Mark Ansorge, PhD

My lab investigates the developmental origins of neuropsychiatric disorders using mouse models.

While the causes of neuropsychiatric disorders such as depression, anxiety, schizophrenia and autism are still quite enigmatic, research from many labs over the past decades has established that these disorders often have their origin in development. In this current thinking many genetic, epigenetic, and environmental factors interact to affect brain development to modulate risk for disorders later in life. Understanding crucial developmental factors, which increase or decrease disease risk, will (1) provide insight into the biology of brain development, (2) increase our understanding of the neurobiology underlying behavior, and (3) allow for improving diagnosis, treatment and prevention strategies for these devastating disorders.

We have found that one such crucial factor is serotonin (5-HT): In mice, increased 5-HT signaling during a critical developmental period increases anxiety and depression-like behavior later in life. This finding extends our basic understanding of developmental 5-HT signaling and its consequences on emotional function. Furthermore, it might explain why humans carrying low expressing allelic variants of the 5-HT transporter gene are more susceptible to depression and anxiety disorders as adults. Lastly, it suggests that drugs affecting 5-HT signaling might adversely impact emotional behavior of exposed fetuses and young children in their adult life. We have identified anatomical, physiological, and circuitry-related changes elicited by increased developmental 5-HT signaling in the raphe, the hippocampus, and the medial prefrontal cortex—brain structures involved in emotional and cognitive processing and regulation. Based on these findings, we hypothesize that altered function of these structures and circuitry involving them mediates increased depression- and anxiety-related behaviors caused by developmental 5-HT transporter blockade.

Currently, my lab further characterizes these functional changes in the raphe, hippocampus, and medial prefrontal cortex at the molecular, anatomical, and physiological level. For probing circuit function and testing causality we use pharmacogenetic and optogenetic approaches where applicable. This research shall provide crucial insight into the role of developmental 5-HT signaling on circuit-maturation and -function in relation to emotional behavior.

In the long term, my laboratory will investigate other genetic, epigenetic, and/or environmental factors which impact brain development to alter risk for neuropsychiatric disorders using mouse models. Human studies investigating associations of specific genetic, epigenetic, and/or environmental factors with complex behavioral traits and disease will continue to guide my work. Thus, future mouse model generation will be based on clinical findings and mechanistic hypotheses. Because most neuropsychiatric disorders are phenotypically complex, my lab focusses on modeling and investigating key endophenotypes of the respective disorders.