Schizophrenia: SynCav1 As Potential Target To Restore Neuron Function

MedicalResearch.com Interview with:

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

Dr. Brian Head

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

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

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

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

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

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Genetic Factors Link Communication Competence in Childhood With Autism and Schizophrenia

MedicalResearch.com Interview with:

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

Dr. Beate St Pourcain

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

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

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

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

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

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

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Genetic Predisposition To Schizophrenia Associated With Childhood Impairments

MedicalResearch.com Interview with:
Dr Lucy Riglin

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

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

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

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

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Alcohol and Cannabis Abuse Linked To Increased Risk of Schizophrenia

MedicalResearch.com Interview with:
Dr Stine Mai Nielsen

Copenhagen University Hospital
Mental Health Center Copenhagen
Gentofte, Denmark

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

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

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

MedicalResearch.com Interview with:
Merete Nordentoft DrMSc
Professor, chief Psychiatrist
University of Copenhagen
Mental Health Centre Copenhagen

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

Response: We knew that children born to parents with mental illness had an increased risk for developing a mental disorder them selves, either the same disorder as their parent or another menal disorder. We also knew that some of these children would have pootrt motor function and other difficulties in functioning. However previous studies were smaller, they were not based on a representative sample, and children were at different age. That is the background for The Danish High Risk and Resilience Study-VIA 7, in which a large group of 522 children and their families were thoroughly assessed. The children were seven year old, and 202 had a parent who had schizophrenia, 120 had a parent with bipolar disorder and 200 had parent with neither of these disorders.

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Multiple Genetic Risk Factors May Contribute to Schizophrenia By Damaging Neurons

MedicalResearch.com Interview with:

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

Dr. Roussos

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

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

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

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

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Efficacy of Lurasidone in Schizophrenia

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

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

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

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

MedicalResearch.com Interview with:

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

Dr. Dror Ben Zeev

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

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

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

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

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Adjuvant Raloxifene Treatment Promising For Women With Refractory Schizophrenia

MedicalResearch.com Interview with:

Prof. Jayashri Kulkarni

Prof. Jayashri Kulkarni

Professor Jayashri Kulkarni MBBS, MPM,
FRANZCP, PhD

Director, Monash Alfred Psychiatry research centre
Vic Australia

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

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

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

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Patients With Schizophrenia Often Discharged on Multiple Medications

MedicalResearch.com Interview with:

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

Glorimar Ortiz

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

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

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

MedicalResearch.com Interview with:

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

Dr. Kate Merritt

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

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

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

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

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Alterations in Brain Matter Loss and Gain Identified in Schizophrenia

MedicalResearch.com Interview with:

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

Dr. Lena Palaniyappan

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

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

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

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Smoking During Pregnancy Raises Risk of Schizophrenia in Offspring

MedicalResearch.com Interview with:

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

Dr. Alan Brown

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

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

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

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Candida Yeast Infections Linked to Schizophrenia and Bipolar Disorder

MedicalResearch.com Interview with:

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

Dr. Emily Severance

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

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

Dr. Severance: This research stems in part from anecdotal dialogues that we had with people with psychiatric disorders and their families, and repeatedly the issue of yeast infections came up. We found that Candida overgrowth was more prevalent in people with mental illness compared to those without psychiatric disorders and the patterns that we observed occurred in a surprisingly sex-specific manner.  The levels of IgG antibodies directed against the Candida albicans were elevated in males with schizophrenia and bipolar disorder compared to controls. In females, there were no differences in antibody levels between these groups, but in women with mental illness who had high amounts of these antibodies, we found significant memory deficits compared to those without evidence of past infection.

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

MedicalResearch.com Interview with:

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

Dr. Dolores Malaspina

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

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

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

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

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

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

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

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

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

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

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

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

Citation:

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

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

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

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Brain Reward System May Underlie Tobacco Cravings in Schizophrenia

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

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

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

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

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

MedicalResearch.com Interview with:

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

Dr. Hong Lee

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

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

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

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

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Refugees Granted Asylum More Likely to Have Schizophrenia and Psychotic Disorders

MedicalResearch.com Interview with:

Dr. Anna-Clara Hollander

Dr. Anna Clara Hollander

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

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

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

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

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

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

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Study Identifies Predictors of Treatment-Resistant Schizophrenia

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

Theresa Wimberley

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

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

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

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

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

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Study Links Schizophrenia Genetic Risk with Psychopathology During Adolescence

MedicalResearch.com Interview with:

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

Dr. Hannah Jones

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

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

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

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

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

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

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

Microbiome Differs Between Schizophrenic Patients and Controls

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

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

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

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Patients With Schizophrenia Lack Sufficient Dopamine in Brain

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

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

MedicalResearch: What is the background for this study?

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

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Schizophrenia: Severity of Symptoms Predicts Medication Response

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

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

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

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

Glenn T. Konopaske, MD McLean Hospital, Belmont, Massachusetts Department of Psychiatry, Harvard Medical School Boston, MassachusettsMedicalResearch.com Interview with:
Glenn T. Konopaske, MD
McLean Hospital, Belmont, Massachusetts
Department of Psychiatry, Harvard Medical School
Boston, Massachusetts


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

Dr. Konopaske: Using postmortem human brain tissue this study did reconstructions of basilar dendrites localized to pyramidal cells in the deep layer III of the dorsolateral prefrontal cortex. Tissue from individuals with schizophrenia, bipolar disorder or controls was examined. Dendritic spine density (number of spines per μm dendrite) was significantly reduced in bipolar disorder and also reduced in schizophrenia at a trend level. The number of dendritic spines per dendrite and dendrite length were significantly reduced in subjects with schizophrenia and bipolar disorder.

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Cardiometabolic Risks Begin Early in Schizophrenic Spectrum Disorders

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

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

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

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