple intracellular locations including axons and synapses, and loss of DISC1 function causes deficits in neural development, neuronal proliferation, axonal growth, and cytoskeleton modulation, which are consistent with abnormal neural development in schizophrenia.

SynCav1 means synapsin-driven caveolin construct. Synapsin promoter is neuronal specific which allows us to increase caveolin expression-specifically in neurons. We have previously shown that SynCav1 increases neuronal signaling and dendritic growth and arborization in vitro (Head BP JBC 2011), and when delivered in vivo augments functional neuroplasticity and improves learning and memory in adult and aged mice (Mandyam CD Biol Psych 2015).

Since loss of DISC1 function equates to schizophrenic-like symptoms, then decreased DISC1 expression in Cav-1 KO mice agrees with this premise. Thus, loss of Cav-1 increases their likelihood of developing schizophrenia-like symptoms. Because re-espression of Cav-1 restored DISC1 expression as well as expression of key synaptic proteins, this proof-of-concept findings not only builds upon our previously results demonstrating that Cav-1 is critical for neuronal signaling and functional synaptic plasticity but also strongly links Cav-1 with maintaining normal DISC1 expression levels and potentially attenuating schizophrenia-like symptoms.

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Genetic Factors Link Communication Competence in Childhood With Autism and Schizophrenia

MedicalResearch.com Interview with:

Dr. Beate St Pourcain MSc, PhD(Cardiff) Genetic Epidemiology School of Oral and Dental Sciences MRC Integrative Epidemiology Unit University of Bristol

Dr. Beate St Pourcain

Dr. Beate St Pourcain MSc, PhD(Cardiff)
Genetic Epidemiology
School of Oral and Dental Sciences
MRC Integrative Epidemiology Unit
University of Bristol

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

Response: People with autism and with schizophrenia both have problems interacting and communicating with other people, because they cannot easily initiate social interactions or give appropriate responses in return. On the other hand, the disorders of autism and schizophrenia develop in very different ways. The first signs of Autism Spectrum Disorder (ASD) typically occur during infancy or early childhood, whereas the symptoms of schizophrenia usually do not appear until early adulthood. The researchers asked whether it is possible to disentangle the apparent symptom overlap in ASD and schizophrenia through genetic analyses.

As clinical diagnoses relate to the age of onset of a disorder and do not capture multiple developmental stages, the researchers used a trick. They assumed that there is a continuum between normal and abnormal behaviour and captured social communicative competence – the ability to socially engage with other people successfully – in participants of a population-based birth cohort during development.

Specifically, the researchers studied the genetic overlap between the risk of having these psychiatric disorders and these measures of social communicative competence. Investigating thousands of genetic variants with small effects across the genome, they showed that genes influencing social communication problems during childhood overlap with genes conferring risk for autism, but that this relationship wanes during adolescence. In contrast, genes influencing risk for schizophrenia were most strongly interrelated with genes affecting social competence during later adolescence, in line with the natural history of the disorder.

“The findings suggest that the risk of developing these contrasting psychiatric conditions is strongly related to distinct sets of genes, both of which influence social communication skills, but exert their maximum influence during different periods of development”, explained Beate St Pourcain, senior investigator at the Max Planck Institute and lead author of the study. This is consistent with studies showing that genetic factors underlying social communication behaviour also change to some degree during childhood and adolescence.

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Genetic Predisposition To Schizophrenia Associated With Childhood Impairments

MedicalResearch.com Interview with:
Dr Lucy Riglin

Division of Psychological Medicine and Clinical Neurosciences
MRC Centre for Neuropsychiatric Genetics and Genomics
Cardiff University School of Medicine
Cardiff UK

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

Response: Schizophrenia is a mental disorder that usually occurs after puberty. However, previous research suggests that individuals who go on to develop schizophrenia often presented cognitive, social, behavioural, and emotional impairments in childhood.

Our study found that, in a general population sample, genetic risk for schizophrenia was associated with these childhood impairments as early as age 4 years.

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Alcohol and Cannabis Abuse Linked To Increased Risk of Schizophrenia

MedicalResearch.com Interview with:
Dr Stine Mai Nielsen

Copenhagen University Hospital
Mental Health Center Copenhagen
Gentofte, Denmark

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

Response: Several studies have tested whether use of substances can cause schizophrenia. However due to methodological limitations in the existing literature, uncertainties still remains. We aimed to investigate the association between several types of substance abuses and the risk of developing schizophrenia later in life. We did a nationwide, prospective cohort study using the detailed Danish registers, which enabled us to address some of the limitations from prior findings. Our cohort consisted of more than 3.13 mio. individuals, that we were able to follow up for more than 104 mio. years at risk. We found that dealing with a substance abuse increased the overall risk of developing schizophrenia by 6 times, with abuse of cannabis and alcohol presenting the highest associations (5 and 3 times increased risk). The risk was found to be significant even 10-15 years prior to a diagnosis of substance abuse.

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Children born to parents with bipolar disorder or schizophrenia more likely to suffer mental health issues by age 7

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.

