Rachel Backstrom

Antidepressant Effects of Sleep Deprivation Chronotherapy in Male and Female Sprague-Dawley Rats

April 6, 2021   /  

Student Name: Rachel Backstrom
Major: Neuroscience
Minor: Biology
Advisor: Dr. Amy Jo Stavnezer

Major depressive disorder (MDD) affects a wide range of people and, within that population, some have drug-resistant depression. Previous rodent and human research demonstrates that sleep deprivation chronotherapy may provide antidepressant effects. Sex differences of these effects have not been previously investigated, despite the prevalent sex differences within MDD populations. Using a rodent model, this study aimed to (1) investigate the positive effects of sleep deprivation chronotherapy by assessing learned helplessness behavior in the forced swim test and to (2) identify any significant sex differences of these antidepressant-like effects. We hypothesized that rats treated with sleep deprivation chronotherapy would demonstrate less learned helplessness behavior (decreased immobility), female rats would show more learned helplessness overall, and females would demonstrate greater antidepressant effects of the treatment than males. The experimental rats were sleep deprived for 24 hours via the flowerpot method between days in the standard 2-day forced swim test. Immobility, swimming, and climbing were scored as measures of depressive-like behavior. Males who underwent sleep deprivation showed significantly less immobility than control males. We did not support our predicted sex difference, however, at least for males, sleep deprivation chronotherapy may be a beneficial rapid antidepressant treatment. Sleep deprived males also showed significantly more climbing behavior, which is associated with the noradrenergic systems of the brain. This may indicate that common antidepressant treatments that target serotonergic systems would not be effective for some people suffering from MDD, and that a noradrenergic targeted treatment (possibly sleep deprivation chronotherapy) would be a more effective treatment.

Rachel will be online to field comments on April 16: Noon-2 pm EDT (PST 9am-11am, Africa/Europe: early evening).

43 thoughts on “Antidepressant Effects of Sleep Deprivation Chronotherapy in Male and Female Sprague-Dawley Rats”

  1. Thanks for sharing this important work Rachel! If you had to advice a person seeking pharmaco-treatment for MDD, how would you suggest they advocate for themselves?

    1. I would say that the first step would be educating oneself. The topic of depression from a neuroscientific standpoint can be dense and vague at points, but understanding on a general level what chemicals are theorized to be involved and which medications target these chemicals could be helpful. If someone was prescribed Lexapro, for example, and they weren’t feeling as though they were progressing positively within the typical therapeutic time period and their prescriber wanted to switch them to another SSRI, it might be worthwhile to have a conversation about medications that target other chemicals, like norepinephrine.

  2. Hi Rachel,
    As someone who has dealt with some of the issues you examine in your study, your presentation really hit home. There is so much to learn about the affects of anti-depressants and I hope your study inspires others to dig deeper on the subject.
    I am proud of you and so thankful that Abby has found such a wonderful friend in you these past four years. Congratulations on a job well done at Wooster! Can’t wait to see what you do next!

    1. Thank you so much– I really appreciate it! I’m glad that my research could potentially spread awareness about these topics. I feel so lucky every day that I get to be Abby’s friend and I really cherish these four years we’ve gotten to experience together! Thanks again!

  3. Great job, Rachel! And a really important topic, especially given the current rates of ineffective treatment you cite. A couple questions: How well is it known — or not known — whether sleep disruptions actually cause depression, whether depression causes sleep disruptions, or whether both directions really do occur? Do you think that doing a 48-hour sleep-deprivation trial would produce different results than the 24-hour one?

    1. Thanks! As far as your first question, since there are many unanswered questions about both sleep and depression, there is yet to be a solid answer about the relationship between the two. However, there are some theories that I mentioned in my research that describe the possible directionalities of this relationship. Here’s an excerpt from my I.S. that explains them: “The social zeitgeber theory claims that the development of depression may be due to the disturbance of circadian rhythms, whereas the internal coincidence model suggests that depression may cause the misalignment of a person’s internal biological clock (Pandi-Perumal et al., 2020). This demonstrates the bidirectionality of the relationship between sleep and depression; sleep disruptions could cause depressive symptoms or depression could cause sleep disruptions.” As for your second question, previous research has shown that 48-hour sleep deprivation chronotherapy has similar antidepressant effects as 24-hour sleep deprivation chronotherapy. However, I think that a 24-hour protocol would be much more plausible to implement on a wide-scale.

