Rhythms of life: circadian disruption and brain disorders across the lifespan

In the paper

“Advancing melatonin rhythms using bright light therapy improves ADHD symptoms of hyperactivity and impulsivity in adults independent of changes in sleep time, sleep efficiency, wake time or waking during sleeping87,90.”

What the sources say

• Partly supported

  The Intervention studies section (p. 13) reports that morning light therapy in adults with ADHD alleviated core ADHD symptoms and advanced circadian preference. It does not say that the treatment advanced melatonin rhythms, identify hyperactivity and impulsivity separately, or establish that symptom improvement was independent of the listed sleep measures. (LLM, conf=0.87)

  cites [87] Coogan, A. N. & McGowan, N. M. A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder. Atten. Defic. Hyperact. Disord. 9, 129–147 (2017). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (page unavailable) report that bright light therapy advanced melatonin onset and that larger advances correlated with reduced hyperactive-impulsive ADHD scores. In an actigraphy subset of eight participants, the listed sleep measures showed no significant changes. The paper does not establish that symptom improvement was independent of those measures; the Discussion describes bright light therapy as a possible complementary treatment, rather than a proven cause of improvement. (LLM, conf=0.85)

  cites [90] Fargason, R. E. et al. Correcting delayed circadian phase with bright light therapy predicts improvement in ADHD symptoms: a pilot study. J. Psychiatr. Res. 91, 105–110 (2017). sourceExperimental — accuracy not yet measured

In the paper

“Interestingly, before the age of 3 years, poor sleep quality and shorter sleep durations, which could be the result of inconsistent sleep–wake cycles and less-robust circadian rhythms, are predictive of hyperactivity, cognitive deficits and impulsivity at 6 years of age55,56, even in children showing normative sleep in the interim period57.”

What the sources say

• Not checked yetcites [55] Wolke, D., Meyer, R., Ohrt, B. & Riegel, K. Incidence and persistence of problems at sleep onset and sleep continuation in the preschool period: results of a prospective study of a representative sample in Bavaria [German]. Prax Kinderpsychol. Kinderpsychiatr. 43, 331–339 (1994).
• ?Could not verify

  The citation is attached to the claim that the prediction holds even when children show normative sleep in the interim. The Discussion and Results describe sleep patterns only through age 4; the passages found do not assess hyperactivity, cognitive deficits or impulsivity at age 6, or test whether any association persists after an interval of normative sleep. Searches for those outcomes and interim sleep did not locate evidence for the attributed claim. (LLM, conf=0.75)

  cites [56] Gaylor, E. E., Burnham, M. M., Goodlin-Jones, B. L. & Anders, T. F. A longitudinal follow-up study of young children’s sleep patterns using a developmental classification system. Behav. Sleep Med. 3, 44–61 (2005). sourceExperimental — accuracy not yet measured
• Supported

  This citation is attached to the final clause about children whose sleep subsequently normalized. In “Sleep Duration and Behavioral Outcomes,” the paper reports that sleep duration improved at age 3 in the short-increasing group, yet the risk of high hyperactivity-impulsivity scores at age 6 remained elevated. “Sleep Duration and Cognitive Outcomes” reports a similar finding for Block Design performance. (LLM, conf=0.91)

  cites [57] Touchette, E. et al. Associations between sleep duration patterns and behavioral/cognitive functioning at school entry. Sleep 30, 1213–1219 (2007). source

In the paper

“slow-wave activity during sleep dramatically decreases specifically during adolescence”

What the sources say

• Not checked yetcites [107] Hoel, E. P., Albantakis, L., Cirelli, C. & Tononi, G. Synaptic refinement during development and its effect on slow-wave activity: a computational study. J. Neurophysiol. 115, 2199–2213 (2016). source
• Supported

  The passage labeled Abstract states that sleep-related slow-wave activity undergoes a steep decline of approximately 65% during adolescence. The Discussion also reports diminished slow-wave activity with increasing age in a group of adolescents. (LLM, conf=0.94)

  cites [108] Goldstone, A. et al. The mediating role of cortical thickness and gray matter volume on sleep slow-wave activity during adolescence. Brain Struct. Funct. 223, 669–685 (2017). source

In the paper

“There is also accumulating evidence linking disrupted sleep and circadian rhythms to neurodegenerative disorders in humans and animal models235,236.”

