The 4th Schizophrenia International Research Society Conference, 5 –9 April 2014, Florence, Italy: A summary of topics and trends

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Abstract

The 4th Schizophrenia International Research Society Conference was held in Florence, Italy, April 5–9, 2014 and this year had as its emphasis, “Fostering Collaboration in Schizophrenia Research”. Student travel awardees served as rapporteurs for each oral session, summarized the important contributions of each session and then each report was integrated into a final summary of data discussed at the entire conference by topic. It is hoped that by combining data from different presentations, patterns of interest will emerge and thus lead to new progress for the future. In addition, the following report provides an overview of the conference for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

Introduction

Schizophrenia has been defined as a clinical entity for over a century, but despite decades of research, a definitive set of biological markers for the disorder are still not available, nor are treatments that prevent or cure it. The Schizophrenia International Research Society (SIRS) was formed in 2005 so that progress by communication and sharing of both similar and dissimilar findings between researchers could be facilitated world-wide. This report covers the 4th International Conference conducted by the society, this time with the theme of “Fostering Collaboration in Schizophrenia Research”. Toward that aim a special emphasis was placed on contributions from a geographical dispersed broad group of international investigators from over 40 countries and almost all continents world-wide. Four full days were devoted to topics that ranged from the underlying biology to reviews of the latest ongoing new pharmaceutical trials. Although the current report is organized by topic and thus cuts across multiple sessions in doing so, the highlights of the conference were the four unique plenary sessions that included an update on therapeutics, the impact of genomics and connectomics approaches on schizophrenia research, behavioral and imaging translational paradigms in drug development, and the clinical challenges of comorbidity with addiction and somatic disease. The plenaries were designed to air controversial and major issues in schizophrenia research and to have audience discussion with input from a range of diverse investigators who don't often have the opportunity to think about the topic at hand. Student travel awardees volunteered to serve as “rapporteurs” of oral sessions to summarize the major findings that were reported and the conclusions in discussions that followed. These were then synthesized into the following report that integrates information from separate sessions into a review of the major current trends in research topics pursued. In this way, isolated findings reported in different sessions are merged in an attempt to see patterns in the results that could pave the way to future progress. Reports from the 1st, 2nd and 3rd international conferences were previously published (Abubaker et al., 2009, Baharnoori et al., 2010, Abbs et al., 2012). Thus, the following summarizes the 2014 conference.

Section snippets

Inflammation in schizophrenia

Although inflammatory and immunological measures have long been studied in schizophrenia, this field has recently been revived with the presence of new exciting findings. Dr. Mary Clarke (RCSI Psychology & Psychiatry, Dublin, Ireland) proposed that inflammation was the common underlying process produced by adverse environmental stress and thus measurements of inflammation might potentially be useful as state and trait markers. She based this on studies of fetal stress associated with

Genetic studies

Dr. Patrick Sullivan (University of North Carolina, Chapel Hill, USA), gave a review of current genome-wide association studies (GWAS) undertaken within the large international collaboration network, The Psychiatric Genomics Consortium (PGC). The PGC currently has data from 376 investigators with over 36,000 schizophrenia cases and over 40,000 controls. They succeeded in identifying 128 genome-wide significant loci, and re-confirmed the involvement of DRD2 and NMDA receptor genes including

Studies of the prodromal state, high risk and early psychosis

Whether an attenuated psychosis syndrome (APS) should be its own entity was discussed and different viewpoints represented: Dr. Paolo Fusar-Poli (Institute of Psychiatry, London, UK) presented results on the reliability and validity of APS arguing that it is a much needed diagnostic category. Although the results were quite limited and inconclusive, there was a study showing that test–retest reliability of APS in DSM-5 field trails was good (intraclass kappa = 0.46; Regier et al., 2013). The

Studies of outcome

Dr. Peter Jones (University of Cambridge, Cambridge, UK) presented a ten-year outcome study of psychotic disorders: the AESOP-10 study. Schizophrenia was presented as an illness with a wide range of outcomes. The AESOP cohort followed 557 patients for 10 years, beginning with the first psychotic episode. A better course of illness was observed than that previously assumed, but social outcome was still poor.

