Circadian Forced Desynchrony of the Master Clock Leads to Phenotypic Manifestation of Depression in Rats

Ben-Hamo, Miriam; Larson, Tracy A.; Duge, Leanne S; Sikkema, Carl; Wilkinson, Charles W.; Iglesia, Horacio O. de la; González, Mónica M. C.

doi:10.1523/eneuro.0237-16.2016

Cited by 48 publications

(45 citation statements)

References 63 publications

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“…SCN lesions likely disrupted the diurnal rhythm in activity; subsequent studies examining the role of the SCN in regulating depressive-like behavior have reached the opposite conclusion utilizing animals with an intact SCN 83,84 . Genetic disruption of circadian rhythms in the SCN via SCN-specific Bmal1-knockdown, or forced desynchrony of the SCN via exposure to a T22 light-dark cycle increased depressive-like behavior in mice and rats, respectively 90,91 .…”

Section: Circadian Rhythm Disruption and Major Depressive Disordermentioning

confidence: 99%

Circadian rhythm disruption and mental health

et al. 2020

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Circadian rhythms are internal manifestations of the solar day that permit adaptations to predictable environmental temporal changes. These~24-h rhythms are controlled by molecular clockworks within the brain that are reset daily to precisely 24 h by exposure to the light-dark cycle. Information from the master clock in the mammalian hypothalamus conveys temporal information to the entire body via humoral and neural communication. A bidirectional relationship exists between mood disorders and circadian rhythms. Mood disorders are often associated with disrupted circadian clock-controlled responses, such as sleep and cortisol secretion, whereas disruption of circadian rhythms via jet lag, night-shift work, or exposure to artificial light at night, can precipitate or exacerbate affective symptoms in susceptible individuals. Evidence suggests strong associations between circadian rhythms and mental health, but only recently have studies begun to discover the direct interactions between the circadian system and mood regulation. This review provides an overview of disrupted circadian rhythms and the relationship to behavioral health and psychiatry. The focus of this review is delineating the role of disruption of circadian rhythms on mood disorders using human night shift studies, as well as jet lag studies to identify links. We also review animal models of disrupted circadian rhythms on affective responses. Lastly, we propose low-cost behavioral and lifestyle changes to improve circadian rhythms and presumably behavioral health.

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Section: Circadian Rhythm Disruption and Major Depressive Disordermentioning

confidence: 99%

Circadian rhythm disruption and mental health

et al. 2020

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“…Particular chronobiological properties of the circadian system, such as the acrophase, period, amplitude, and its interactions with the ultradian NREM sleep-REM sleep cycle, as well as phase relations with sleep-wake rhythms, are best studied within certain protocols including free running forced desynchronization or constant routines. These various parameters have been studied in rats, but certain elements have now also been applied to human models of depression(35).The two-process model of sleep, first proposed by Borbély in 1982, explains how homeostatic and circadian factors regulate the quantity and timing of sleep(36)(Fig. 1).…”

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confidence: 99%

Chronobiological theories of mood disorder

Zaki

Spence²,

BaHammam

et al. 2017

Eur Arch Psychiatry Clin Neurosci

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Major depressive disorder (MDD) remains the most prevalent mental disorder and a leading cause of disability, affecting approximately 100 million adults worldwide. The disorder is characterized by a constellation of symptoms affecting mood, anxiety, neurochemical balance, sleep patterns, and circadian and/or seasonal rhythm entrainment. However, the mechanisms underlying the association between chronobiological parameters and depression remain unknown. A PubMed search was conducted to review articles from 1979 to the present, using the following search terms: "chronobiology," "mood," "sleep," and "circadian rhythms." We aimed to synthesize the literature investigating chronobiological theories of mood disorders. Current treatments primarily include tricyclic antidepressants and selective serotonin reuptake inhibitors, which are known to increase extracellular concentrations of monoamine neurotransmitters. However, these antidepressants do not treat the sleep disturbances or circadian and/or seasonal rhythm dysfunctions associated with depressive disorders. Several theories associating sleep and circadian rhythm disturbances with depression have been proposed. Current evidence supports the existence of associations between these, but the direction of causality remains elusive. Given the existence of chronobiological disturbances in depression and evidence regarding their treatment in improving depression, a chronobiological approach, including timely use of light and melatonin agonists, could complement the treatment of MDD.

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“…It is clear from animal studies that decreasing the amplitude or chronically shifting rhythms can increase anxiety and/or depressive-like behavior. For example, repeated advances in the LD schedule, constant light and non-24 hr LD cycles can all disrupt rhythms and increase depressive and/or anxiety-like behavior in rodents [32][33][34][35][36][37] . Previously, we found that unpredictable chronic mild stress, a well-established paradigm to increase depressive and anxiety-like behavior, dampened locomotor activity, body temperature, and SCN rhythms in mice 38 .…”

Section: Suprachiasmatic Nucleus Regulates Anxiety Behaviormentioning

confidence: 99%

The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice

Vadnie

Eberhardt

Hildebrand

et al. 2020

Preprint

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250 words Manuscript: 4,996 words Suprachiasmatic Nucleus Regulates Anxiety Behavior 2 Abstract Circadian rhythms are commonly disrupted in individuals with depression and/or anxiety disorders. Animal studies indicate that circadian rhythm disruption can cause increased depressive and anxiety-like behavior, but the underlying mechanisms are unclear. Currently, there is conflicting evidence as to whether the master pacemaker in the brain, the suprachiasmatic nucleus (SCN), plays a key role in regulating psychiatricrelated behavior. To investigate the role of the SCN in regulating depressive and anxiety-like behavior in mice, we directly manipulated the neural activity of the SCN using two chronic optogenetic stimulation paradigms. Repeated stimulation of the SCN late in the active phase (circadian time 21, CT21) shortened the period and dampened the amplitude of homecage activity rhythms. Repeated stimulation of the SCN at unpredictable times during the dark phase dampened, fragmented and reduced the stability of homecage activity rhythms. In both SCN optogenetic stimulation paradigms, dampened homecage activity rhythms (decreased amplitude) was associated with increased measures of anxiety-like behavior, but not in control mice. Increased fragmentation and decreased day-to-day stability of homecage activity also correlated with increased anxiety-like behavior. Unexpectedly the change in period of homecage activity rhythms was not directly associated with any psychiatric-related behavior. Furthermore, we did not observe consistent correlations between homecage activity amplitude and depressive-like behavior in stimulated mice. Taken together, these results indicate that SCN-mediated dampening of rhythms is directly correlated with increased anxiety-like, but not depressive-like behavior in mice. This work is an important step in understanding how specific SCN neural activity disruptions affect mood and anxiety-related behavior.

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Circadian Forced Desynchrony of the Master Clock Leads to Phenotypic Manifestation of Depression in Rats

Abstract: Visual Abstract

Cited by 48 publications

References 63 publications

Circadian rhythm disruption and mental health

Circadian rhythm disruption and mental health

Chronobiological theories of mood disorder

The Suprachiasmatic Nucleus Regulates Anxiety-Like Behavior in Mice

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