REVIEW
published: 25 January 2022
doi: 10.3389/fpsyt.2021.827541
Sleep Disturbances and Depression
Are Co-morbid Conditions: Insights
From Animal Models, Especially
Non-human Primate Model
Meng Li † , Jieqiong Cui † , Bonan Xu, Yuanyuan Wei, Chenyang Fu, Xiaoman Lv*, Lei Xiong*
and Dongdong Qin*
Edited by:
Sheng Wei,
Shandong University of Traditional
Chinese Medicine, China
Reviewed by:
Jiaojian Wang,
University of Electronic Science and
Technology of China, China
Chengbiao Wu,
California College San Diego,
United States
Zhiqiang Meng,
Shenzhen Institutes of Advanced
Technology, Chinese Academy of
Sciences (CAS), China
*Correspondence:
Dongdong Qin
qindong108@163.com
Lei Xiong
xlluck@sina.com
Xiaoman Lv
lxm.cc@foxmail.com
† These
authors have contributed
equally to this work
Specialty section:
This article was submitted to
Psychopathology,
a section of the journal
Frontiers in Psychiatry
Received: 02 December 2021
Accepted: 31 December 2021
Published: 25 January 2022
Citation:
Li M, Cui J, Xu B, Wei Y, Fu C, Lv X,
Xiong L and Qin D (2022) Sleep
Disturbances and Depression Are
Co-morbid Conditions: Insights From
Animal Models, Especially Non-human
Primate Model.
Front. Psychiatry 12:827541.
doi: 10.3389/fpsyt.2021.827541
Frontiers in Psychiatry | www.frontiersin.org
School of Basic Medical Sciences, Yunnan University of Chinese Medicine, Kunming, China
The incidence rates of depression are increasing year by year. As one of the main
clinical manifestations of depression, sleep disorder is often the first complication.
This complication may increase the severity of depression and lead to poor prognosis
in patients. In the past decades, there have been many methods used to evaluate
sleep disorders, such as polysomnography and electroencephalogram, actigraphy,
and videography. A large number of rodents and non-human primate models have
reproduced the symptoms of depression, which also show sleep disorders. The
purpose of this review is to examine and discuss the relationship between sleep
disorders and depression. To this end, we evaluated the prevalence, clinical features,
phenotypic analysis, and pathophysiological brain mechanisms of depression-related
sleep disturbances. We also emphasized the current situation, significance, and insights
from animal models of depression, which would provide a better understanding for the
pathophysiological mechanisms between sleep disturbance and depression.
Keywords: depression, sleep, non-human primate, brain development, animal model
INTRODUCTION
Sleep is an essential physiological requirement for human and most animals. A mechanistic link is
evident between sleep and depression at the molecular and neurophysiological level. The periodic
regulation of awake and sleep requires the participation of many neurotransmitters, including
excitatory neurotransmitters (such as acetylcholine) and inhibitory neurotransmitters (such as
gamma aminobutyric acid, GABA). Abnormalities of these neurotransmitter systems not only lead
to sleep-wake rhythm disorders, but also can contribute to developing depression. Depression and
sleep disturbances are common co-morbid conditions (1, 2). More than 90% percent of patients
with major depressive disorder will suffer from sleep disorders, which changed the patients’ sleep
structure. A further demonstration of the link between depression and sleep is that sleep can
be improved by most clinically effective antidepressant drugs. Compared with lower mammals,
the sleep of non-human primates (NHPs) is better comparable with that of humans. Recently,
significant progress has been made in the study of using NHPs to establish depression models.
Monitoring the sleep status of animals during modeling will help us further understand the role of
sleep in the development of depression, and provide an objective biomarker for the early diagnosis,
treatment, and efficacy evaluation.