Dr. Matti Isohanni (University of Oulu, Oulu, Finland) presented data from the Northern

Substance abuse

Various substances are thought to be risks for later psychotic illness. Various amphetamines have long been implicated. Dr. Callaghan (University of Northern British Columbia, Canada) presented results of a large population based study of patients in California with methamphetamine related problems, showing that methamphetamine abusers may have a higher risk of schizophrenia than population matched controls. The level of risk was as high as cannabis and greater than cocaine and opioid users.

Dr.

Violence and schizophrenia

Acts of violence by people with schizophrenia, particularly those who are untreated frequently make the news world-wide. Violent behavior is 4 times more frequent in people with schizophrenia than in the general population, although it is often noted that only a small portion of violent acts in total are completed by people with schizophrenia. Dr. Seena Fazel (University of Oxford, Oxford, UK) presented a systematic review and a meta-analysis of the risk and protective factors of violence in

General cognition

Dr. James MacCabe (King's College, London, UK) discussed a cognitive trajectory between ages 10, 13 and 18 and risk for psychosis in adulthood for a Swedish longitudinal cohort study. Previous studies postulated that cognitive deficits are assumed to result from neurodevelopmental changes (Murray and Lewis, 1987). He reported that poor cognitive function is associated with increased risk of depression; alcohol dependence, cardiovascular disease, and mortality. Further, findings suggested that

Social cognition, negative symptoms and their treatments

Dr. Michael Green (UCLA, Los Angeles, USA) contrasted high and low levels of social cognition in schizophrenia. Mentalizing, an example of high level social cognition, was impaired in schizophrenia, and associated levels of functional neural activity were also aberrant. In contrast, emotional mirroring, a lower level of social cognition, was not as profoundly affected in schizophrenia. Dr. Robert Buchanon (University of Maryland, USA) probed lower level social cognition further by comparing

Social defeat as a risk factor

It is widely accepted that a hyperactive mesolimbic dopamine system is associated with the positive symptoms of schizophrenia. While the causes of such a dysregulation are not clear, a hypothesis known as social defeat (Selten and Cantor-Graae, 2005) postulates that social risk factors such as migration or particular health conditions (experienced as a stigma) may induce social defeat, sensitize the mesolimbic dopamine system and increase the risk of developing schizophrenia. Dr. Andreas

Reward processing

Dr. Nicholas Simon and Dr. Bita Moghaddam (University of Pittsburgh, USA) reported dissociations in electrophysiological signals between adolescent and adult rats in the orbital frontal cortex (OFC) during the performance of a reward-driven operant behavior using single unit recording. Phasic neuronal activity in the OFC was increased in adolescent rats, during reward collection, whereas OFC activity was inhibited in adults.

Dr. Alison Adcock (Center for Cognitive Neuroscience, Duke University,

Studies using brain imaging

“Connectomics” is a new field that has emerged from brain imaging and provides an approach to understanding brain functioning based on data from shared imaging studies. His approach has been in development since 2005 with new concepts of trackable networks (“hubs and nodes”, “rich clubs”). Dr. Ed Bullmore (University of Cambridge, Cambridge, UK) gave a brief description of connectivity-based functional magnetic resonance brain image parcellation, which results in the statistical brain-map model

Oligodendrites and glia

Dr. Natalya Uranova (Russian Academy of Medical Sciences, Moscow, Russia) and her group have studied white and gray matter in prefrontal cortex of postmortem brains. They found evidence of a deficiency of glial cells and damage of oligodendrocytes in schizophrenia when compared with healthy controls. The frequency of pathological fibers in gray matter was increased in patients with predominately positive symptoms and in contrast, the frequency of altered fibers in white matter was increased in

Pharmacologic treatment

Dr. Anthony Grace (University of Pittsburgh, USA) proposed that a better approach to treat schizophrenia would be to target the site of pathology. He reported the effects of a selective GABA-A alpha-5 benzodiazepine in the MAM (methylazoxymethanol acetate) developmental model of schizophrenia. The drug decreased ventral hippocampal excitability, but the effect was not observed in animals treated with haloperidol for three weeks, which raises the possibility that clinical trials fail because the

The metabolic syndrome and other medication side-effects

People with psychotic disorders are at high risk for obesity, metabolic abnormalities, and early cardiovascular morbidity and mortality. Clinical trials demonstrate the role of anti-psychotic treatment on these parameters; however there is limited data on how anti-psychotic medication affects children and adolescents. This symposium seeks to bridge this knowledge gap. Dr. Cherrie Galletly (University of Adelaide, Adelaide, South Australia) presented the analyses of data from the 2010 Australian