What the sources say

• Supported

  The Abstract reports disrupted sleep–wake cycles in people with neurodegenerative disorders and says animal-model data support these findings. The section “Sleep and circadian disruptions are common in neurodegenerative disease” describes a large and growing body of clinical evidence linking the conditions. (LLM, conf=0.94)

  cites [235] Mattis, J. & Sehgal, A. Circadian rhythms, sleep, and disorders of aging. Trends Endocrinol. Metab. 27, 192–203 (2016). source
• Supported

  The Introduction explicitly describes accumulating evidence linking sleep and circadian disruption to neurodegeneration. The Sleep and Neurodegeneration and Circadian function and neurodegeneration sections discuss findings in humans and mouse models. The supplied passages do not provide page numbers. (LLM, conf=0.94)

  cites [236] Musiek, E. S. & Holtzman, D. M. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science 354, 1004–1008 (2016). source

In the paper

“This mouse study reveals that reductions of sirtuin activity in the SCN leads to a gradual age-dependent dampening of SCN activity and locomotor rhythms.”

What the sources say

• Supported

  The Discussion reports that SIRT1 levels and circadian regulatory proteins decline in the SCN of aged mice, alongside declines in central circadian control. The Results also report lower locomotor activity in young mice lacking brain SIRT1 and an age-related activity decline that SIRT1 overexpression partly rescues. The paper describes these as age-associated changes rather than measuring a continuous, gradual decline. (LLM, conf=0.88)

  cites [241] Chang, H. C. & Guarente, L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153, 1448–1460 (2013). This mouse study reveals that reductions of sirtuin activity in the SCN leads to a gradual age-dependent dampening of SCN activity and locomotor rhythms. source

In the paper

“Several first-line pharmacological treatments for psychiatric disorders, such as lithium for bipolar disorder and SSRIs for major depressive disorders, modulate the circadian clock216,217,329–331.”

What the sources say

• Not checked yetcites [216] Johansson, A. S., Brask, J., Owe-Larsson, B., Hetta, J. & Lundkvist, G. B. Valproic acid phase shifts the rhythmic expression of Period2::Luciferase. J. Biol. Rhythms 26, 541–551 (2011). source
• Not checked yetcites [217] Sprouse, J., Braselton, J. & Reynolds, L. Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing. Biol. Psychiatry 60, 896–899 (2006). source
• Not checked yetcites [329] Stewart, K. T., McEachron, D. L., Rosenwasser, A. M. & Adler, N. T. Lithium lengthens circadian period but fails to counteract behavioral helplessness in rats. Biol. Psychiatry 30, 515–518 (1991). source
• Supported

  This paper supports the lithium-for-bipolar-disorder example in the multiply cited sentence. Its Introduction describes lithium’s effects on clock rhythms, and its reported results show changes in PER2 rhythm amplitude and period in cultured cells. The SSRI example is not the part this lithium study is offered to support. (LLM, conf=0.90)

  cites [330] McCarthy, M. J. et al. Genetic and clinical factors predict lithium’s effects on PER2 gene expression rhythms in cells from bipolar disorder patients. Transl Psychiatry 3, e318 (2013). source
• Not checked yetcites [331] Sprouse, J., Reynolds, L., Braselton, J. & Schmidt, A. Serotonin-induced phase advances of SCN neuronal firing in vitro: a possible role for 5-HT5A receptors? Synapse 54, 111–118 (2004). source

In the paper

“Environmental factors such as light exposure, social cues, meal times and work schedules also influence the period, phase and amplitude of these rhythms6,7.”

What the sources say

• Not checked yetcites [6] Roenneberg, T. & Merrow, M. Entrainment of the human circadian clock. Cold Spring Harb. Symp. Quant. Biol. 72, 293–299 (2007). source
• Not checked yetcites [7] Foster, R. G. et al. Sleep and circadian rhythm disruption in social jetlag and mental illness. Prog. Mol. Biol. Transl Sci. 119, 325–346 (2013). source

In the paper

“Most people have sleep–wake and activity rhythms that, in the absence of environmental cues, are slightly longer than 24 hours3,4, but the length of this period can be affected by circadian gene variants5.”

