Abstract
The circadian system, composed of a network of brain and peripheral 24-hour clocks and oscillators, allows organisms to anticipate and synchronize to natural daily events. The day–night cycle is the dominant timing signal to align circadian clocks to the external time. Thereby, exposure to aberrant light–dark cycles leads to disruptions of the circadian system, evoking different health issues, including mental or affective ones. Humans with circadian misalignments, such as those observed in jet-lag-exposed people or shift workers, and animal models of clock disturbances show mood alterations such as anxiety and depressive-like behaviors. The mechanisms underlying the physiopathology of mood disorders in circadian disruption may imply an altered functioning of the main clock in the suprachiasmatic nucleus, from other central oscillators, or a loss of internal synchrony between them. This Review outlines the current knowledge on the link between circadian perturbations and mood disorders in humans and animal models, and the possible neurobiological mechanisms involved.
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References
Pittendrigh, C. S. Temporal organization: reflections of a Darwinian clock-watcher. Annu. Rev. Physiol. 55, 16–54 (1993).
Chellappa, S. L., Morris, C. J. & Scheer, F. Circadian misalignment increases mood vulnerability in simulated shift work. Sci. Rep. 10, 18614 (2020).
Hastings, M. H., Maywood, E. S. & Brancaccio, M. Generation of circadian rhythms in the suprachiasmatic nucleus. Nat. Rev. Neurosci. 19, 453–469 (2018).
Takahashi, J. S. Transcriptional architecture of the mammalian circadian clock. Nat. Rev. Genet. 18, 164–179 (2017).
Ono, D., Honma, K. I. & Honma, S. Roles of neuropeptides, VIP and AVP, in the mammalian central circadian clock. Front. Neurosci 15, 650154 (2021).
Aton, S. J. et al. Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons. Nat. Neurosci. 8, 476–483 (2005).
Mieda, M. et al. Cellular clocks in AVP neurons of the SCN are critical for interneuronal coupling regulating circadian behavior rhythm. Neuron 85, 1103–1116 (2015).
Hattar, S. et al. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J. Comp. Neurol. 497, 326–349 (2006).
Golombek, D. A. & Rosenstein, R. E. Physiology of circadian entrainment. Physiol. Rev. 90, 1063–1102 (2010).
Takahashi, J. S. et al. Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms. Nature 308, 186–188 (1984).
Khalsa, S. B. et al. A phase response curve to single bright light pulses in human subjects. J. Physiol. 549, 945–952 (2003).
Dibner, C., Schibler, U. & Albrecht, U. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu. Rev. Physiol. 72, 517–549 (2010).
Abe, M. et al. Circadian rhythms in isolated brain regions. J. Neurosci. 22, 350–356 (2002).
Abraham, U. et al. Independent circadian oscillations of Period1 in specific brain areas in vivo and in vitro. J. Neurosci. 25, 8620–8626 (2005).
Granados-Fuentes, D. et al. Daily rhythms in olfactory discrimination depend on clock genes but not the suprachiasmatic nucleus. J. Biol. Rhythms 26, 552–560 (2011).
Herz, R. S. et al. The influence of circadian timing on olfactory sensitivity. Chem. Senses 43, 45–51 (2017).
Hu, H., Cui, Y. & Yang, Y. Circuits and functions of the lateral habenula in health and in disease. Nat. Rev. Neurosci. 21, 277–295 (2020).
Salaberry, N. L. et al. A suprachiasmatic-independent circadian clock(s) in the habenula is affected by Per gene mutations and housing light conditions in mice. Brain Struct. Funct. 224, 19–31 (2019).
Guilding, C., Hughes, A. T. & Piggins, H. D. Circadian oscillators in the epithalamus. Neuroscience 169, 1630–1639 (2010).
Zhao, H. & Rusak, B. Circadian firing-rate rhythms and light responses of rat habenular nucleus neurons in vivo and in vitro. Neuroscience 132, 519–528 (2005).
Olejniczak, I. et al. Light affects behavioral despair involving the clock gene Period 1. PLoS Genet. 17, e1009625 (2021).
Kaiser, C. et al. The human habenula is responsive to changes in luminance and circadian rhythm. Neuroimage 189, 581–588 (2019).
Fernandez, D. C. et al. Light affects mood and learning through distinct retina–brain pathways. Cell 175, 71–84 e18 (2018).