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Multiple Genetic Risk Factors May Contribute to Schizophrenia By Damaging Neurons

MedicalResearch.com Interview with:

Panagiotis (Panos) Roussos, MD, PhD Assistant Professor Department of Genetics and Genomic Sciences and Department of Psychiatry Icahn Institute for Genomics and Multiscale Biology Friedman Brain Institute Icahn School of Medicine at Mount Sinai The Leon and Norma Hess Center for Science and Medicine New York, NY 10029

Dr. Roussos

Panagiotis (Panos) Roussos, MD, PhD
Assistant Professor
Department of Genetics and Genomic Sciences and Department of Psychiatry
Icahn Institute for Genomics and Multiscale Biology
Friedman Brain Institute
Icahn School of Medicine at Mount Sinai
The Leon and Norma Hess Center for Science and Medicine
New York, NY 10029

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

Response: Schizophrenia is a complex neuropsychiatric illness and multiple genetic risk factors contribute to the disease. However, it is unclear how these genetic risk factors act and which molecular functions are affected in brain cells of patients with schizophrenia. In this study, we used neurons derived from pluripotent stem cells of patients with schizophrenia and control samples with no history of neuropsychiatric disease. We identified changes related to the way DNA transcribes (a.k.a. gene expression) in schizophrenia compared to controls during activation of the neurons.

These changes affect genes that have been genetically associated with schizophrenia. Our study provides evidence that multiple genetic risk factors might lead to schizophrenia because of a damaging effect on the activity of neurons.

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Efficacy of Lurasidone in Schizophrenia

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

Response: Lurasidone hydrochloride (HCl) is an atypical antipsychotic approved by the FDA for the treatment of schizophrenia in 2010. There are a number of publications on lurasidone studies, pooled data that were included in a network meta-analysis of RCTs in schizophrenia. The meta-analysis compares lurasidone with other antipsychotics using RCTs where both medications were studied at the same time. Such approach (meta-analysis of similarly designed trials) allows for a state of the art review of efficacy, safety and tolerability of medications where direct head-to-head trials are not available.

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Study Shows Many Patients With Schizophrenia Can Use Mobile Phone Technology To Help Prevent Relapse

MedicalResearch.com Interview with:

Dror Ben Zeev, PhD Associate Professor of Psychiatry Director, mHealth for Mental Health Program Dartmouth College Hanover, NH

Dr. Dror Ben Zeev

Dror Ben Zeev, PhD
Associate Professor of Psychiatry
Director, mHealth for Mental Health Program
Dartmouth College
Hanover, NH

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

Response: We deployed a mobile phone intervention called FOCUS as part of a larger multi-component effort called Improving Care Reducing Costs (ICRC).

ICRC was the first technology-aided relapse prevention program of its kind for people with schizophrenia; a very exciting multi-state project funded by the Center for Medicare and Medicaid Innovation (CMMI) led by Dr. John Kane at the Zucker Hillside Hospital and a team of researchers from multiple institutions. Several other technological interventions were used in concert with mHealth, including a web intervention called Coping with Voices Developed by Dr. Jen Gottlieb and a Daily Support Website developed by Dr. Armando Rotondi. A truly multi-disciplinary effort designed to help prevent re-hospitalization in people with psychosis who were recently discharged from the hospital; this is a group that is at very high risk for relapse.

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Adjuvant Raloxifene Treatment Promising For Women With Refractory Schizophrenia

MedicalResearch.com Interview with:

Prof. Jayashri Kulkarni

Prof. Jayashri Kulkarni

Professor Jayashri Kulkarni MBBS, MPM,
FRANZCP, PhD

Director, Monash Alfred Psychiatry research centre
Vic Australia

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

Response: Schizophrenia is a complex psychiatric disorder and many patients are not able to achieve remission on the available treatments. There are clear sex differences in many aspects of the illness, which not only implicates a role for the sex hormone estrogen in schizophrenia, but also highlights the need for sex-specific treatments.

Our group has conducted many clinical trials using adjunctive estradiol treatment, with excellent improvement in psychotic symptoms- however, there can be physical side effects with longer term estradiol use. Raloxifene and other selective estrogen receptor modulators ( SERMs) – the so-called “brain estrogens”, with their more specific brain impacts and less body side effects – provide an option to use longer term estrogen in people with refractory schizophrenia. We conducted the first ever pilot study of raloxifene in 2010, and now present findings from a bigger study of adjunctive raloxifene treatment in schizophrenia.

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Patients With Schizophrenia Often Discharged on Multiple Medications

MedicalResearch.com Interview with:

Glorimar Ortiz, MS Senior Researcher/Statistician NRI-National Association of State Mental Health Program Directors Research Institute Falls Church, VA 22042

Glorimar Ortiz

Glorimar Ortiz, MS
Senior Researcher/Statistician
NRI-National Association of State Mental Health Program Directors Research Institute
Falls Church, VA 22042

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

Response: Despite the lack of empirical evidence that antipsychotic polypharmacy produces greater outcomes to antipsychotic monotherapy, and that several clinical guidelines recommend against it, patients with a diagnosis of schizophrenia continue to being discharged on polypharmacy. Over the past few years, attempts have been made to lower the rate of antipsychotic polypharmacy throughout the country. Most of the existing literature on this topic are based on Medicaid claims data which exclude data for patients discharged from state psychiatric inpatient hospitals. Our study is very important because it is the first time that data on the use of antipsychotic medications are analyzed using a large sample of discharges from state psychiatric inpatient hospitals. These hospitals now have the opportunity to benchmark their antipsychotic medication use rate with national rates more accurately, and therefore, develop and implement performance improvement activities that are more precise. The study found that 12% of all discharges were prescribed two or more antipsychotic medications. Of those patients discharged on at least one antipsychotic medication, 18% were prescribed two or more antipsychotics. The study also found that patients with a schizophrenia diagnosis and an inpatient hospital stay of 3 months or longer are more likely of being discharged on polypharmacy, and that the main reason for this was to reduce patient’s symptoms. Antipsychotic polypharmacy affects nearly 10,000 patients with schizophrenia annually in state psychiatric inpatient hospitals.
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Schizophrenia Associated With Elevated Glutamate in Several Brain Regions

