Biological Rhythms as a Basis for Mood Disorders

Biological Rhythms as a Basis for Mood Disorders

Patrick C. Marino Rochester Institute of Technology

Biological rhythms control much of the body's normal functions, including performance, behavior, sleep and endocrine rhythms. These functions are primarily regulated by the circadian clock, a cluster of nerves located on the hypothalamus in the brain. The circadian clock relies on environmental cues to regulate its function, primarily light cues from the day/night cycle. Abrupt shifts in routine, such as shift changes, or travel resulting in jet lag can alter the sleep cycle and have a detrimental effect on normal circadian rhythms. Additionally season changes, which are accompanied by a decrease in the number of daylight hours, can negatively impact the function of the circadian clock, primarily the secretion of melatonin to induce sleep. If the alterations in biological rhythms are strong enough they may lead to mood disorders including mild depression and seasonal affective disorder.

The following is an analysis of the relation of biological rhythms to mood disorders. The goal is to identify and describe the various cycles that exist within the body to maintain a harmonious rhythm, including circadian rhythms, chronobiological factors, and biopsychosocial rhythms, specifically their relation to the seasons. Once an understanding these rhythms has been gained it is possible to determine external factors, which act to significantly, disrupt their harmony.
Finally by relating the function of biological rhythms to the psyche, specifically their impact on mood and personality it is possible to show how a shift can result in a disorder. In addition to reviewing the stated relationships this analysis will also cover methods of preventing and treating mood disorder that result from changes in biological rhythms.

Biological Rhythms
By taking the two words and breaking them down into their separate meanings a definition of biological rhythms evolves as, life which involves a recognizable pattern of change over time. There are two major categories of biological rhythms, endogenous, and exogenous. Endogenous rhythms come from within and are regulated by the organism itself, for example the body temperature cycle. Exogenous rhythms are the result of external factors, such as a change in the seasons, or the transition from day to night. Environmental stimuli that help to maintain these cycles are called zietgebers, which comes from German and translates as "time givers." Zietgebers include sunlight, noise, food, and even social interaction, all cues that help the biological clock maintain a 24-hour day.
There are four categories of biological rhythms that extend beyond just classifying them based on internal and external sources. This system maintains that criteria, but extends to include the duration of the cycle as a defining factor. The resulting categories are circadian rhythms, diurnal rhythms, ultradian rhythms, and infradian rhythms.

Circadian Rhythms
Circadian rhythms are defined as an endogenous rhythm pattern that cycles on a daily (approximately 24 hour) basis under normal circumstances. The name circadian comes from the Latin circa dia, meaning about a day. The circadian cycle regulates changes in performance, endocrine rhythms, behavior and sleep timing (Duffy, Rimmer, & Czeisler, 2001). More specifically these physiological and behavioral rhythms control the waking/sleep cycle, body temperature, blood pressure, reaction time, levels of alertness, patterns of hormone secretion, and digestive functions. Due to the large amount of control of the circadian rhythm cycle it is often referred to as the pacemaker.
Two specific forms of circadian rhythms commonly discussed in research are morning and evening types. There is a direct correlation between the circadian pacemaker and the behavioral trait of morningness-eveningness (Duffy et al., 2001). People considered morning people rise between 5 a.m. and 7 a.m. go to bed between 9 p.m. and 11 p.m., whereas evening people tend to wake up between 9 a.m. and 11 a.m. and retire between 11 p.m. and 3 a.m. The majority of people fall somewhere between the two types. Evidence has shown that morning types have more rigid circadian cycles evening types, who display more flexibility in adjusting to new schedules (Hedge, 1999). One theory is that evening types depend less on light cues from the environment to shape their sleep/wake cycle, and therefore exhibit more internal control over their circadian rhythms.

Diurnal Rhythms
Diurnal rhythms are an extension of circadian rhythms. Simply put the diurnal cycle is identical to the circadian cycle, with the one additional corollary that it must be in sync with the day and night cycle. In other words, for an individuals circadian rhythms to become diurnal that subject must be awake and functioning normally during daylight hours and sleeping during night hours on a fairly consistent basis. Note that it is possible to have a circadian cycle without being diurnal but not visa versa.

