Rhythm and blues: social rhythms in depression— from diagnosis to therapy




Patrick LEMOINE
MD, PhD, ScD
Clinique Lyon-Lumière
Meyzieu – FRANCE

Rhythm and blues:
social rhythms in depression—
from diagnosis to therapy

>Interview wi th P. Lemoine,France

The principal synchronizer in human beings is light. Like almost all beings that inhabit the Earth, the predominant periodicity in humans is circadian. It is light that realigns rhythms that, in turn, are controlled by oscillators— notably the suprachiasmatic nuclei. It appears that the general reduction in sleeping time of nearly 2 hours nightly, observed since the introduction of electric light sources, has had notable consequences on the body weight and blood sugar levels of poor sleepers and insomniacs. It may also favor depression and aggressiveness. In the event of light deficiency, other synchronizers such as work, mealtimes, or group activities can compensate. To measure rhythms in a research context, the core body temperature can be recorded in continuous mode. The blunting or flattening of circadian body temperature rhythms constitutes the biologicalmarker that remains themost specific physiological trait in depression. In clinical practice, it ismore practical to use sleep diaries and an actimeter to measure rhythms, before turning to polygraphic sleep recordings. All these measuring instruments enable an objective view of relatively specific criteria for depression. Mood that is worse in the morning and better in the evening is one of the principal clinical markers for major depression, although it is difficult to determine whether this is the cause or consequence of physiological anomalies.

Medicographia. 2010;32:178-182 (see French abstract on page 182)

What are social zeitgebers and social rhythms?

What are the consequences if they are disturbed?

Originally, human beings were mammals that were both diurnal and arboreal, which means that their strongest sense was that of sight, their principal synchronizer or zeitgeber was light, and like almost all beings inhabiting Earth, their predominant rhythm was circadian, notably their vigilance/sleep rhythm.1 Since the invention of electricity, humans have probably lost an average of 2 hours of sleep per night. To be more precise, it is generally considered that 1 lost hour of sleep can be attributed to artificial lighting, and an additional hour to television, the Internet, or other electronic stimuli.

It is, however, difficult to confirm such theories objectively and quantitatively, because clearly no sleep recordings existed before electricity was invented. To gain an idea of the real sleeping time of pre-electricity humans, it would be necessary to record the everyday habits of humans in the rare, inaccessible regions of Africa, New Guinea, and the Amazon basin, where a few ethnic groups still live without artificial light according to a purely day/night rhythm. This would provide an objective view of the average time we would sleep under so-called “natural” conditions. It would not, however, inform us about natural conditions in temperate regions of the world.2

Nevertheless, in a recent andmore precisely-conducted study performed in the general population of North America (USA), subjects tested were reported to have probably lost an average of 21.5 minutes of nightly sleep per decade since 1960.3 If this phenomenon persists, we will reach a total of 107.5 minutes’ less nightly sleep in 2010 than in 1960, or indeed nearly 2 hours less. This is a considerable amount, and no one has a precise idea as to its effects on health, but it would be astonishing if there were none. Indeed, there is nothing to suggest that this downward trend is starting to slow, and who knows what figures might ultimately be reached, because we cannot determine the incompressible, “hard core” duration of sleep.

It is generally considered that the ideal amount of nightly sleep in humans averages around 7 to 8 hours, but with major individual variations. The sleep debt is associated with an increased consumption of alcohol, tobacco, and caffeine. Body mass index is correlated with sleep time, which suggests that chronic sleep deprivation at the continental level in North America may be linked to the obesity epidemic that is invading this region of the world.3

Some authors4 consider that the sleep debt is likely to be associated with a risk of diabetes. Although this suggestion remains controversial, it is generally true that insulin resistance is aggravated as sleeping time diminishes. A reduction in sleeping time may also be correlated with a rise in blood pressure.2 Chronic insomniacs have been shown to have lower levels of education and less favorable career paths than those who sleep well. Finally, it is also known that chronic insomnia favors depression or is even a precursor of this condition, to the point where it is thought by some that 20-yearold insomniacs will become 40-year-old depressives.5

However, it should not be forgotten that by definition, epidemiological studies demonstrate associations of phenomena, but never any causal relationships. In other words, one can say that although more obesity is found in insomniacs, this does not necessarily mean that the former is responsible for the latter. Indeed, it is possible to imagine the inverse situation, whereby those who are obese sleep less well because of their weight (experiencing different types of pain, difficulty in breathing, sweating, etc); one can also imagine that if a person sleeps badly, they may go to the refrigerator and eat what they find there. In this latter case, insomnia is the indirect cause of obesity.

