Have you ever noticed that when people get older their personalities change? That often mental diseases start surfacing during the old age? Why is it so?

There may be an evolutionary answer to these quirks of human life.

Scientists from two distinct disciplines, namely, cognitive science and genomics, have uncovered an interesting connection. Clinicians at NIMHANS, Bengaluru and geneticists from the Institute of Genomics at University of Tartu, Estonia, have conducted a study that points to an evolutionary basis to the manifestation of what are called severe mental illness (SMI), such as schizophrenia, bipolar disorder, dementia, obsessive compulsive disorder and addiction.

One important aspect that the scientists noted is that the uniform prevalence of the diseases across populations shows that there seemed to have been ‘little impact on selection for fitness.’ But what actually could have happened, as the research suggests, is that earlier selection could have created ‘a bias towards certain kinds of variation, that may cause disease later in life.’ So, the same processes which ‘may protect against inflammation or infection when young, only to predispose towards disease when one is older.’

The study compared the genetic sequences of exomes (the gene sequence regions that are translated into proteins) from individuals of 80 unique individuals from India coming from families with two or more individuals with severe mental illness and compared them against the African and the South Asian population.

Through a method called Population Branch Statistics (PBS) they identified 74 genes as candidates for positive selection. Positive selection or Darwinian selection is that process where a manifestation of a particular gene sequence gets selected because of the advantage it confers and starts to dominate in the gene pool of a species.

The genes thus identified for positive selection are those involved in ‘immunological and defense responses, including activation and regulation of interferon-gamma, cytokine and immune system, and different signaling pathways’ explains Dr. Ajai K. Pathak, the lead author of the study who is with the Institute of Genomics at University of Tartu.

Of these 74 genes identified for positive selection, almost 20 genes – that is 1/4th – have been found to be implicated in in the risks of schizophrenia, dementia, Parkinson’s disease etc and also general attributes such as intelligence and cognitive abilities. Dr.Pathak explained to Swarajya, ‘It is seen that genetic variants that cause mental illness or schizophrenia, many times are significant to cognitive ability and immunity of individuals.. And probably that's why these variants go through positively selection as they provide fitness in other cases.’

That is a very interesting Darwinian trade-off he points out, ‘Cognitive ability and immunity are more important and useful for survival than the diseases they bring along with.’

Another senior author of the paper, Dr. Mayukh Mondal said, ‘We also looked for evidence of Neanderthal genes in the sample, as the persistence of these ancient genomes in modern humans seems to correspond to some traits, as well as risk of disease.’

Dr. Pathak pointed out that while a few papers have already brought out the presence of Neanderthal elements in the South Asian population, in this study the team discovered Neanderthal derived genome in one of the genes - AHNAK2 gene. But while usually Neanderthal-derived elements have significance for adaptive value, this particular Neanderthal SNP has no such value in the context of the problem studied.

Dr. Meera Purushottam of NIMHANS, one of the authors, pointed out to the complex relations between neuro-immunological dynamics and the gene expression in the press release related to the paper: