Professor of Psychiatry and Molecular Medicine
Hofstra Northwell School of Medicine
Hempstead, New York, USA
Investigator, Center for Psychiatric Neuroscience
Feinstein Institute for Medical Research
Manhasset, New York, USA
Medical Director, Recognition and Prevention (RAP) Program
The Zucker Hillside Hospital, Department of Psychiatry
Psychotherapy and pharmacotherapy are the two most important first line treatments of adult depression. In this presentation I will present the outcomes of a series of meta-analyses on psychotherapy, pharmacotherapy and their combination in the treatment of depression. The data are based on a large meta-analytic project in which all randomized trials comparing psychotherapy to any other intervention or control group are systematically collected every year.
I will first present some of the most important findings for psychotherapies, and then focus more specifically on the meta-analyses we did of randomized trials comparing psychotherapy, pharmacotherapy and combined treatments.
I will show that combined treatment is more effective than either pharmacotherapy and psychotherapy alone, in moderate and severe depression. Comparable results are found in chronic depression. Acceptability of treatment is higher in psychotherapy and combined treatment than in pharmacotherapy. In this presentation I will also go into the problems of blinding in these trials and their effects on the outcomes, as well as on sponsorship bias.
Pim Cuijpers is Professor of Clinical Psychology at the Vrije Universiteit Amsterdam (The Netherlands. He is specialised in conducting randomised controlled trials and meta-analyses on prevention and psychological treatments of common mental disorders. Much of his work is aimed at prevention of mental disorders, psychological treatments of depression and anxiety disorders, and Internet-delivered treatments. Pim Cuijpers has published more than 900 peer-reviewed papers, chapters, reports and professional publications, including more than 700 papers in international peer-reviewed scientific journals. He is on the Thomson-Reuter Web of Science lists of the ‘highly cited researchers’ since the first edition of this list in 2014 (http://highlycited.com/).
Research on schizophrenia is challenging due to the heterogeneity of patients at the level of genetics, pathophysiology and clinical phenomenology. Following a shift in clinical approach towards preventive strategies, Dr Kim Do will discuss a translational program aimed at the identification of reliable, mechanism based biomarkers in the early phase of psychosis, allowing better stratification of patients, personalization of their treatment and monitoring of disease progression. She will show how the interaction of genes and environment risk factors during neurodevelopment converge on a hub made of neuroinflammation, NMDA receptor hypofunction, dysregulation of mitochondria, dopamine, and redox balance, inducing oxidative stress and reinforcing each other in a damaging feedforward mechanism (Hardingham &Do 2016; Steullet &al 2016). This would affect parvalbumin interneurons (PVI), including their associated gamma synchronization, and impact myelination, thus leading to structural and functional alterations of local microcircuits and long-range connections, essential for cognitive, affective and social functioning. Animal models of these various mechanisms showed that additional insults at peripuberty, but not in adulthood, lead to PVI impairments that persist until adulthood. This finding, highlighting childhood and peripuberty as critical periods of high vulnerability for environmental adverse insults, has led to the study of a differential impact of traumatic early- versus late- life events in early psychosis patients (Alameda & al2016). It emphasized the critical contribution of redox imbalance: high blood oxidation status, small hippocampal volume together with childhood trauma represented important markers for poorer psychopathological and neurocognitive profile, allowing patients’ stratification (Alameda &al 2018). Finally, the potential therapeutic effect of the antioxidant N-acetyl cysteine (NAC) observed in models (Duarte &al 2012, Cabungcal &al 2014) was tested in patients with chronic schizophrenia where it improved negative symptoms (Berk &al 2008) and NMDA and related potentials in EEG (Lavoie &al 2008). In early psychosis patients, NAC improved cognition (Conus &al 2018), as well as structural (Klauser &al 2018), and functional connectivity (Mullier &al 2019). The beneficial effect of NAC to reduce positive symptoms was also predicted by a baseline blood marker of redox imbalance, paving the way for biomarker guided treatment in early psychosis.
I started my career in basic research in chemistry (University of Neuchâtel, Switzerland), molecular biology (Federal School of Technology Zurich, ETHZ, Switzerland) and neurobiology (Brain Research Institute, Zurich University), where I highlighted the important role of neuro-glial interaction in excitatory amino acids and nitric oxide transmission. In 1999, I moved towards "bench to bed" research at the Center for Psychiatric Neuroscience (Department of Psychiatry, Lausanne University Hospital, CHUV). I set up a translational research program aimed at a better understanding of the causes and mechanisms leading to schizophrenia phenotypes in order to develop markers for early diagnosis, new drug targets as well as preventive and therapeutic measures. I established close collaboration with psychiatrists and developed a multidisciplinary team of excellent young researchers. More importantly, I achieved to promote and mentor a new generation of psychiatrists with combined clinical and neuroscientific expertise. Building on an innovative and pioneering hypothesis, I demonstrated that oxidative stress/redox dysregulation in interaction with NMDAR hypofunction, neuroinflammation and dopamine imbalance, induced among others by glutathione (GSH) deficit, may represent a "hub" on which both genetic and environmental risk factors converge during neurodevelopment, leading to the impairment of neural connectivity and synchronization, and to cognitive deficits as observed in patients. These mechanisms have been comprehensively documented in experimental models. Based on these relevant neurobiological data, I spearheaded clinical studies supplementing N-acetylcysteine (NAC), a precursor of GSH. In chronic schizophrenia patients, the «proof of concept» RCT with NAC, revealed for the first time an improvement in negative symptoms, as well as in the event related potential mismatch negativity in EEG and in local synchronization. A second RCT in early psychosis patients revealed a good target engagement for NAC as it increased brain GSH levels. NAC also improved neurocognition, specifically the processing speed, the “preattentional “component, NMDAR related, mismatch negativity, the white matter integrity in the fornix, and the resting state functional connectivity along the cingulum bundle. We also showed that in a subgroup of patients with a high blood oxidative marker at baseline, NAC significantly improved positive symptoms, in parallel with changes in the peripheral redox status. Our translational research thus paves the way for promising biomarker guided treatment. Besides these clinical trials with NAC, my translational work has also inspired other “pre-emptive” interventions in high-risk individuals for psychosis such as “ESPRIT” (Enhancing Schizophrenia Prevention and Recovery through Innovative Treatments). In parallel to my research activities, I also work on professional education and public outreach towards better care and cure of major psychiatric disorders.
