Given that many studies have provided evidence that infection in pregnant women is associated with increased risk for autism and schizophrenia in the offspring, Alan Brown and his colleagues in Finland measured the levels of C-reactive protein (CRP), an established biomarker of inflammation, in maternal serum. This was done in a large national birth cohort of 1.2 million, with an extensive serum biobank and national psychiatric registries consisting of virtually all treated autism cases in the population. They found that elevated maternal CRP levels are significantly associated with autism in offspring. This adds to the findings in earlier posts here showing that elevated cytokines in amniotic fluid or maternal serum are also associated with increased risk for autism in the offspring.
Adding to the evidence of immune dysregulation in schizophrenia, a new meta-analysis of the literature (by Mark Rapaport and colleagues at Cedars-Sinai Medical Center) reports that CRP levels are significantly increased in schizophrenia patients. Consistent with this, Paul Tooney in Sydney finds that blood cells from schizophrenia patients display changes in gene expression related to inflammation and immunity, and most importantly, these changes are ameliorated following anti-psychotic medication. I’ve noted here previously that such drugs have anti-inflammatory actions in studies of cultured cells. Tatiana Falcone and colleagues at the Cleveland Clinic report that pediatric patients hospitalized with a first episode of psychosis display elevated blood levels of cytokines.
Minocycline is a tetracycline antibiotic that has been tested for a wide variety disorders because it has a good safety profile and it has a plethora of positive effects on cultured cells and in animal models. I follow the literature on this drug because it has anti-inflammtory properties. There are a number of papers showing that minocycline has positive effects in mouse models of fragile X syndrome (FXS), and a small, open label, add-on (added to usual medications) study in FXS patients showed significant improvement in symptoms. Thus, it is of interest that Randi Hagerman’s group at UC Davis now reports results of a randomized, double-blind, placebo-controlled trial of minocycline in children and adolescents with FXS. They find a 3 month treatment results in modest but global improvement in symptoms. Moreover, a large, 1 year add-on trial of minocyline in England, Brazil and Pakistan found amelioration of negative symptoms in schizophrenia.
Another promising FXS treatment was just reported by Susumu Tonegawa of MIT and collaborators at Afraxis, Inc. in La Jolla. They developed a new inhibitor of PAK, an enzyme that plays a role in the remodeling of synaptic connections. In adult FXS mice, this inhibitor can reverse all of the abnormal behaviors tested, and corrects the altered synaptic connections. These are remarkable results because they were found in adult mice, a short time after a subcutaneous injection of the inhibitor. It will be interesting to follow the future studies of this approach, and how it compares to ongoing FXS human trials.