In our study, we demonstrated differences in rest-activity, peripheral temperature, and light intensity rhythms in depressive patients compared with healthy subjects. Additionally, we described the capacity of chronobiological variables to discriminate among the different stages (acute and chronic) of a depressive disorder.
With regard to the rest-activity rhythm, we observed that patients in their first depressive episode showed a decrease in amplitude compared with the control group. The amplitude was also reduced in patients with chronic depression. The differences in amplitude might have been due to the subjects’ different activity levels because these differences were reduced according to the severity of the illness
. Because this variable was found to be a high coefficient for discriminating chronic depressive patients, it could be an important tool in clinical practice to evaluate the stage and prognosis of major depressive disorder. The increased circadian amplitude in the rest-activity rhythm of healthy subjects could also be explained by the increased entrainment to external Zeitgebers, most likely by the maintenance of robust social and biological Zeitgebers that are essential for life
In the current study, we found that the duration of time that the temperature remained above the mean was higher in the depressive groups than in the control group, suggesting that this variable is a good indicator of the time that subjects might have been in bed or had a low activity level. Activity level is decreased with the severity of the pathology. Several hypotheses have been proposed attempting to relate circadian differences with mood disorders
, including the phase advance hypothesis, and reduced amplitudes in depressed patients. Findings from previous studies on the amplitude of the temperature rhythm in depressed patients have been inconsistent, perhaps reflecting differences in the samples of depressed patients studied due to differences in the stage or aetiology of the disorder. Therefore, an elevated nocturnal temperature has been reported by some authors
[32, 33], whereas a blunted or unchanged temperature rhythm has been observed by others
In our study, the amplitude of the activity rhythm was capable of discriminating healthy people from acutely depressed patients. This result might be a marker of the beginning of the disorder because the coefficient of the amplitude of activity presented as the highest discriminant value (0.8). However, the amplitude of peripheral temperature was insufficient to identify differences among groups, although the PV of the temperature rhythm had a tendency to increase with the severity of the pathology, suggesting a more stable rhythm in peripheral temperature values of depressed patients.
Peripheral temperature can be influenced by activity. However, in our study, we observed that there were differences between day and night for temperature values for the same relative level of activity. This observation suggests that peripheral temperature followed a real endogenous rhythm independent of activity. Healthy subjects demonstrated fewer differences between temperature values during the day and night, which is consistent with lower amplitude values in this variable. This suggested that high activity in healthy people might have masked the temperature rhythm. However, this suggestion is not completely valid, because for all levels of activity, the differences between nocturnal and diurnal values were lowest in the control group (Figure
The peripheral temperature rhythm is partly the result of alternate balances between parasympathetic (vasodilatation) and sympathetic (vasoconstriction) actions in the peripheral skin vessels, which are driven by the SCN
[35, 36]. Therefore, the lower levels of peripheral temperature during the day in depressed patients could be attributable to higher activity of the sympathetic system. This relationship supports the idea that, in depression, there might be an imbalance in the autonomic system, which could be due to abnormalities in circadian system regulation
Additionally, the results of intrinsic biological rhythms must be interpreted by examining the external rhythms induced by light exposure. The fit of the amplitude of light was highest in the control, indicating that these subjects were exposed to higher levels of light intensity. The amplitude and stability of the light rhythms were lower in the depressive groups than in the control group, which indicated that light may have had less influence on endogenous rhythms in depressed patients than in controls. Our results demonstrated that although the amplitude of light intensity was not different among the groups, the PV of light intensity values was higher in the control group than in the depressive groups, indicating more stability of this variable in the control group. Some studies have demonstrated a relationship between light intensity and seasonal depression
[38, 39]. One hypothesis that may help explain abnormalities in the regulation of circadian rhythms has suggested that changes in the length of the endogenous period leads to changes in the phase angle of light synchronisation
. Therefore, the intensity and period when the subject is exposed are important, as well as the phase and the spectrum.
The simultaneous assessment of light, activity, and temperature rhythms in the current study was essential because all three variables provided information on the functioning of the circadian pacemaker, as well as possible masking due to light exposure, and its effects on the pacemaker. Discriminant analysis provided important information about the capability of chronobiotic parameters to be considered as a tool for the diagnosis and prognosis of depression. The next step in future research is to perform a prospective study to evaluate the sensitivity, specificity, and predictive value of these parameters .
One alternative explanation for our findings related to the changes in chronobiological parameters may be related to the antidepressant treatment used in the chronically depressed patients. One study using an agonist at MT(1)/MT(2) melatonin receptors and an antagonist at 5-HT(2C) serotonin receptors showed a significant difference in the relative amplitude of the circadian rest-activity cycle
. Additionally, antidepressant treatments, including tricyclic medications, increase the circadian amplitude of temperature
. In our study, the effect of medication could not be clearly considered. Notably, the Dc patients were chronic patients who had received medication. However, in spite of their treatment, they scored higher on the depressive scales than did the Dfe patients. Therefore, we conclude that, in the current study, alterations in circadian rhythms were due to severity of the pathology and not necessarily to the medication itself.
Limitations due to the design of the study are as follows: (i) this was a cross-sectional study, and therefore, we could not establish a direct cause-consequence relationship; (ii) depressive subjects with more intense symptoms were under treatment; therefore, we could not affirm that the changes in rhythm were due only to the effect of the severity of the symptoms; and (iii) in this study, we assessed the intensity but not the quality of the light.
Finally, this study raises some hypotheses to be tested in longitudinal studies. First, it suggests that in subjects with diseases, there is a shift in circadian rhythm to adapt and maintain the energy needed for survival. Second, the results in this study underscore the theory that the lack of synchronisation between rhythms can be decoded by physiological systems as a stressor. This chronodisruption is capable of starting, accelerating, perpetuating, and exacerbating neuropsychiatric symptoms because the rhythms are integrated into basic cellular endocrine rhythms that build rhythmic, structural, and functional networks.