Aging, Author Interviews, Autism, Mental Health Research, PLoS, Schizophrenia / 25.01.2016

[caption id="attachment_20922" align="alignleft" width="127"]Dr. Richard Deth PhD Professor of Pharmacology Department of Pharmaceutical Sciences Nova Southeastern University Dr. Richard Deth[/caption] MedicalResearch.com Interview with: Dr. Richard Deth PhD Professor of Pharmacology Department of Pharmaceutical Sciences Nova Southeastern University Medical Research: What is the background for this study? Dr. Deth: Vitamin B12 plays a crucial role in regulating and promoting methylation reactions (the attachment of a carbon atom to molecules), including DNA methylation. Recent research has identified methylation of DNA and consequential changes in gene expression as crucial factors in brain development, as well as in memory formation and maintenance of brain function during aging. More specifically, the cause(s) of neurodevelopmental disorders such as autism remain obscure, although numerous studies have demonstrated oxidative stress and low plasma levels of the antioxidant glutathione (GSH) in autism.  Medical Research: What are the main findings? Dr. Deth: We found that brain levels of vitamin B12, especially the methylation-regulating form known as methylB12, decrease significantly with age, even though blood levels don’t show a similar decrease. Importantly, much lower levels of methylB12 were found in subjects with autism and schizophrenia compared to normal subjects of a similar age. Animal studies showed that impaired GSH formation is associated with decreased brain B12 levels.
Author Interviews, Nutrition, Schizophrenia / 19.12.2015

[caption id="attachment_20204" align="alignleft" width="200"]Zoltan Sarnyai, M.D., Ph.D. Associate Professor of Pharmacology Head, Laboratory of Psychiatric Neuroscience Australian Institute of Tropical Health and Medicine (AITHM) Comparative Genome Centre Centre for Biodiscovery and Molecular Development of Therapeutics James Cook University Townsville, Australia Dr. Zoltan Sarnyai[/caption] MedicalResearch.com Interview with: Zoltan Sarnyai, M.D., Ph.D. Associate Professor of Pharmacology Head, Laboratory of Psychiatric Neuroscience Australian Institute of Tropical Health and Medicine (AITHM) Comparative Genome Centre Centre for Biodiscovery and Molecular Development of Therapeutics James Cook University Townsville, Australia Medical Research: What is the background for this study? Dr. Sarnyai: Schizophrenia has long been conceptualized as a disease contributed by the increased activity of the neurotransmitter system that provides dopamine for the brain. All clinically used antipsychotic drugs inhibit dopamine transmission in the brain by blocking dopamine receptors. These drugs have only a limited efficacy on a certain set of symptoms associated with schizophrenia. More recent research has uncovered that abnormal glucose and energy metabolism in the brain may contribute in the development of schizophrenia. This is not altogether surprising considering that our brain is using a disproportionately high amount of glucose to fuel neurotransmission (cell-to-cell communication in the brain), to maintain normal electrical activity of nerve cells and to deal with damaging free oxygen radicals. Therefore, even relatively small changes in the machinery that is required to provide energy for the brain cells can have very significant impact on brain function. In fact, recent studies have identified altered expression of genes and proteins that are responsible for enzymatic breakdown of glucose and proper handling of the metabolites to create the energy-rich molecule ATP. In addition, recent research shows decreased number and impaired function of the mitochondria, the powerhouses of the cell, in the brain of individuals with schizophrenia.  These recent results that show abnormal energy metabolism in schizophrenia raise the possibility of targeting metabolic pathways for therapeutic benefit in this condition. Ketogenic diet provides and alternative source of energy to the brain through fatty acids. Furthermore, since this diet is very low in carbohydrates, almost all the energy needs of the cells comes from breaking down fat (fatty acids) as opposed to glucose. This can circumvent the classic glucose metabolic pathways that maybe impaired in the disease. Also, breaking down fatty acids produces 40% more of the energy-rich molecule ATP than breaking down the carbohydrate glucose. Altogether, ketogenic diet may provide extra energy and can help neurotransmission in the brain, leading to the improvement of neurobiological processes underlying schizophrenia.
Author Interviews, Brigham & Women's - Harvard, Genetic Research, JAMA, Neurological Disorders, Schizophrenia / 12.11.2015