MedicalResearch.com Interview with:

Kate Merritt Post-Doctoral Research Worker NOC Study (Nitric Oxide in Cognition) Institute of Psychiatry De Crespigny Park London

Dr. Kate Merritt

Kate Merritt PhD
Post-Doctoral Research Worker
NOC Study (Nitric Oxide in Cognition)
Institute of Psychiatry
De Crespigny Park
London

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

Dr. Merritt: Research has indicated that levels of one of the main chemicals in the brain, glutamate, may be abnormal in schizophrenia. Almost sixty studies have measured glutamate levels in schizophrenia, however the findings are inconsistent, and it is thought that changes in glutamate levels may vary with the length or the severity of illness. This study therefore analysed all the published reports of glutamate in schizophrenia.

The main findings are that, overall, schizophrenia is associated with elevated glutamate in several brain regions; namely the medial temporal cortex, the basal ganglia and the thalamus. These changes also differed with the stage of illness; in the medial frontal cortex, glutamate was increased in people at risk for developing schizophrenia, but not in people who had been diagnosed with schizophrenia for several years, whereas in the medial temporal lobe the opposite pattern was detected.

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Alterations in Brain Matter Loss and Gain Identified in Schizophrenia

MedicalResearch.com Interview with:

Lena Palaniyappan Medical Director Prevention & Early Intervention Program for Psychoses (PEPP) London, Ontario

Dr. Lena Palaniyappan

Lena Palaniyappan
Medical Director
Prevention & Early Intervention Program for Psychoses (PEPP)
London, Ontario

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

Response: It is now well established that patients with schizophrenia show reduced thickness of brain’s grey matter in Magnetic Resonance Imaging studies, indicating either a developmental or an acquired deficit in the amount of brain tissue. Such reductions are seen both in treated and untreated patients, suggesting that current treatments do not reverse the process of tissue loss, if at all this is occurring in patients. We wanted to study if subtle increase in brain tissue also accompanied this reduction. We observed that across the group of 98 medicated patients, reduced thickness was consistently accompanied by subtle, but nevertheless noticeable increases in thickness. Such increases were more pronounced in those with a longer duration of illness.

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Smoking During Pregnancy Raises Risk of Schizophrenia in Offspring

MedicalResearch.com Interview with:

Alan S. Brown, M.D., M.P.H. Professor of Psychiatry and Epidemiology Columbia University Medical Center Director, Program in Birth Cohort Studies, Division of Epidemiology New York State Psychiatric Institute

Dr. Alan Brown

Alan S. Brown, M.D., M.P.H.
Professor of Psychiatry and Epidemiology
Columbia University Medical Center
Director, Program in Birth Cohort Studies, Division of Epidemiology
New York State Psychiatric Institute

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

Dr. Brown: Smoking during pregnancy is a risk factor for several pregnancy-related outcomes including low birthweight and preterm birth. Evidence for a link with schizophrenia is scant. We analyzed a maternal biomarker of smoking called cotinine, a nicotine metabolite, in mothers of nearly 1,000 schizophrenia cases and 1,000 controls in a national birth cohort in Finland. We found that heavy smoking in pregnancy was related to a 38% increase in schizophrenia risk in offspring and that as cotinine levels increased even in the more moderate smokers risk of schizophrenia also increased.

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Candida Yeast Infections Linked to Schizophrenia and Bipolar Disorder

MedicalResearch.com Interview with:

Emily G. Severance, Ph.D Stanley Division of Developmental Neurovirology Department of Pediatrics Johns Hopkins University School of Medicine Baltimore, MD

Dr. Emily Severance

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.

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Within the Umbrella of Schizophrenia Are Separate Diseases For Which Specific Treatments Can Be Developed

MedicalResearch.com Interview with:

Dolores Malaspina, MD, MPH The Anita and Joseph Steckler Professor, Department of Psychiatry and Professor, Department of Child & Adolescent Psychiatry NYU Langone Medical Center

Dr. Dolores Malaspina

Dolores Malaspina, MD, MPH
The Anita and Joseph Steckler Professor, Department of Psychiatry
and Professor, Department of Child & Adolescent Psychiatry
NYU Langone Medical Center 

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

Dr. Malaspina: Although over one hundred single nucleotide variations in the human genetic code are associated with schizophrenia, using big data these account for a small portion of schizophrenia risk and most of them overlap with risks for other mental conditions.

In a completely different hypothesis generated approach, we focused on identifying rare or novel variations in genes that we earlier found had brand new disrupting mutations for cases with no family history compared to healthy parents.

Four or 5 cases were found with other rare sequences in 4 such influential genes. The respective groups of cases markedly differed in clinical presentations.  

MedicalResearch.com: What should clinicians and patients take away from your report?

Dr. Malaspina: Within the umbrella diagnosis of Schizophrenia are separate diseases for which specific treatments can be developed. For these genes we identified groups with a developmental condition, early adult deterioration, one with specific working memory dysfunction and one with slow processing speed.

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

Dr. Malaspina: Removing the 30% of cases harboring one of these genes from the patient mix will allow faster progress on the other cases for person specific treatments.

MedicalResearch.com: Is there anything else you would like to add?

Dr. Malaspina: In humans as in other mammals, most new gene disruptions arise in the paternal germ line and are transmitted to young in association with paternal age. This replenishes psychosis genes into the population since persons with the disease have fewer offspring. Once these genes arise the can then be inherited and produce inherited forms of the disease.

