Albert Lab

Paul Albert profile picture

Contact Information

Paul Albert, PhD
613-562-5800 8307

OHRI (Neuroscience)
451 Smyth Road
Ottawa, ON K1H-8M5

What We Do

Successful therapy of major depression and anxiety with antidepressant compounds (e.g., serotonin-specific reuptake inhibitors, SSRIs) enhances the activity of the serotonin (5-HT) system, which originates in the raphe nuclei of the brain.  However, desensitization of inhibitory serotonin-1A (5-HT1A) autoreceptors correlates with SSRI response, and allows for enhanced firing of 5-HT neurons to increase 5-HT.  Because of the chronic time course of the disease and its treatment, we have focused on understanding the transcriptional regulator of 5-HT genes including the 5-HT1A receptor gene.  We have identified several regulatory DNA elements, and a genetic variant (GG-1019) that leads to increased 5-HT1A autoreceptors and reduced post-synaptic 5-HT1A receptors, and is associated with increase risk for depression and suicide, and resistance to SSRIs (Figure below).

To address the molecular events that impact chronic depression, we examine the mechanisms of functional promoter polymorphisms, like the GG-1019 5-HT1A change, and of chronic stress-induced epigenetic modifications on gene expression, behavior, and antidepressant response in human and mouse models of mental illness.  Our fundamental research has identified the molecular mechanisms that regulate key genes in the serotonin (5-HT) and dopamine systems, including the 5-HT1A and dopamine-D2 receptor genes and the TPH2 gene.  Starting with the key DNA elements that regulate 5-HT1A receptor expression, we have cloned the novel regulators that target these elements, including Freud-1, Freud-2 and Deaf1/NUDR.  Using conditional and inducible mouse knockout models to knockout these factors, we are addressing their roles in regulation of serotonin in vivo, and in anxiety and depression like behavior.  In addition, we have developed and investigated new models of depression, recently showing that chronic stress induces DNA methylation pattern of the 5-HT1A promoter sites that can be reversed by chronic antidepressant treatment.  By identifying risk polymorphisms for anxiety, depression and suicide, and defining how they affect gene regulation, we provide new approaches for better treatment of anxiety and depression. 

Professor Albert has established research collaborations with the Royal Ottawa Hospital (Institute for Mental Health Research) and worldwide to apply this work in the areas of depression, anxiety and schizophrenia. He is also a member of the Heart and Stroke Foundation Canadian Partnership for Stroke Recovery and the University of Ottawa Brain and Mind Research Institute.

Selected Publications

Five Key Publications

Albert lab members in bold
Publications archived at: ResearchGate

1. Turcotte-Cardin V, Vahid-Ansari F, Luckhart C, Daigle M, Geddes SD, Tanaka KF, Hen R, James J, Merali Z, Beique JC, Albert PR (2019) Loss of adult 5-HT1A autoreceptors results in a paradoxical anxiogenic response to antidepressant treatment. J Neurosci 39, 1334-46. PDF

2. Le François B, Zhang L, Mahajan GJ, Stockmeier C, Friedman E, Albert PR (2018) A novel alternative splicing mechanism that enhances human 5-HT1A receptor RNA stability is altered in major depression. J Neurosci 38, 8200-10. PDF

3. Vahid-Ansari F, Daigle M, Manzini MC, Tanaka KF, Hen R, Geddes SD, Beique JC, James J, Merali Z, Albert PR. (2017) Abrogated Freud-1/CC2D1A repression of 5-HT1A autoreceptors induces fluoxetine-resistant anxiety/depression-like behavior. J Neurosci 37, 11967-11978. PDF

4. Philippe TJ*, Vahid-Ansari F*, Donaldson ZR, Le François B, Zahrai A, Turcotte-Cardin V, Daigle M, James J, Hen R, Merali Z, Albert PR (2018) Loss of MeCP2 in adult 5-HT neurons induces 5-HT1A autoreceptors, with opposite sex-dependent anxiety and depression phenotypes. Scientif Reports 8:5788, 1-13. *co-first authors. PDF

5. Vahid-Ansari F and Albert PR (2018) Chronic fluoxetine induces activity changes in recovery from post-stroke anxiety, depression and cognitive impairment. Neurotherapeutics 15, 200-215. PDF.

Meet the Albert Lab