[caption id="attachment_19334" align="alignleft" width="150"]Frederick W. Vonberg, MA, MBBS Research Fellow in Neurocritical Care Boston Children's Hospital and Harvard Medical School Dr. Vonberg[/caption] MedicalResearch.com Interview with: Frederick W. Vonberg, MA, MBBS Research Fellow in Neurocritical Care Boston Children's Hospital and Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Response: An association between schizophrenia and epilepsy has long been suspected, ever since people noticed similarities in some aspects of the presentation of the two conditions, and in their epidemiology. For example, people with epilepsy are thought to be more at risk of developing schizophrenia. Furthermore, a psychosis resembling schizophrenia can characterize some forms of epilepsy. Whether this link reflected an overlap in the genetics of the two conditions has remained a mystery, however. In this study, we used a recently developed computational technique to show that there is a significant positive correlation between the genetic variants that are associated with epilepsy and with those that are associated with schizophrenia.
Author Interviews, Columbia, Schizophrenia / 04.02.2015

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.
Author Interviews, JAMA, Schizophrenia / 06.01.2015

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.
Author Interviews, Bipolar Disorder, JAMA, Schizophrenia / 23.10.2014

Glenn T. Konopaske, MD McLean Hospital, Belmont, Massachusetts Department of Psychiatry, Harvard Medical School Boston, MassachusettsMedicalResearch.com Interview with: Glenn T. Konopaske, MD McLean Hospital, Belmont, Massachusetts Department of Psychiatry, Harvard Medical School Boston, Massachusetts Medical Research: What are the main findings of the study? Dr. Konopaske: Using postmortem human brain tissue this study did reconstructions of basilar dendrites localized to pyramidal cells in the deep layer III of the dorsolateral prefrontal cortex. Tissue from individuals with schizophrenia, bipolar disorder or controls was examined. Dendritic spine density (number of spines per μm dendrite) was significantly reduced in bipolar disorder and also reduced in schizophrenia at a trend level. The number of dendritic spines per dendrite and dendrite length were significantly reduced in subjects with schizophrenia and bipolar disorder.
Author Interviews, JAMA, Schizophrenia / 09.10.2014

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.
Author Interviews, JAMA, Mental Health Research, Schizophrenia / 06.09.2014

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.
Author Interviews, Genetic Research, JAMA, Schizophrenia / 31.07.2014

Dr Angelica Ronald Genes Environment Lifespan (GEL) laboratory Centre for Brain and Cognitive Development Department of Psychological Sciences Birkbeck, University of London London WC1E 7HXMedicalResearch.com Interview with: Dr Angelica Ronald Genes Environment Lifespan (GEL) laboratory Centre for Brain and Cognitive Development Department of Psychological Sciences Birkbeck, University of London London WC1E 7HX Medical Research: What are the main findings of the study? Dr. Ronald: Psychotic experiences, such as paranoia, hallucinations and disorganised thinking, are commonly reported by adolescents. Until now it has not been understood whether mild variations in psychotic experiences in the community are part of the same construct as more severe psychotic experiences in adolescence. Our findings suggest that they are. In our study, over 10,000 16-year-old adolescents in England and Wales were assessed on measures of psychotic experiences. The study identified a close link between normal, less frequent psychotic experiences and more severe and frequent experiences in the general population. A classic twin design was employed, which enabled us to conduct analyses investigating the role of genetic and environmental influences on psychotic experiences. The same genetic influences appeared to play a role across the spectrum of severity of psychotic experiences. The study found that psychotic experiences are moderately heritable in adolescence in the general population. This suggests it would be worth directing molecular genetic endeavours towards this area, which has so far received very little attention in terms of causal explanations. We also show that psychotic experiences have considerable environmental influence; in fact, environmental influence appears to play a larger role in causing psychotic experiences in adolescence than for diagnosed psychotic disorders in adults, such as schizophrenia. This result suggests a fruitful avenue will be to tackle what environmental risk factors influence adolescents to have psychotic experiences.
Author Interviews, Schizophrenia, Sleep Disorders / 08.07.2014

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.
Author Interviews, Genetic Research, Mayo Clinic, Schizophrenia / 11.06.2014

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.  
Author Interviews, Compliance, JAMA, Pharmacology, Schizophrenia / 23.05.2014

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.
Author Interviews, Mental Health Research, Schizophrenia / 13.05.2014

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.
Author Interviews, Cannabis, Schizophrenia / 16.12.2013

MedicalResearch.com Interview with: Dr. Matthew J. Smith PhD Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 710 N. Lake Shore Drive, 13th Floor, Abbott Hall, Chicago, IL 60611 MedicalResearch.com: What are the main findings of the study? Dr. Smith: We observed that the shapes of brain structures involved in a working memory brain circuit seemed to collapse inward in a similar fashion among both of the groups that had a history of daily cannabis use. These cannabis-related changes in shape were directly related to the participants’ poor performance on working memory tasks. Some of the shape abnormalities were more severe in the group with schizophrenia and the history of daily cannabis use. We also found that participants with an earlier age of daily cannabis use had more abnormal brain shapes.