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Sleep Disturbances and Depression
SLEEP STRUCTURE AND RELATED
NEUROTRANSMITTERS
and BF neurons (containing acetylcholine or GABA) (5). Lesions
along this path, especially in the left hemisphere and the rostral
midbrain, produce the most profound and lasting drowsiness
and even coma. The neurons in each monoaminergic nucleus
involved in this pathway discharge fastest during waking, slow
down during NREMs and completely stop during REMs. It
should be noted that all these ascending pathways pass through
the regions at the junction of forebrain and brainstem. While, the
descending pathways responsible for synchronizing phenomena
still remain largely unknown at the brain-stem level.
The pathogenesis of sleep disorder is closely related to
sleep-wake homeostasis, but the specific mechanism remains
still unclear. During NREMs and REMs, different kinds of
neurotransmitters are released in the brain. The interaction
between aminergic neurons and cholinergic neurons at the mesopontine junction leads each other to bring about the Ultradian
rhythms alternation of REMs and NREMs. During NREMs,
aminergic inhibition is decreased and cholinergic excitation
is increased. At the onset of REMs, aminergic inhibition is
turned off, cholinergic excitability reaches a peak, and other
outputs are inhibited (2). When awake, the pontine aminergic
system is tensely activated and the pontine cholinergic system
is inhibited. In addition to aminergic and cholinergic neurons,
other neurotransmitter systems are also involved in modulating
REMs/NREMs alternation and may interact with aminergic
and cholinergic systems (2, 6, 7). Extrinsically augmented
dopaminergic neurotransmission can influence both REMs
and NREMs cycles. Moreover, gamma-amino butyric acid and
glutamate also affect the REMs/NREMs cycle (2).
In short, the growth and decline of these neurotransmitters
promote the mutual transformation between sleep and wake.
If these related neurotransmitters are released abnormally,
it will cause sleep problems, such as difficulties in falling
asleep and maintaining sleep state, changes of REMs latency,
abnormal REMs behavior, and disturbed alternating pattern
of REMs/NREMs.
Sleep is vital for human beings and most animals, and
control mechanisms are embodied in all levels of biological
organizations, from genes and intracellular mechanisms to
cell population networks, and then to all central nervous
systems, including systems that control movement, arousal,
autonomic function, behavior, and cognition. Mammalian sleep
is characterized by the periodic alternation of rapid eye
movement sleep (REMs) and non-rapid eye movement sleep
(NREMs). NREMs includes two stages: slow-wave sleep (SWS)
and light sleep. In humans, SWS and REMs, which are the specific
modes of potential electric field oscillations and neuromodulator
activities, dominate the first half of the night and the latter half of
the night, respectively (3).
The mutual transformation between sleep and wakefulness is
caused by the excitation or inhibition of many neurotransmitters
in the brain, which are released by sleep-promoting neurons
in the anterior hypothalamus or sleep-inhibiting neurons in
the lateral and posterior hypothalamus activity. These neurons
release excitatory or inhibitory neurotransmitters to promote the
brainstem to control the mutual transformation of wakefulness
and sleep (2, 4).
