Schmack lab

Neural Circuits and Immunity in Psychosis Laboratory

: Immune signals

We investigate how immune signals contribute to psychotic symptoms to identify new biological mechanisms underlying psychosis. We think that a deeper biological understanding of psychosis will evolve with knowledge about how the immune system and the brain interact.

Because the etiology of psychotic disorders is multifactorial, it is challenging to causally model psychosis in model organisms. However, a variety of environmental and genetic factors point to an involvement of the immune system. For instance, psychotic disorders are associated with variants in immune-related genes, early-life infections, and autoimmune disorders. In line with this, patients with psychotic disorders show signs of increased immune activation in the blood and in the cerebrospinal fluid. This suggests that the brain-directed immunity might be a common causal endpoint that could potentially be modeled in mice.

We therefore study how immune signals directed at the brain might lead to psychotic symptoms. Using immune phenotyping and transcriptomic-proteomic profiling, we test which immune cells and proteins are altered in the blood and cerebrospinal fluid of patients with acute psychosis. We then probe in mice how the identified alterations can lead to psychosis-like experiences as measured with our behavioral-computational approach. Our cross-species approach allows us to move back and forth between our mouse model and psychotic patients to elucidate the role of brain-directed immunity in psychosis. The goal is to uncover mechanisms by which the immune system and the brain interact in psychosis. Ultimately, this will enable the development of novel immune-related treatment targets for psychotic disorders.