Non-pharmacologic treatment

Studies have identified possible subgroups of patients who can obtain remission of psychotic symptoms without using anti-psychotic medication on a long-term basis. Dr. Ditte Gotfredsen (University of Copenhagen, Denmark) presented a Danish cohort study of patients diagnosed with schizophrenia spectrum disorders. At the 10-year follow-up, the proportion of patients who obtained stable remission without the use of anti-psychotic medication was 30% of the patient population. Remission was

Clinical staging for specific treatments in psychosis

Dr. Seetal Dodd (Deakin University, Burwood, Australia) discussed clinical staging in schizophrenia in the context of neuroprogression and neuroprotection. Dodd reviewed evidence of neuroprogression, describing changes in brain structure over time, and potential mechanisms of change. Dodd proposed that inflammatory oxidative and nitrosative stress (IO&NS) may be driving neuroprogression at a biological level (Brown and Derkits, 2010, Song et al., 2009). Strategies discussed involved agents that

Oxytocin, social cognition and schizophrenia

Dr. Robert Buchanan, presenting the findings of James Koenig (Maryland Psychiatric Research Center, Catonsville, USA), discussed the use of animal models to evaluate the known risk factors for developing schizophrenia and the implications for future treatments. The study exposed offspring rats to prenatal stress conditions by subjecting the rats' mothers to malnutrition, psychological stress, and immune system challenges during gestation. The prenatally stressed rats showed significant social

Modeling schizophrenia using patient derived cells

The use of patient derived cells as an in vitro preclinical model for brain disorders has become increasingly popular since the advent of induced pluripotent stem cells (iPSC) during the last decade (Takahashi and Yamanaka, 2006). The olfactory epithelium is another important source of patient derived neurons, although their potency is limited compared to iPSC (Mackay-Sim, 2013). Dr. Jane English (Royal College of Surgeons, Dublin, Ireland), reported analysis of olfactory derived neurospheres

Addressing measurement variability in schizophrenia research

Dr. Janet Williams (Columbia University Medical Center, New York, USA; SVP Global Science. MedAvante, New Jersey, USA) focused on issues related to variability in reporting symptom scores in clinical trials, and different types of reporting ranging from clinician-based assessment to self rating to centralized rating. Self-reporting by the patient, although firsthand information, is subjective and not reliable in patients with lack of insight and cognitive dysfunction. Ratings using

The road forward to deconstruction of the psychoses into biologically meaningful constructs

Dr. Werner Strik (University of Bern, Switzerland) discussed brain systems underlying thought disorder, hallucinations and catatonia. Strik proposed that formal thought disorder and auditory verbal hallucinations are related to abnormalities in certain neuronal systems, especially brain regions associated with language (e.g., left dominant fronto-temporal regions, such as Broca's and Wernicke's areas, and the arcuate fascicle). Strik presented research linking paranoid anxiety in schizophrenia

Role of funding source

A travel award program funded by NIMH (R13MH082446) and NIDA (R13DA036925) with additional funds from the Schizophrenia International Research Society provided partial coverage of expenses to students, some of whom took on the additional role of becoming rapporteurs for oral sessions.

Contributors

Each of the following authors, Olukayode Abayomi, Davide Amato, Candace Bailey, Byron Bitanihirwe, Lynneice Bowen, Shimon Burshtein, Alexis Cullen, Montserrat Fusté, Ana P Herrmann, Babak Khodaie, Sanja Kilian, Qortni A Lang, Elizabeth E Manning, Raffael Massuda, Milawaty Nurjono, Sarosh Sadiq, Teresa Sanchez-Gutierrez, Tamara Sheinbaum, Venkataram Shivakumar, Nicholas Simon, Anneliese Spiteri-Staines, Suttajit Sirijit, Nanna Gilliam Toftdahl, Sunali Wadehra, Yi Wang, Rebekah Wigton, Susan

Conflict of interest

The authors declare that there are no conflicts of interest.

Acknowledgments

The information in this report and the accuracy of each statement were the sole responsibility of each rapporteur and based on personal interpretation of what was heard. Where possible, speakers were contacted by the rapporteurs to verify statements made. Note that speakers mentioned were designated by the American custom as “Dr.” rather than the European custom of professor for senior academicians; thus the speakers' professorial status was not indicated.

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