The ascend arousal system mainly comes from a group of
explicit cells with definite neurotransmitters. The arousal system
actually consists of two channels (5). The ascending pathway to
the thalamus is the first branch, which activates the thalamus
and is essential to relay neurons for transmitting information
to the cerebral cortex. The main sources of input from the
upper brainstem to the thalamic-relay nucleus, the thalamic
reticular nucleus, the pedunculopontine, and laterodorsally
tegmental nucleus (PPT/LDT) are a couple of acetylcholine
producing cell populations. The neurons in PPT/LDT discharge
fastest during awake and REMs, and are often accompanied
by cortical activation, loss of body muscle tone and active
dreams. During NREMs, the activity of these cells is much
lower. They are important for the input of reticular nucleus,
because they are located between thalamic relay nucleus and
cerebral cortex. It is very important for arousal that they can
block the transmission between thalamic and cerebral cortex,
thus acting as a gating mechanism. From the reticular structure
and PPT/LDT, monoamine nervous system and parabrachial
nucleus in the upper part of the brain stem, have more extensive
input to the midline of thalamus and tabular nucleus. The
laminar nucleus and midline nucleus are also considered to
play a role in cortical arousal (5). Bypassing the thalamus and
activating the neuronal pathway of the lateral hypothalamic
area, basal forebrain (BF), and the whole cerebral cortex is
the second branch of the ascending arousal system. This
pathway, which covers noradrenergic locus coeruleus, serotonin
dorsal nucleus, and median raphe nucleus, dopaminergic
midbrain periaqueductal gray matter ventral and histaminergic
nodule papillary neurons, is derived from monoamine neurons
in the upper brainstem and caudal hypothalamus. Cortical
input is increased by hypothalamic lateral peptidergic neurons
(containing melanin concentrating hormone or orexin/retinol)
Frontiers in Psychiatry | www.frontiersin.org
CLINICAL CHARACTERISTICS AND
RELATED NEUROTRANSMITTERS OF
SLEEP DISORDERS IN DEPRESSION
Depression is the main cause of the burden of mental healthrelated diseases in the world, and about 300 million people
around the world are affected by depression (8). One aspect
of efforts to understand depression focuses on its relationship
with sleep. In many cases, the onset of depression is announced
through sleep disorders, and sleep deterioration occurs before
depression and manic episodes (9). There are many forms of
sleep disorders reported in patients with depression. It may
be only exhibited by the shortening of sleep time, but it also
indicates a reduction in sleep efficiency. The latter is defined
as the ratio of total sleep time to total time spent in bed
over the night. Lack of sleep increases the risk of depressive
episodes and depression relapses. Likewise, depression increases
the risk of sleep disorders. However, the self-assessment of sleep
quality in patients with depression is unreliable. Similarly, there
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Li et al.
Sleep Disturbances and Depression
are differences in the subjective and objective assessment of
daytime alertness (10). This leads to bias in the evaluation of
sleep efficiency.
Epidemiological investigations confirm that there is a closer
relationship between insomnia and the onset of depression. It is
reported that most patients often have insomnia and depressive
episodes at the same time (11). Approximately 90% of major
depressive disorder (MDD) patients have been found to suffer
from sleep disorders, including initial insomnia, difficulty in
sleep maintenance, non-restorative sleep, and early morning
awakenings (12, 13). In reality, the most common subjective
sleep complaints reported by depressed patients are insomnia
(up to 88%) and hypersomnia (27%) (14). The insomnia and
emotional symptoms are bidirectional correlated that poor sleep
may precede the onset of depression, and depressive mood
may also disrupt sleep patterns. In addition, patients with
MDD are three times more likely to suffer from insomnia
than those without (15, 16). Furthermore, fatigue, hypersomnia,
and sleepiness are closely related to depressive symptoms (14).
Many depressed patients complain about non-recovery sleep and
excessive daytime sleepiness (16), and about 15% of patients
report symptoms of daytime sedation and hypersomnia (17).
However, these findings are inconsistent (16). Depression and
hypersomnia are two conditions linked in a complex and
bidirectional manner. In addition, many patients with depression
call their complaints a combination of daytime sleepiness and
nighttime anxiety.
Since the 1960s, polysomnography (PSG) sleep studies
have repeatedly shown that depression is also associated
with disrupted sleep architecture. These abnormalities include
increase in RA (REMs activity) and RD (REMs density), as well
as a decrease in REMs latency and SWS (18). During REMs,
patients with depression often show short latency, prolonged
cycle, and increased density (19). Disorders of REMs usually
persist throughout the clinical episode, and it is considered
to increase the possibility of recurrence, and may reduce the
therapeutic effect (19–21). After antidepressant treatment, the
number of REMs is decreased and the latency of REMs is
increased. Most antidepressants inhibit REMs in patients and
healthy volunteers (22).