Ultradian Rhythms
Ultradian rhythms are defined as an endogenous rhythm pattern that occurs on a shorter time scale than circadian rhythms. As a result of the brief cycle time the frequency of occurrence is much higher. A prime example of an ultradian rhythm is feeding patterns. For the average person this cycle repeats about 3 times a day. Unlike diurnal rhythms ultradian rhythms are share no overlapping relationship with circadian rhythms.

Infradian Rhythms
Infradian rhythms are defined as an endogenous rhythm pattern that has a cycle duration longer than circadian rhythms, that is more than 24 hours per cycle. Due to the longer time frame for each cycle the frequency of occurrence in these cycles is lower than that of the circadian rhythms. The female menstrual cycle is an example of an infradian rhythm. It is a cyclical biological event that occurs in a fairly regular pattern on a monthly basis. Similar to the ultradian cycle the infradian rhythms are not directly linked to circadian and diurnal rhythms. Additionally these rhythms are not believed to be influenced by the daytime/nighttime schedule or changes in available natural light due to the fact that infradian rhythms occur in an unrelated time pattern.
By reviewing the function of these various biological rhythms it is clear to see that a majority of our physiological systems, and behaviors are directly controlled or influenced by these patterns. The question that arises is what external factors help to establish biological rhythms? Additionally what happens if the cycle is altered by a change in those external factors? In the following sections the answers to those questions will be explored, specifically as they related to mood disorders.

Factors Influencing Biological Rhythms
The major biological rhythms discussed thus far are primarily endogenous, or internal in nature. That is to say they originate from within the organism. Theoretically if we could isolate an individual from all outside influences it would be possible for their biological rhythms to normalize and occur on a strict schedule. In reality, however, we are subjected to a wide variety of changing stimuli all the time. It is not surprising then, that some of these changing stimuli have been shown to influence the regularity of our biological rhythms.

The Circadian Clock
In the physical sense circadian cycles are controlled by the circadian clock, a cluster of approximately ten thousand nerve cells located on the suprachiasmatic nuclei (SCN) found on the hypothalamus in the brain. The circadian clock's primary function is to interpret external changes of light and darkness, as well as social contact, in order to establish diurnal rhythms. It is not uncommon for the circadian clock to be disrupted temporarily, events such as changes in work schedule from day to night, changing time zones (also referred to as jet lag) and to some extent old age can impact the consistency of circadian rhythms.

Influence of Light
Light is an important factor for maintaining biological rhythms. The circadian clock relies heavily on changes in light to determine transitions from night to day. During periods of darkness the SCN clock sends out the hormone melatonin, which induces sleep. It is plain to see how changing work schedules from the day shift to the night shift would create the need to reverse this process, which takes time and will in turn disrupt normal rhythmic patterns. Circadian rhythms in shift workers were shown to adjust an hour or two per day (Hedge, 1999). This means that it could take over one week for an individual to fully adjust to an 8-hour shift change.
Another major disruptive factor related to the circadian clock's interpretation of light is season changes. During winter months there are fewer daylight hours, as a result the level of melatonin secretion increases along with the number of hours of darkness.

Disruptions in Feeding Cycles
Previously it was mentioned that ultradian rhythms regulate short-term patterns, such as feeding cycles. Crystal (2001) has shown that behavior related to feeding is indeed caused by a biological rhythm and not external environmental cues. In order to do so he first showed that there was an increase in anticipatory activity before food was presented when a regular feeding schedule was used on rats. The schedule was made to extend beyond a 24-hour period in order to rule out time of day and environmental cues such as sunlight. It was shown that the anticipatory activity still increased even when food was withheld. Additionally the rats in the study showed a tendency to gradually adjust to changes in the feeding pattern, much as shift workers gradually altered their sleep/wake patterns after a change in working hours.
Although it has been shown that the circadian clock, located on the SCN is apparently not responsible for regulating feeding intervals, the studies conducted on rats showed that rats on a feeding cycle between 22 and 26 hours (the circadian range) where better able to anticipate food arrival than rats fed on schedules outside this range, including 7 and 34 hour intervals. Based on this information it can be shown that a drastic change in meal times would have a similar effect on the ultradian rhythms as a change in work shift has on circadian rhythms.

