Wait…birds with OCD? Well, animal models of OCD (e.g., in mice) do exist and help us learn more about how obsessive-compulsive disorder (OCD) develops, is maintained, and can be treated. In this case though, we are talking about “night owls” and “morning larks.” 

These terms describe people whose biological clocks are programmed to feel and function best earlier (larks) or later (owls) in the environmental day. Variability in functioning across the day has been studied for decades, but whether differences in one’s biological clock — circadian rhythms —  are related to psychopathology has only begun to be examined. In individuals with OCD, there is evidence that differences in sleep behavior and biological clocks may be associated with symptoms and responses to existing treatments. Work examining these relations is carried out across the globe and garnering more attention, as more research publications and presentations are being published year after year.

The IOCDF’s Young Investigator Award program just completed its support of my project, which examined circadian rhythms of melatonin (a hormone associated with the sleep-wake cycle) production in individuals undergoing intensive residential treatment for OCD. With the support from the IOCDF, my team recruited 23 individuals to participate in a study where the timing of their bodies’ production of melatonin was measured at four time points during their residential treatment. Typically, diurnal species like humans produce essentially no melatonin during the daytime and have a rapid onset of melatonin release in the evening, usually a couple of hours before they fall asleep. Melatonin production is suppressed by bright light (like sunlight), and so the saliva samples collected in our study were collected in dim light. This allowed us to determine the time of onset of melatonin production, which is known as the dim-light melatonin onset (DLMO) and represents the transition of one’s biological clock from “daytime” mode to “nighttime” mode. In “daytime” mode, our bodies are organized to interact with the environment and gather what we need (e.g., solve problems, maintain relationships, eat, etc.). In “nighttime” mode, our bodies are organized to focus on internal processes (e.g., restoring, cleaning, consolidating memories, etc.). 

My team adapted a method for estimating when participants would produce melatonin and then collected saliva samples to capture the moment when their bodies actually started producing it. This was a first in residential treatment for OCD and was highly successful (98% of samples collected passed quality control checks, and DLMO was identified in 82% of the acceptable-quality samples). As a pilot study, this demonstrates that this process of collecting data is effective, reliable, and valid.

Adding these DLMO data to established self-report measures of sleep/wake behavior, we      were able to observe the way that sleep behavior and biological clocks changed over the course of residential treatment. Average sleep duration at admission to treatment was 7 hours and 17 minutes. This average increased slightly by the second week of treatment (7 hours and 22 minutes), and then again by the fourth week of treatment (7 hours and 36 minutes). At the time of admission to treatment, participants were going to bed close to midnight (11:58 PM), which shifted earlier by the second week (11:05 PM), and earlier still by the fourth week of treatment (10:46 PM). At admission, patients’ average DLMO was at 10:38 PM, which is approximately one hour later than that estimated in the general population (Burgess et al., 2003) and overlapped with populations with clinically significant delayed sleep/wake schedules (Reis & Paiva, 2019). 

However, by the second week of treatment, their average DLMO shifted earlier to 9:45 PM, and remained earlier than at admission at the fourth week (10:06 PM); at the time of discharge, it was at its earliest (9:25 PM). Together, these data indicate that sleep duration, timing, and biological circadian rhythms shifted toward general population averages across residential treatment. Our team hypothesizes that the shifts in DLMO times were due to supported bed and wake times during treatment (e.g., curfew, scheduled morning groups). Whether these changes are associated with the effect of treatment on OCD symptoms is yet to be determined.

I previously hypothesized that misalignment between one’s biological circadian rhythms and the environment’s demands can maintain symptoms of psychopathology. I’ve called this a “second hit” model (Nota et al., 2015; Nota et al., 2016) where vulnerabilities (the first “hits”) in attention and cognition that are associated with OCD (e.g., response inhibition, set-shifting, etc.) are specifically affected (the second “hits”) by sleep disturbance and circadian rhythm misalignment. 

In this study we defined alignment between circadian rhythms and daily schedule using midpoint of sleep phase angle (Mid-PA). Mid-PA measures the gap between one’s body shifting to “night” mode (i.e., DLMO) and the midpoint of the period of sleep for the night. There is always a gap between these, and a larger gap is associated with better alignment between your circadian rhythm and your sleep/wake schedule, as one is therefore sleeping during the time their body is “programmed” to do so and interacting with the environment at the time their body is most prepared to do so. 

For our final analyses of these pilot data, we looked for hints as to whether changes in biological clocks could potentially affect OCD symptoms by first examining whether such changes      preceded changes in OCD symptoms during residential treatment. We used a specialized data analysis called a cross-lagged panel model (CLPM). This type of model cannot determine whether the changes in either clocks or OCD symptoms cause changes in the other, but can test whether changes in one reliably predicts anything about subsequent change in the other. This analysis is important because if changes in OCD symptoms can be predicted by alignment of circadian rhythms with the environment, future experiments could test whether shifting the internal clock could help patients with OCD. 

We modeled the relations between Mid-PA and OCD symptoms across the first four weeks of treatment and identified a significant cross-lagged path between Mid-PA and OCD symptom severity. This suggests that shorter phase angle at admission (a smaller gap between your body shifting to “night” mode and the midpoint of your sleep for the night, indicating poorer alignment between your circadian rhythm and the environment) was associated with less severe OCD symptoms at the second week of treatment (Figure 1). In other words, individuals who had the shortest phase angle at admission were the ones who had the least severe OCD symptoms at the second week of treatment. Interestingly, this pattern then reversed in the next weeks, with shorter phase angle at the second week of treatment being associated with more severe OCD symptoms at the fourth week of treatment (Figure 2).