A certain number of other arguments highlight the clear link between emotional control and sleeping time. It suffices to spend a night without sleep to understand the degree to which a simple reduction in sleeping time can cause moodiness, aggressiveness, episodes of crying, explosions of rage, and other emotional reactions. All these symptoms are directly linked to the most archaic parts of our brains, collectively called the limbic zone. Under normal circumstances, these areas are linked to the prefrontal lobe, which is the “adult” and reasonable area responsible for our intelligence. Indeed, many authors think that human beings are above all a “prefrontal animal.”

It was in order to allow the development of the prefrontal lobe that our ancestors experienced a gradual diminution of the supraorbital ridge and disappearance of the receding forehead characteristic of most large apes. This part of our brain, capable of controlling instinctive and affective movements, is probably the anatomical seat of what differentiates humans from other animals. Indeed, it has been shown that experimental conditions of sleep deprivation will “disconnect” the prefrontal lobe from the limbic zone. This disconnection deprives the conscious and reasonable part of our brain of any control over emotions, hence an increase in emotiveness and ultimately in violence and aggressiveness. It is therefore possible to hypothesize fromthesemechanisms that chronic sleep deprivation favors depression, which would help to explain the increased incidence of this condition at a general epidemiological level.6

However, synchronizers other than light do exist in man, but they are difficult to clarify because of the preponderant importance of light. It is in the totally blind, who by definition are deprived of sight and any light stimulation, that these synchronizers can best be demonstrated. In this population, a higher prevalence of insomnia and depression has been noted. When deprived of sight, humans as social animals call upon donors of social rhythms in order to synchronize themselves with their environment, principally by means of hearing: working or family hours indicated by the alarm clock or time clock, television programs, meals, and group activities at fixed times, or in other words, anything that “requires” an individual to adopt regular rhythms.

It is the time of getting up in the morning that forms the basis for different social rhythms, and the “chronotherapist” should use this when proposing a resynchronization program to a depressive patient.2

How can one measure rhythm disruption in depression?

In terms of fundamental research, themost important chronobiological parameter is the circadian rhythm of body temperature. Depression is probably the best example of a disease that results from circadian malfunction. The now historical data acquired by Beersma7 demonstrated an “extreme blunting or even flattening of circadian body temperature rhythms in depressives.” Body temperature rhythms drive all other circadian rhythms (blood pressure, heart rate, hormones, receptor sensitivity, mitosis, meiosis, etc). They are governed by the suprachiasmatic nuclei (oscillators) and are correlated with what has become known as “form,” ie, a combination of levels of vigilance, physical and intellectual performance, and mood.

If we accept that major depression is associated with abnormal functioning of the central oscillators, it becomes easy to understand why it is accompanied by excessive vigilance during the night, because there is no change (or only a slight reduction) in nocturnal temperature, and daytime somnolence. This is particularly flagrant in the event of major depression with “melancholy” (Diagnostic and Statistical Manual of Mental Disorders Fourth Edition; DSM IV), where time-related disturbances are of particular importance. Nevertheless, for technical reasons, it remains difficult to record variations in body temperature in everyday clinical practice.

In the context of clinical practice rather than research, a detailed clinical interview regarding lifestyle, and particularly a sleep diary, will enable the best assessment of rhythm disturbances in depression.1 This simple self-assessment tool for clinical use provides a clear picture of circadian, weekly (social), and monthly rhythms (the latter of particular value in women). The opportunity for a depressed patient to visualize, and thus become aware of, regular variations in rhythm and mood can thus constitute an important therapeutic tool. A “mental pain” item can also be added to the sleep diary that the subject can complete twice a day, once in the morning when getting up and once at around 6 PM, so as to provide an objective assessment of mood fluctuations over the day. The situation most frequently cited is that of the “melancholic feature” of major depression in DSM IV, where a worsening of pain is regularly found in the morning, and an improvement (or lightening) of mood is observed in the evening. This symptom can be considered as a marker of the severity of what was previously referred to as the endogeneity of depression.

In subjects who work, it is common to observe a worsening of depressive mood at the beginning of the week, when social rhythms have been lost during the weekend and have not yet been retrained by professional constraints (Monday mornings). Finally, in women, a gradual and general worsening of mood between ovulation and the start of menstruation, correlated with a blunting of circadian body temperature rhythms, helps us to understand why cases of attempted and successful suicides are significantly more numerous during the week preceding menstruation. Premenstrual syndrome can then be considered as equivalent to depression, as progesterone is a hormone that is both thermogenic (nocturnal), sedative, and depressogenic.2

In clinical practice, it is also possible to use an actimeter, an inexpensive instrument like a wristwatch that can continuously record rhythms of movement and inactivity for periods of up to a month. This easy-to-use device can objectively demonstrate vigilance/sleep rhythms and reveal the degree of slowing of depressed subjects during the day.