Rath, M. F., Rohde, K. & Moller, M. Circadian oscillations of molecular clock components in the cerebellar cortex of the rat. Chronobiol. Int. 29, 1289–1299 (2012).
Li, J. Z. et al. Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. Proc. Natl Acad. Sci. USA 110, 9950–9955 (2013).
Logan, R. W. et al. Sex differences in molecular rhythms in the human cortex. Biol. Psychiatry 91, 152–162 (2022).
Lim, A. S. et al. Sex difference in daily rhythms of clock gene expression in the aged human cerebral cortex. J. Biol. Rhythms 28, 117–129 (2013).
Ketchesin, K. D. et al. Diurnal rhythms across the human dorsal and ventral striatum. Proc. Natl Acad. Sci. USA 118, e2016150118 (2021).
Hampp, G. et al. Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood. Curr. Biol. 18, 678–683 (2008).
Hood, S. et al. Endogenous dopamine regulates the rhythm of expression of the clock protein PER2 in the rat dorsal striatum via daily activation of D2 dopamine receptors. J. Neurosci. 30, 14046–14058 (2010).
Logan, R. W. et al. Chronic stress induces brain region-specific alterations of molecular rhythms that correlate with depression-like behavior in mice. Biol. Psychiatry 78, 249–258 (2015).
Landgraf, D., Long, J. E. & Welsh, D. K. Depression-like behaviour in mice is associated with disrupted circadian rhythms in nucleus accumbens and periaqueductal grey. Eur. J. Neurosci. 43, 1309–1320 (2016).
Guilding, C. et al. A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus. Mol. Brain 2, 28 (2009).
Amir, S. & Stewart, J. Motivational modulation of rhythms of the expression of the clock protein PER2 in the limbic forebrain. Biol. Psychiatry 65, 829–834 (2009).
Mure, L. S. et al. Diurnal transcriptome atlas of a primate across major neural and peripheral tissues. Science 359, eaao0318 (2018).
Yan, L., Smale, L. & Nunez, A. A. Circadian and photic modulation of daily rhythms in diurnal mammals. Eur. J. Neurosci. 51, 551–566 (2020).
Aschoff, J. Circadian rhythms in man. Science 148, 1427–1432 (1965).
Aschoff, J. & Wever, R. Human circadian rhythms: a multioscillatory system. Fed. Proc. 35, 236–32 (1976).
Roenneberg, T. & Merrow, M. The circadian clock and human health. Curr. Biol. 26, R432–R443 (2016).
Aschoff, J., Gerecke, U. & Wever, R. Desynchronization of human circadian rhythms. Jpn J. Physiol. 17, 450–457 (1967).
Scott, M. R. & McClung, C. A. Bipolar disorder. Curr. Opin. Neurobiol. 83, 102801 (2023).
Malhi, G. S. & Mann, J. J. Depression. Lancet 392, 2299–2312 (2018).
Lemke, M. R. et al. Motor activity and daily variation of symptom intensity in depressed patients. Neuropsychobiology 36, 57–61 (1997).
Wehr, T. A., Muscettola, G. & Goodwin, F. K. Urinary 3-methoxy-4-hydroxyphenylglycol circadian rhythm. Early timing (phase-advance) in manic-depressives compared with normal subjects. Arch. Gen. Psychiatry 37, 257–263 (1980).
Wehr, T. A. et al. Phase advance of the circadian sleep–wake cycle as an antidepressant. Science 206, 710–713 (1979).
Robillard, R. et al. Circadian rhythms and psychiatric profiles in young adults with unipolar depressive disorders. Transl. Psychiatry 8, 213 (2018).
Robillard, R. et al. Delayed sleep phase in young people with unipolar or bipolar affective disorders. J. Affect. Disord. 145, 260–263 (2013).
Winkler, D. et al. Actigraphy in patients with seasonal affective disorder and healthy control subjects treated with light therapy. Biol. Psychiatry 58, 331–336 (2005).
Wolff, E. A. 3rd, Putnam, F. W. & Post, R. M. Motor activity and affective illness. The relationship of amplitude and temporal distribution to changes in affective state. Arch. Gen. Psychiatry 42, 288–294 (1985).
Wong, M. L. et al. Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone. Proc. Natl Acad. Sci. USA 97, 325–330 (2000).
Claustrat, B. et al. A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol. Psychiatry 19, 1215–1228 (1984).
