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Approved Research

Effects of skin-mediated signaling pathways on neurological and psychiatric disease

Principal Investigator: Dr David Fisher
Approved Research ID: 68588
Approval date: June 16th 2021

Lay summary

1. There is a known correlation between incidence of Parkinson's Disease and Melanoma, though the directionality and nature of the relationship is poorly understood. There is also a known link between Parkinson's Disease and red hair: a known risk factor for melanoma. Anecdotal observations by dermatologists also suggest that a subset of patients with Parkinson's Disease see a dramatic increase in melanoma incidence after starting therapy for PD. We aim to study this in humans and hypothesize that melanoma incidence increases in red-haired patients with Parkinson's after therapy is initiated. Given the rapid, significant increase in number of new melanomas with PD treatment, we believe that better explaining this connection may lead to a dramatic improvement in melanoma care for a subset of PD patients, primarily those with red hair.  The public health impact is significant given the large number of new melanomas that rapidly develop in this subset. 

2. Red hair has been associated with increased pain thresholds and increased opioid sensitivity in humans and in mice. We have previously demonstrated in mouse models that this is due to defective endogenous opioid signaling in individuals with red hair. Next, we aim to extend these experimental findings and test whether hair color predicts increased opioids use in humans. We beieve that harboring certain polymorphisms in Mc1r and Mc4r genes, which are involved in determining an individual's hair color, could predict an increased risk of developing opioid dependency.   Therefore, significant changes to current opioid prescribing practices may be warranted in this patient population. 

3. We have previously demonstrated that UV light can affect blood levels of endogenous opioids: a class of hormone which is known to have a wide variety of effects on behavior.  Given that a strong epidemiological correlation has been demonstrated between time of year and both seasonal affective disorder and bipolar disorder, we are interested in exploring the role of UV exposure and both incidence and treatment response in these diseases.

Current Scope:

Our aims are based on preclinical observations conducted in our lab. We wish to further validate our findings in the following areas.

  1. How does Parkinson's disease and its management influence melanoma incidence in the red-haired background.
  2. How does red hair color predict responses to opioid analgesics and their consumption.
  3. How does endogenous opioid signaling modify incidence and manifestations of mood disorders with a seasonal pattern, including Seasonal Affective Disorder and Bipolar Disorder

New Scope:

How does hair pigmentation predict incidence, chronicity, and recurrence of inflammatory and noninflammatory alopecia and how can this knowledge improve treatment/prevention strategies? Specifically, 1) do pigment-related proteins and the balance of eu- vs. pheomelanin contribute to the balance of pro- vs. anti-inflammatory signals in the skin and hair follicles and 2) what is the role of pigmentation in other autoinflammatory diseases of the hair, skin, and CNS and 3) do other alopecias without a clear autoimmune component (androgentic and scarring alopecias) display similar characteristics?