Peter McGuffin, who has died aged 74, showed the importance of trying to establish how genetic and non-genetic factors act together to predispose people to psychiatric disorders: so-called gene-environment interplay. He was also one of the first to see the potential of the DNA revolution for understanding psychiatric disorders, and his work laid the foundations for the application of genomics to psychiatry.
It used to be assumed that depression could be divided into two forms: one the result of adverse circumstances (reactive depression) and the other the result of intrinsic factors such as genetic risk (endogenous depression).
Working at the Institute of Psychiatry in London during the 1980s, Peter showed that this is not the case, and that adverse circumstances and genetic risk frequently combine to increase the likelihood of depression.
These findings implied that biological treatments, such as antidepressants, as well as approaches to prevention and treatment based on reducing exposure to, or the impact of, adverse circumstances, are likely to be broadly applicable to depression.
He also found that adverse circumstances as well as depression tended to run in families. In subsequent work in Cardiff, he and his wife, Anne Farmer, an academic psychiatrist with whom he published many papers, showed that the explanation for this is complex, and adverse events reflect a combination of a hazard-prone lifestyle, a propensity to over-perceive adversity and a tendency for adverse events to be shared by relatives. This pointed to the need for a much more careful dissection of gene-environment interplay.
Psychiatric diagnoses are largely made based on clinical symptoms and signs rather than special investigations such as brain scans or blood tests. Nevertheless, it was widely believed that the different diagnoses identified distinct conditions.
Peter’s work with twins in the 90s challenged this conclusion when he showed that the genetic components of schizophrenia and bipolar disorder overlap, as well as there being components that are specific to each syndrome.
Subsequently, he observed a similar pattern of shared and specific genetic components in bipolar disorder and major depression. These findings were among the first to point to the now widely held view that our current diagnostic approaches do not define distinct disorders and that we need better ways of defining severe mental illness.
Until the 90s, research into the causes of childhood psychiatric conditions had focussed largely on social and psychological factors. Peter undertook influential research, again using twin studies, that demonstrated the additional need to consider biological and particularly genetic factors.
He showed that genes influence the occurrence of depressive symptoms in children, but that the genetic effects, while particularly important in adolescence, are much less so in younger children. He also conducted some of the earliest studies demonstrating the heritability of ADHD, paving the way for subsequent genomic work identifying specific genetic risk factors.
Born in Belfast, Peter was the eldest of three children of Martha (nee Burnison) and William McGuffin, a merchant navy officer. When William was appointed as a Trinity House pilot for the port of Southampton in 1959, they moved to the Isle of Wight. From Sandown grammar school he went to medical school at the University of Leeds, where he met Anne. They married in 1972, the year that he graduated.
In his subsequent training he became interested in genetics, and, while a junior doctor, together with Anne, carried out a genetic marker study of schizophrenia suggesting an association with the HLA system, a finding subsequently confirmed by genomic studies.
He completed his training as a psychiatrist at the Maudsley hospital, London, was awarded a Medical Research Council fellowship to study genetics, and subsequently became an MRC senior clinical fellow at the Institute of Psychiatry (now the Institute of Psychiatry, Psychology and Neuroscience and part of King’s College London).
He was appointed to the chair of psychological medicine at the University of Wales College of Medicine in Cardiff (now part of Cardiff University) in 1987, a position he held until 1998, when I succeeded him. During this period, he laid the foundations for Cardiff becoming a centre of excellence in psychiatric genetics and trained several young researchers who would go on to make important contributions to this field.
While in Cardiff, he was one of the founders of the International Society of Psychiatric Genetics and its second president. He was quick to see that the application of genomics would require large-scale international collaboration and established a European Science Foundation programme to bring together psychiatric genetics research across Europe in the 80s and 90s. This laid the foundations for international collaborations that continue successfully to this day.
From Cardiff he went on to head the MRC Social Genetic & Developmental Psychiatry Research Centre (SGDP) in London.
This was entirely appropriate, since his early work on depression had been a major stimulus for establishing this centre, whose aim is to integrate genetics with social and developmental research. He led the SGDP with great distinction, developing a supportive and nurturing environment that allowed its many stars to shine while also developing the careers of numerous students and junior scientists.
The SGDP expanded under his leadership, attaining international recognition for its excellence in multidisciplinary psychiatric research, and Peter successfully raised the funding for a new building to house it.
His skills as an administrator were recognised by his appointment in 2007 as dean of the Institute of Psychiatry, a post he held for three years, during which he rescued the IOP from a financial crisis. Through all this, he remained a productive researcher, retiring as director of the SGDP in 2012, and as a consultant psychiatrist in 2014. Two years later he was appointed CBE.
He is survived by Anne, their three children, Catrina, Liam and Lucy, and five grandchildren.