Souetre, E. et al. Circadian rhythms in depression and recovery: evidence for blunted amplitude as the main chronobiological abnormality. Psychiatry Res. 28, 263–278 (1989).
Brown, R. et al. Differences in nocturnal melatonin secretion between melancholic depressed patients and control subjects. Am. J. Psychiatry 142, 811–816 (1985).
Voderholzer, U. et al. Circadian profiles of melatonin in melancholic depressed patients and healthy subjects in relation to cortisol secretion and sleep. Psychiatry Res. 71, 151–161 (1997).
Markianos, M. & Lykouras, L. Circadian rhythms of dopamine-beta-hydroxylase and c-AMP in plasma of controls and patients with affective disorders. J. Neural Transm. 50, 149–155 (1981).
Wu, X. et al. Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression. Brain Struct. Funct. 222, 4079–4088 (2017).
Wu, Y. H. et al. Alterations of melatonin receptors MT1 and MT2 in the hypothalamic suprachiasmatic nucleus during depression. J. Affect. Disord. 148, 357–367 (2013).
Naismith, S. L. et al. Delayed circadian phase is linked to glutamatergic functions in young people with affective disorders: a proton magnetic resonance spectroscopy study. BMC Psychiatry 14, 345 (2014).
Solberg, L. C. et al. Altered hormone levels and circadian rhythm of activity in the WKY rat, a putative animal model of depression. Am. J. Physiol. Regul. Integr. Comp. Physiol. 281, R786–R794 (2001).
Loizeau, V. et al. Behavioural characteristics and sex differences of a treatment-resistant depression model: chronic mild stress in the Wistar-Kyoto rat. Behav. Brain Res. 457, 114712 (2024).
Shiromani, P. J. et al. Diurnal rhythm of core body temperature is phase advanced in a rodent model of depression. Biol. Psychiatry 29, 923–930 (1991).
Landgraf, D. et al. Genetic disruption of circadian rhythms in the suprachiasmatic nucleus causes helplessness, behavioral despair, and anxiety-like behavior in mice. Biol. Psychiatry 80, 827–835 (2016).
Vadnie, C. A. et al. The suprachiasmatic nucleus regulates anxiety-like behavior in mice. Front. Neurosci. 15, 765850 (2021).
Spencer, S. et al. Circadian genes Period 1 and Period 2 in the nucleus accumbens regulate anxiety-related behavior. Eur. J. Neurosci. 37, 242–250 (2013).
Vetter, C. et al. Aligning work and circadian time in shift workers improves sleep and reduces circadian disruption. Curr. Biol. 25, 907–911 (2015).
Czeisler, C. A., Moore-Ede, M. C. & Coleman, R. H. Rotating shift work schedules that disrupt sleep are improved by applying circadian principles. Science 217, 460–463 (1982).
Waterhouse, J. et al. Jet lag: trends and coping strategies. Lancet 369, 1117–1129 (2007).
Cho, K. Chronic ‘jet lag’ produces temporal lobe atrophy and spatial cognitive deficits. Nat. Neurosci. 4, 567–568 (2001).
Zhang, F. et al. The effect of jet lag on the human brain: a neuroimaging study. Hum. Brain Mapp. 41, 2281–2291 (2020).
Inder, M. L., Crowe, M. T. & Porter, R. Effect of transmeridian travel and jetlag on mood disorders: evidence and implications. Aust. N. Z. J. Psychiatry 50, 220–227 (2016).
Jauhar, P. & Weller, M. P. Psychiatric morbidity and time zone changes: a study of patients from Heathrow airport. Br. J. Psychiatry 140, 231–235 (1982).
Young, D. M. Psychiatric morbidity in travelers to Honolulu, Hawaii. Compr. Psychiatry 36, 224–228 (1995).
Moon, J. H. et al. Advanced circadian phase in mania and delayed circadian phase in mixed mania and depression returned to normal after treatment of bipolar disorder. eBioMedicine 11, 285–295 (2016).
Boivin, D. B., Boudreau, P. & Kosmadopoulos, A. Disturbance of the circadian system in shift work and its health impact. J. Biol. Rhythms 37, 3–28 (2022).
Healy, D., Minors, D. S. & Waterhouse, J. M. Shiftwork, helplessness and depression. J. Affect. Disord. 29, 17–25 (1993).