Caffeine's Influence on the Circadian Clock
In addition to these major influences there are a variety of other environmental factors that may have an impact on biological rhythms. A stand out among those currently being researched is caffeine. A series of experiments on caffeine revealed differences in the effects of the drug depending on time of day. In the morning caffeine was shown to hinder low impulsives while helping high impulsives, while the opposite was true in the evening (Revelle, Humphreys, Simon, & Gilliland,1980). This finding suggests that low impulsives and high impulsives differ in the phase of their diurnal rhythms, which resulted in a difference in the effects of caffeine.
By establishing an understanding of the environmental factors that influence biological rhythms it is possible to begin drawing connections between the resulting shifts and mood disorders. It is important to note also that a significant shift must occur before a mood disorder, or any other mental or physical health problem will develop. Most living things experience fluctuations in waking/sleeping cycles and feeding cycles for example, however the amplitude of those fluctuations is generally small enough that normal rhythmic cycles can adapt without a detrimental impact on health. The question that arises is when do health problems, specifically mood disorders; develop as a result of shifts in biological rhythms, and what combination of environmental factors leads to those shifts? Furthermore, what can be done to prevent mood disorder causing shifts, and how can existing mood disorders of this form be treated?

Mood Disorders and Biological Rhythms
Mood disorders are characterized by opposite polar moods: depression, which involves extreme feelings of sadness and dejection, and mania, which involves unrealistic feelings of excitement and joy. There are a variety of unipolar mood disorders, which involve mania or depression, and bipolar disorders, which are characterized by both mania and depression.
Sleep and Depression
As previously discussed the circadian clock is responsible for controlling sleep patterns. Melatonin secretion from this region of the brain actually induces sleep. Commonly depressed patients experience a wide variety of sleep disorders. It should come as little surprise then that there is a connection between disruptions of the circadian cycle and depressive disorders. Generally a decreased amount of deep sleep per night comes just before the onset of depression. Therefore a drastic change in sleep schedule caused by extensive occurrences of jet lag, or multiple shift changes may result in a disruption of circadian rhythm function. In these instances it is possible for the circadian clock to induce REM sleep 15 to 20 minutes earlier in the sleep cycle, resulting in decrease in the amount of deep sleep, and ultimately leading to the beginning stages of depression (Butcher, Mineka, & Hooley, 2004).
In order to help prevent disruptions in the circadian sleep cycle it is important to maintain a regular sleep schedule, which includes retiring and waking at approximately the same time each day, and sleeping a consistent number of hours each night. This is especially important for people with morningness tendencies because their circadian cycles are less adaptable to changes in behavior.

Seasonal Affective Disorder
In recent years psychologists have recognized the impact of seasonal changes on mood and behavior. Seasonal affective disorder (SAD) is a unipolar mood disorder in which patients are highly responsive to the total amount of light available in the environment (Oren & Rosenthal, 1993). Individuals who suffer from seasonal affective disorder show signs of depression during the fall and winter months when there are fewer hours of sunlight each day. Disturbances in mood are the main psychological component of seasonality (Ennis & McConville, 2004).
Persons suffering from seasonal depression generally show an increase in appetite and hypersomnia, which oddly is opposite of the behavior normally associated with most other forms of depression. This behavior is consistent with research conducted on animals and may be related to baser survival instincts. The explanation behind this theory is that like some animals people may have a natural tendency towards increasing fat stores in the body during the winter, as well as sleeping more often in order to preserve energy levels.
Several more recent studies suggest that suffers of seasonal affective disorder display disturbances in their circadian cycles, as indicated by less consistent rhythm patterns. A common therapy used to treat seasonal affective disorder is light exposure therapy (Oren & Rosenthal, 1993). Though the effects of light exposure are not completely understood it has been shown that the presences of either natural or artificial light seems to work towards correcting circadian disturbances caused by seasonality.

