We used to have a dog, Hubert Beagle-Basset, who suffered from a severe case of separation anxiety. Whenever we came back home, even if we had only been gone for a short period of time, he used to run joyous circles around the dining room table—we used to call them victory laps (My humans came home! My humans came home!)
Our present dog Sherman, a big black lab, suffered from depression when we got him from the San Francisco SPCA shelter. He had already been there twice. We tried to let him know that he had hit the jackpot coming to live with us. But he was so insecure that he didn’t wag his tail for a whole year.
He’s fine now—he wags his tail a lot—but he is still pretty “weird.” If he isn’t out for a walk or eating, he is hiding out in our closet. He loves the small dark space and he loves being alone.
I am pretty sure Sherman would qualify for the canine diagnosis of an introverted personality. Ask any veterinary psychiatrist (yes, they exist) and they will tell you that dogs suffer from almost every psychiatric disorder that afflicts humans—all except one: schizophrenia.
If we played the quasi-philosophical game of “what defines us as human?” my first choice would be our capacity to hope and the ability to plan for the medium and distant future. But a close second is the uniquely human malady of schizophrenia.
Now, I am not being flippant. No other species is “endowed” with this psychiatric disorder. Interestingly, as I have written before, schizophrenia is associated with creative genius, a characteristic that is also uniquely human. What’s the connection, if any?
Related content: Does Your Dog Have Personality? But of Course!
Genetics of schizophrenia
If you wanted to identify all the genes that are somehow associated with schizophrenia, you would do the obvious. That is, compare the whole genome of people with schizophrenia to that of people without the disorder. That sounds easy, but actually it’s quite an undertaking.
Despite the huge strides made in DNA sequencing, the accurate sequencing of a whole human genome is still far from trivial. Also, you would need to sequence thousands of individuals both with and without the disorder.
Why the need for massive numbers? Because the genome of every individual is, well, uniquely individual. This is because we are all continuously subject to random mutations, the vast majority of which are ‘neutral’, neither beneficial nor deleterious.
Furthermore, we all live in different environments. And as it turns out, the environment can exert its influence on our genes by inducing chemical changes, called epigenetic changes, that affect the expression of specific genes.
So, to get to the “core genome,” we have to cancel out all the “noise” in any individual genome. This can only be done by determining the sequence of thousands of genomes.
No single scientist could possibly accomplish such an undertaking. It would require the collaboration of hundreds of laboratories around the world. But, indeed this was done.
The Schizophrenia Working Group study
A study, published in Nature, is the result of a collaboration among more than 300 scientists from 35 countries. This collaboration is called the Schizophrenia Working Group of the Psychiatric Genomics Consortium. The researchers compared the whole genomes of nearly 37,000 people with schizophrenia with more than 113,000 people without the disorder. And the results?
They found 128 gene variants associated with schizophrenia, in 108 distinct locations in the human genome. The vast majority of them had never before been linked to the disorder.
Bear in mind, a study like that cannot identify specific genes that cause the disease. But, it does provide a list of genes that will become the subject of detailed investigations as to their role in the causation of the disease. But with such a long list of genes, where do you start?
An evolutionary approach to the genetics of schizophrenia
Why is schizophrenia uniquely human? Researchers at Mount Sinai Medical School came up with a brilliant evolutionary approach to the question.
Schizophrenia is relatively prevalent in humans despite being detrimental. The condition affects over 1% of adults. So it must be associated with something that confers a selective advantage. And that “something” must be uniquely human.
Indeed, there are segments of our genome that are called human accelerated regions, or HARs. HARs are short stretches of DNA that while conserved in other species, underwent rapid evolution in humans following our split with chimpanzees. This is presumably because they provided some benefits specific to our species.
What do HARs do?
The genes found in those HAR stretches don’t code for proteins, instead, they regulate other genes in their vicinity. Could some schizophrenia-associated genes happen to be in the neighborhood of some HARs?