The increase of serotonin content may be the main reason
affecting REMs (23). Antidepressants that increased the contents
of serotonin (5-HT) in synapses are effective inhibitors of
REMs. 5HT1A agonists can be used as antidepressants and can
significantly inhibit REMs (24). However, tryptophan depletion
leads to a decrease in serotonin, which has been shown to reverse
REMs inhibition caused by antidepressants (25). In addition,
trazodone and nefazodone are also used as antidepressants
because they have a strong antagonistic effect on serotonergic 5HT2 receptors, which often promotes sleep and improves sleep
continuity (26). The percentage of REMs was most significantly
decreased in the early stage of treatment. Additionally, a
subsequent study evaluated the changes in sleep structure of 20
patients with unipolar MDD after administration of sustainedrelease bupropion, and the results showed that 8 weeks of
bupropion treatment significantly prolonged REMs latency,
Frontiers in Psychiatry | www.frontiersin.org
increased REMs activity and density in the first REMs period,
which led to increased total REM density (27).
Glutamatergic and GABAergic neurons also play a role
in the generation of REMs (28). Ketamine is a rapidacting antidepressant (29), and AMPA-mediated increased
neurotransmission is the basis of the antidepressant-like
behavioral effects of ketamine (30, 31). The enhancement of
AMPA receptor signal is participated in the pathophysiology
and the mediation of ketamine-induced rapid antidepressant
treatment (32, 33). Importantly, increased levels of ionic AMPA
receptor could promote net synaptic strength and induce
prolonged waking time in rodents and humans (34).
The REMs density of patients with depression continues to
increase, which is regarded as an endophenotype. The reduction
of the initial latency and the delta sleep ratio (DSR, the
ratio of SWS between the first two NREMs episodes) of the
rapid eye movement can be explained by cholinergic-aminergic
imbalance (35). The monoaminergic inhibition of PPT/LDT
cholinergic cells in patients with depression is weakened and/or
the cholinergic-driven effect in pontine reticular formation
is enhanced, resulting in an increase in REMs tendency
and intensity.
The initiation and maintenance of NREMs also seem to
be dependent on the role of monoamine neurotransmitters
(26). Sedative antidepressants enhance SWS and prolong sleep
duration. For instance, selective serotonin reuptake inhibitors
(SSRIs) and non-sedating tricyclic antidepressants (TCA) can
result in lighter sleep. In patients with depression, SWS and
DSR tends to be low (36, 37). Compared with REMs latency,
the measurement of SWS and DSR distribution may be a more
reliable predictor of clinical response of antidepressant treatment
and recurrence of depressive symptoms. Higher DSR may be
more conducive to the treatment of depression (38). Some lines
of evidence suggest that ketamine administration significantly
increased the intensity of both SWS and DSR in humans and
rats (39–41).
In addition, other types of antidepressants can also improve
sleep. For example, antidepressants with anti-histaminergic
action, such as mirtazapine and ipsapirone, act on their own
receptors to support homeostatic maintenance of monoamine
levels, block specifically monoamine receptors to enhance
serotoninergic neurotransmission. Some patients’ sleep can
become better even after the first treatment of mirtazapine (42).
However, increased levels of noradrenergic and dopaminergic
neurotransmission, and raised activation of serotonergic 5-HT2
receptors can worsen the quality of sleep, which are also
adverse effects of several antidepressants, such as serotonin and
norepinephrine reuptake inhibitors, norepinephrine reuptake
inhibitors, monoamine oxidase inhibitors (MAOI), SSRIs, and
activated TCA (43). During REMs, monoaminergic neurons
reduced significantly their discharge rate or stop their activity,
but cholinergic neurons become highly active (44). However,
MAOI increases the amounts of monoamine by preventing
enzyme degradation and tends to cause the absence of REMs.
One possible explanation is the antagonism of three receptors,
namely H1 histamine or cholinergic receptor and postsynaptic
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Sleep Disturbances and Depression
TABLE 1 | Comparison of different animal models used to study sleep disturbances and depression.
