Mr John F. Nash Jr, an American mathematician who won the 1994 Nobel Prize for Economics, was killed on May 23, along with his wife, in a car crash in New Jersey. He was the subject of a book and a film, both titled A Beautiful Mind. For the greater part of his 86 years, he suffered from schizophrenia.
It was Swiss psychiatrist Eugen Bleuler who coined the term schizophrenia more than a century ago - deriving it from the Greek words schizein, indicating "splitting", and phren, meaning "soul, mind".
He meant for it to denote the "more or less clear splitting of the psychological functions... a dislocation of every faculty - of time, space and body" that seemed to him the essence of this disorder.
There have since been voluminous research, diverse opinions with some rejecting not only the biological roots but also the very existence of this disorder and a proliferation of treatments, some of which were desperate, bizarre and dangerous.
About the author
Professor Chong Siow Ann, 53, is vice-chairman of Medical Board (Research) at the Institute of Mental Health (IMH), a senior consultant psychiatrist and chairman of IMH's clinical research committee.
A member of Singapore's National Medical Research Council, he was also part of the Director of Medical Services Taskforce, which helped launch the first National Mental Health Blueprint and Policy in 2007.
He was the principal investigator of the recently completed Well-Being in Elderly Study. He also led the five-year Translational and Clinical Research Flagship Programme in Psychosis, which aimed to determine biomarkers - clinical and biological factors that can be measured - to identify and track the disease trajectory of schizophrenia and related psychoses.
He has won several research awards, including the Inaugural 2006 World Health Organisation and State of Kuwait Prize for Research in Mental Health Promotion, and the Clinician-Scientist Investigator Award from Singapore's Biomedical Research Council and National Medical Research Council in 2007. In 2008, he was given the National Healthcare Group Distinguished Award. That year, he and his team won the inaugural National Medical Excellence team award. And in 2011, he was awarded the Galloway Memorial Lecture and Gold Medal by the Academy of Medicine (Singapore).
He is a board member of the Singapore Millennium Foundation and Silver Ribbon (Singapore) and is a regular contributor to the Opinion pages of The Straits Times.
But Dr Bleuler's seminal observation that schizophrenia is a physical disease characterised by exacerbations and remissions where the sufferer is never completely "cured" holds true to this day.
Mr Nash developed schizophrenia when he was 30 and, by then, he was celebrated as one of the mathematical geniuses of his time.
What followed this meteoric rise was a descent that was both precipitous and protracted. He started hearing voices and believed he was being spied on, and that his career was being ruined by aliens.
He wandered for a while in Europe, sending postcards with cryptic messages to his wife and colleagues.
The manifestation of schizophrenia is multifarious. The auditory hallucinations and delusions he experienced are what are referred to as the "positive" symptoms of schizophrenia, emergent pathological experiences which are normally absent in the human psyche.
Two out of 10 people with schizophrenia have "negative" symptoms apathy and withdrawal, a profound not caring... or not caring about not caring", writes law professor Elyn Saks of the University of Southern California (who also has schizophrenia), in her book, The Centre Cannot Hold.
These negative symptoms are stumbling blocks, preventing people from living independently, finding and sustaining employment, forming personal relationships and even attending to the minutiae of daily living. Core to the illness too, are various impairments of many of the most important aspects of human cognition: attention, memory and reasoning.
There is still no effective drug treatment for these negative and cognitive symptoms. Researchers are turning to other approaches, including activation of certain regions of the brain using transcranial magnetic stimulation. This form of experimental therapy involves placing an electromagnetic coil over the head. The emitted magnetic pulses cause nerve cells in the brain to fire. It is still too early to determine its efficacy.
Schizophrenia is now considered a brain disorder or a disorder of brain circuits. Neuroimaging studies show differences in the brain structure of people with schizophrenia and several aberrant circuits have been identified, especially within the prefrontal cortex (the same area targeted with transcranial magnetic stimulation).
But what causes schizophrenia remains elusive, though what is certain is that the disorder results from a combination of genetic and environmental factors.
Early studies on twins have shown that as much as 80 per cent of the risk of developing schizophrenia comes from the genes (Mr Nash's parents didn't have schizophrenia but his son developed it).
Technological advances have enabled scientists to scan people's DNA to detect variations. As such studies require huge numbers of subjects, researchers worldwide have come together to form the Psychiatric Genomics Consortium.
This collaboration gathers genetic data from researchers from more than 80 institutions (including Singapore's Institute of Mental Health) across 25 countries.
The consortium published findings of the largest study of its kind last year in the journal Nature. This landmark study examined nearly 37,000 cases of schizophrenia and over 113,000 controls and found 108 different areas in the genome that are associated with the illness.
A number of genes within these areas are involved in the signalling between cells in the brain or in the immune system. This discovery offers some support for a previously hypothesised link between schizophrenia and immunological processes, raising the intriguing possibility that schizophrenia is, in part, a disorder of acquired immunity.
Cardiff University's Professor Michael O'Donovan, who led the research, said: "Finding a whole new bunch of genetic associations opens a window for well-informed experiments to unlock the biology of this condition and we hope, ultimately, new treatments."
Schizophrenia can rob a person of many things, a terrible toll which extends beyond that individual.
As in most cases of untreated schizophrenia, Mr Nash was incapacitated for decades. His condition began to improve when he was in his 50s.
He decided to "intellectually reject some of the delusionally influenced lines of thinking".
What helped significantly in his recovery was the support of family, friends and colleagues - and a wife who stood staunchly by him and provided a safe haven while he was ill. Therein lies an important aspect in the rehabilitation of someone with schizophrenia.
Studies have shown that patients in developing countries - India, in particular - seem to fare better than their Western counterparts in terms of social impairment and the duration of active psychotic symptoms.
This goes against the grain of the usual observation that, for most diseases, the richer and more developed the country, the better the patient outcome.
With schizophrenia, it is postulated that the different social-cultural milieu in developing countries with its greater dependence on family members for care and support, plus a more accepting community, is making the difference.
"It is, at the heart of things, a relationship," writes Prof Saks. "Often, I'm navigating my life through uncertain, even threatening, waters - I need the people in my life to tell me what's safe, what's real and what's worth holding on to."
Sadly, that is hard to come by for many people with schizophrenia.