Interview with Dr. Gena Glickman

Could you tell us a little bit about yourself and your research?

I’m an Assistant Professor in the Departments of Psychiatry and Neuroscience at Uniformed Services University of the Health Sciences as well as Director of the Chronobiology, Light, and Sleep Lab in Bethesda, Maryland. Immediately prior to arriving at USUHS, I was in San Diego, where I did my graduate studies in Behavioral Neuroscience at the University of California, San Diego. We’ll probably talk a little bit more about my research, but I did some animal work there. And after completing my dissertation, I shifted back to human research in my positions with the Center for Circadian Biology at UCSD and the Naval Health Research Center, also in San Diego. My research throughout has focused on circadian rhythms and the physiological effects of light, and most recently, my lab has been translating basic science findings by developing and testing novel lighting interventions.

Thanks for that! I’m very interested to hear more about your research, did you mention that you’ve previously worked with animals? What kind?

Well, prior to working with animals, I was at Thomas Jefferson University in the lab of Dr. Bud Brainard, where I contributed to an action spectrum study for melatonin suppression in humans. We characterized the response to different wavelengths of light and found a peak sensitivity in the short wavelength region of the visible spectrum. What was so cool about that study was that this spectral sensitivity was distinct from that of all the known photoreceptors at the time, suggesting the existence of some unidentified photopigment, which indeed turned out to be the case. Contributing to that work got me hooked on studying the physiological effects of light, and one issue we often talked about back then was the potential influence of light history. This had me thinking not only about how does prior light exposure influence subsequent responses to light. But also, what is the relevant timeframe? Is it just the minutes, hours, days, or possibly months, years, or even a lifetime that can have an impact?

And so that is what led me to animal research in graduate school because you can control their entire light history and then begin examining the effects at multiple levels of regulation, which is something you just can’t do in humans. I did that work at UCSD, in the lab of Dr. Michael Gorman, who shared an interest in light history. And my focus there was largely on the influence of seasonal changes in photoperiod, or day length, on various responses to light. For those studies, we used both hamsters and mice- two different kinds of hamsters, actually, Siberians and Syrians. 

That reminds me of a blog post that our CTO wrote last year about the seasonal effects on your body’s circadian clock. That’s when I learned that our body’s clock does keep seasonal information. I found that very interesting because I feel like people look at light exposure as a very immediate response to your body.

Yes, the interaction between seasonality and circadian rhythms is a really interesting and understudied area. In our studies, we found a 40-fold increase in sensitivity to light for phase shifting the clock in hamsters previously maintained under a winter versus a summer photoperiod. We also looked at protein expression in the clock in the brain (you can do that in animal models) and found the same pattern of results. However, we did not see these same effects on the melatonin suppression response. So, based on those combined findings, there are only a few possible underlying mechanisms for this seasonal modulation of light sensitivity, and once you have that, you can start to develop pharmacological targets that might potentiate the circadian response to light. This was all work that was done as part of my dissertation. After that, however, I moved back into human research.

Speaking of that, we’ve heard that you’re doing research on infant activity. Could you tell us a little bit about that?

I actually became interested in circadian rhythms and sleep in children with autism when I was at UCSD. A friend of mine who did research on children with autism said to me, “Hey, I’ve been hearing from the parents, and their main complaint is sleep.” The kids just weren’t sleeping very well. Which, of course, also affects the parent’s sleep. After asking her what the nature of these sleep problems was, she said that she really wasn’t sure, just that they weren’t sleeping well. That’s when I started reviewing papers on the topic. It was kind of messy literature, but the takeaway was that sleep problems were pervasive among these kids. There was also a hint that maybe there was some circadian disruption because there were also reported hormone abnormalities, but no one, at least at the time, had really put these things together.

After publishing a review article on sleep, circadian rhythms, and autism, I decided to apply for a grant to start looking at these relationships. Again, similar to the light history topic, I wondered, “Where do we start? When are these kids first developing sleep problems? And what about their hormone profiles?” And so, it seemed we needed to start very early in development. However, sleep and circadian rhythms change very rapidly in the first months of life and, because of that, can be highly variable across individuals at a given age. This makes it difficult to detect systematic differences and is best done with longitudinal studies within the same children, which can be particularly hard to do in unique populations. 

So, we capitalized on a bigger project that was going on at UCSD at the time, led by Dr. Karen Dobkins, who was tracking the development of infant siblings of children with autism to identify early biomarkers. We started characterizing sleep and hormone profiles starting at 3 months old, with the idea that, if we could identify autism sooner via sleep or circadian abnormalities, then we could potentially begin intervening at the earliest of stages, which would be really great. Because the earlier the treatment, the better the outcomes.

