Mark Ansorge, Ph.D.
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.
- MS, Biochemistry, University of Potsdam (Germany)
- PhD, Neurobiology, Free University of Berlin (Germany)
- Postdoc, Columbia University, NY
- Rebello TJ, Yu Q, Goodfellow NM, Caffrey Cagliostro MK, Teissier A, Morelli E, Demireva EY, Chemiakine A, Rosoklija GB, Dwork AJ, Lambe EK, Gingrich JA, Ansorge MS. Postnatal day 2 to 11 constitutes a 5-HT-sensitive period impacting adult mPFC function. J Neurosci. 2014 Sep 10;34(37):12379-93. doi: 10.1523/JNeurosci.1020-13.2014.
- Suri D, Teixeira CM, Cagliostro MK, Mahadevia D, Ansorge MS. Monoamine-sensitive developmental periods impacting adult emotional and cognitive behaviors. Neuropsychopharmacology. 2015 Jan;40(1):88-112. doi: 10.1038/npp.2014.231. Epub 2014 Sep.
- Yu Q, Teixeira CM, Mahadevia D, Huang YY, Balsam D, Mann JJ, Gingrich JA, Ansorge MS. Optogenetic stimulation of DAergic VTA neurons increases aggression. Mol Psychiatry. 2014 Jun;19(6):635. doi: 10.1038/mp.2014.45. No abstract available.
- Goodfellow NM, Sargin D, Ansorge MS, Gingrich JA, Lambe EK. Mice with compromised 5-HTT function lack phosphotyrosine-mediated inhibitory control over prefrontal 5-HT responses.
- J Neurosci. 2014 Apr 23;34(17):6107-11. doi: 10.1523/JNeurosci. 3762-13.2014.
- Yu Q, Teixeira CM, Mahadevia D, Huang Y, Balsam D, Mann JJ, Gingrich JA, Ansorge MS. Dopamine and serotonin signaling during two sensitive developmental periods differentially impact adult aggressive and affective behaviors in mice. Mol Psychiatry. 2014 Mar 4.
- Rebello TJ, Yu Q, Goodfellow NM, Caffrey Cagliostro MK, Teissier A, Morelli E, Demireva EY, Chemiakine A, Rosoklija GB, Dwork AJ, Lambe EK, Gingrich JA, Ansorge MS. Postnatal Day 2 to 11 Constitutes a 5-HT-Sensitive Period Impacting Adult mPFC Function. J Neurosci. 2014 Sep 10;34(37):12379-93.
- Suri D, Teixeira CM, Cagliostro MK, Mahadevia D, Ansorge MS. Monoamine-sensitive developmental periods impacting adult emotional and cognitive behaviors. Neuropsychopharmacology. 2014 Sep 2.
- Goodfellow NM, Sargin D, Ansorge MS, Gingrich JA, Lambe EK. Mice with Compromised 5-HTT Function Lack Phosphotyrosine-Mediated Inhibitory Control over Prefrontal 5-HT Responses. J Neurosci. 2014 Apr 23;34(17):6107-11.
- Morelli E, Moore H, Rebello TJ, Gray N, Steele K, Esposito E, Gingrich JA, and Ansorge MS. Chronic 5-HT Transporter Blockade Reduces DA Signaling to Elicit Basal Ganglia Dysfunction. J. Neurosci. 2011; 31 15742-15750.
- Oberlander TF, Gingrich JA and Ansorge MS. Sustained Neurobehavioral Effects of Exposure to SSRI Antidepressants during Development: Molecular to Clinical Evidence. Clinical Pharmacology & Therapeutics. 2009 Dec;86(6):672-7.
- Ansorge MS, Morelli E, Gingrich, JA. Inhibition of Serotonin But Not Norepinephrine Transport during Development Produces Delayed, Persistent Perturbations of Emotional Behaviors in Mice. J Neurosci. 2008 Jan 2;28(1):199-207.
- Ansorge MS, Hen R, Gingrich JA. Neurodevelopmental origins of depressive disorders. Curr Opin Pharmacol. 2007 Feb;7(1):8-17. Review.
- Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA. Early life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science. 2004 Oct 29;306(5697):879-81.
For a complete list of publications, please visit PubMed.gov