Conclusion
There are four types of biological rhythms that regulate cycles within the body. The primary type, circadian rhythms, controls performance, endocrine rhythms, behavior and sleep timing, and is regulated by the circadian clock, a collection of nerves located on the hypothalamus. Diurnal Rhythms are a specialized form of circadian rhythms, which are closely synchronized with day and night cycles. Both cycles have a duration of approximately 24 hours. Ultradian rhythms are biological rhythms, which operate on a shorter time scale than circadian rhythms, feeding schedules for example. Infradian rhythms are those with cycles longer than 24 hours, the most commonly studied example is the human menstrual cycle.
Although all of these biological rhythms are controlled internally there are a number of external factors that are capable of influencing their regularity. Some of the most prominent examples are exposure to light, specifically the changes caused by seasonal transitions, alterations in work shift which change sleeping schedules, jet lag, and caffeine. With the exception of light affects the other influencing factors cause sleeping patterns to change. Due to the fact that circadian rhythms can only shift one to two hours each day drastic changes in sleep patterns can have a detrimental effect on the circadian clock.
Seasonal changes cause an alteration in the amount of light that individuals are exposed to. During the months where the days are shorter, primarily in the winter, circadian patterns are disrupted. The reason is that the circadian clock is programmed to release melatonin to induce sleep, a function that is initiated by darkness. Because the sun sets earlier in winter months this reaction begins occurring earlier in the evening, which results in a disrupted sleep pattern, a common problem for depressed patients. Individuals with Seasonal affective disorder are more likely to experience the affects of this change, and are prone to an increased amount of sleep, known as hypersomnia, and an increased appetite.
There is still a great deal that is not known about the relationship between biological rhythms and mental and physical health disorders, however there is enough existing evidence to support further study in this field. By gaining a better understanding of the rhythms and environmental factors that influence them it is possible to begin making connections to mood disorders. Once the link can be traced it is possible that new treatments may develop which are designed to correct disruptions in biological rhythms, or perhaps even prevention methods, which help to avoid major disruptions.

Peer Commentary

Choosing to Work at Night: Influences on Disruption of Circadian Rhythms
Amanda K. Bruskin
Rochester Institute of Technology
Although "Biological Rhythms as a Basis for Mood Disorders" by Patrick C. Marino discussed the various biological rhythms that regulate cycles within the body, the drastic changes that can disrupt these cycles, and the psychological disorders that can arise from such disruptions, the paper lacked discussion of the effects of night-shift workers' personality and lifestyle choices on their physical and mental health. As a diurnal species, humans typically sleep at night and are awake during the day. Consequently, engaging in shift work often induces conflict between people's internal body clocks and the actual time of day. These conflicts make shift workers work when their body is preparing for sleep, and sleep when their body is preparing for wakefulness. It is clear, however, that the extent to which a worker's circadian rhythms adjust to a new schedule dictates how severely the shift work will affect the worker.
In attempts to reduce the problems of night-shift workers, companies have focused on the design of shift systems, generally agreeing that those systems that minimize circadian rhythm disruption are preferable to those that do not. One of the main debates is whether or not to maintain a permanent night-shift system, or to implement a rotating-shift system, whether it is a slow or rapid rotation. While it seems preferable to use a permanent schedule to maximize worker adaptation and decrease disruption of lifestyle, rotating shift systems offer the benefits of minimized adaptation, and thus less disruption, as the number of consecutive night-shifts is reduced.
Despite concerns that permanent night-shift workers' circadian rhythms never fully adjust to a nocturnal lifestyle, studies have shown that permanent night-shift workers report fewer sleep or social-related problems than rotating-shift nurses do. In addition, permanent night-shift workers reported fewer health complaints than rotating-shift workers did, despite their older mean average age (Burton & Folkhard, 2001).
One explanation of these differences might be that night-shift work is more appealing to some individuals, as it allows flexibility in child-care, and an increased pay scale. As a result, night-shift workers are more likely to organize their lives to take account of unusual work schedules. Rotating-shift workers have not specifically chosen to work at night, but work nights as a part of a rotating schedule. Thus, these workers are more likely to find night shifts a disruption to their typical diurnal schedule.
An alternative explanation might involve differences in circadian type that allows people to readily adjust to shift work, and those who do not. Researchers have defined circadian types as having three dimensions, including flexibility of sleep timing, ability to overcome drowsiness, and a preference for evening activity as opposed to morning activity (Folkard, Monk, & Lobban, 1979).
In addition to finding that permanent night-shift workers report fewer health, sleep, social, and domestic complaints that rotating-shift workers, Burton (1994) discovered that these problems were drastically reduced in workers who had specifically made the decision to work at night. In contrast, it did not appear beneficial to have chosen to work a rotating-shift schedule. The strength of these findings is increased when one considers the large age discrepancy between the two groups: permanent night-shift workers were significantly older than the rotating-shift workers were. Thus, given the association between increased age and intolerance to shift work, one might have expected more problems to be reported by the permanent night-shift workers.
The results of this study contain obvious implications for the future design of shift systems, particularly in industries currently moving away from permanent night-shift systems towards systems of internal rotation. Contrary to much of the shift-system design literature (e.g., Knauth, 1993), permanent night-shift work does not appear detrimental to individual health and well-being, when compared with systems of rotation. This permanent system may even result in fewer problems if workers specifically made the choice to work at night.
Marino very clearly explained the body's circadian rhythms' origins, influences, and their relation to specific psychological disorders like depression and seasonal affective disorder. While briefly touching on events that can disrupt the body's circadian rhythms, Marino provides an excellent introduction to the study of circadian rhythms and their influences on our physical and mental health.
As our society continues to grow, industries seek to maximize production time, increasing the need for night-shift workers. Hospitals requiring round-the-clock care have always faced the issue of employing night-shift workers while simultaneously ensuring that their workers' health is not in jeopardy. Our species has evolved to be diurnal, and while the circadian rhythms that make us drowsy and hungry seem unchangeable, drastic shocks to the system, like traveling through multiple time zones in one trip, or working a rotating-shift schedule, can disrupt these innate systems, leading to serious physical and mental health problems.