To find out, Dudley and colleagues used data culled from the Psychiatric Genomics Consortium that I mentioned above. They first assessed whether schizophrenia-related genes sit close to HARs along the human genome—closer than would be expected by chance.
It turns out they do, suggesting that HARs may play a role in regulating genes contributing to schizophrenia. And, what makes those genes even more interesting is that they were found to be under stronger evolutionary selective pressure compared with other schizophrenia genes. This implies that the human variants of these genes are beneficial to us in some way despite harboring schizophrenia risk.
To help understand what these benefits might be, Dudley’s group then turned to gene expression profiles. Gene sequencing is important, but it can give us only their structure, not their function. So the most we could say about them is that they are associated with the disease.
To find a causal connection we need to know the function of the gene when it is turned on and off, and in what tissues. That’s what gene profiling does.
Dudley’s group found that HAR-associated schizophrenia genes are found in regions of the genome that influence other genes expressed in the prefrontal cortex (PFC). Inputs into this area arrive from the rest of the brain and are integrated to carry out higher cognitive functions that we associate with being human, such as judgment, planning, decision making, and the like.
Many of those inputs are mediated by the neurotransmitter dopamine. Others are mediated by acetylcholine, and norepinephrine, and glutamate. But all of them are excitatory. They deliver a positive signal.
Nothing in biology is unregulated
Now, nothing in biology is left unchecked or unregulated. Too much of a good thing can be highly disruptive to the stability of the system. Just imagine if a whole cacophony of signals assaulted the PFC. Ideas rushing in uncensored, images flooding in unfiltered, voices unrelentingly filling our consciousness—we would go crazy.
To prevent this dismal state of affairs, we need an inhibitory system, a yang force to counteract the yin, if you will.
Thankfully, we have such a system. There are neurons that secrete an inhibitory neurotransmitter called GABA, which tamps down the cacophony of the various signals and maintains our sanity.
So what did the gene profiling of those HAR-associated genes find? They found that they are involved in various essential human neurological functions within the PFC, including the synaptic transmission of the neurotransmitter GABA.
Not surprisingly, GABA’s impaired transmission is thought to be involved in schizophrenia. If GABA malfunctions, dopamine runs wild, contributing to the hallucinations, delusions, and disorganized thinking common to psychosis. In other words, the schizophrenic brain lacks restraint.
Schizophrenia: It’s all about balance
Very few things in biology are all-or-none, like a light switch. They are more like a rheostat, dimming or brightening the light. In biology, we also refer to it as a dose-response. If you have a strong stimulus, you get an appropriately strong response.
So would it be much of a stretch if, neurobiologically speaking, creative geniuses may have a hyper-stimulated dopamine system, or alternatively, an underactive GABA system?
If so, it could go a long way toward understanding their almost universal description of ideas flooding in, of visualizing sounds, of hearing conversations in their heads? And how far is that from crossing the threshold into the incapacitating pathology that we label schizophrenia?
Psychiatric disorders and imbalance
Of course, we still don’t know for a fact that all this really happens in the brains of creative people. But one thing does seem clear, many psychiatric conditions, in addition to schizophrenia, may be related to the imbalance of signals reaching the PFC.
Paranoid ideation is closely related to schizophrenia. And, OCD, despite its frequent portrayal as a behavioral quirk, is a vicious and debilitating mental illness, with some similarities to the experiences of schizophrenia.
People with OCD can have some of the same dark ideas, thoughts, and images as someone with schizophrenia, but the person with OCD is fully aware that they generate the thoughts themselves.
The bottom line: Why dogs don’t get schizophrenia
The studies we cited reveal how wonderfully complex the human brain is, and how exceptional the human species is. They also make it is increasingly clear, that schizophrenia and its associated psychiatric disorders, are part and parcel of us becoming what we are today. They are the price we pay for our wonderfully crafted, uniquely human brain.
More by the author:
Age-Related Memory Loss and What Can You Do About It?