Khan, W. A. A. et al. The relationship between shift-work, sleep, and mental health among paramedics in Australia. Sleep Health 6, 330–337 (2020).
Violanti, J. M. et al. Shift-work and suicide ideation among police officers. Am. J. Ind. Med. 51, 758–768 (2008).
Koshy, A. et al. Disruption of central and peripheral circadian clocks in police officers working at night. FASEB J. 33, 6789–6800 (2019).
Sack, R. L., Blood, M. L. & Lewy, A. J. Melatonin rhythms in night shift workers. Sleep 15, 434–441 (1992).
Baba, M. et al. Analysis of salivary cortisol levels to determine the association between depression level and differences in circadian rhythms of shift-working nurses. J. Occup. Health 57, 237–244 (2015).
Park, C. H. et al. Sleep disturbance-related depressive symptom and brain volume reduction in shift-working nurses. Sci. Rep. 10, 9100 (2020).
Wittmann, M. et al. Social jetlag: misalignment of biological and social time. Chronobiol. Int. 23, 497–509 (2006).
Levandovski, R. et al. Depression scores associate with chronotype and social jetlag in a rural population. Chronobiol. Int. 28, 771–778 (2011).
Kang, S. G. et al. Weekend catch-up sleep is independently associated with suicide attempts and self-injury in Korean adolescents. Compr. Psychiatry 55, 319–325 (2014).
Juda, M., Vetter, C. & Roenneberg, T. Chronotype modulates sleep duration, sleep quality, and social jet lag in shift-workers. J. Biol. Rhythms 28, 141–151 (2013).
Roenneberg, T., Wirz-Justice, A. & Merrow, M. Life between clocks: daily temporal patterns of human chronotypes. J. Biol. Rhythms 18, 80–90 (2003).
Park, H., Lee, H. K. & Lee, K. Chronotype and suicide: the mediating effect of depressive symptoms. Psychiatry Res. 269, 316–320 (2018).
Merikanto, I. & Partonen, T. Eveningness increases risks for depressive and anxiety symptoms and hospital treatments mediated by insufficient sleep in a population-based study of 18,039 adults. Depress. Anxiety 38, 1066–1077 (2021).
Esaki, Y. et al. Higher prevalence of intentional self-harm in bipolar disorder with evening chronotype: a finding from the APPLE cohort study. J. Affect. Disord. 277, 727–732 (2020).
Gaspar-Barba, E. et al. Depressive symptomatology is influenced by chronotypes. J. Affect. Disord. 119, 100–106 (2009).
Haraden, D. A., Mullin, B. C. & Hankin, B. L. Internalizing symptoms and chronotype in youth: a longitudinal assessment of anxiety, depression and tripartite model. Psychiatry Res. 272, 797–805 (2019).
Chen, S. J. et al. The trajectories and associations of eveningness and insomnia with daytime sleepiness, depression and suicidal ideation in adolescents: a 3-year longitudinal study. J. Affect. Disord. 294, 533–542 (2021).
Vulser, H. et al. Chronotype, longitudinal volumetric brain variations throughout adolescence, and depressive symptom development. J. Am. Acad. Child Adolesc. Psychiatry 62, 48–58 (2023).
Nguyen, C. et al. In vivo molecular chronotyping, circadian misalignment, and high rates of depression in young adults. J. Affect. Disord. 250, 425–431 (2019).
Cajochen, C. et al. Evening exposure to a light-emitting diodes (LED)-backlit computer screen affects circadian physiology and cognitive performance. J. Appl. Physiol. 110, 1432–1438 (2011).
Obayashi, K. et al. Exposure to light at night and risk of depression in the elderly. J. Affect. Disord. 151, 331–336 (2013).
Lemola, S. et al. Adolescents’ electronic media use at night, sleep disturbance, and depressive symptoms in the smartphone age. J. Youth Adolesc. 44, 405–418 (2015).
Tonon, A. C. et al. Sleep disturbances, circadian activity, and nocturnal light exposure characterize high risk for and current depression in adolescence. Sleep 45, zsac104 (2022).
Min, J. Y. & Min, K. B. Outdoor light at night and the prevalence of depressive symptoms and suicidal behaviors: a cross-sectional study in a nationally representative sample of Korean adults. J. Affect. Disord. 227, 199–205 (2018).
