Dr. Grossi's Blog
OCD is a common, often debilitating, psychiatric disorder that shows improvement about fifty percent of the time, but is rarely fully resolved. The core of the treatment for the last twenty-some years has been serotonergic agents such as the SSRIs (Prozac, Zoloft, Celexa, Lexapro, Luvox, and Paxil) and the SRI, clomipramine. Due to inadequate clinical response, augmentation is frequently employed using the atypical antipsychotics which are dopamine/serotonergic agents. The marginal response to treatment as well as its often disabling impact has motivated many researchers and treating psychiatrists to look for alternatives that would produce more robust treatment results.
In the February 2010 issue of Journal of Clinical Psychopharmacology, Stewart and colleagues reported on the use of Memantine augmentation in 22 of 44 patients. They found evidence for the effectiveness of Memantine augmentation. It is a glutaminergic agent. There have also been reports that riluzole (Rilutek) which also effects glutamate metabolism, has been an effective augmenting agent.
One of the co-authors with Stewart was Nicholas Dodman who is a veterinarian at Tufts University School of Veterinary medicine. Having a veterinarian as a co-author on this article shows that someone is thinking outside the box in that they must be considering an animal model for a psychiatric illness. Dodman and colleagues published an article, "Pharmacologic Treatment of Equine Self-Mutilation Syndrome," in Journal of Applied Research in Veterinary Medicine in 2004. In that study the authors recruited eight flank-biting horses with equine self-mutilation syndrome (ESMS), a condition thought to be similar to Tourette's syndrome in humans. They used ten different drugs which either stimulated or inhibited central opioid, dopamine, norepinephrine, and serotonin neurotransmitter systems. The opioid antagonist, naltrexone, and the serotonin agonist, buspirone, as well as a dopamine blocker and the alpha-2 antagonist all produced reductions in these behaviors which were videotaped and counted. The manipulation of these various neurotransmitter systems in horses with ESMS alter the frequency of behavioral expressions that are similar to what one would expect in humans.
Dodman and colleagues have also reported on some additional work on 92 Doberman pinschers with the canine compulsive disorder of pica and flank sucking (FS) and blanket sucking BS). These behaviors appear in early social maturity and are often precipitated by stress. This looks like obsessive-compulsive behavior. DNA was genotyped. They found that a variant of the gene for a protein called cadherin-2 (neural cadherin) was over-represented in extremely compulsive Dobermans.
This type of work represents a shift in thinking about psychiatric disorders. Psychiatric researchers have sought to create animal models before with knockout and knockin mice, as referred to in a prior blog, but looking at an animal that presents behaviors that look like or suggest human behaviors is difficult to get one's head around. Dodman and his group contend that looking at animals with behavioral traits is very promising indeed. He believes that the behaviors are often instincts that have gone to excess,e.g., grooming gone overboard feather pulling), licking gone to excess (compulsive paw licking), gathering run wild (hoarding). Dr. Elaine Ostrander (who was on the team that found that variation in one gene - IGF-1, which codes for a protein hormone called insulin-like growth factor 1 - is very strongly associated with small stature across all dog breeds studied) is the lead investigator on a study of spinning (severe tail chasing) in bull terriers. Dodman thinks that this study is very promising because this breed also manifests asocial and withdrawn behavior, episodes of explosive aggression, and seizures. If cadherin is further implicated, we will really be onto something big.