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

Citation:

Thorsten M. Kranz, Adam Berns, Jerry Shields, Karen Rothman, Julie Walsh-Messinger, Raymond R. Goetz, Moses V. Chao, Dolores Malaspina.

Phenotypically distinct subtypes of psychosis accompany novel or rare variants in four different signaling genes. EBioMedicine, 2016; DOI: 10.1016/j.ebiom.2016.03.008

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

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Brain Reward System May Underlie Tobacco Cravings in Schizophrenia

MedicalResearch.com Interview with:
Stéphane Potvin, PhD
Associate professor, Department of Psychiatry
Eli Lilly Chair in Schizophrenia Research
University of Montreal

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

Dr. Potvin:  Life expectancy is substantially reduced in schizophrenia, and one of the main factors contributing to this is the high prevalence of cigarette smoking in these patients. The leading hypothesis for cigarette smoking in schizophrenia is the self-medication hypothesis. Although some empirical results show that nicotine improves cognitive performance in schizophrenia, some authors have criticized the self-medication hypothesis for its implied (and unintented) justification of cigarette smoking in schizophrenia. About a decade ago, it has been hypothesized that cigarette smoking may be more reinforcing in schizophrenia patients, due to biological dysfunctions common to schizophrenia and tobacco use disorder. However, that model had not been formally tested.

Based on recent findings showing that cigarette cravings are increased in schizophrenia smokers, compared to smokers with no comorbid psychiatric disorder, we performed a neuroimaging study on cigarette cravings in schizophrenia. Unless we are wrong, this was most probably the first study to do so. We found that relative to control smokers, smokers with schizophrenia had increased activations of the ventro-medial prefrontal cortex in response to pleasant images of cigarette. What is is interesting is that the ventro-medial prefrontal cortex is one of the core regions of the brain reward system, which mediated the reinforcing effects of several psycho-active substances, including tobacco. As such, our results tend to confirm the assumption that cigarette might be more reinforcing in schizophrenia smokers.

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Women With High Genetic Predisposition to Schizophrenia Tend To Have First Child at Earlier or Later Age

MedicalResearch.com Interview with:

S. Hong Lee, PhD Queensland Brain Institute, The University of Queensland, Brisbane School of Environmental and Rural Science, University of New England, Armidale Australia

Dr. Hong Lee

S. Hong Lee, PhD
Queensland Brain Institute, The University of Queensland, Brisbane
School of Environmental and Rural Science, University of New England, Armidale
Australia 

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

Response: Previous studies reported increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for schizophrenia tend to have children at an earlier or later age.

We found evidence for a significant overlap between genetic factors associated with risk of schizophrenia and genetic factors associated with Age at First Birth (AFB). We observed a U-shaped relationship between schizophrenia risk and maternal AFB, consistent with the previously reported relationship between schizophrenia risk in offspring and maternal age when not adjusted for age of the father.

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Refugees Granted Asylum More Likely to Have Schizophrenia and Psychotic Disorders

MedicalResearch.com Interview with:

Dr. Anna-Clara Hollander

Dr. Anna Clara Hollander

Anna-Clara Hollander PhD
Division of Social Medicine, Department of Public Health Sciences
Karolinska Institutet, Stockholm, Sweden.

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

Response: The humanitarian crises in Europe, the Middle East, north Africa, and central Asia have led to more displaced people, asylum seekers, and refugees worldwide than at any time since the second world war. Refugees are known to be at an increased risk of mental health problems, such as post-traumatic stress disorder and other common mental disorders, compared to non-refugee migrants, but little is known about their risk of psychosis.

The aim of the study was to determine the risk of schizophrenia and other non-affective psychotic disorders among refugees, compared to non-refugee migrants, and the general Swedish population. We used a linked national register data to examine more than 1.3 million people in Sweden, and tracked diagnoses of non-affective psychotic disorders among the population. The cohort included people born to two Swedish-born parents, refugees, and non-refugee migrants from the four major refugee generating regions: the Middle East and north Africa, sub-Saharan Africa, Asia, Eastern Europe and Russia.

Results showed 3,704 cases of non-affective psychotic disorders during the 8.9 million person years of follow up. Refugees granted asylum were on average 66% more likely to develop schizophrenia or another non-affective psychotic disorder than non-refugee migrants. In addition, they were up to 3.6 times more likely to do so than the Swedish-born population. Incidence rates for non-affective psychosis were 385 per million in those born in Sweden, 804 per million in non-refugee migrants, and 1264 per million in refugees.

The increased rate in refugees was significant for all areas of origin except sub-Saharan Africa, for whom rates in both groups were similarly high relative to the Swedish-born population. One possible explanation is that a larger proportion of sub-Saharan Africa immigrants will have been exposed to deleterious psychosocial adversities before emigration, irrespective of refugee status. Alternatively post-migratory factors, such as discrimination, racism, and social exclusion may explain these high rates.
Overall, our findings are consistent with the hypothesis that increased risk of non-affective psychotic disorders among immigrants is due to a higher frequency of exposure to social adversity before migration, including the effects of war, violence, or persecution.

