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Jerry Overman, PharmD, BCPP
Administrative Chair, 2018 Program Committee

Our own CPNP President, Deanna Kelly to present cutting edge research connecting gluten to schizophrenia.

Deanna Kelly, PharmD, BCPP, Professor, University of Maryland School of Medicine, will discuss the emerging association of inflammation and immune activity in schizophrenia, reviewing data that helps characterize subgroups of patients with antigliadin antibodies (AGA IgG) and presenting ongoing work for treatment targets and mechanisms of action connecting gluten to schizophrenia. This exciting work suggests that more personalized treatments targeting diet modulation or immune/inflammation may play future roles in schizophrenia treatment.

Deconstructing the illness of schizophrenia is of particular interest as this heterogeneous disorder may be composed of etiologically distinct disorders with different mechanisms which could all serve as treatment targets for components of the disorder. Although the underlying pathophysiology of schizophrenia remains unknown, leading theories to date suggest it is associated with disruption of dopamine or glutamate systems. More recently, emerging evidence suggests inflammation may play a role in this illness as demonstrated by a variety of evidence. For example, increased levels of cytokines in blood and cerebrospinal fluid in schizophrenia relative to controls have been reported. Other evidence suggests that maternal infections and inflammation results in higher risk of offspring with schizophrenia. Furthermore autoimmune diseases have been associated with increased risk for schizophrenia, genes in the major histocompatibility regions are associated with increased risk for schizophrenia and some anti-inflammatory agents have shown promise in schizophrenia treatment

One specific group with elevated peripheral and central inflammatory response is those with schizophrenia having elevations in antigliadin antibodies (AGA IgG). Gliadin is a protein found in wheat, barley and rye. Research suggests that these antibodies are present in about 1/3 of the schizophrenia population, compared to about 10% of healthy controls. These antibodies are distinct and nonoverlapping with antibodies for Celiac Disease and may represent a group with gluten sensitivity. In addition to high inflammation, this subgroup with AGA IgG elevations may be distinct by having lower positive symptoms and high kynurenic acid levels. It remains unclear, however, how these elevations in AGA IgG and immune activation in this subgroup may contribute to the illness and schizophrenia psychopathology; however it may be related to gut permeability or mimicry/cross reactivity to proteins present. This population may represent a subgroup which may have personalized and targeted treatments developed.

In the past, removing the gluten antigen from the body has been shown to be effective for diminishing or eliminating schizophrenia symptoms in case reports and small clinical trials, but not consistently. The ability to screen for AGA IgG was not developed until the 1990’s, so that not a single one of the previous trials screened schizophrenia patients for AGA IgG, meaning that most participants in these studies would be unlikely to benefit from the intervention.  However, an open label study and a recently completed clinical trial with a strictly controlled gluten free diet (GFD) in the subgroup of schizophrenia patients with high AGA IgG both found benefits in negative symptoms, leading the way for more robust, follow up studies to replicate these findings.

Following this session, attendees should be able to:

  1. Describe the emerging role of inflammation in schizophrenia
  2. Discuss ongoing research to characterize subgroup of schizophrenia patients with immune response and inflammation to gluten
  3. Recognize potential pathophysiologic mechanisms related to an immune response to  gluten
  4. Understand ongoing work for personalizing treatment in this subgroup of schizophrenia with potential gluten sensitivity

You won’t want to miss this exciting session led by Dr. Kelly at the CPNP 2018 Annual Meeting in Indianapolis on Tuesday, April 24!

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