Rahman, S. A. et al. Spectral sensitivity of circadian phase resetting, melatonin suppression and acute alerting effects of intermittent light exposure. Biochem. Pharmacol. 191, 114504 (2021).
LeGates, T. A. et al. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 491, 594–598 (2012).
Brown, T. M. et al. Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults. PLoS Biol. 20, e3001571 (2022).
Wirz-Justice, A., Skene, D. J. & Munch, M. The relevance of daylight for humans. Biochem. Pharmacol. 191, 114304 (2021).
Bauer, M. et al. Association between solar insolation and a history of suicide attempts in bipolar I disorder. J. Psychiatr. Res. 113, 1–9 (2019).
Graw, P. et al. Winter and summer outdoor light exposure in women with and without seasonal affective disorder. J. Affect. Disord. 56, 163–169 (1999).
Rosenthal, N. E. et al. Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch. Gen. Psychiatry 41, 72–80 (1984).
Wirz-Justice, A. et al. ‘Natural’ light treatment of seasonal affective disorder. J. Affect. Disord. 37, 109–120 (1996).
Burns, A. C. et al. Time spent in outdoor light is associated with mood, sleep, and circadian rhythm-related outcomes: a cross-sectional and longitudinal study in over 400,000 UK Biobank participants. J. Affect. Disord. 295, 347–352 (2021).
Figueiro, M. G. et al. The impact of daytime light exposures on sleep and mood in office workers. Sleep Health 3, 204–215 (2017).
Boubekri, M. et al. Impact of windows and daylight exposure on overall health and sleep quality of office workers: a case-control pilot study. J. Clin. Sleep Med. 10, 603–611 (2014).
Reddy, A. B. et al. Differential resynchronisation of circadian clock gene expression within the suprachiasmatic nuclei of mice subjected to experimental jet lag. J. Neurosci. 22, 7326–7330 (2002).
Chen, R. et al. Chronic circadian phase advance in male mice induces depressive-like responses and suppresses neuroimmune activation. Brain Behav. Immun. Health 17, 100337 (2021).
Horsey, E. A. et al. Chronic jet lag simulation decreases hippocampal neurogenesis and enhances depressive behaviors and cognitive deficits in adult male rats. Front. Behav. Neurosci. 13, 272 (2019).
Davidson, A. J. et al. Chronic jet-lag increases mortality in aged mice. Curr. Biol. 16, R914–R916 (2006).
de la Iglesia, H. O. et al. Forced desynchronization of dual circadian oscillators within the rat suprachiasmatic nucleus. Curr. Biol. 14, 796–800 (2004).
Ben-Hamo, M. et al. Circadian forced desynchrony of the master clock leads to phenotypic manifestation of depression in rats. eNeuro 3, ENEURO.0237–16.2016 (2016).
Haraguchi, A. et al. Use of a social jetlag-mimicking mouse model to determine the effects of a two-day delayed light- and/or feeding-shift on central and peripheral clock rhythms plus cognitive functioning. Chronobiol. Int. 38, 426–442 (2021).
Walker, W. H. 2nd et al. Acute exposure to low-level light at night is sufficient to induce neurological changes and depressive-like behavior. Mol. Psychiatry 25, 1080–1093 (2020).
Bedrosian, T. A. et al. Nocturnal light exposure impairs affective responses in a wavelength-dependent manner. J. Neurosci. 33, 13081–13087 (2013).
Fonken, L. K. et al. Dim nighttime light impairs cognition and provokes depressive-like responses in a diurnal rodent. J. Biol. Rhythms 27, 319–327 (2012).
An, K. et al. A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice. Nat. Neurosci. 23, 869–880 (2020).
Weil, T. et al. Daily changes in light influence mood via inhibitory networks within the thalamic perihabenular nucleus. Sci. Adv. 8, eabn3567 (2022).
Leach, G., Adidharma, W. & Yan, L. Depression-like responses induced by daytime light deficiency in the diurnal grass rat (Arvicanthis niloticus). PLoS ONE 8, e57115 (2013).
Itzhacki, J. et al. Light rescues circadian behavior and brain dopamine abnormalities in diurnal rodents exposed to a winter-like photoperiod. Brain Struct. Funct. 223, 2641–2652 (2018).
Bilu, C. et al. Beneficial effects of daytime high-intensity light exposure on daily rhythms, metabolic state and affect. Sci. Rep. 10, 19782 (2020).
