A new study has described the accidental discovery of a novel protein that may be associated with the anxiety and stress behaviors seen in obsessive compulsive disorder (OCD). Blocking the expression of this protein in mice reduced anxious behaviors, opening up the possibility of a future antibody treatment for a variety of mental health disorders.
“There is mounting evidence that the immune system plays an important role in mental disorders,” explains Fulvio D'Acquisto, study leader on the new research. “And in fact people with auto-immune diseases are known to have higher than average rates of mental health disorders such as anxiety, depression and OCD. Our findings overturn a lot of the conventional thinking about mental health disorders being solely caused by the central nervous system.”
The genesis of the new study came by accident. The researchers were studying mice engineered to over-express a protein called Annexin-A1. This protein plays a key role regulating immune cell activities so it is of great interest to researchers looking for novel autoimmune disease treatments.
The researchers noticed the mice with increased Annexin-A1 expression displayed high levels of anxiety behaviors, such as compulsive digging. Further study revealed an over-active gene in the animals’ T-cells was excessively producing a protein that had not previously been identified. The novel protein was dubbed Immuno-moodulin, or Imood. And, when the researchers blocked production of Imood the anxious behaviors of the animals disappeared.
Of course, identifying a mechanism such as this in animal studies doesn’t mean a great deal unless it can be validated in human subjects. So, the researchers sampled immune T-cells from 20 healthy subjects and 23 subjects with OCD. Imood expression was approximately six times higher in the OCD subjects compared to the healthy controls.
It is still incredibly early days for the research, with a great deal more work needed to understand exactly how immune cells expressing this protein could lead to specific behavioral responses. The researchers hypothesize possible ways this protein could be influencing brain cells linked to mental health disorders, however, more clinical study is necessary before a mechanism can be seriously proposed.
“This is work we still have to do to understand the role of Imood,” says D'Acquisto. “We also want to do more work with larger samples of patients to see if we can replicate what we saw in the small number we looked at in our study.”
Nevertheless, the general implications of this discovery are compelling, suggesting immune-modulating antibody treatments could hypothetically be deployed to treat mental health disorders. The researchers note subsequent study by other scientists has found a link between Imood and Attention-Deficit/Hyperactivity Disorder.
A team from Queen Mary University of London is now working to develop a human antibody to modulate Imood levels, but D’Acquisto notes this will take time. Any human clinical trials deploying this kind of antibody treatment would be at least five years away.
“It is early still, but the discovery of antibodies – instead of the classical chemical drugs – for the treatment of mental disorders could radically change the life of these patients as we foresee a reduced chance of side effects,” says D’Acquisto.
The new research was published in the journal Brain, Behavior, and Immunity.
Source: Queen Mary University of London
