Epidemiology in Schizophrenia Research: Moving from Trait to State of the Art

Image result for random news cartoonThis weekend marks the beginning of the 16th International Congress on Schizophrenia Research, the biennial international meeting this year taking place in the pleasant climes of San Diego, US. The meeting offers a chance to hear about groundbreaking research across a range of domains, including cell biology, animal models, cognitive neuroscience and psychiatric genetics. Moreover, there is a collaborative, friendly atmosphere, with junior and senior colleagues engaging in meaningful, critical discourse in and out of the formal sessions.

Despite the warm reception, the inclusion of epidemiological research in the Congress’ program has traditionally been cool. The 16th meeting will not reverse that trend, with one session devoted specifically to epidemiological research, with 10 talks crammed into a mammoth two and a half hour session on Saturday afternoon. To an outsider – or one of the forty or so people attending the sparsely populated ballroom – there will have been little to convince the field, or future programme committees, that epidemiology should move from a mild trait of schizophrenia research to a discipline which should be emblematic of the state of all science conducted within psychiatric and schizophrenia research.

Of the ten scheduled talks, two speakers did not show up, apparently with no prior apologies to the chair. Although there might have been genuine, unavoidable reasons for these cancellations, the lack of courtesy shown to the audience, other speakers, chair and meeting organisers manifests itself as apathetic; a trait that will rarely endear the discipline to future conference committees. To get an oral presentation accepted at a major international meeting should be viewed as an honour – if in doubt, one needs to look no further than the thousands of wonderful poster presentations at ICOSR, of whom I suspect any one would be delighted to receive a wider audience for their research.

Perhaps most concerningly, the quality of the epidemiological research on show was not able to shine through with all the wonderful, disciplined and principled methods that good epidemiological training should permit. In the age of big data, computational psychiatry and causal inference, the session was pockmarked by a series of poorly controlled studies, negative findings (of themselves potentially important, if we can establish that the findings are likely to be true, having considered the caveats of possible chance, bias and confounding) and problematic interpretation of results and their translational meaning for public mental health. There were some highlights in the session, notably some interesting work on polygenetic risk scores which appear not to confound associations between urban living and later psychosis risk, despite people in urban areas having slightly higher PRS for schizophrenia.

As a field, those of us in psychiatric epidemiology have a duty to do more. We need to engage with modern, state of the science with regard to causal inference and other techniques which potentially allow observational epidemiology to inform psychiatric research about aetiological mechanisms in the same way that experimental research has the potential to. Before that, good basic training in epidemiology can serve the whole field of schizophrenia research. Some of psychiatry’s greatest thinkers come from a background in epidemiological training and reasoning. Our core business as epidemiologists is not to show associations between risk factor X and outcome Y, but to bring to bear the principles of designing unbiased, unfounded and robust studies to answer clear research questions with carefully formulated hypotheses. On our MSc in Clinical Mental Health Sciences at UCL, which attracts 80 budding psychologists each year, the epidemiological training our students receive does not seek to teach them how to conduct an epidemiological study, but how to apply critical thinking and epidemiological reasoning to any research “evidence” they may encounter in their future careers. In this respect, our discipline should be proud; we can take a lead in research design across all areas of schizophrenia research, whether in the cell, the mouse or the human. Never has there been a more exciting time to work in mental health research; converging data from social neuroscience, neuropsychology, psychiatric genetics and epidemiology suggest a mix of genetic and environmental factors are critical to shaping psychosis vulnerability. Epidemiologists need to be central to those conversations.

Fortunately, great epidemiological research in schizophrenia does exist, addressing fundamental questions of variance in incidence, prevalence and causes worldwide. For example, forthcoming data from the international multi-site European Network of National Schizophrenia Networks Studying Gene Environment Interactions (EU-GEI) study has brought together a multidisciplinary team of researchers worldwide to test vital questions about how genetic and environmental factors may combine to increase psychosis risk. Such major consortia are never undertaken lightly, and the fruits of this study – amongst many other carefully designed epidemiological studies – should come to bear in future meetings. Until then, let’s promote and celebrate the uses of epidemiological reasoning throughout schizophrenia research, and be part of the conversation about the strength of evidence across the state of science in our field.

PsyLife attends MQ Mental Health Science Meeting

By Jean Stafford

This month the PsyLife team attended the annual MQ Mental Health Science Meeting. Following on from MQ’s recent ‘We Swear’ campaign (right), the meeting was focused on the role of research in improving our understanding of the aetiology, treatment and prevention of mental health problems. The event was interdisciplinary with speakers and attendees including psychologists, neuroscientists, epidemiologists, clinicians, policy makers, and mental health service users united by a shared interest in mental health.

