Schizophrenia is a constellation of symptoms such as hearing voices, false beliefs and trouble with thinking and concentration, and its cause is not exactly known. In that sense, schizophrenia is still an enigma.
Studies of schizophrenia among groups of varied ethnicities across the world have shown associations of the disease with alleles (variant genes) related to the human leukocyte antigen – an important part of the immune system and related to a group of genes on chromosome six. However, the specific allele that was found to be associated with schizophrenia varied from group to group.
Recently, a pilot study on a south Indian, Tamil-speaking group consisting of 97 people with schizophrenia and 103 controls was carried out by Schizophrenia Research Foundation (SCARF) and Jeevan Stem Cell Foundation, in Chennai. The study, published in International Journal of Immunogenetics finds an association of specific alleles with the disease.
The paper shows an association between HLA variations and schizophrenia. “HLA is important for proper functioning of immune system and its variations can lead to immunological abnormalities. When the immune system acts up, as in autoimmune disorders, generating anti-NMDA receptor antibodies, for example, it can lead to schizophrenia,” says Dr Vijaya Raghavan, Consultant Psychiatrist, Research, SCARF.
Earlier studies indicate that different variants of specific genes (these variants are called alleles) may be involved in different ethnic groups.
“Studies done in Saudi Arabia and Tunisia have shown a particular HLA allele (DRB1*03) to be a risk factor for schizophrenia but in [a study involving a] Japanese population it was a different allele (DRB1*01) which predisposed to the disease condition,” says Dr S. Vani Laboratory Director, Jeenomics, Jeevan Stem cell Foundation, Chennai, in an email to The Hindu. She is a principal investigator of the present study along with Dr. Vijaya Raghavan.
The occurence of different variants itself is not a problem, as HLA genes are extremely variable and are very different across human populations, according to Prof. Sanjeev Jain, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bengaluru, who was not involved in the study. “The reasons are not entirely clear, but perhaps selection and ‘memory’ of past selection pressures (infections) play a role,” he adds.
In the present study, the researchers found that there was a higher frequency of HLA class I alleles ( HLA-A*01:01:01, -B*37:01:01 and -C*01:02:01) in individuals with schizophrenia as compared to the controls. Individuals carrying these alleles could be susceptible to schizophrenia.
They also found a negative correlation with some alleles (HLA-B*35:03:01 and HLA-DRB1*04:03:01) which were found in lower frequency in individuals with schizophrenia. These could be protective alleles in schizophrenia.
“The paper adds a valuable piece of information, on the relation between immune response genes and schizophrenia,” says Prof. Jain. “It is a small sample, and the associations are observed only in a subset (often females only); correcting for multiple comparisons may reduce the significance of the findings…” he adds.
The researchers also studied the type of amino acid present in the peptide binding groove of HLA molecule and compared it among patients and controls, finding a significant difference. “The amino acid level association study has not been reported earlier in schizophrenia,” says Dr. Vani, adding that the results need to be strengthened further using a larger sample size.