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Study Identifies Predictors of Treatment-Resistant Schizophrenia

Theresa Wimberley PhD student National Centre for Register-based Research School of Business and Social Sciences Aarhus University

Theresa Wimberley

MedicalResearch.com Interview with:
Theresa Wimberley
PhD student
National Centre for Register-based Research
School of Business and Social Sciences
Aarhus University

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

Response: Approximately 30% of patients with schizophrenia suffer from treatment-resistant schizophrenia, i.e. they do not respond to first-line antipsychotic treatment. Identification of high-risk patients as early as possible is crucial in order to optimize treatment and improve prognosis. In a large population-based cohort of patients diagnosed with schizophrenia we found the following candidate predictors of treatment resistance:

  • younger age at diagnosis,
  • living in less urban areas,
  • paranoid schizophrenia subtype,
  • a history of psychiatric hospital admission,
  • personality disorder,
  • suicide attempt, and
  • psychotropic drug use.

    Additionally, as opposed to other studies using treatment-based proxies for treatment-resistant schizophrenia, this study not only considered clozapine users as treatment resistant. We extended the proxy definition to include patients eligible for clozapine, as clozapine is considered to be under-prescribed. We found similar results regardless of definition used.

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Study Links Schizophrenia Genetic Risk with Psychopathology During Adolescence

MedicalResearch.com Interview with:

Hannah J. Jones, PhD Centre for Academic Mental Health, School of Social and Community Medicine, 2Medical Research Council (MRC) Integrative Epidemiology Unit University of Bristol, Bristol, England

Dr. Hannah Jones

Hannah J. Jones, PhD
Centre for Academic Mental Health, School of Social and Community Medicine,
Medical Research Council (MRC) Integrative Epidemiology Unit
University of Bristol, Bristol, England

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

Dr. Jones: Schizophrenia is a highly heritable condition characterised by relatively diverse symptoms and frequent comorbid disorders. However, at present we don’t know how genetic risk for schizophrenia is expressed in children/adolescents in the general population.

To investigate this, we studied data from individuals within the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort which consists of approximately 14,000 children born to women living in the former Avon Health Authority area in England with an expected delivery date from April 1, 1991, to December 31, 1992.

We used genetic data from approximately 5,000 ALSPAC children and measures from adolescence relating to psychopathology to determine whether genetic risk for schizophrenia is associated with variation in psychotic experiences (e.g. delusions, hallucinations), negative symptoms (e.g. apathy, withdrawal), depressive disorder and anxiety disorder during this developmental period.

We derived a score of genetic risk for schizophrenia in each individual within our study. This score is normally distributed such that most people have some genetic risk and a few people have very high or very low genetic risk.

We found very weak evidence of an association between genetic risk for schizophrenia and psychotic experiences in adolescence and no evidence of an association with depressive disorder. However, we found strong evidence of association between genetic risk for schizophrenia and negative symptoms and anxiety disorder.  Continue reading

Microbiome Differs Between Schizophrenic Patients and Controls

Keith A. Crandall, PhD Director - Computational Biology Institute George Washington University Innovation Hall Suite 305 Ashburn, VA 20147-2766MedicalResearch.com Interview with:
Keith A. Crandall, PhD
Director – Computational Biology Institute
George Washington University
Innovation Hall Suite 305
Ashburn, VA 20147-2766

Medical Research: What is the background for this study? What are the main findings?

Dr. Crandall: We wanted to investigate whether or not there were significant differences in the microbiome (microbial composition) of patients with schizophrenia versus controls.  The other researchers have demonstrated a connection between microbiome diversity and brain development and behavior modulation associated with a variety of disorders.  Our initial study focuses on the oropharyngeal as a target for the microbiome characterization, but we have additional work relating to other microbiomes (e.g., gut) for which we are still in the process of analyzing the data.     Collected microbiome data from 16 individuals with schizophrenia and 16 controls (matched as best we could and corrected statistically for differences between the populations), we showed differences in the microbiome taxonomic diversity and functional diversity.  Specifically, we identified a significant increase in the number of metabolic pathways related to metabolite transport systems; whereas, carbohydrate and lipid pathways and energy metabolism were abundant in controls.

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Patients With Schizophrenia Lack Sufficient Dopamine in Brain

Mark Slifstein, PhD Associate Professor of Neurobiology (In Psychiatry) Dept. of Psychiatry Columbia University NYSP Dr New York NY 10032 MedicalResearch.com Interview with:
Mark Slifstein, PhD

Associate Professor of Neurobiology (In Psychiatry) Dept. of Psychiatry
Columbia University NYSP
Dr New York NY 10032

MedicalResearch: What is the background for this study?

Dr. Slifstein: There has been considerable basic and clinical neuroscience research showing that the neurotransmitter dopamine plays a role in tuning cognitive processes taking place in the cortex. It has long been thought that dopamine is involved in the cognitive difficulties experienced by patients with schizophrenia, but it has been challenging to study dopamine in the cortex and other parts of the brain except in a deep structure rich in this neurotransmitter and its receptors, the striatum. In our study, we used an experimental design with Positron Emission Tomography (PET) imaging that allowed us to infer the amount of dopamine in the cortex.

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Schizophrenia: Severity of Symptoms Predicts Medication Response

MedicalResearch.com Interview with:
Toshiaki A. Furukawa, MD, PhD

Professor and Chair, Department of Health Promotion and Human Behavior
Professor, Department of Clinical Epidemiology
Kyoto University Graduate School of Medicine / School of Public Health,
Yoshida Konoe-cho, Sakyo-ku, Kyoto Japan

Medical Research: What is the background for this study? What are the main findings?