  4. Great and interesting work about the possibility of sleep deprivation as a method of alleviating depression.

  5. Hi Rachel,
    This is sort of piggybacking on Brian’s question about sleep disturbances in depression. How would this technique transfer to a person that suffers from sleep disturbances such as increased latency to onset of sleep, insomnia, or waking in the night?

    Awesome work and very nice presentation.

    Polly

    1. Thank you for your interest! It is thought that those with depression have some clock-gene abnormalities, which can trigger some of the sleep disturbances you’ve mentioned. These sleep disturbances can further negatively progress depression symptoms, worsening sleep disturbances. Sleep deprivation chronotherapy is thought to act as a “reset button”, rebooting the involved neurotransmitter systems, possibly normalizing the chemical levels and their activity. This “rebalancing” of systems is thought to create the antidepressant effects. So not only may this treatment aid in relieving depression symptoms, but it may normalize the clock-gene systems as well (normalizing sleep cycles, decreased sleep disturbances).

  6. Nice job, Rachel! Would your next steps be to investigate those differences in sex that you mentioned, or would you want to take your research in a different direction?

    1. Thank you for watching my presentation! I think this is a field of research that has so many unanswered questions, so therefore I think there are so many directions for future research! I would love to run this experiment again using a transgenic depression model rat (WKY strain). I think this would offer a different perspective on this treatment method and its effects (FST seems to me to model the social/environmental aspects of depression whereas the WKY strain would model more of the genetic aspects of depression). I think it would also be interesting to analyze the brain tissue of the animals who underwent this treatment in order to look at possible differences in neurotransmitters, specifically norepinephrine.

  7. Congratulations, Rachel!
    I hadn’t heard of this as a possible therapy before. Do males and females differ in how many have sleep-related problems with their depression?

    1. Thank you! Women have been shown to experience more atypical symptoms, particularly seasonal affective disorder (SAD). This would suggest that women may be more sensitive to light exposure/day length changes. I would predict that this potentially increases women’s vulnerability to sleep disturbances related to depression, at least more so then men.

  8. Rachel-

    Congratulations on this interesting study. Especially impressive in this crazy C0vid-influenced year.

    I have never heard of sleep depravation as a treatment for depression. Have any studies been done measuring how long the anti-depressive effect lasts? How common is this a treatment used for humans?

    Again, congratulations on completing this study.

    Enjoy the rest of your senior year!!

    1. Thank you so much! This is a relatively new treatment method, with a very limited amount of both human and rodent research. I didn’t even know of this treatment until I began researching potential topics for this project a year ago. I think that this treatment potentially could fill what I see as a large treatment gap for depression, particularly because the effects are rapid, which is greatly lacking in common methods. The longevity of the effects varies– some sources report that the effects may go away once the individual has regained their sleep patterns and some report lasting effects for months after treatment. I think that this treatment is most promising in that it can be paired with many other treatments (like bright light therapy, talk therapy, and medication) to increase and prolong the effects (triple chronotherapy is a very interesting, sleep-targeted depression treatment). Sleep deprivation chronotherapy has also been shown to increase responsiveness to pharmacological treatments, as well.

  9. ABSOLUTELY BRILLIANT PRESENTATION!!!! Very professional–we’re (mom, Gpa, Gma) very proud of you!!! Can’t wait to see what you do next!!

    Questions from Gpa and Gma: Do you suspect that differences in hormones between males and females is somehow related to your statistically significant findings?

    1. THANK YOU SO MUCH! I’m so glad you could watch my presentation! While I’m not sure if sex-related hormones played a role in my results specifically, the literature discusses their potential role in human sex differences in depression. Estradiol may play a role in these sex differences, as this hormone impacts serotonin activity, which may influence how the sexes respond to some pharmacological treatments. It would be a very interesting future study to focus on the effects of sex hormones and their role in depression treatment methods! Love and miss you all!

  10. Hi Rachel! This is such an interesting and thought provoking study and I appreciate the chance to learn more. Very relevant and timely!

    We cherish the time we’ve spent getting to know you and think of you as our third daughter! We are here for you with much love and support!