Animal
models
Main application fields
Pros
Cons
Zebrafish
Molecular mechanisms of sleep/wake rhythm
Low cost; high gene-editing efficiency and
relatively well-defined behavioral
phenotypes
Not yet evaluated for depression-related
sleep disturbances
(47–57)
Cat
Neuroendocrine mechanisms of sleep and
sleep deprivation
Quantitative research of neurotransmitters
Not yet evaluated for depression and
depression-related sleep disturbances
(58–60)
Dog
Sleep-wake cycle; narcolepsy; geriatric
insomnia; obstructive sleep apnoea;
sleep-associated epilepsy; and REMs
disorder
Shared risks of many sleep disturbances
with humans
More variable and fragmented sleep
pattern; not yet evaluated for
depression; and depression-related
sleep disturbances
(61–67)
Rodents
Depression and sleep homeostasis; sleep
structure; sleep-wake cycle; neurotransmitter
receptor sensitivity and neuroendocrine
stress response; as well as the effects of
antidepressants on sleep
Low cost; easy to manipulate and
gene-editing
Nocturnal animals; shorter durations of
REMs and NREMs cycles
(68–82)
Non-human
primates
Sleep-related neurobiology; neuroendocrine;
and behavioral pharmacological studies
Highly similar to humans in brain structure,
behavior, metabolism, sleep
characteristics, and circadian rhythms
Difficult to directly measure mood or
thoughts; limited behavioral screening
tools; and lack of the effects of
antidepressants on sleep
(83–97)
sleep structure (103). External stressors or risk factors of diseases
can affect the number or pattern of REMs (22, 104, 105). In
humans, REMs latency is negatively correlated with the severity
of depression (37). In rodents, changes in the REMs can precede
those of other sleep/wake stages. For example, mice that were
applied to water immersion for 2 h and restraint stress exhibited
an immediate reduction in REMs (106).
As for the effect of stress on rodents’ total sleep time, the
primary stressors are immobilization and mild electrical shock.
Immobilization increased the time spent in SWS and REMs,
while electrical shock resulted in a decrease in total sleep time and
total REMs time (107). Similarly, fear conditioning paradigms
can also induce a decrease in REMs during both the shock
training and cue exposure (104). Chronic unpredictable mild
stress can lead to changes in the amplitude of both physiological
(i.e., locomotion, temperature) and molecular circadian rhythm,
which may cause depressive-like behaviors (108).
Continuous light exposure (LL) increases depressive-like
behavior in mice, and light exposure at night (LAN) can lead to
depressive-like behavior in diurnal rodents, such as grass rats and
hamsters (109–111). This may be because LL brings about the
interrupted rhythm of locomotion, temperature, and hormonal
release, causing the disruption of circadian rhythm, and increases
of NREMs during the rest period and REMs in the active period
(112, 113).
For social species such as rats and mice, repeated fighting
and/or defeat may be a more natural source of stress. Often,
the consequences of chronic social defeat stress (CSDS) can
persist until the termination of the stressors, which makes it a
particularly attractive method to model stress-related psychiatric
illnesses (114). Previous studies have found that CSDS has a
direct effect on subsequent sleeping. Specifically, it can increase
both the total time of REMs and NREMs, as well as the density
of NREMs. However, the number of REMs is significantly
decreased in the first few hours after conflict (114, 115). Another
5HT2C receptor (26, 45). Therefore, most antidepressants
alleviate depressed symptoms by improving sleep quality.
ANIMAL MODELS USED IN THE STUDY OF
SLEEP DISTURBANCES AND
DEPRESSION
It is necessary to obtain the best animal model for studying
disease in biomedical research. Validity of animal models
depends on the extent to which how they can mimic human
diseases. Researchers have made exogenous and endogenous
animal models to simulate the symptoms of depressed patients
and elucidate the mechanisms of antidepressant action, involving
acute and chronic stress model, secondary depression model,
and genetic model (46). Translation validity of animal models
is the key to sleep disorders research. As shown in Table 1,
zebrafish, mice, rats, cats, dogs, and monkeys are generally useful
to develop animal models to study sleep disorders (49, 62, 98–
101). Among them, the most used laboratory animals are mice
and rats. However, they are quite different from humans as
they are nocturnal and adopt a monophasic sleep schedule.
