Author Interviews, JAMA, Karolinski Institute, Pharmacology, Schizophrenia / 09.06.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Autism, Genetic Research, Schizophrenia, UCLA / 26.05.2017

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 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. (more…)
Author Interviews, NYU, Schizophrenia / 08.05.2017

MedicalResearch.com Interview with: Donald C. Goff, MD Marvin Stern Professor Vice Chair for Research Department of Psychiatry NYU Langone Medical Center MedicalResearch.com: What is the background for this study? Response: Since their introduction in the 1950’s antipsychotic drugs have been an integral part of the treatment of schizophrenia. However, over the past decade concerns have been raised about whether these drugs might negatively affect the long-term course of the illness—either by causing supersensitivity of dopamine receptors, which might make patients more prone to psychosis and relapse, or by direct toxic effects on the brain. To address these concerns, we convened a panel of international experts to review the evidence supporting these concerns, including findings from clinical studies, brain imaging studies, post-mortem examination of the brains of people treated with these drugs, and studies in which these drugs were administered to animals. (more…)
Author Interviews, Johns Hopkins, Microbiome, Probiotics, Schizophrenia / 10.04.2017

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. (more…)
Author Interviews, Columbia, Global Health, Schizophrenia / 16.03.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Compliance, Lancet, Mental Health Research, Schizophrenia / 27.02.2017

MedicalResearch.com Interview with: Ernst L Noordraven MSc, PhD student Department of Psychiatry Epidemiological and Social Psychiatric Research institute Erasmus University Medical Center Rotterdam Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Provision of financial incentives is a promising intervention for improving adherence in patients taking antipsychotic medication. We aimed to assess the effectiveness of this intervention for improving adherence to antipsychotic depot medication in patients with psychotic disorders, irrespective of their previous compliance. Our 12-month randomized controlled trial showed that financial incentives improved adherence to antipsychotic depot medications in patients with psychotic disorders, regardless of their level of compliance at study entrance. Patients received either treatment as usual plus a financial reward for each depot of medication received (€30 per month if fully compliant; intervention group) or treatment as usual alone (control group). Based on the use of depot registrations from 155 patients (92%), the adjusted difference in adherence was 14·9% (95% CI 8·9–20·9%; p<0·0001) in favour of the intervention group. Our study is also the first to demonstrate that the effects on medication adherence persist after monetary rewards are discontinued, for at least a 6-month follow-up period (adjusted difference 6·5%, 95% CI 2·0–10·9; p=0·047). (more…)
Author Interviews, Nature, Schizophrenia / 06.02.2017

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Diabetes, JAMA, Schizophrenia / 13.01.2017

MedicalResearch.com Interview with: 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. (more…)
Abuse and Neglect, Genetic Research, Schizophrenia, UCSD / 06.01.2017

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 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. (more…)
Author Interviews, Autism, Genetic Research, Nature, Pediatrics, Schizophrenia / 04.01.2017

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 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. (more…)
Author Interviews, Genetic Research, Lancet, Pediatrics, Schizophrenia / 22.12.2016

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. (more…)
Alcohol, Author Interviews, Cannabis, Schizophrenia / 27.10.2016

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. (more…)
Author Interviews, Bipolar Disorder, Mental Health Research, Pediatrics, Schizophrenia / 21.10.2016

MedicalResearch.com Interview with: Merete Nordentoft DrMSc Professor, chief Psychiatrist University of Copenhagen Mental Health Centre Copenhagen MedicalResearch.com: What is the background for this study? Response: We knew that children born to parents with mental illness had an increased risk for developing a mental disorder them selves, either the same disorder as their parent or another menal disorder. We also knew that some of these children would have pootrt motor function and other difficulties in functioning. However previous studies were smaller, they were not based on a representative sample, and children were at different age. That is the background for The Danish High Risk and Resilience Study-VIA 7, in which a large group of 522 children and their families were thoroughly assessed. The children were seven year old, and 202 had a parent who had schizophrenia, 120 had a parent with bipolar disorder and 200 had parent with neither of these disorders. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 14.10.2016