Dr. Furukawa: The efficacy of antidepressants in the treatment of depressive
disorders has recently been called into question as some studies
suggested they may have less efficacy for the milder spectrum of the
disorder. It is not known if the same would apply to antipsychotics,
which constitute the mainstay in the treatment of schizophrenia. We
found that, in patients with schizophrenia with acute treatment as
well as with predominant negative symptoms, the severer the baseline
severity, the greater the magnitude of the benefit from the active
treatment in comparison with placebo.
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Pathology Reveals Overlap Between Schizophrenia and Bipolar Disorder

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.

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Cardiometabolic Risks Begin Early in Schizophrenic Spectrum Disorders

Christoph U. Correll, MD Professor of Psychiatry and Molecular Medicine Hofstra North Shore LIJ School of Medicine Medical Director, Recognition and Prevention (RAP) Program The Zucker Hillside Hospital Investigator Feinstein Institute for Medical Research North Shore Long Island Jewish Health SystemMedicalResearch.com Interview with:
Christoph U. Correll, MD
Professor of Psychiatry and Molecular Medicine
Hofstra North Shore LIJ School of Medicine
Medical Director, Recognition and Prevention (RAP) Program
The Zucker Hillside Hospital Investigator
Feinstein Institute for Medical Research
North Shore Long Island Jewish Health System

Medical Research: What are the main findings of the study?

Dr. Correll: The main findings of the study of 398 patients with first-episode schizophrenia-spectrum disorders who were on average in their mid twenties are that:

  • 1) despite their young age, an average of only 47 days lifetime antipsychotic exposure and overweight/obesity figures that were comparable to similarly aged US population members, there was a clear pattern of increased smoking and several metabolic risk parameters compared to similarly aged persons in the general US population;
  • 2) dyslipidemia, a constellation of at least one relevant abnormal blood fat value, was as frequent as in a 15-20 years older general US population;
  • 3) body composition related risk markers were significantly associated with longer total psychiatric illness duration, whereas metabolic risk markers were significantly associated with the overall very short mean lifetime antipsychotic treatment duration; and
  • 4) relevant for treatment choice and recommendations for patients, significantly higher continuous metabolic risk factor values were associated with olanzapine treatment and, less so, with quetiapine treatment.
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Obsessive-Compulsive Disorder Increases Risk Of Schizophrenia

MedicalResearch.com Interview with:
Sandra M. Meier, PhD
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH,
National Centre for Register-Based Research
Aarhus University, Aarhus, Denmark

Medical Research: What are the main findings of the study?

Dr. Meier: People with an obsessive-compulsive disorder are at a 6 to 7 times higher risk of developing schizophrenia than people without an obsessive-compulsive disorder. If the parents are diagnosed with an obsessive-compulsive disorder, their offspring experience a 3 to 4 times higher chance to develop schizophrenia.
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Sleep Deprivation Can Induce Symptoms Resembling Schizophrenia

Prof. Dr. Ulrich Ettinger Departments of Psychology University of Bonn Bonn, GermanyMedicalResearch.com Interview with:
Prof. Dr. Ulrich Ettinger
Departments of Psychology
University of Bonn
Bonn, Germany

Medical Research: What are the main findings of the study?

Prof. Ettinger: We found that 24-hour sleep deprivation induced subjective cognitive, perceptual and emotional alterations resembling the symptoms of schizophrenia. We also observed that sleep deprivation led to a deficit in a sensorimotor filter mechanism called prepulse inhibition (PPI), similar to the disturbance seen in schizophrenia.
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Single Gene Mutation May Predispose to ADHD

Dr. Anders Nykjaer MD, PhD Mayo Clinic in Florida and Aarhus University in DenmarkMedicalResearch.com Interview with:
Dr. Anders Nykjaer MD, PhD
Mayo Clinic in Florida and
Aarhus University in Denmark

MedicalResearch: What are the main findings of the study?

Dr. Nykjaer: It is well known that ADHD is a complex condition caused by a number of factors including genetic and environment. However, approximately 75% etiology is considered to be genetic and a large body of investigations suggests that it is multiple genes each with a moderate effect that is responsible for conferring susceptibility to ADHD. We have here found one single gene the dysfunction of which is sufficient to trigger the disease.  The gene encodes a receptor, SorCS2, which ensures correct wiring our reward system during embryonic development. Malfunction of the receptor causes ADHD-like symptoms in mice. It is well accepted that ADHD predisposes to psychiatric disorders and genetic reports have linked variations in the SorCS2 gene with schizophrenia. Studies are currently ongoing to evaluate if mutations disrupting the function of SorCS2 may also result in schizophrenia. If this is the case we have come closer to an explanation for the link between ADHD and psychiatric disorders. In the future when prenatal genetic screening becomes established, non-sense mutations in the SorCS2 gene can be used to predict that the child will develop ADHD with 100% certainty.   Continue reading

Schizophrenia Treatment Maintenance: Comparison of Long Acting Injectable Medications

Scott Stroup, MD, MPH Professor of Psychiatry Director, Program for Intervention Effectiveness Research, Associate Director for Adult Services, Division of Mental Health Services and Policy Research,  New York State Psychiatric Institute Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New YorkMedicalResearch.com Interview with:
Scott Stroup, MD, MPH
Professor of Psychiatry
Director, Program for Intervention Effectiveness Research,
Associate Director for Adult Services, Division of Mental Health Services and Policy Research,  New York State Psychiatric Institute
Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, New York

MedicalResearch: What are the main findings of the study?