Huang, L. et al. A visual circuit related to habenula underlies the antidepressive effects of light therapy. Neuron 102, 128–142e8 (2019).
Lewy, A. J. et al. Antidepressant and circadian phase-shifting effects of light. Science 235, 352–354 (1987).
Millan, M. J. et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J. Pharmacol. Exp. Ther. 306, 954–964 (2003).
Loving, R. T., Kripke, D. F. & Shuchter, S. R. Bright light augments antidepressant effects of medication and wake therapy. Depress. Anxiety 16, 1–3 (2002).
Sahlem, G. L. et al. Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study. J. Psychiatr. Res. 59, 101–107 (2014).
Mistlberger, R. E. & Skene, D. J. Nonphotic entrainment in humans? J. Biol. Rhythms 20, 339–352 (2005).
Mistlberger, R. E. & Antle, M. C. Entrainment of circadian clocks in mammals by arousal and food. Essays Biochem. 49, 119–136 (2011).
Qian, J. et al. Daytime eating prevents mood vulnerability in night work. Proc. Natl Acad. Sci. USA 119, e2206348119 (2022).
Talamanca, L., Gobet, C. & Naef, F. Sex-dimorphic and age-dependent organization of 24-hour gene expression rhythms in humans. Science 379, 478–483 (2023).
Duffy, J. F. et al. Sex difference in the near-24-hour intrinsic period of the human circadian timing system. Proc. Natl Acad. Sci. USA 108, 15602–15608 (2011).
Wong, I. S. et al. For better or worse? Changing shift schedules and the risk of work injury among men and women. Scand. J. Work Environ. Health 40, 621–630 (2014).
Chellappa, S. L. et al. Sex differences in light sensitivity impact on brightness perception, vigilant attention and sleep in humans. Sci. Rep. 7, 14215 (2017).
McClung, C. A. et al. Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc. Natl Acad. Sci. USA 102, 9377–9381 (2005).
Chung, S. et al. Impact of circadian nuclear receptor REV-ERBα on midbrain dopamine production and mood regulation. Cell 157, 858–868 (2014).
Dallmann, R. et al. Impaired daily glucocorticoid rhythm in Per1 (Brd) mice. J. Comp. Physiol. A 192, 769–775 (2006).
Li, Y. et al. Depression-like behavior is associated with lower Per2 mRNA expression in the lateral habenula of rats. Genes Brain. Behav. 20, e12702 (2021).
Bae, K. et al. Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Neuron 30, 525–536 (2001).
Zhang, L. et al. A PERIOD3 variant causes a circadian phenotype and is associated with a seasonal mood trait. Proc. Natl Acad. Sci. USA 113, E1536–E1544 (2016).
Qiu, P. et al. BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders. Natl Sci. Rev. 6, 87–100 (2019).
van der Horst, G. T. et al. Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 398, 627–630 (1999).
De Bundel, D. et al. Cognitive dysfunction, elevated anxiety, and reduced cocaine response in circadian clock-deficient cryptochrome knockout mice. Front. Behav. Neurosci. 7, 152 (2013).
Sokolowska, E. et al. The circadian gene Cryptochrome 2 influences stress-induced brain activity and depressive-like behavior in mice. Genes Brain Behav 20, e12708 (2021).
Wang, W. et al. Desynchronizing the sleep–wake cycle from circadian timing to assess their separate contributions to physiology and behaviour and to estimate intrinsic circadian period. Nat. Protoc. 18, 579–603 (2023).
Opperhuizen, A. L. et al. Rodent models to study the metabolic effects of shiftwork in humans. Front. Pharmacol. 6, 50 (2015).
Ohta, H., Yamazaki, S. & McMahon, D. G. Constant light desynchronizes mammalian clock neurons. Nat. Neurosci. 8, 267–269 (2005).
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This work is supported by the Agence National de la Recherche (ANR-14-CE13-0002-01 ADDiCLOCK JCJC), the consortium Danone/Foundation pour la Recherche Medicale (FRM), and the Centre National de la Recherche Scientifique (CNRS). I acknowledge colleagues whose relevant contributions could not be cited in the present work due to space limitations.
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Mendoza, J. Circadian disruptions and brain clock dysregulation in mood disorders. Nat. Mental Health 2, 749–763 (2024). https://doi.org/10.1038/s44220-024-00260-y
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DOI: https://doi.org/10.1038/s44220-024-00260-y