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 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. (more…)
Author Interviews, Pharmacology, Schizophrenia / 10.10.2016

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. (more…)
Author Interviews, Mental Health Research, Schizophrenia, Telemedicine / 26.08.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, JAMA, Schizophrenia / 26.07.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Mental Health Research, Pharmacology, Schizophrenia / 21.07.2016

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 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. (more…)
Author Interviews, Bipolar Disorder, JAMA, Schizophrenia / 06.07.2016

MedicalResearch.com Interview with: Thomas M. Lancaster, PhD Neuroscience and Mental Health Research Institute Cardiff University Brain Imaging Research Centre Cardiff University, Cardiff, United Kingdom   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Psychotic disorders such as schizophrenia and bipolar disorders are heritable. Part of this genetic risk may be conferred by the combined effects of common risk alleles identified via genome wide association studies. Individuals with psychosis are also more likely to experience alterations in the ventral striatum (VS); a key node in the brain’s reward processing network. We hypothesized that common genetic risk for psychosis may confer risk via alterations in the VS. Using functional magnetic resonance imaging (fMRI) data from an adolescent sample (the IMAGEN cohort), we showed that increased psychosis risk was associated with increased BOLD (blood oxygen level dependency) in the VS, during reward processing. (more…)
Author Interviews, JAMA, Schizophrenia / 16.06.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, MRI, Schizophrenia / 30.05.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Lancet, OBGYNE, Schizophrenia, Smoking / 25.05.2016

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 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. (more…)
Author Interviews, Bipolar Disorder, Infections, Johns Hopkins, Mental Health Research, Microbiome, Schizophrenia / 05.05.2016

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  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. (more…)
Author Interviews, Schizophrenia, Smoking / 20.04.2016

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. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 26.03.2016

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  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. (more…)
Author Interviews, BMJ, Karolinski Institute, Mental Health Research, Schizophrenia / 16.03.2016

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 04.02.2016

MedicalResearch.com Interview with: 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.  (more…)
Author Interviews, Autism, Genetic Research, JAMA, Schizophrenia / 30.01.2016

MedicalResearch.com Interview with: Andrea J. Gonzalez-Mantilla, M.D. Postdoctoral Fellow Andres Moreno-De-Luca, M.D. Investigator I Autism & Developmental Medicine Institute Department of Radiology Geisinger Health System Danville, PA 17822 Medical Research: What is the background for this study? What are the main findings? Response: Developmental brain disorders (DBD), such as autism, intellectual disability, and schizophrenia are a group of heterogeneous conditions characterized by deficits that affect multiple functional domains, such as cognition, behavior, communication, and motor skills. Previous studies provide strong evidence of common underlying molecular pathways and shared genetic causes among apparently different DBDs. Large-scale genomic studies of individuals with developmental brain disorders have found that identifying multiple, independent de novo pathogenic loss-of-function (pLOF) variants in the same gene among unrelated individuals is a powerful statistical approach to reliably identify disease-causing genes. However, genomic data from smaller cohorts and case reports are not routinely pooled with data from larger studies. Moreover, most previous studies have been restricted to cohorts of individuals ascertained based on a single diagnosis (e.g., a study will focus on only individuals with a diagnosis of autism and not consider other genomic data from individuals with a different diagnosis). Therefore, genomic data from individuals across DBD are not being jointly analyzed in search of pLOF variants in the same gene that may help build evidence for a causative role in developmental brain disorders. In this study, we carried out data mining of previously published data to identify genes related to the DBD phenotype. We expanded the aforementioned method and developed a multilevel data-integration approach, which capitalizes on three genotype-phenotype data sources: (1) genomic data from structural and sequence pLOF variants, (2) phenotype data from six apparently distinct DBD (autism, intellectual disability, epilepsy, schizophrenia, bipolar disorder and attention-deficit/hyperactivity disorder), and (3) data from large scale studies, smaller cohorts, and case reports. We identified 241 candidate genes for developmental brain disorders, including 17 genes that had not previously been associated with developmental brain disorders. (more…)
Aging, Author Interviews, Autism, Mental Health Research, PLoS, Schizophrenia / 25.01.2016

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. (more…)