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New Delhi: Schizophrenia, with its dramatic manifestations, has often garnered attention from all areas of interest, from scientists to writers and filmmakers. A disabling disease that affects 1% of the world population, schizophrenia causes deficits in thought processes, perceptions and emotional responsiveness. A person with schizophrenia can suffer from hallucinations that involve seeing, hearing and smelling imaginary things, and experience the paranoia of being targeted.

But unfortunately, schizophrenia—considered one of the top 10 most disabling diseases—is poorly understood, preventing the development of better cures and diagnostic tools.

What is known is that a mix of genetic and environmental factors causes the disease. Scientists around the world have over the years identified a number of genes that are behind the disease. In January, the authors of two studies published in Nature magazine about gene sequencing of schizophrenic patients said both papers demonstrated genome sequencing will continue to be a powerful tool in the study of schizophrenia. But many more samples will need to be sequenced before the genetics of this complex disorder can be fully understood.

“Increasingly, it is becoming established that adverse events during the developmental period of a baby in the womb might have a major impact on the etiology of this disorder," said Venkatasubramanian Ganesan, additional professor of Psychiatry at National Institute of Mental Health and Neuro Sciences (Nimhans), Bangalore.

“These genetic factors and prenatal adverse events certainly add to the vulnerability of a person to develop schizophrenia. In addition, it is believed that further interactions involving stressful environmental factors during early development (childhood and adolescence) along with certain neurobiological factors result in abnormal brain development. Together, all these factors culminate in abnormalities related to chemicals that mediate brain functions and precipitate the onset of this disorder typically in adolescence or early adult years," he added.

These factors were confirmed after studies in 1998 and 2005 showed that during the 1944-45 Dutch Hunger Winter when a sharp and time-limited decline in food intake occurred in Holland, the most exposed group of children conceived during the famine showed a two-fold increased risk of schizophrenia. Similar results were proven for children conceived during the 1959-1961 famine in China, thus establishing that nutritional deficiency during a pregnancy has an impact on the child’s vulnerability to schizophrenia in the pre-adolescent days.

Not much is understood about the hallucinations either, according to Sanjeev Jain, professor of psychiatry at Nimhans. “If you see the brain of a schizophrenic, the same parts of the brain light up that light up when you hear real voices. The brain seems to be using oxygen in a very different way," he said.

Scientists at Nimhans have been involved in brain imaging studies examining schizophrenia patients using a variety of techniques such as magnetic resonance imaging (MRI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI). Venkatasubramanian explained that the brain of a schizophrenia patient is reduced in overall volume with increase in the size of the ventricles (parts of the brain that contain cerebrospinal fluid). The team also concluded that certain parts of the brain, such as hippocampus, superior temporal gyrus, prefrontal cortex, inferior parietal lobule, basal ganglia and thalamus, are considered more responsible for the development of this disorder.

“Our research has established widespread brain abnormalities in structure, function, neurochemical profile as well as connectivity between different brain regions in schizophrenia patients," Venkatasubramanian said.

Several researchers say that evolution may be one of the forces behind the development of schizophrenia. Venkatasubramanian is one of the believers of this theory.

“One of the strong reasons behind this view is that despite adverse fertility, this disorder is still persistent over the past thousands of years. Given the strong genetic basis of this disorder, one would expect this to have become extinct a long time ago—this puzzling observation is called the central paradox of schizophrenia," said Venkatasubramanian.

Research studies by many experts, including those from Nimhans, show that the disorder might be related to various evolutionarily significant factors like acquisition of complex language, creativity or exceptional skills, and protection from certain disease conditions like cancer.

“Certain anecdotal observations like Albert Einstein’s son having suffered from schizophrenia, Isaac Newton developing symptoms of this disorder late in his age, Nobel laureate John Nash having schizophrenia, along with population-based studies showing increased prevalence of exceptional skills in relatives of schizophrenia patients support the creativity-insanity link," said Venkatasubramanian.

He said such a link with adaptive evolutionary factors might have facilitated the persistence of this disorder. “I am of the view that the evolutionary biological factors that underpin the development of exceptional skills or those that influence various medical diseases interact with the risk for developing schizophrenia," said Venkatasubramanian.

With regards to treatment of this disorder, anti-psychotic medication needs to be complemented with intensive psychological, social and adaptive lifestyle-based interventions with active contribution and involvement from family members.

“In India, the biggest problem is access to treatment for schizophrenic patients and late diagnosis. The resources for the illness are so poor and they are detected so late. The longer you remain untreated, the longer it will take to treat a patient," said Sujit John, research coordinator at Schizophrenia Research Foundation (SCARF), India.

There are a mere 4,000 trainedpsychiatrists for the whole population, 70% of whom are in cities, according to SCARF. India has 0.301 psychiatrists per 100,000 population, according to the World Health Organization.

There are only 10,000 psychiatric beds in general hospitals across India. “The generally accepted figure in India is that 90% of the schizophrenic patients in India do not receive appropriate treatment," John said. “There is also a huge stigma for schizophrenia patients, especially women, who are often divorced if found to be schizophrenic, and are shunned by families."

A major problem with schizophrenia medication is the side-effects, which can include drowsiness, restlessness, muscle spasms, tremor, dry mouth and blurred vision. The degree of side effects varies with medication.

“I would say treating a patient with schizophrenia is a challenge in terms of balancing between the science, considering the host of complex bio-psycho-social factors and medication related side-effects, and the art which involves choosing the optimal combination of treatment options that will address the needs of a person with schizophrenia as an individual," said Venkatasubramanian.

Studies over the years have substantially increased the scientific community’s understanding of the development of the disease. However, given the complex nature of schizophrenia and especially the varying clinical manifestations of this disorder in different patients, these research findings are yet to be transformed into clinical applications for diagnosing schizophrenia, according to Venkatasubramanian.

“ECG (electrocardiography) machines are only 40 years old, but heart attacks have been known for 400 years. Schizophrenia is a recently discovered disease," said Jain of Nimhans. “Technology might be too imprecise to get to the bottom of the disease, and the scientific accuracy might be less, but that does not mean the disease does not exist. We don’t know enough, but with advancements in technology, and systems biology, we will know more."

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