Lauren Jacobson, PhD

My laboratory investigates the influence of glucocorticoid receptors in specific brain regions on emotion-related behavior. Glucocorticoid steroids from the adrenal cortex are necessary for survival, and have a variety of actions to increase blood glucose, increase blood pressure, limit immune system reactivity, enhance appetite, and influence cognition and mood. The best-characterized neural action of glucocorticoids is negative feedback, by which glucocorticoids limit their own secretion and biological effects by inhibiting the hypothalamic factors stimulating glucocorticoid release. However, glucocorticoids also have other neural effects that are much less well understood, including the ability to induce diverse changes in mood ranging from depression, anxiety and psychosis to euphoria and mania.

My current research originated from the apparent contradiction between glucocorticoid feedback resistance in depression and the mood-altering effects of glucocorticoids. Glucocorticoids are often elevated in depression, suggesting that glucocorticoid receptors responsible for negative feedback are impaired. However, elevated glucocorticoids can themselves cause depression-related symptoms, and some forms of depression can be alleviated with glucocorticoid-blocking therapies. I have hypothesized that multiple brain regions mediate the disparate effects of glucocorticoids on mood, and that targets for the psychoactive effects of glucocorticoids are likely to be different from targets for glucocorticoid negative feedback. In support of this hypothesis, my laboratory has shown that:

1.) Antidepressants have drug- and brain region-specific effects on glucocorticoid receptor expression. These findings better explain how antidepressants can correct abnormal glucocorticoid feedback in depression without accentuating the adverse effects of glucocorticoids on mood.

2.) Antidepressants have glucocorticoid-dependent effects on the rate-limiting enzymes for serotonin and norepinephrine synthesis.  These results suggest that glucocorticoid receptors in brainstem monoaminergic neurons can influence both normal mood and antidepressant response.

3.) Deletion of glucocorticoid receptors from the serotonergic dorsal raphe nucleus reduces depression- and anxiety-like behavior in mice without chronic effects on endocrine activity of the adrenal cortex.   These findings confirm emotion-related functions for dorsal raphe glucocorticoid receptors and show that specific glucocorticoid receptor populations can have behavioral rather than endocrine functions.

I am currently using virally-transduced, cell type-specific glucocorticoid receptor gene deletion to identify potential serotonergic and noradrenergic mechanisms for glucocorticoid effects on mood. This work could ultimately identify more effective treatments for depression and anxiety disorders.