Calcium signaling during neural development in mental disorders

The overall aim of our research is to determine pathophysiological mechanisms during neural development in the context of severe mental disorders, including bipolar disorder (BD).

BD is highly hereditary and large genome-wide association studies (GWAS) have revealed multiple risk genes, where the calcium (Ca2+) channel gene CACNA1C is one example.

However, there is a large gap of knowledge in the understanding of pathophysiology, which hinders efficient treatment and worsens the prognosis.

Today, there are no good animal models and patient derived samples cannot be used for experimental studies.In this project, I propose a dual approach including 1) modeling of neural development with the use of induced pluripotent stem (IPS) cells from meticulously characterized patients and controls and 2) analysis of unique patient cohorts linked with national registers.

I recently showed the importance of Cacna1c during murine neural development both in vitro and in vivo (Smedler et al.

PNAS 2022), and have intriguing preliminary data on potential involvement of Ca2+ signaling in the pharmacodynamics of the BD drug lithium.

I hypothesize that CACNA1C gene variants disturb Ca2+ signaling during neural development, leading to erroneous neural networking that increases the risk for bipolar disorder.