Several speakers presented findings about risk factors for mental illness. We heard from Professor Louise Arsenault and Dr Jean-Baptiste Pingault about the association between bullying victimisation and future mental health problems. Both talks were very interesting, and highlighted the need to focus on both the experiences of being bullied as well as predictors of bullying itself. We also heard from Professor Ezra Susser, one of psychiatry’s pre-eminent epidemiological thinkers, on his work examining the potential role of prenatal micronutrient deficiencies in neurodevelopmental disorders in offspring. Professor Susser highlighted the need for randomised controlled trials with long-term follow-ups, and/or the use of techniques such as Mendelian randomisation to further explore this topic.

Numerous talks focused on depression in young people. We heard about Professor Myra Weissman’s pioneering work showing the transmission of depression across three generations. Dr Frances Rice discussed antecedents of depression in at-risk adolescents and highlighted the importance of future studies examining the role of social support in this group.

Several talks demonstrated the role that neuroscience can play in improving our understanding of mental health problems and developing interventions. Dr Susanne Ahmari presented her work on the neural circuits underlying obsessive-compulsive disorder and how this could translate to future treatments. Professor Carmen Sandi discussed the impact of genes and environment on brain development, demonstrating that rodents exposed to early life stress showed structural and functional brain alterations and were hyper-aggressive later in life.

Professor Jonathan Mill discussed how epigenetic research could help to improve our understanding of mental illness, but also warned us not to believe all the media hype. To much amusement and shock from the audience, Professor Mill presented some of the media misrepresentations and pseudoscience surrounding epigenetics, including the advertisement of epigenetic spray and an epigenetic orthodontist!

It was interesting to hear several talks on psychosis from different perspectives. Professor Mary Cannon showed that children and adolescents who experience psychotic symptoms are at increased risk of developing future mental health problems, including schizophrenia, although these symptoms have a low positive predictive value and intervening early could therefore be problematic. Dr Graham Murray showed that, in people with chronic schizophrenia, the jumping to conclusions bias can largely be attributed to noisy decision making, whereas those with first-episode psychosis seem to genuinely jump to conclusions: perhaps due to perception of a high cost of gathering information.

Of great interest to our lab was Professor Andreas Meyer-Lindenberg’s talk on the relationship between the social environment and the brain. The talk focused on urbanicity and migrant status: two well-established environmental risk factors for psychosis identified in epidemiological research. Urban birth, urban living, and migrant status were found to be associated with structural and functional differences in brain regions implicated in social stress processing (such as the amygdala and the perigenual anterior cingulate cortex). These findings demonstrate how associations observed in epidemiological research can be further examined using psychology and neuroimaging techniques. However, participants in most of these studies were from the general population. It would be of great interest to see whether findings replicate in those with psychosis.

One further highlight of the conference was the thought-provoking panel discussion entitled ‘What good is a diagnosis?’. Megan Haste, a mental health blogger and service user, described the relief she felt when she was given a diagnosis, and Professor Susser pointed out that diagnoses can be helpful for constructing a personal narrative around mental health problems. However, he also discussed the challenges of using the same diagnoses across different cultures given cross-cultural variation in perceptions of mental illness. Professor Wessely highlighted the importance of diagnoses for providing appropriate treatments for patients, whereas Professor Wolpert suggested that it may be more beneficial to focus on a given patient’s symptoms and treatment needs, rather than categorisation.

The event also included a poster session where early career researchers presented work spanning a wide range of topics. I presented findings from a review of the incidence of very late-onset psychotic disorders, which I am carrying out as part of my PhD. This provided an opportunity to receive feedback on my work and to hear about current research on psychotic disorders, as well as other mental health problems, from across disciplines.

Overall, the meeting was a great opportunity to hear about some of the latest research targeting mental health problems in young people. The importance of addressing this issue is discussed from a clinician’s perspective by Dr Daria Monteforte, a psychiatrist from Verona currently on a research visit at PsyLife:

“As a medical doctor working in the field of mental health I really appreciated the choice of subject and the interventions discussed. It is now widely understood that psychiatric disorders often affect patients during youth, sometimes from childhood, and that only a small proportion of those in need are diagnosed and treated. A delay in intervention can undermine future opportunities for young people because of the destructive impact that mental health problems can have on many areas of life, including: building relationships, school, university, and career. More and more patients and their relatives are struggling with barriers to accessing services, diminishing resources in mental health services, and concerns about stigma. We work with many young adults who may have had a better prognosis if they had received the support they needed as children and adolescents. Research and discussion about mental health in young people helps us to understand the scale of the problem, what these particular patients need, and in which direction we should focus our efforts.”