Does it make sense to try to explain human behavior on the basis of information from animal research? Well, sometimes it does, and sometimes it doesn't, and we don't necessarily know which is correct until a good deal of information has been collected. Nevertheless, researchers consider it a breakthrough when they find a usable "animal model"-- an animal whose responses or spontaneous behavior seem to provide a strong analogy to what happens in humans. These models are useful because not only are the researchers less constrained by the ethical concerns that regulate experimentation on human beings, but animal models usually have the great advantage of dealing with short lifespans and short reproductive periods, so many generations can be studied.
Recent work by Mario Capecchi and his colleagues (described at http://bit.ly/OCD-mice ) suggests that there may be an animal model for Obsessive-Compulsive Disorder (OCD). The mutant mice involved obviously can't lock and re-lock doors or check again and again whether the coffee maker is turned off, but they show intense, repetitious grooming behavior which Capecchi and others have compared to human obsessive and compulsive behaviors. Unlike normal mice, who do a thorough grooming job and then stop, these mice groomed themselves until they pulled out fur and caused sores, and they groomed other mice at length, as well.
Capecchi's group compared the mouse behavior to human obsessive and compulsive behavior. They noted that the excessive grooming of the mice was like the human behavioral problem trichotillomania, the compulsive pulling out of hair--- although most humans with OCD do not pull out their hair, and it is not very clear whether OCD and trichotillomania are actually the same thing.
Whether or not the human and mouse behaviors were closely related, however, there were some thought-provoking outcomes in the mouse study. The particular mutation in these mice, a defect in the gene Hoxb8, apparently does not affect neurons directly, but instead affects cells called microglia, part of the immune system, that are created in bone marrow but can move to the brain. When bone marrow with the defective Hoxb8 gene was transplanted into the bones of normal mice, those mice began to groom compulsively; when bone marrow from normal mice was transplanted into Hoxb8-deficient mice, they stopped their intense grooming behavior. It looked as though the immune system material had a powerful effect on the animals' behavior.
Testing humans with trichotillomania to see whether they have mutant genes is a much more difficult matter than testing mice. Whether there are microglia in the brain with a deficiency in Hoxb8 is a question that can be answered only by autopsy. In addition, as one commentator at http://bit.ly/OCD-mice has pointed out, even the presence of a deficient gene would not necessarily show that the gene in and of itself caused the peculiar behavior. A given gene can cause different phenotypes (physical and behavioral outcomes) when in combination with different groups of genes, so what happens with one strain of mice may not happen with others-- and obviously what works with mice may not work with humans. In addition, different genes in different combinations can cause the same physical or behavioral phenotypic result, so without further evidence we should not assume that the gene that causes excessive grooming in mice is necessarily the same one that causes compulsive behavior in humans.
I don't mean to suggest doubts about the connection between genes, other structures such as microglia, and human moods or behavior. There is already much evidence about genetic factors associated with very specific behaviors like hand-wringing that form parts of known behavioral syndromes. However, some caution is warranted when we still have questions both about the occurrence of similar defective genes in human brains, and about the connections between excessive mouse grooming and human hair-pulling, and between human hair-pulling and Obsessive-Compulsive Disorder. It's not time for anyone to rush about looking for bone-marrow transplants or for any other treatment that might affect the immune system, at least not with a view to reducing compulsive behaviors.
What I'd really like to know about the Hoxb8-deficient mice is this: Mother mice wash and groom their babies carefully, and they have to do this properly for the babies to survive. Grooming the babies tears open and removes the amniotic membranes which would otherwise suffocate the pups. Grooming also stimulates the digestive functions and brings about defecation. If a pup is dead, the mother eats it-- but sometimes she gets overly zealous and eats live pups too. Is this connected with Hoxb8? Are deficiencies in this gene also associated with early problems with mouse mothering? Unfortunately, as so often happens, the Capecchi article doesn't even say which sex the mice were (see recent letters in Science on this fact), much less refer to other aspects of behavior that might be involved. Research works one step at a time, of course, but it would be fascinating to know how that gene influences maternal behavior.