    1. Thank you so much for taking the time to watch my presentation! I can’t tell you how much I’ve appreciated all your love and support, and for raising my best friend. I can never thank your family enough for everything they’ve done for me. Love and miss you all– I can’t wait to see you at graduation!

  11. Hi Rachel,

    Congratulations on an excellent study and wonderful presentation! We are looking forward to following this very interesting topic and seeing what other amazing things you accomplish in the future!

    Anne & Dave

    1. Thank you so much!! I miss you guys tons and hope to get to see you soon! Love you all!

  12. Fantastic work Rachel! I am so proud of all that you’ve accomplished this year, especially with IS. Your tenacity and work ethic is so inspiring, and I am so glad that I was able to watch you grow throughout this year.

    Being your friend here at Wooster as been the greatest joy in my life, and I am so grateful to have gotten to know you. Can’t wait for many more adventures and accomplishments to come. Love you always ❤️

    1. Hunny you’ve got me crying in Low. I LOVE YOU SO MUCH!! I’ll never be able to thank you for all the love and support you’ve given me these four years; whether that’s in the form of Bachelor nights, spilling tea at din, or simply being there for me whenever I need it. I am so lucky that I met you at ARCH and have been friends with you since day 1. You’ve helped me grow more than you know and I’ll be forever grateful for that <3

  13. Amazing job Rachel! I’m so proud of you and your hard work, and I think your study is so interesting and important! I’m so glad we could keep each other sane while finishing IS! Thanks for being the best roomie and friend ever, I love you so much! Congratulations!

    1. I honestly don’t know if I could have gotten through this process *drink* without you. We kept each other motivated and sane (as much as we could) throughout I.S. and now we get to celebrate together! This time is so bittersweet– I feel so lucky that I found you at Wooster because you’re the best friend I’ve ever had and I will always cherish all the memories we’ve made. I’m going to miss being your roommate so much and I’ll always be thankful for how much you’ve done for me. You’ve helped me grow and realize so much about myself, and I’m a better person because of you. I love you so so much!

  14. Congratulations on an awesome project, Rachel! Your findings were really thought-provoking and I feel like I understand medication for depression much better after learning about your research. Wishing you all the best!

  15. Thank you for your excellent work. I enjoyed your presentation and. hope you have the opportunity to move on in graduate school with your research interests. Important topic.
    Fran Hall (Matt’s grandmother)

  16. Hi Rachel! This was such a cool project that caught my eye immediately, and is super inspiring for a Freshman, like myself, to listen to! It’s super clear how passionate you are about the material and all the hard work that went into the study.

    I was wondering, how often would human patients receive sleep deprivation chronotherapy should this form of treatment work for them? Also, you mentioned that woman tend to show more depressive disorders than men do. Is this based on hormonal differences or could it be related to environmental factors in humans?

    Congratulations!!

    1. Thank you so much for your interest! I wish you well in the rest of your college career! As far as your questions, sleep deprivation chronotherapy is an emerging treatment method, so there isn’t a ton of information about repeated use. I would think that the treatment could be implemented multiple times when rapid effects were needed, but that overall the treatment would be most effective when paired with other treatments (therapy, bright light treatment, medication, etc.). Also there are theories as why the depression rates in women are greater than men, including societal impacts, sex hormones, and differences in neurotransmitter system functioning.

  17. Rachel,

    This is really interesting work and has real implications for the field! Congrats!!

    Are you interested in continuing this type of work in the future?

    1. Thank you so much for watching!! I would love to look more into the fields of sleep and mental health, as well as furthering this particular research as well. I was really surprised and fascinated by my results, so I’d love to do more research.

  18. Congratulations Rachel!! Your presentation was really interesting and insightful, and I am wishing you the best as you move forward from your time at Wooster!!

  19. Awesome job, Rachel! You’re my neuro inspiration, and I’m glad to see all your hard work come together. Thanks for sharing!!

    1. You’re too sweet!! Thank you so much! I’ve really been inspired by you and loved all the different conversations we’ve gotten to have both in and outside of class!

  20. Wow
    What a fantastic study and presentation. Will you be doing more study’s on these topics, maybe grad school? Congratulations again.
    Peace and Love

    1. Thank you!! I would love to investigate these topics more— I think that the results I got in my research could lead to some interesting studies.

  21. Awesome job Rachel! You should be super pleased to know you’ve contributed to such an important field…work that will directly improve the lives of many!

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