There were unanticipated logistical issues with some of this, of course. I don’t know if you’ve ever tried putting an actigraph watch on a baby, but you have to put it on their ankles, because even on the tightest setting, the watch band slips right over their hands. You still get pretty robust patterns in activity data but one of the issues with this study was that they all had older siblings, and some of them liked to play with the watches, and so the watches sometimes went missing.

Yeah, I can only imagine how often those watches do get lost.

Right! Just collecting the data was surprisingly difficult. The families already had a lot going on because they had young children, some with special needs. So, it was challenging, but these families were great.

The other challenge was that babies have polyphasic sleep. That makes scoring and analyzing activity data for common sleep parameters a little tricky because the babies are sleeping at all times of the day and night. As they get older, their sleep gets more and more consolidated, and then it becomes easier to analyze in the ways we normally do. But it’s hard to look at maturation because you can’t analyze their sleep in exactly the same way across all these ages. You can, however, easily see this beautiful consolidation of sleep in the first months of life, and we did find hints of certain differences in high-risk infants. Ultimately though, I just don’t think we had enough power in this pilot study, with so much individual variability. It would be great if we could follow up on it further. That was a really fun study.

What does a circadian-aware future look like to you? What do you think will be the biggest difference in how we talk about circadian rhythms now versus in the future?

Oh, I hope it will be treated less like its own isolated thing and become more integrated into our thinking about health and well-being more generally. We would see such an improvement in healthcare if we took into account the timing of our individual biological clock. Like, for example, what time of day is best to evaluate particular symptoms, administer medications, etc. This is a fundamental change that some in the field are already trying hard to address. Many health and safety issues could be treated more effectively, if they were considered in the context of the circadian system.

Yeah, that’s a really good point. People often hear the words circadian rhythm or circadian clock and they automatically associate it with only sleep. When in fact, every major organ in your body has a circadian clock.

Right, yeah. It’s funny you say that because, as I mentioned earlier, I usually consider my expertise to be in circadian biology. So, whenever someone mentions sleep, I’m like, well, I don’t really know that much about sleep because I am primarily focused on the circadian system. Because of that though, I also think about circadian health more broadly, and I hope that becomes the norm as we move forward, rather than this hyperfocus on just sleep.

Of course, I also think getting a sufficient number of hours of sleep is incredibly important. Sleep is important. But that’s sometimes the sole focus. Getting high quality sleep is also very important, and that is significantly impacted by timing. If you’re not sleeping at a time when your circadian physiology supports it, it may not be very good quality sleep. For example, someone could get 10 hours of sleep but if it’s poor in quality because their brain thinks they should be up and about, they may not feel rested and maybe aren’t getting what they need from sleep, even though they’re spending a lot of time doing it. In this way, quality can be just as important as quantity.

What do you think is the coolest thing about light that people don’t know?

Firstly, light’s profound influence on our health and well-being continues to blow me away, and I think many people still don’t have a full appreciation for that. But another thing I think is cool is the fact that light acts like a drug, though without all the side effects. There is even a dose response to light, just like you see with many medications. You need a certain amount of light to get any kind of benefit. Then, as you increase the amount of light, you get more and more of an effect until it sort of maxes out, and more light isn’t going to make a difference. That’s how we characterize medications. The fact that we see this with light is so cool to me, and I think that this dose response sometimes helps people believe that the physiological effects of light are a real phenomenon, and that light has the potential to impact our health just as much as a medication.

Right. Getting people to understand how much light impacts them can be a hurdle. 

That’s right, it really is. I don’t know how you get around it because it’s not an experience that we’re conscious of, for the most part. Especially in the context of circadian regulation. I think the effects of light on alertness or mood may be a little bit easier to notice, maybe also because they occur across a shorter time scale. But I think people find it hard to believe that getting more light in their morning, and avoiding too much light at night, is the reason why their sleep or metabolic health has improved.

Definitely. Are there any aspects of your research that we haven’t touched on that you’d like to highlight?

Well, we recently developed an educational program called Circadian, Light, and Sleep Skills, or CLASS. It’s a brief, 30-minute program that teaches the basics of sleep and circadian physiology, and offers concrete tips for how to optimize health under real life circumstances. The program has been tailored to multiple different populations, and we have found it increases sleep and circadian knowledge, positively changes sleep-related behaviors, and improves sleep quality, which also improves mental health.

We also do a lot of studies in shift workers, and a big part of our research program right now has been to develop novel lighting strategies using spectral engineering to help people stay more alert during work shifts, or to facilitate adjustment to non-standard schedules. I think there are definitely some ways that we can improve the lives of shift workers. I mean, we’re not going to get rid of shift work altogether; however, we can help those working non-standard schedules to stay alert and safe, and adapt as best as possible. So, those are some of the things we’re thinking about.