Is Mental Illness the Evolutionary Cost of Our Big Brain?

Mental health disorders are common. In America, about fifty percent of us will suffer from a mental health disorder in our lifetime. Unfortunately, efficacious treatments have been difficult to develop. One of the reasons that the development of therapies has been so difficult is that science lacks valid or reliable animal models of these mental diseases. The effectiveness of our therapies is often determined by the validity of our animal models. Finding treatments is more difficult because the human brain is incredibly complex and our understandings still incomplete. Another major issue is in identifying animal behaviors that correspond to “mental illness” behaviors seen in humans. For example, how does a mouse express anxiety? Do they even experience anxiety? Shouldn’t these psychiatric symptoms have placed the suffering individuals at an evolutionary disadvantage? Neuroscientists assume that brains work the same across all animals and that their dysfunctions are like ours.

A recent study investigated two common forms of mental illness in humans. Schizophrenia, characterized by delusions and hallucinations as well as impaired communication and social function, has a lifetime prevalence of roughly 0.5%. Autism shows characteristics like schizophrenia in its etiology and pathophysiology and has a similar global prevalence of roughly 0.5%.

Neuroscientists have speculated that the origin of schizophrenia and autism coincided with the divergence of modern humans. The theory is that two neurodevelopmental disorders still persist in us today because they are a maladaptive by-product of changes in the brain that led to the human-specific traits of language, social cognition, and interpersonal behavior, as well as increased brain size and improvements in connectivity (Crow, 1997).

Is this true? Are mental illness genes the evolutionary cost of having big smart brains?

A recent study tried to answer these questions by focusing on the molecular evolution of protein-coding genes that are known to be associated with schizophrenia and autism and comparing the presence of these genes across other mammalian species. The focus of the study was on primates, including chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, baboon, marmoset, and squirrel monkey. The study took advantage of recent genome-wide association studies that have identified multiple genomic loci associated with autism and schizophrenia. Using these datasets, it was possible to test whether mutations have occurred recently and uniquely in the evolution of humans, or whether similar changes are seen in other mammals.

Currently, more than 7500 genes have been shown to have linkage with schizophrenia. Seven hundred and twenty-seven were considered in the current study. This includes not only genes associated with the disease but also those that undergo expression changes in specific cases. There are more than 500 genes that have been associated with autism. Many of these gene mutations are found in both diseases.

In addition to a long list of primates, the study also quantified these risk genes in non-primates, including the platypus, opossum, Tasmanian devil, armadillo, Florida manatee, hedgehog, African elephant, European shrew, horse, white rhinoceros, pig, cow, sheep, killer whale, bottlenosed dolphin, cat, dog, ferret, giant panda, Pacific walrus, rabbit, chinchilla, naked mole-rat, Guinea pig, squirrel, hamster, rat and mouse.

Is there an evolutionary conservation among genes associated with mental health disorders?

The study found no significant indication that the relative occurrence of the risk genes for schizophrenia or autism has increased in humans as compared to apes and other primates. However, there was one interesting exception within the extended group of mammals examined: the cetacean bottlenosed dolphin (Tursiops truncatus). The dolphin branch showed significantly different evolutionary constraints on genes associated with schizophrenia and autism, as compared to almost all other mammals. This suggests that at some point in their evolution this species experienced significant changes in the genes that modern science associates with schizophrenia and autism.

Given the incidence of neurodevelopmental disorders, in recent years scientists have hypothesized that diseases like schizophrenia and autism are uniquely human. If this is true, identifying changes in specific genes underlying the diseases might help to identify the genetic changes that have led to the evolution of the human brain. In the current study, the genes associated with schizophrenia and autism were not associated with humans alone, but were seen in apes and old-world monkeys, and rather curiously, dolphins. Why? Toothed cetaceans and primates are known to share similar patterns of molecular evolution (McGowen et al., 2012), especially related to the relaxation of constraint on encephalization (i.e., developing big brains), and an overall greater brain-to-body mass ratio when compared to other mammals (Boddy et al., 2012). These genetic modifications may have contributed to enhanced social behaviors. So, apparently, dolphins, like humans, evolved big brains to support a complex social life. Whether they suffer from mental illness as well has not been determined.