Dr. Stroup: We conducted a study sponsored by the National Institute of Mental Health that compared long-acting injectable antipsychotics for people with schizophrenia. Long-acting injectable antipsychotics, also known as depot antipsychotics, are used to promote treatment adherence.  We compared a newer injectable antipsychotic, paliperidone palmitate, to an older one, haloperidol decanoate.  We did not find an advantage for the newer drug in overall effectiveness.  The drugs performed very similarly, and were tolerated about the same.
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Schizophrenia: Impact of Estradiol on Psychosis Symptoms

prof_jayashri_kulharniMedicalResearch.com Interview with:
Professor Jayashri Kulkarni MBBS, MPM, FRANZCP, PhD
Monash University

MedicalResearch.com: What are the main findings of the study?

Professor Kulkarni: Persistent schizophrenia is difficult and unfortunately common, despite advances over the past years in antipsychotic drug development. New treatment approaches are urgently needed. Also, a specific focus for women with schizophrenia is still somewhat lacking and there is a need to consider the special issues facing women with schizophrenia.

Over many years, we have been conducting clinical trials to develop the role of adjunctive estradiol use to treat symptoms of schizophrenia. This study is the largest clinical trial in the world of this type and we found that in an 8 week, three arm, double blind, placebo-controlled, adjunctive trial of transdermal estradiol (200mcg v 100mcg v placebo) in 183 women with schizophrenia, that the women who received either 200mcg or 100mcg transdermal estradiol made a better recovery. The women who received 200mcg transdermal estradiol made a slightly better recovery than women receiving 100mcg transdermal estradiol. Both estradiol groups were significantly better than the group who received adjunctive transdermal placebo.

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Using biomarkers to identify and treat schizophrenia

In the current online issue of PLoS ONE, researchers at the University of California, San Diego School of Medicine say they have identified a set of laboratory-based biomarkers that can be useful for understanding brain-based abnormalities in schizophrenia. The measurements, known as endophenotypes, could ultimately be a boon to clinicians who sometimes struggle to recognize and treat the complex and confounding mental disorder.

“A major problem in psychiatry is that there are currently no laboratory tests that aid in diagnosis, guide treatment decisions or help predict treatment response or outcomes,” said Gregory A. Light, PhD, associate professor of psychiatry and the study’s first author. “Diagnoses are currently based on a clinician’s ability to make inferences about patients’ inner experiences.”

Diagnosing and treating schizophrenia is a particularly troubling challenge. The disorder, which affects about 1 percent of the U.S. population or roughly 3 million people, is characterized by a breakdown of normal thought processes and erratic, sometimes dangerous or harmful, behaviors.

“Schizophrenia is among the most severe and disabling conditions across all categories of medicine,” said Light, who also directs the Mental Illness, Research, Education and Clinical Center at the San Diego VA Healthcare System.

The precise cause or causes of schizophrenia are not known, though there is a clear genetic component, with the disorder more common in some families.

Clinicians typically diagnose schizophrenia based upon inferences drawn from the patient’s inner experiences. That is, their ability to describe what’s happening inside their minds.

“But even the best clinicians struggle with diagnostic complexities based on sometimes fuzzy clinical phenomenology,” said Light. The clinical challenge is compounded by the fact that “many schizophrenia patients have cognitive and functional impairments,” said Light. They may not be able to reasonably explain how or what they think.

Light and colleagues investigated whether a select battery of neurophysiological and neurocognitive biomarkers could provide clinicians with reliable, accurate, long-term indicators of brain dysfunction, even when overt symptoms of the disorder were not apparent. These markers ranged from tests of attention and memory to physiological assessments of basic perceptual processes using scalp sensors to measure brain responses to simple sounds.

The researchers measured the biomarkers in 550 schizophrenia patients, and then re-tested 200 of the patients one year later. They found that most of the markers were significantly abnormal in schizophrenia patients, were relatively stable between the assessments and were not affected by modest fluctuations in clinical status of the patient.

Light said further research is required, including whether the endophenotypes can differentiate other psychiatric disorders, be used to anticipate patient response to different kinds of drugs or non-pharmacological interventions or even be used to predict which subjects are at high risk of developing a psychotic illness.

“We believe this paper is an important step towards validating laboratory-based biomarkers for use in future genomic and clinical treatment studies of schizophrenia,” Light said.

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Co-authors are Neal R. Swerdlow, Anthony J. Rissling and Marlena Pela, Department of Psychiatry, UCSD; Allen Radant, Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; Catherine A. Sugar, Departments of Psychiatry and Biostatistics, UCLA; Joyce Sprock, Mark A. Geyer and David L. Braff, Mental Illness, Research, Education and Clinical Center, San Diego VA Healthcare System and Department of Psychiatry, UCSD.

Source: Eurekalert July 11 2012

Study finds genetic ‘overlap’ between schizophrenia, bipolar disorder

Knowledge about the biological origin of diseases like schizophrenia, bipolar disorder and other psychiatric conditions is critical to improving diagnosis and treatment.

In an effort to push the field forward, three UCLA researchers, along with scientists from more than 20 countries, have been taking part in one of the largest collaborative efforts in psychiatry — a genome-wide study involving more than 50,000 study participants aimed at identifying which genetic variants make people susceptible to psychiatric disease.

This collaborative, the Psychiatric Genome-Wide Association Study Consortium (PGC), now reports in the current online edition of the journal Nature Genetics that it has discovered that common genetic variants contribute to a person’s risk of schizophrenia and bipolar disorder.

The PGC’s studies provide new molecular evidence that 11 regions on the genome are strongly associated with these diseases, including six regions not previously observed. The researchers also found that several of these DNA variations contribute to both diseases.

The findings, the researchers say, represent a significant advance in understanding the causes of these chronic, severe and debilitating disorders.