Peer Commentary

Depression Caused by Lack of Sleep? What a Nightmare!
Alexandria K. Cherry
Rochester Institute of Technology
Biological rhythms affect many aspects of general health and mental well-being. These rhythms, however, cannot cause a major disorder. An example of this, taken from the paper in question, is jet lag. A person who has jet lag may often seem to have a mood disorder, with a state of mania and/or a state of depression. This person, however, does not stay in this state and will probably never experience it again after the first occurrence. This suggests that biological rhythms, when changed drastically, can affect one's well-being for a period of time, but the effect is not permanent.
The idea that biological rhythms affect one's physical and mental states seems logical. It also is clear that when one of these rhythms is altered drastically, it can cause symptoms similar to those of a mood disorder. This in no way means that biological rhythms cause mood disorders, as this paper suggests. The flaw is that a person exhibiting these symptoms moves back to a normal pattern after a while. This is not to say that there may not be some relation between biological rhythms and mood disorders, but one does not cause the other. To suggest such, as this paper does, is absurd.

Peer Commentary

Do We Really Know How to Read the Clock?
Jeremiah E. Harmon
Rochester Institute of Technology
The study of physiological rhythms is a relatively new science, and the impact those rhythms have on a person's mental health is even less understood. As a result, much of the perception of experts in this field is based on minimal research. Although what has been found is valuable, it must be interpreted carefully.
For example, changes in sleep pattern have been found to be correlated to major depression. Specifically, decreased amounts of sleep have been known to happen before depression. This could mean that poor sleep patterns due to environmental variables like jet lag or shift changes on the job could reduce a person's amount of deep sleep, causing the first stages of depression (Butcher, Mineka, & Hooley, 2004). Does this mean that depression can be caused by sleep loss?
To take one example, a significant number of depressed persons are in their teens. At this age, a significant amount of external environmental variables are controlled. For example, minors in school cannot work night shifts or excessive hours per week. Their sleep schedule is further moderated by a regular schedule, which promotes regularity in time spent sleeping each night. Few would argue that sleep patterns and mood disorders are unrelated, but to determine which is caused by the other still must be done, and when more research is completed we might even find that it varies on a case by case basis.
Another consideration is confounding variables. Many disorders are related to depression and cause sleep disturbances of their own, such as generalized anxiety disorder. Certainly some number of depressed participants in a study have comorbid afflictions. A worthy pursuit of future research would be to gauge the impact of such complications on depression and sleep habits. Despite these issues, there is certainly some link between the two.
There are many other psychosocial and interpersonal benefits to a regular sleep schedule as well. It is well accepted that deficits in interpersonal relationships can contribute heavily to the onset of depression and depressive episodes. In modern times of less family contact and support, a person has far fewer options and opportunities for interpersonal contact late at night and in the morning than in everyday activities. This is particularly true of someone living alone. Certainly a more regular sleep schedule has the added benefit of providing a patient with more, healthier, social contacts and supports to act a as a protective factor against depression. This could also be affected by the impact of light on the psyche discussed in the paper. A person who is awake to enjoy the benefits of natural light during the day has an advantage over someone who sleeps through much of the day and remains awake at night, without this protective factor.
It is common when dealing with issues regarding depression to find that depressive episodes can be brought on by life changes that cause stress, such as moving or changing jobs. Put conversely, a regular pattern in one's life can help prevent depression by avoiding situations that cause stress and a perceived lack of control. Many biological rhythms, such as sleeping and eating patterns, could be viewed in the same way. Indeed, maintaining what most would consider an unusual pattern such as a lack or excess of sleep can be handled more easily than frequent transitions between too much and too little. Achieving homeostasis is one of the most basic functions of the human body, and to impede that by introducing environmental changes is known to contribute to depression. Without a doubt, more attention should be paid in the future to these rhythms and their impact on mental health.

