In a series of studies since 1996, psychiatrists Dr Vishwajit Nimgaonkar of the University of Pittsburgh, and his sister, Dr Smita Deshpande of the Ram Manohar Lohia Hospital in Delhi, have teamed up with the Delhi University genetics department to investigate genes that are associated with schizophrenia. The research has focused on Caucasians and north Indians under the Indo-US Programme for Genetics and Psychoses.
They have found that predisposing genes are mostly similar in both ethnic groups but the genetic variants, which could have a role in developing schizophrenia, are largely different. Several clinical manifestations of the disease have also thrown up contradictions between the two ethnic groups — such as the likelihood of patients resorting to suicide, consumption of tobacco, marriage and bearing children.
Dr Deshpande, who heads the psychiatry department at RML Hospital and is principal investigator of the project in India, said: “While it is too early to say that the identified genes have a direct causal relationship with schizophrenia, we can say they definitely make people susceptible to the disease, increasing the risk factor. So, preventive steps can be taken from an early stage.”
Genetic or hereditary factors have a strong role to play but environmental and behavioural patterns equally influence the likelihood of the disease and this made the siblings compare the role of the same genes in different ethnic groups.
Dr Nimgaonkar, who heads the programme in genetics and psychoses at the University of Pittsburgh and is principal investigator for the collaboration in the United States, said: “We recognised early on that schizophrenia, like most common diseases, is caused by inherited as well as environmental risk factors. Therefore, it was appealing to examine the same sets of genetic variants in different environmental settings. As environmental factors in India and the US are very different, it provided an appealing setting for this type of study.”
The studies have been funded by the National Institute of Health (NIH) in the US and the Department of Biotechnology and Department of Science and Technology in India.
Under the collaboration, doctors have primarily studied genes responsible for the pathways used by neurotransmitters, endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. For each gene, single nucleotide polymorphisms — DNA sequence variations — and microsatellite markers have been compared.
Over 1,000 diagnosed schizophrenia patients and an equal number of control patients from India have participated in the programme since 1996. For some genes, an analysis of siblings and/or parents of the patients has also been done, and compared across the two ethnic groups.
The genetic mapping for Indian patients has been done under the supervision of Dr B K Thelma, professor of genetics in Delhi University. The role of every gene has been published as a separate paper — the latest on Neuregulin 1 (NRG1) has appeared in the January issue of the journal Schizophrenia Research.
A study to evaluate suicidal tendencies found that 42 per cent of patients in the US sample had “a serious desire to die during their most serious suicide attempt”. In the Indian sample, only 18 per cent of the cases reported similar intent.
Among Caucasians, male patients were “significantly more likely” to be single and childless compared to females — 77.8 per cent males of the US sample had no children. In contrast, there were no significant gender differences in the larger Indian sample.
Dr Triptish Bhatia, research psychologist at RML Hospital who performed the cognitive analysis, said these differences could also be attributed to environmental factors like the presence of strong family support in India.
Dr Prachi Kukshal, who performed the laboratory analysis of the genes for the NRG1 study, said: “This was one of the genes where we found significant similarities with US patients. The only other gene which showed similarity was the NOTCH 4 gene.”
According to Dr Deshpande, researchers expected the same polymorphisms to affect both populations since the symptoms appeared to be universal. “But in our studies so far, the genes which increase susceptibility appear to be different.”
Commenting on this, Dr Nimgaonkar said: “There are two possible explanations — any individual genetic risk is neither necessary nor is it sufficient to cause schizophrenia, so it is plausible that different sets of variants confer risk in two different samples. Also many of the variants we examined may be correlated with as yet unidentified variants. In other words, the variants we examined could be proxies for the actual causative variants.”