While, humans follow a polyphasic sleep pattern and are very
flexible in choosing the sleep time (80, 102). Similar to humans,
more fragmented and polyphasic sleep patterns are observed in
monkeys, and they are generally active during the day and sleep
at night (84). In view of this, compared with other animals, the
sleep pattern of monkeys is closer to that of humans.
RODENT MODELS
Rodents are more usual choice of preclinical models to develop
new pharmacological and non-pharmacological strategies. In the
study of sleep deprivation, rodents (i.e., rats, mice) and humans
have many similarities in sleep electroencephalogram (EEG) and
Frontiers in Psychiatry | www.frontiersin.org
References
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Sleep Disturbances and Depression
between early adversity, chronic stress and depression was
also investigated in adolescent monkeys. Eight male rhesus
monkeys went through unpredictable chronic stress for 2
months and exhibited significant depression-like behaviors
(88). The mechanisms underlying stress-induced depression
were also explored in monkeys, and it was found that
cortisol hypersecretion interacted with stress to accelerate the
development of depressive behaviors (129).
In addition, researchers have employed NHPs animal model
to make many beneficial explorations on the association between
light deprivation and depression. The results showed that
monkeys could develop the main symptoms of seasonal affective
disorder under short lighting conditions (130). Analogous to
depression in humans, sleep disorders have been also reported
in spontaneous depressed monkeys (86). Notably, only the
hypersomnia subgroup of spontaneously depressed monkeys
shows a specific response to acute ketamine administration,
characterized as extended wakefulness and shortening of
nocturnal sleep. As a matter of fact, these changes are similar
to sleep deprivation in depressed patients, suggesting alternation
of nocturnal sleep pattern might help improve depressed mood
(86, 119, 131).
experiment also reported a brief increase in REMs time following
10 days of social conflict, but no changes in SWS were detected
(115, 116). Interestingly, there was no difference in NREMs and
slow-wave activity between winner and loser, suggesting it is a
consequence induced by the conflict process.
NON-HUMAN PRIMATE MODELS
NHPs bridge the gap between rodents and humans (117). Like
humans, NHPs have stable sleep at night and some nap during the
day. Many kinds of non-human primates, such as baboon, Kenya
baboon, South African ape, macaque, cynomolgus monkey, Pada
monkey, lemur, and chimpanzee, can be used to study sleep.
By comparing the sleep of non-human primates, researchers
generally believe that chimpanzee, olive baboon, and rhesus
monkey are better model animals. In monkeys, four sleep EEG
patterns can be easily identified. Due to its stable and perfect
sleep architecture, macaque has become the best model to study
the biological characteristics of human sleep (118–121). During
the whole night, macaques experienced the alternation of awake,
NREMs and REMs, and the total sleep time of rhesus monkey is
about 10.5 h per day. It has been found that REMs time accounts
for 23%, each of which lasts about 6 min and occurs every 51 min.
In the early stage, it is mainly deep sleep, such as SWS. While, it is
mainly REMs in the late stage of sleep. These sleep characteristics
are very similar to humans that the interval of this cycle is
about 90 min. Nevertheless, in rats, the interval is only 13 min.
Like humans, obvious theta waves cannot be recorded in the
hippocampus during macaques’ sleep (122, 123).
EEG is a common method in sleep research, which can
provide objective functional indexes for sleep (124). Although
EEG can be performed in constrained animals under laboratory
conditions, this technique is invasive. Even if it is minimally
invasive, it also needs to drill holes in the skull and implant
electrodes directly on the brain. PSG plays a cornerstone role in
long-term recording of sleep, and has become the gold standard
to evaluate sleep disorders. The recorded parameters include
the brain activity (EEG), electrooculogram (EOG), expanded
EEG montages, and transcutaneous or end-tidal capnography
waveform, which are used to comprehensively monitor the
normal and abnormal physiological indicators during sleep (125).