Want to Know Why You Procrastinate?
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This post was first published on 09/20/15. It has been reviewed and updated by the author for republication on 3/22/2020
Dov Michaeli, MD, PhD
Dov Michaeli, M.D., Ph.D. (now retired) was a professor and basic science researcher at the University of California San Francisco. In addition to his clinical and research responsibilities, he also taught biochemistry to first-year medical students for many years.
During this time he was also the Editor of Lange Medical Publications, a company that developed and produced medical texts that were widely used by health professionals around the world.
He loves to write about the brain and human behavior as well as translate knowledge and complicated basic science concepts into entertainment for the rest of us.
He eventually left academia to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early-stage biotech company that developed products to improve post-surgical pain control.
Now that he is retired, he enjoys working out for two hours every day. He also follows the stock market, travels the world, and, of course, writes for TDWI.
Interesting article. We have a three year old Golden Retriever that has a few things wrong with him. He is a loving dog, but is scared of his own shadow. If you open the door in the room he is in he will bark then run and hide. He is always looking around as if something is after him and that brought me to think he has Paranoia or if he suffers from Schizophrenia. He’s been to the vet many times and has been prescribed Trazadone to calm him down but it mostly makes him sleepy and we don’t like to give it to him as we want a happy dog. If he is put outside, to use the restroom, once finished he will pace the back door to come in. He is such a beautiful dog and is a very good one and we will keep him for life, but I wish there was something that could help with his Anxiety, Paranoia or what ever bothers him. Until then we’ll just love him like our other dogs and like I tell the wife he’s just our special needs little one. :)
Thanks for sharing this, Tim. I am so glad you love him like all of your other dogs. He seems he has special needs and you are happy to accommodate (and love) him.
Our prior dog had been returned to the shelter twice before we adopted him, despite being a gorgeous, loving pure black lab. It took him a year with us before he wagged his tail. He hit the jackpot when he came to live with us because we work from home, take long walks every day, and loved him greatly. To his dying day he was never “normal” – he seemed more autistic to us than schizophrenic. He was madly in love with my husband (but only tolerated me). However, I think, in the end, he had a good life and we had a good dog.
Our new dog was found on the streets of LA, pregnant. She was so nervous on the day we adopted her and drove her home that she shit in the car and then vomited twice. She tried to run away as we were cleaning the car and, when we got her home, she tried to jump the fence and escape. After a while, she decided this was where she would live.She calmed down but had incredible separation anxiety. Now, a few months later, I would say she is close to “normal” and is incredibly affectionate (you can’t pet her enough).
I think we underestimate how traumatic these early experiences are for our pets. We know from the ACE (Adverse Childhood Events) studies of human children how trauma (like being abandoned) can affect the child’s entire life. I bet it will be turn out to be true of our doggie family members too.
phew…quite a lot to unpack here, well not really anything because it’s all made up nonsense. I’ll just make it simple please provide verifiable cases of dogs suffering from the following:
Alcohol Use Disorder
Alice in Wonderland Syndrome
Body dysmorphic disorder
I’ll stop here, but if you can actual provide a genuine source, and not some bored housewife’s blog claiming their dog has one of these, there’s quite a few more.
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We have a conscious too which may explain a-lot. :-)
I may be wrong but am I correct when I say that animals don’t feel guilt?
The things are very simple. Evolution is normal so it is not HAR. What is not normal was migration. Of course, migration was instigated by higher mental capacities. When the first 1000 people left Africa, it was a havoc on their immune systems. Climate changes, a lot of new unknown unpredictable environments in a very short period of time. Blood groups formed etc., but things happened quickly. Animals never went through such intercontinental migrations. Food changes, climate, and immune systems suffered. We know that cytokines are increased with schizophrenics. It is epigenetic accumulation of stresses
When a dog is trained he is broken. That act should heal 80-90 percent. They experience anxiety, dementia, similar to panic attacks and schizophrenia. Is it just the genetic cation similar response?
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