Cognitive Changes Mapped Over Time in Young Persons at Risk for Psychosis

MedicalResearch.com Interview with:

Richard Keefe PhD Professor in Psychiatry and Behavioral Sciences Duke Institute for Brains Sciences

Dr. Keefe

Richard Keefe PhD
Professor in Psychiatry and Behavioral Sciences
Duke Institute for Brains Sciences

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

Response: A lot of studies have shown that cognitive deficits are present in young people at risk for psychosis. There have been calls for investigations of the idea that cognition declines over time in the young people who are at highest risk, but longitudinal studies are hard to conduct so not much work has been done to address this question.

The main finding from our study is that the cognitive architecture – the way the various aspects of cognitive functioning appear to be organized in each individual’s brain based upon their pattern of performance – changes over time in those young people who are in the midst of developing psychosis. Interestingly, cognitive architecture also becomes more disorganized in those whose high-risk symptoms do not remit over a two year period, and is related to the functional difficulties they may be having. The young people whose high risk symptoms were present at the beginning of the study but remitted later actually improved cognitively over the two year period of the study. Continue reading

Machine Learning Can Help Identify First Episodes of Schizophrenia, As Well As Treatment Response

MedicalResearch.com Interview with:

Bo Cao, Ph.D. Assistant Professor Department of Psychiatry Faculty of Medicine & Dentistry University of Alberta Edmonton

Dr. Bo Cao

Bo Cao, Ph.D.
Assistant Professor
Department of Psychiatry
Faculty of Medicine & Dentistry
University of Alberta
Edmonton

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

Response: Schizophrenia is a severe psychiatric disorder that comes with delusions, hallucinations, poor motivation, cognitive impairments.

The economic burden of schizophrenia was estimated at $155.7 billion in 2013 alone in the United States. Schizophrenia usually emerges early in life and can potentially become a lifetime burden for some patients. Repeated untreated psychotic episodes may be associated with irreversible alterations of the brain. Thus, it is crucial to identify schizophrenia early and provide effective treatment. However, identifying biomarkers in schizophrenia during the first episode without the confounding effects of treatment has been challenging. Limited progress has been made in leveraging these biomarkers to establish diagnosis and make individualized predictions of future treatment responses to antipsychotics.

In a recent study by Dr. Cao and his colleagues, they successfully identified the first-episode drug-naïve schizophrenia patients (accuracy 78.6%) and predict their responses to antipsychotic treatment (accuracy 82.5%) at an individual level by using a machine learning algorithm and the functional connections of a brain region called the superior temporal cortex.  Continue reading

Protein Functions of DISC1 Gene Linked to Schizophrenia Identified

MedicalResearch.com Interview with:
Marcelo Pablo Coba PhD
Assistant Professor of Psychiatry
Zilkha Neurogenetic Institute
Keck School of Medicine of USC

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

Response: Psychiatric diseases such as schizophrenia (SCZ) are complex brain disorders where a multitude or risk factors have been implicated in contributing to the disease, with a low number of genes that have been strongly implicated in a very low number of cases.

One of these genes is Disrupted in schizophrenia 1 (DISC1), which was first described in 2000 as a balanced translocation that segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Because DISC1 does not have an identified protein function such as enzymatic, channel, transporter, etc… the field moved to try to understand what proteins are associated (physically connected) to DISC1 and to try to explain DISC1 function through the function of its protein interactors. This means that if DISC1 binds proteins X, Y and Z, then mutations in the DISC1 gene should affect the functions of   these proteins. Therefore, there has been much effort in trying to identify DISC1 protein interactors. However this task has not been straightforward.

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Functional Brain ‘Fingerprint’ Identified in Schizophrenia

MedicalResearch.com Interview with:

Tobias Kaufmann UiO Institute of Clinical Medicine

Dr. Kaufmann

Tobias Kaufmann PhD
Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen 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: Over the past years, a lot of work has pointed toward impaired brain networks in schizophrenia. With this work we assessed brain network stability across different loads of a cognitive task using functional magnetic resonance imaging of the brain.

Based on our earlier work on adolescents with pre-clinical signs of mental illness who showed decreased stability of networks across different tasks and conditions, we hypothesized that brain networks in adults with schizophrenia show similar properties of decreased stability. Our results confirmed this hypothesis. Stability was reduced in several large-scale brain networks across the sampled age range from early adulthood to the sixties. Further, network stability was associated with polygenic risk for schizophrenia as well as cognitive task performance.

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Psychosis: Early Integrated Bests Usual Care

MedicalResearch.com Interview with:

Christoph U. Correll, MD Professor of Psychiatry and Molecular Medicine The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Hempstead, NY Investigator, Center for Psychiatric Neuroscience Feinstein Institute for Medical Research Medical Director, Recognition and Prevention (RAP) Program The Zucker Hillside Hospital, Department of Psychiatry

Dr. Correll

Christoph U. Correll, MD
Professor of Psychiatry and Molecular Medicine
The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell
Hempstead, NY
Investigator, Center for Psychiatric Neuroscience
Feinstein Institute for Medical Research
Medical Director, Recognition and Prevention (RAP) Program
The Zucker Hillside Hospital, Department of Psychiatry

 

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

Response: Schizophrenia and other psychotic disorders are still all to often chronic and recurring mental health conditions that not uncommonly take a course during which individuals have varying degrees of significantly impaired personal, social and educational/vocational functioning.