Professor Emeritus of Psychiatry and Behavioral Sciences
Psychiatry & Behavioral Sciences, General Psychiatry
School of Medicine
Professor Patrick D. McGorry AO, MBBS, MD, PhD, FRCP, FRANZCP, FAA, FASSA, FAHMS is Executive Director of Orygen and Professor of Youth Mental Health at the Centre for Youth Mental Health, University of Melbourne. He is also a Founding Director of the National Youth Mental Health Foundation (headspace). Professor McGorry is a world-leading researcher in the area of early psychosis and youth mental health and his innovative research has played an integral role in the development of safe, effective treatments for young people with emerging mental disorders, notably the psychotic and severe mood disorders.
Professor McGorry has published over 800 refereed journal articles and book chapters and has edited nine books. He serves as Editor-in-Chief of Early Intervention in Psychiatry. He is a Fellow of the Australian Academy of Science, the Academy of the Social Sciences in Australia, and the Australian Academy of Health and Medical Science. He is current President of the International Association of Youth Mental Health and past President of the Society for Mental Health Research (2013-2017) and the Schizophrenia International Research Society (2016-2018). He has been the recipient of numerous awards, including the Society of Biological Psychiatry Humanitarian Award in 2019, the NHMRC Research Excellence Award in 2019, the Schizophrenia International Research Society Lifetime Achievement Award in 2018, the Brain and Behavior Research Foundation Lieber Prize for Outstanding Achievement in Schizophrenia Research in 2015, the NAMI Scientific Research Award in 2013, and Australian of the Year in 2010.
The challenge of development, research and implementation of novel technologies, ranging from big data to momentary assessment of mental variation to non-invasive neurostimulation, in the area of psychiatry is tremendous.
The stochasticity and non-determinedness of within-person mental variation makes that the promise of big-data applications, despite much heralded pilots, likely will not be fulfilled any time soon in clinical care.
Virtual reality and momentary assessment technology, on the other hand, may have some use in clinical care although there are issues of scale and usability.
Wireless neurostimulation technology may be useful in overcoming the issues of small-trial uncertainty and imprecise targetting of brain areas that are currently surrounding results of deep brain stimulation in psychiatry.
Importantly, the issue of technology in psychiatry should not detract from the fact that re-analysis of evidence-based medicine data in the area of psychiatry favours a model of relational care rather than specific technological ingredients mediating change required for favourable mental health outcomes.
Jim van Os is Professor of Psychiatric Epidemiology and Chairman of the Division Neuroscience at Utrecht University Medical Centre, Utrecht, The Netherlands, and Visiting Professor of Psychiatric Epidemiology at the Institute of Psychiatry, London, UK. He trained in Psychiatry in Casablanca (Morocco), Bordeaux (France) and finally at the Institute of Psychiatry and the Maudsley/Bethlem Royal Hospital in London (UK) and after his clinical training was awarded a three-year UK Medical Research Council Training Fellowship in Clinical Epidemiology at the London School of Hygiene and Tropical Medicine. In 1995, he moved to Maastricht University Medical Centre and in 2017 to Utrecht University Medical Centre
He is on the editorial board of European and US psychiatric journals such as Acta Psychiatrica Scandinavica, European Psychiatry, Psychological Medicine, Schizophrenia Research, Schizophrenia Bulletin, Early Intervention in Psychiatry, Epidemiology and Psychiatric Sciences, Psychosis Journal, The Journal of Mental Health and the Journal of Psychiatry and Neurological Sciences. He is also an Academic Editor at PLoS ONE.
In 2011, he was elected member of the Royal Netherlands Academy of Arts and Sciences (KNAW); in 2016 he became a Fellow at King’s College London; he appears since 2014 on the Thomson-Reuter Web of Science list of the worlds’ ‘most influential scientific minds’ of our time.
Over the period 2009-2015, Jim van Os was coordinator of a €12M EU FP7 IP project on gene-environment interactions in schizophrenia, and is also active in clinical gene-environment interaction research in depression and bipolar disorder.
He was a member of the Psychosis Group of the DSM-5 Task Force, and was co-chair of the APA DSM/ICD conference Deconstructing Psychosis.
He leads the Division Neuroscience at Utrecht University Medical Centre and works on the challenge of integrating people-centred care, technology and big data in the area of mental health. One of the areas he is involved in concerns the application of momentary assessment technology, virtual reality and big data analysis in psychiatry.