Finally, polygraphic sleep recordings can be envisaged in some specific cases of insomnia or depressive hypersomnia.8 However, this remains a complicated procedure when not performed in a research context. The anomalies observed are almost constant, although not very specific when taken in isolation. They are focused on three main areas:

_ Continuity of sleep: this is the first disorder to have been noted, with a prolongation of sleep latency, and an increase in the number and duration of nighttime awakenings and waking early in the morning, all of which cause a fragmentation phenomenon that reduces the efficacy of sleep.

_ Diminished delta sleep: this trait has been found by all authors, even if it does not concern all types of depression. Spectral analysis shows that this loss of delta sleep is of major importance during the initial period of sleeping, but that it also persists throughout the night; there is an abnormal distribution of delta sleep, because it is less well represented during the first sleep episode than during the second episode.

_ Paradoxical sleep (PS): classically, there is a reduction in the latency of onset of the first period of paradoxical sleep (<90 minutes), and an increase in the duration of this first episode, often accompanied by increases in the density of rapid eye movements and the percentage of PS compared with total sleep.

The specificity of the reduction in PS latency for depressive sleep can reach 70%, and if several of the aforementioned parameters are combined, it is possible to clearly distinguish depressive from healthy sleep, and the sleep of elderly individuals with depression and pseudo-dementia from that of those with Alzheimer’s disease. The association of latency of the first PS episode and prolongation of the first PS episode is a clear sign of depression, although this parameter is not unanimously recognized; some authors consider it as a simple reflection of the number of daytime naps, as depressed individuals adopt clinophiliac behavior like those who take naps under normal physiological conditions.

Morningness and eveningness: are they predictors of depression?

In a recent, as yet unpublished study, we tried to correlate “morningness” and “eveningness” types of individual with various psychiatric disorders managed by clinical psychiatrists. Two thousand subjects were assessed. No correlations were found with any psychiatric disorder.

However, the aforementioned clinical rhythms in depressed individuals may give a temporary illusion of “eveningness,” as patients are generally in better form in the evening than in the morning. In addition, clinical experience quite frequently shows that in depressed individuals, behavior that mimics “evening” subjects with late arising in the morning (more than 30 minutes after spontaneous awakening) causes a morose mood and a certain number of depressive symptoms. It is then possible to consider that for a “morning” subject with a chronorigid nature, extending morning sleep time or traveling eastward by plane, ie, creating almost experimental conditions of phase delay, represents an increased risk of depressive decompensation.

It is based on this type of clinical observation that some authors have proposed phase advance for therapeutic purposes; in practice, they propose that individuals get up much earlier in the morning and definitively ban any morning lie-ins. Getting up quite early, always at the same time, followed by healthy rhythm measures such as physical exercise, a hot shower, exposure to a brilliant white light with an intensity of 10 000 lux for 30 minutes, and a relatively high-protein breakfast, can enhance living conditions for depressives, and (although it remains speculative) bring about a reduction in the risk of relapse after remission.2

Diurnal mood rhythms in depression: do they result from weakened circadian function? Are there core or associated symptoms more specifically treated by social rhythm therapy?

This issue could be compared to that of the chicken and the egg: which comes first? Is it an anomaly of circadian temperature rhythms that provokes depression, or does the particular behavior of depressed individuals alter their circadian rhythms? At present, it is impossible to answer this question with certainty.9 Nevertheless, the polysomnographic anomalies observed, notably at the level of PS and delta sleep, appear to persist during remission, which might suggest that they are more a trait of depressives than an effect (state) of depression. It is then possible to hypothesize that a reduction in circadian rhythms, notably those of body temperature, are crucial to the problem of depression, at least in major, severe, and endogenous (unipolar and bipolar) depression.

What type of alleviation of symptoms can social rhythm therapy provide?

Whether we consider antidepressants, thymoregulators, electroconvulsive therapy, light therapy, or cognitive and behavioral therapies,10 there is a common, final pathway in the event of a positive response, which is an increase in the amplitude of circadian body temperature rhythms. Partial or total sleep deprivation also produces the same result.

Therapy involving adjustment of rhythms must be considered as supplementary to the therapies referred to above. It is thus necessary to reinforce the circadian rhythms through behavioral measures: getting up earlier in the morning (always at the same time), physical exercise immediately on rising, a long hot shower, a relatively high-protein breakfast, and exposure to brilliant white light at 10 000 lux. In the evening, no intensive physical exercise or excessively stimulating or stressful activities, an evening meal containing slow-release carbohydrates, a warm bath, and low lighting to encourage the release of endogenous melatonin.

When these recommendations regarding healthy rhythms are respected, a rapid improvement can be observed in general wellbeing and a reduction in residual symptoms: morning tiredness, insomnia, morning gloominess. Although there is a dearth of studies in this area, it is possible that rigorous compliance with this chronotherapy may to some extent reduce the risk of recurrence. _

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