After 6 years behind bars, Tip was executed for the murder of William McCarmant in 1894. It was deemed Tip was mentally unstable and posed too great a risk to the public. Yet Tip didn’t spend his time on death row in a Victorian asylum; he spent it in a zoo. Tip was an 18-year-old circus elephant, which begs the question; “to what extent can animals suffer from mental illness?
The question stretches beyond the desire to diagnose our pets’ psychological maladies. It’s central to both progressing our understanding of, and developing novel treatments for neuropsychiatric disorders such as schizophrenia, clinical depression and bipolar disorder. The practical and ethical limitations of experimenting on humans means animal models are a critical tool in researching mental illness.
So what does the science say? It suggests animals might suffer versions of the mental illnesses that humans experience. Genetically engineered mice over-groom to the point of self-injury, a behaviour thought to correspond with obsessive-compulsive-disorder in humans. Working horses can suffer from depressive syndrome, becoming withdrawn and indifferent to novel stimuli in their home environment. Indeed, a recent study showed depression can arise in macaques under socially induced competition (e.g. for food, sex etc.), with certain group members exhibiting a string of abnormal behaviours from different walking patterns to solitary huddling.
Image taken from Fan Xu et al. (2015) Photographs taken by Dr. Fan Xu.
In the image above, red arrows show healthy controls, blue arrows show behaviours of depressed subjects.
However, it requires an intellectual leap to say that animals suffer from the same mental illnesses as some humans. A lot of the symptoms used to establish psychiatric diagnoses in humans (e.g. delusions, hallucinations, dejection) are impossible to detect in animals. This means that whilst animal models of mental illness can be quite sophisticated, they are unlikely to fully mirror their human neuropsychiatric disorder equivalents. Take the “OCD mice” for example: it’s a tad anthropocentric to assume the mice are experiencing the same disorder as humans when we are clueless of the cognitive and emotional context of the mice.
Schizophrenia is one such example of a disorder restricted to humans only. The devastating disorder affects about 1% of the population and is characterised by an interplay of symptoms from hallucinations and impoverished speech to memory deficits. Historically, sufferers have been subjected to atrocious stigmatization. Ernst Rüdin, a Swiss psychiatrist and advocate of schizophrenia being determined by a single gene, justified the horrific sterilisation and murder of people with schizophrenia and as late as 1970 there was a movement which outright rejected the disorder’s existence.
A meta-analysis of 150,000 people by the Psychiatric Genomics Consortium (PGC) recently established that schizophrenia is a disease caused by many genes functioning in unison, ousting any older claims that it was a disorder without biological roots. This study implicated 108 regions (loci) of DNA associated with schizophrenia. Dr. Joel Dudley and colleagues sifted through the information provided by the PGC to gain important insights into the genetic architecture underlying schizophrenia.
Dudley was interested in human accelerated regions (HARs): short signposts in our genomes which hastily mutated in humans but have remained relatively conserved in non-humans. Dudley et al. first found that HARs were closer than should be expected by chance to the loci that the PGC had proved were associated with schizophrenia. HARs regulate the expression of genes, hinting that the HARs were regulating schizophrenia genes in some way. In addition, these HAR-associated schizophrenia genes were under stronger evolutionary selection than other schizophrenia genes. This suggests some selective advantage to the human variants of schizophrenia genes which outweighs (or neutralises) the occupational hazard of developing the disorder.
Although the researchers’ intention was to better understand the genetic forces underpinning schizophrenia, they also forwarded a hypothesis which explained the evolutionary persistence of the disease and its mysterious exclusivity to humans. They found HAR-associated schizophrenia genes to be involved in the expression of other genes in the prefrontal cortex, an area of the brain involved with high-order thinking which, when impaired, might contribute to psychosis. Furthermore, the culprit human variant genes were found to be involved in such neurological functions in the PFC as synaptic transmission of the neurotransmitter GABA. GABA-related abnormalities in the brain are often found post-mortem in schizophrenic brains and are associated with some of the cognitive deficits characteristic of schizophrenia.
In Dr. Dudley’s words: “GABA is critical to speech, language and many other aspects of higher-order cognition. The fact that our evolutionary analysis converged on GABA function in the prefrontal cortex seems to tell an evolutionary story connecting schizophrenia risk with intelligence.” Put another way, it could be that the human-specific genomic alterations which enable our complex thought were a bittersweet genetic endowment. United with our brain’s complex genetic architecture is the occasional neurological glitch, predisposing some of us to schizophrenia and maybe other neuropsychiatric disorders.
It’s not the first time that schizophrenia’s roots have been assigned to our evolutionary past. This study posited that the disproportionately high energy consumption of the human brain might increase humans’ susceptibility to schizophrenia. But Dudley’s study is the first genome-wide molecular evaluation of the hypothesis that maybe our brain’s marvellous cognitive ability came at a price.
Every silver lining has a cloud.