The UCLA researchers who contributed to the schizophrenia study are Roel A. Ophoff, a professor of psychiatry and human genetics and one of the founding principal investigators of the schizophrenia portion of the study; Dr. Nelson Freimer, a professor of psychiatry and director of the Center for Neurobehavioral Genetics at the Semel Institute for Neuroscience and Human Behavior at UCLA; and Rita Cantor, a professor of psychiatry and human genetics.

Schizophrenia and bipolar disorder are common and often devastating brain disorders. Some of the most prominent symptoms of schizophrenia are persistent delusions, hallucinations and cognitive problems. Bipolar disorder is characterized by severe, episodic mood swings. Both affect about 1 percent of the world’s population and usually strike in late adolescence or early adulthood.

Despite the availability of treatments, these illnesses are usually chronic, and patients’ response to treatment is often incomplete, leading to prolonged disability and personal suffering. Family history, which reflects genetic inheritance, is a strong risk factor for both schizophrenia and bipolar disorder, and it has generally been assumed that dozens of genes, along with environmental factors, contribute to disease risk.

In the schizophrenia study, a total of seven locations on the genome were implicated in the disease, five of which had not been identified before. When similar data from the bipolar disorder study, which ran concurrently, were combined with results from the schizophrenia study, three gene locations were identified that proved to be involved in both disorders, suggesting a “genetic overlap” between schizophrenia and bipolar disorder.

“Genetic factors play an important role in the susceptibility to develop schizophrenia,” Ophoff said, “but identifying these genetic factors has been very difficult. We know that schizophrenia is not caused by a single gene that explains everything but an interplay of many genetic and non-genetic factors.”

At the same time, he said, the disease itself is not uniform but manifests itself in different ways; currently, there is no objective biological marker or “sign” that can be used for diagnosis.

“This so-called heterogeneity at the genetic and clinical level is the biggest challenge for genetic studies of neuropsychiatric disorders,” Ophoff said. “One way to deal with these difficulties is to increase the size of the study so there is sufficient ‘power’ to detect genetic effects, even amidst this clinical and genetic diversity.”

The fact that even this large study resulted in a limited number of schizophrenia and bipolar genes demonstrates once again, he said, the complex nature of the disease.

The research was funded by numerous European, American and Australian funding bodies. Funds for coordination of the consortium were provided by the National Institute of Mental Health in the U.S.

 

Sporadic Mutations cause more than half the cases of Schizophrenia

Columbia University Medical Center researchers have shown that new, or “de novo,” protein-altering mutations—genetic errors that are present in patients but not in their parents—play a role in more than 50 percent of “sporadic” —i.e., not hereditary—cases of schizophrenia. The findings will be published online on August 7, 2011, in Nature Genetics.

A group led by Maria Karayiorgou, MD, and Joseph A. Gogos, MD, PhD, examined the genomes of patients with schizophrenia and their families, as well as healthy control groups. All were from the genetically isolated, European-descent Afrikaner population of South Africa.

These findings build on earlier studies by Karayiorgou, professor of psychiatry at Columbia University Medical Center. More than 15 years ago, Karayiorgou and her colleagues described a rare de novo mutation that accounts for 1-2 percent of sporadic cases of schizophrenia. With advances in technology, three years ago the Columbia team was able to search the entire genome for similar lesions that insert or remove small chunks of DNA. The mutations found accounted for about 10 percent of sporadic cases.

Encouraged by their progress, they wondered whether other, previously undetectable, de novo mutations accounted for an even greater percentage of sporadic cases. Using state-of-the-art “deep sequencing,” they examined the nucleotide bases of almost all the genes in the human genome. This time they found 40 mutations, all from different genes and most of them protein-altering. The results point the way to finding more, perhaps even hundreds, of mutations that contribute to the genetics of schizophrenia—a necessary step toward understanding how the disease develops.

“Identification of these damaging de novo mutations has fundamentally transformed our understanding of the genetic basis of schizophrenia,” says Bin Xu, PhD, assistant professor of clinical neurobiology at Columbia University Medical Center and first author of the study.

“The fact that the mutations are all from different genes,” says Karayiorgou, “is particularly fascinating. It suggests that many more mutations than we suspected may contribute to schizophrenia. This is probably because of the complexity of the neural circuits that are affected by the disease; many genes are needed for their development and function.” Karayiorgou and her team will now search for recurring mutations, which may provide definitive evidence that any specific mutation contributes to schizophrenia.

The potentially large number of mutations makes a gene-therapy approach to treating schizophrenia unlikely. Researchers suspect, however, that all of the mutations affect the same neural circuitry mechanisms. “Using innovative neuroscience methods,” says co-author Dr. Joseph Gogos, MD, PhD, and associate professor of physiology and neuroscience at Columbia University Medical Center, “we hope to identify those neural circuit dysfunctions, so we can target them for drug development.”

The study’s results also help to explain two puzzles: the persistence of schizophrenia, despite the fact that those with the disease do not tend to pass down their mutations through children; and the high global incidence of the disease, despite large environmental variations.

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The study’s authors are Bin Xu (CUMC), J. Louw Roos (University of Pretoria), Phillip Dexheimer (HudsonAlpha Institute), Braden Boone (HudsonAlpha Institute), Brooks Plummer (HudsonAlpha Institute), Shawn Levy (HudsonAlpha Institute), Joseph A. Gogos (CUMC), and Maria Karayiorgou (CUMC).

The study was supported by NIMH, the Lieber Center for Schizophrenia Research at Columbia University, and NARSAD.

The authors declare no financial conflict of interest.