However, an important limitation of PSG is that it requires
electrodes and sensors (126). In addition, expensive and longterm recording intervals may be another limitation. Obviously,
these are difficult and impossible to use in freely moving
monkeys. A recent study compared videography and actigraphy
methods in 10 cynomolgus monkeys during seven nights. It
is verified that in the sleep study of NHPs, actigraphy can be
regarded as a supplementary technique for routine EEG and/or
video analysis to measure the sleep (127).
Researchers have used NHPs to make great efforts in the
research of depression. It has been demonstrated for the first time
that long-term intracerebroventricular administration of IFNα (5 days/week for 6 weeks) can induce the monkeys showing
considerable depressive-like symptoms with changes in the
concentration of monoamine metabolites (128). The relationship
Frontiers in Psychiatry | www.frontiersin.org
CONCLUSION AND PERSPECTIVES
There is increasing evidence that sleep plays a causal role
in emotional processing and regulation (132). Depression
and sleep disturbances are common co-morbid conditions,
and almost all depressed patients show some types of sleep
disturbances (133, 134). Most antidepressants can change
sleep, and the effects appear to be most significant and
consistent on REMs (135). Selective REMs deprivation (such
as forced awakenings) can produce an antidepressant effect,
illustrating the closer association between REMs regulation
and mechanisms involved in the development of depression
(136). Some neurotransmitter reuptake inhibitors can alleviate
depression by suppressing REMs through inhibition of serotonin
and norepinephrine reuptake (26). However, many questions
remain to be answered in future studies. Firstly, in previous
studies, it was found that the effects of antidepressants on
sleep initiation and maintenance were inconsistent. Secondly,
the mechanism of different effects of antidepressants on sleep
continuity is unclear. In rodent experiments, many paradigms
of chronic stress have been used to simulate the pathogenesis
of human depression, but it is hard to provide a unified
description about the impact of chronic stress on sleep patterns.
In fact, in addition to the types of stress, the number and
persistent time are also important factors for stress responses,
which must be carefully considered. NHPs are suitable animal
models for experiments related to sleep, however, the study of
depression and sleep disorders is far from enough. Although
researchers have made continuous efforts and good progress
in relevant animal models, it must be recognized that there
are deficiencies.
In any way whatever, the research on animal models
of sleep disorders provides a good clue and basis for
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Sleep Disturbances and Depression
FUNDING
clinical diagnosis and treatment of depression. NHPs
are considered as a further valuable and translational
animal model, which is necessary for sleep and related
diseases (137, 138). It is also an important entry
point for increased efforts dedicated to collaborative
translational endeavors.
This work was supported by the National Natural Science
Foundation of China (31960178, 82074421, and 82160923), the
Applied Basic Research Programs of Science and Technology
Commission Foundation of Yunnan Province (2019FA007), the
Joint Project of Applied Basic Research of Yunnan University
of Chinese Medicine & Yunnan Provincial Science and
Technology Department [2019FF002(-001)], Yunnan Provincial
Department of Education Science Research Fund Project
(2020Y0203), the Key Realm R&D Program of Guangdong
Province (2019B030335001), the China Postdoctoral Science
Foundation (2018M631105), and the Yunnan Provincial
Academician and Expert Workstation (202005AF150017
and 2019IC051).
AUTHOR CONTRIBUTIONS
DQ, LX, XL, and ML designed the structure. ML, JC, BX, YW,
CF, and DQ wrote the first draft of the manuscript. DQ, LX, and
XL supervised and revised the final version of the manuscript. All
authors contributed substantially to the scientific process, writing
of the manuscript, and have approved the final version of the
manuscript being submitted.
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January 2022 | Volume 12 | Article 827541