Prior individual studies examining early specialty intervention services, which integrate multiple different and complementary treatment components, had shown that this treatment approach can yield superior outcomes for people with early-phase schizophrenia and other psychotic disorders compared to usual care given to all people with psychotic disorders. However, we were lacking a broad overview of the type and results of treatment programs that had been conducted across different countries, continents and mental health service delivery systems. Moreover, we did not yet have a synthesis across all important outcomes that had been examined across these individual studies. This first comprehensive meta-analysis on this topic provides previously missing information on the different early intervention programs and their components as well as on all relevant outcomes for people who did or did not receiving early integrated care, also recently called ‘coordinated specialty care.’

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Schizophrenia: Medications Reduce Psychotic Symptoms But Don’t Improve Real-Life Funtioning

MedicalResearch.com Interview with:

Silvana Galderisi MD President of the European Psychiatric Association Professor of Psychiatry University of Campania "Luigi Vanvitelli" Italy

Dr. Galderisi

Silvana Galderisi MD
President of the European Psychiatric Association
Professor of Psychiatry
University of Campania “Luigi Vanvitelli”
Italy

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

Response: The goal of schizophrenia treatment has gradually shifted from reduction of symptoms and prevention of relapse to improvement of real-life functioning. In fact, these outcomes not always coincide and, in spite of progress in treatments reducing symptoms and preventing relapses, people with schizophrenia live 15-20 years less than the general population, are often unemployed, and show severe disabilities.

Enhanced understanding of factors associated with real-life functioning is instrumental to design effective integrated and personalized treatment plans for persons with schizophrenia.

To this aim, the Italian Network for Research on Psychoses, including 26 twenty-six Italian university psychiatric clinics and/or mental health departments, has focused on the identification of variables influencing real-life functioning, in particular on the interrelationships among illness-related variables, personal resources, context-related variables and real-life functioning. The number of variables and subjects included in the study was larger than in any other study on this topic, and for the first time the network analysis was used to model the interplay among cognitive, psychopathological and psychosocial variables in a large sample of community dwelling subjects with schizophrenia. The network analysis is a data-driven approach; it does not rely on an a priori model of relationships among variables, provides quantitative measures of variable centrality within the network, thus indicating which variables play a key role in the network, and which ones are instead more peripheral. In addition, by inspecting the network, it is possible to understand the extent to which variables belonging to the same construct are connected, and how different constructs are mutually interacting and reinforcing each other.  Continue reading

Greater Risk of Breast Cancer in Women With Schizophrenia

MedicalResearch.com Interview with:
Chuanjun Zhuo, MD, PhD

Department of Psychiatric Laboratory
Department of Psychiatric Neuroimaging Faculty
Tianjin Mental Health Center
Tianjin, China 

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

Response: According to previous epidemiological studies, women with schizophrenia may be associated with significantly increased risk of breast cancer. However, the results of these studies were not always consistent. In view of the fact that medical care for patients with schizophrenia is becoming multidisciplinary, we aimed to evaluate the risk of breast cancer in women with schizophrenia via a meta-analysis of relevant cohort studies. We included twelve cohorts and adopted the recently proposed prediction interval to evaluate the heterogeneity among the included studies.

We found that schizophrenia was associated with about 30% increased risk of breast cancer incidence in women. However, significant heterogeneity existed of the included studies, which indicates that more extensive researches into the potential mechanisms underlying the associations between schizophrenia and breast cancer risk are needed.

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Add-On Preservative May Improve Outcomes in Refractory Schizophrenia

MedicalResearch.com Interview with:

Hsien-Yuan Lane

Dr. Hsien-Yuan Lane

Hsien-Yuan Lane, MD,PhD
Distinguished Professor, Director, Graduate Institute of Biomedical Sciences
China Medical University, Taichung, Taiwan
Director, Brain Diseases Research Center (BDRC), Addiction Research Center, and Department of Psychiatry,
China Medical University and Hospital, Taichung, Taiwan
PI, Taiwan Clinical Trial Consortium for Mental Disorders 

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

Response: Schizophrenia is a chronic and severe mental illness affecting more than 21 million people worldwide. Clozapine has been regarded as the last-line antipsychotic agent for patients with refractory schizophrenia. However, an estimated 40–70% of patients with refractory schizophrenia fail to improve even with clozapine , referred to as “clozapine-resistant”. To date, there is no convincing evidence for augmentation on clozapine.

Activation of N-methyl-D-aspartate (NMDA) receptors, including inhibition of D-amino acid oxidase (DAAO) that may metabolize D-amino acids, has been reported to be beneficial for patients receiving antipsychotics other than clozapine.

Sodium benzoate is a DAAO inhibitor. A recent randomized, double-blind, placebo-controlled clinical trial found that add-on sodium benzoate improved the clinical symptoms in patients with clozapine-resistant schizophrenia, possibly through DAAO inhibition and antioxidation as well.

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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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