Peter McGuffin, who has died aged 74, showed the importance of identifying how genetic and non-genetic factors work together to predispose people to psychiatric disorders: the so-called interplay of genes and environment. He was also one of the first to recognize the potential of the DNA revolution for understanding psychiatric disorders, and his work laid the foundation for the application of genomics in psychiatry.
It was previously believed that depression could be divided into two forms: one due to adverse circumstances (reactive depression) and the other due to intrinsic factors such as genetic risk (endogenous depression).
Peter worked at the Institute of Psychiatry in London in the 1980s and showed that this is not the case, and that adverse conditions and genetic risks often combine to increase the risk of depression.
These findings implied that biological treatments, such as antidepressants, as well as prevention and treatment approaches based on reducing exposure to or impact of adverse conditions, are likely to be broadly applicable to depression.
He also discovered that adverse circumstances and depression often run in families. In subsequent work in Cardiff, he and his wife, Anne Farmer, an academic psychiatrist with whom he published many articles, showed that the explanation for this is complex, and that side effects reflect a combination of a risk-prone lifestyle, a tendency towards excessive behavior. – Perceiving adversity and the tendency for adverse events to be shared by family members. This pointed to the need for a much more careful dissection of gene-environment interactions.
Psychiatric diagnoses are made largely on the basis of clinical symptoms and signs, rather than on special testing such as brain scans or blood tests. Nevertheless, it was generally accepted that the different diagnoses identified different conditions.
Peter’s work with twins in the 1990s challenged this conclusion when he showed that the genetic components of schizophrenia and bipolar disorder overlap, and that there are also components specific to each syndrome.
He then 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 widespread view that our current diagnostic approaches do not define discrete disorders and that we need better ways to define serious mental illness.
Until the 1990s, research into the causes of psychiatric disorders in children largely focused on social and psychological factors. Peter conducted influential research, again using twin studies, which showed that additional consideration should be given to biological and especially genetic factors.
He showed that genes influence the occurrence of depressive symptoms in children, but that the genetic effects, although especially important in adolescence, are much less the case in younger children. He also conducted some of the first studies demonstrating the heritability of ADHD, paving the way for subsequent genomic research identifying specific genetic risk factors.
Born in Belfast, Peter was the eldest of three children of Martha (née Burnison) and William McGuffin, a merchant navy officer. When William was appointed 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 he graduated.
During his subsequent training he became interested in genetics, and while a junior doctor, together with Anne, conducted a genetic marker study on schizophrenia, which suggested a link with the HLA system, a finding subsequently confirmed by genomic studies.
He completed his training as a psychiatrist at Maudsley Hospital in 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 partly MRC). by King’s College London).
In 1987 he was appointed Professor of Psychological Medicine at the University of Wales College of Medicine in Cardiff (now part of Cardiff University), a position he held until 1998, when I succeeded him. During this period he laid the foundation for Cardiff to become a center of excellence in psychiatric genetics and trained several young researchers who would go on to make significant contributions to this field.
While in Cardiff he was a founding member of the International Society of Psychiatric Genetics and its second president. He quickly recognized that the application of genomics would require large-scale international collaboration and set up a European Science Foundation program in the 1980s and 1990s to bring together research into psychiatric genetics across Europe. This laid the foundation for international collaborations that continue successfully to this day.
From Cardiff he became head of the MRC Social Genetic & Developmental Psychiatry Research Center (SGDP) in London.
This was entirely appropriate, as his early work on depression had been a major impetus for the establishment of this center, which aims to integrate genetics with social and developmental research. He led the SGDP with great distinction, developing a supportive and nurturing environment for its many stars to shine, while also developing the careers of countless students and young scientists.
The SGDP expanded under his leadership and gained international recognition for its excellence in multidisciplinary psychiatric research, and Peter successfully raised funding for a new building to house it.
His skills as an administrator were recognized by his appointment in 2007 as Dean of the Institute of Psychiatry, a position he held for three years, during which time he rescued the IOP from a financial crisis. Despite all this, he remained a prolific researcher; he retired as director of the SGDP in 2012 and as 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.