Saeedeh Noroozi [email protected]
Areas of Interest
Research in the Akil laboratory focuses on understanding the neurobiology of emotions, including pain, anxiety, depression and substance abuse.
Early studies, which focused on the role of the endorphins and their receptors in pain and stress responsiveness, led to the first physiological evidence for a role of endogenous opioids in the brain. This demonstrated that endorphins are activated by stress and cause pain inhibition, a phenomenon Akil’s team termed Stress-Induced Analgesia. They defined how the posttranslational processing of opioid precursors is modulated by stress, and demonstrated the coordinate actions of the neuropeptide products on behavior.
A series of studies in collaboration with Dr. Stanley Watson characterized the anatomy of opioid peptides and their receptors. The Akil and Watson research groups collaboratively cloned two types of opioid receptors and conducted structure-function analyses defining the molecular basis of high affinity and selectivity towards the endogenous ligands.
The Akil laboratory investigated the molecular and neural mechanisms underlying stress reactivity and their relation to anxiety and depression. They have focused on the role of steroid stress hormone receptors in emotionality, demonstrating the involvement of the mineralocorticoid receptor in human depression. The group has created a transgenic mouse that overexpresses the glucocorticoid receptor selectively in the forebrain and exhibits increased emotional lability and responsiveness to antidepressants, two features of bipolar illness.
A major focus of current research in the Akil lab is to develop animal models to understand the genetic and developmental basis of differences in temperament, and the implications of these inborn differences for vulnerability to anxiety, depression and substance abuse.
Akil’s research group is one of six nodes in the Pritzker Neuropsychiatric Research Consortium[SZ1] , an integrated collaborative effort using genomic tools to uncover the neural phenotypes associated with major depression and bipolar illness in human postmortem brains. In this context, they have implicated, for the first time, the FGF (Fribroblast Growth Factor) system in major depression. Other Pritzker Consortium efforts include the search for the genes responsible for bipolar disorder, genome-wide characterization of epigenetic changes in normal and psychiatric brains, and the identification of biomarkers for psychiatric disorders.
Akil is also investigating factors that influence the vulnerability and resilience to developing anxiety and depression symptoms in the University of Michigan freshmen student population. The study is funded by the Office of Naval Research, and the students can study from home or Ann Arbor.
Research in the Akil laboratory relies on a range of molecular, genetic, anatomical, behavioral and clinical approaches, all utilized in a highly interdisciplinary environment. The goal is to use a convergence of strategies to understand the biology of emotions.
- Turner C.A., Watson S.J., Akil H. The fibroblast growth factor family: Neuromodulation of affective behavior. Neuron, 2012. Oct 4, 76(1):160-74. doi 10.1016/j.neuron.2012.08.037. PMID: 23040813. PMC3476848.
- McEwen BS, Akil H. Revisiting the Stress Concept: Implications for Affective Disorders. J Neurosci. 2020 Jan 2;40(1):12-21. PMID: 31896560. PMC6939488.
- Emery MA, Akil H. Endogenous Opioids at the Intersection of Opioid Addiction, Pain, and Depression: The Search for a Precision Medicine Approach. Annu Rev Neurosci. 2020 Jul 8;43:355-374
- Birt IA*, Hagenauer MH*, Clinton SM, Aydin C, Blandino P, Stead JDH, Hilde KL, Meng F, Thompson RC, Khalil H, Stefanov A, Maras P, Zhou Z, Hebda-Bauer EK, Goldman D, Watson SJ, Akil H. Genetic liability for internalizing versus externalizing behavior manifests in the developing and adult hippocampus: Insight from a meta-analysis of transcriptional profiling studies in a selectively-bred rat model. Biological Psychiatry- 2021 Feb15;89(4):339-355. PMID: 32762937. PMC7704921.