Author Response

Impact of Changes in Biological Rhythms
Patrick C. Marino
Rochester Institute of Technology
I would like to start by offering my thanks to those who read my paper and offered additional insights that I was unable to cover in the original paper. I feel that many of the topics touched on are important, and I am glad it was possible to include them in this manner.
In response to Bruskin's commentary entitled "Choosing to Work at Night: Influences on Disruption of Circadian Rhythms," I would like to make several points. First, I am pleased that someone elaborated on this topic, as I have worked many late shifts. In the commentary, Bruskin mentioned how a consistent night shift schedule is less detrimental than a rotating work schedule. I am in agreement with this concept. As stated in the original paper, it takes approximately one week for the circadian cycle to adjust to an 8-hour shift change. Clearly in a constantly changing schedule, a weeklong period of adjustment rarely occurs; however, for those who have worked a night shift for many years, their bodies have long been adjusted to this routine.
Another interesting point made was that those who chose to work a night shift showed fewer problems and complaints than those who chose to work a rotating schedule. I would be interested to see some further investigation as to the motivation behind those choices--specifically whether they were made owing to preference or necessity. The last point that I wanted to touch on was the concept that older night shift workers showed fewer complaints than younger rotating shift workers. It was my finding that age plays a role in length of time required to adjust to a new schedule but not in the number of problems arising as a result of the change. Therefore, it is hard to draw any conclusion from this finding, owing to the fact that a consistent schedule, regardless of time of day, is always better than a rotating one. I would like to see additional data showing the number of complaints of older workers on a rotating basis versus complaints of young night shift workers; I believe such data would illustrate that age is not a major factor in this scenario.
Cherry's commentary "Depression Caused by Lack of Sleep? What a Nightmare!" chose the opposing viewpoint toward the influence of biological rhythms on mood disorders. Cherry argued that the concept of jet lag causing a major mood disorder is absurd, because jet lag is a temporary condition, the effects of which are not drastic enough to cause such a disorder. I agree. The intention of my paper was not to argue that minor disruptions in normal circadian rhythms lead to major mood disorders. The examples given were intended to clarify common changes in normal rhythmic patterns. The underlying concept, however, was that prolonged exposure to these changes, such as occurs in shift work (see the commentary by Bruskin) can build up, thus causing a mood disorder such as depression. Understandably, one case of jet lag is not enough to cause symptoms lasting long enough to meet DSM-IV criteria for a mood disorder, but consider a flight attendant who is exposed to these effects daily for months on end, and it becomes easier to see how the constant changing in cycles could result in a mood disorder.
Harmon, in "Do We Really Know How to Read the Clock?" offered further insight into the field of physiological rhythms. As Harmon mentioned, this is a relatively new field and there is still not an extensive amount of research regarding the importance of biological rhythms. One of the major debates that was touched on is whether changes in sleep patterns are a cause of mood disorders, which is my viewpoint, or whether the change in sleep patterns is a result of some other factor such as an anxiety or mood disorder. Others argue that a causal relation cannot be inferred between the two, as depression and anxiety, which go hand in hand with disruptions in the sleep cycle, may be the result of another factor such as the loss of a job or the end of a relationship. I agree with Harmon in that more attention should be paid to the relation between biological rhythms and mental health, and I look forward to seeing what future research in this area may bring.

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