What the sources say

• Not checked yetcites [3] Selemon, L. D. A role for synaptic plasticity in the adolescent development of executive function. Transl Psychiatry 3, e238 (2013). source
• Not checked yetcites [4] Mighdoll, M. I., Tao, R., Kleinman, J. E. & Hyde, T. M. Myelin, myelin-related disorders, and psychosis. Schizophr. Res. 161, 85–93 (2015). source

In the paper

“Epidemiological studies report increased risks of preterm delivery, low birthweights and miscarriage in pregnant women who are chronic shift-workers37–40.”

What the sources say

• Not checked yetcites [37] Bisanti, L., Olsen, J., Basso, O., Thonneau, P. & Karmaus, W. Shift work and subfecundity: a European multicenter study. European Study Group on Infertility and Subfecundity. J. Occup. Environ. Med. 38, 352–358 (1996). source
• Not checked yetcites [38] Aspholm, R. et al. Spontaneous abortions among Finnish flight attendants. J. Occup. Environ. Med. 41, 486–491 (1999). source
• Not checked yetcites [39] Cone, J. E., Vaughan, L. M., Huete, A. & Samuels, S. J. Reproductive health outcomes among female flight attendants: an exploratory study. J. Occup. Environ. Med. 40, 210–216 (1998). source
• Not checked yetcites [40] Mahoney, M. M. Shift work, jet lag, and female reproduction. Int. J. Endocrinol. 2010, 813764 (2010). source

In the paper

“Circadian rhythms of melatonin along with corticosteroid are detectable in the umbilical artery and vein, along with fetal circulation35,36.”

What the sources say

• Not checked yetcites [35] Seron-Ferre, M., Riffo, R., Valenzuela, G. J. & Germain, A. M. Twenty-four-hour pattern of cortisol in the human fetus at term. Am. J. Obstet. Gynecol. 184, 1278–1283 (2001). source
• Not checked yetcites [36] Kennaway, D. J., Goble, F. C. & Stamp, G. E. Factors influencing the development of melatonin rhythmicity in humans. J. Clin. Endocrinol. Metab. 81, 1525–1532 (1996).

In the paper

“Fetal rhythms are also entrained by maternal core body temperature, feeding and hormone release27 (FIG. 3).”

What the sources say

• Not checked yetcites [27] Reppert, S. M. Interaction between the circadian clocks of mother and fetus. Ciba Found. Symp. 183, 198–207; discussion 207–111 (1995).

In the paper

“The suprachiasmatic nucleus (SCN) in the hypothalamus serves as the master pacemaker that sets the timing of rhythms by regulating neuronal activity, body temperature and hormonal signals2 (FIG. 1).”

What the sources say

• Not checked yetcites [2] Colwell, C. S. Linking neural activity and molecular oscillations in the SCN. Nat. Rev. Neurosci. 12, 553–569 (2011). source

In the paper

“By mid-to-late gestation, rhythms of metabolic activity and gene expression are evident in the SCN of rodents and NHPs23–25; however, the functional importance of early prenatal development of the SCN for fetal rhythms and physiology is less well understood.”

What the sources say

• Not checked yetcites [23] Rivkees, S. A. Developing circadian rhythmicity in infants. Pediatr. Endocrinol. Rev. 1, 38–45 (2003).
• Not checked yetcites [24] Swaab, D. F. Development of the human hypothalamus. Neurochem. Res. 20, 509–519 (1995). source
• Not checked yetcites [25] VanDunk, C., Hunter, L. A. & Gray, P. A. Development, maturation, and necessity of transcription factors in the mouse suprachiasmatic nucleus. J. Neurosci. 31, 6457–6467 (2011). source

In the paper

“Moreover, the rhythms of the expression of circadian genes (specifically, Bmal1 (also known as Arntl) and Per2) and genes encoding NMDA receptor subunits (including Grin1b, Grin3a and Grin3b) are suppressed in the hippocampus of adult offspring of rats exposed to constant light during pregnancy46.”

What the sources say

• Not checked yetcites [46] Vilches, N. et al. Gestational chronodisruption impairs hippocampal expression of NMDA receptor subunits Grin1b/Grin3a and spatial memory in the adult offspring. PLOS ONE 9, e91313 (2014). source

In the paper

“Much of the currently available evidence linking brain disorders to circadian dysfunction is correlational and may not be surprising, given the importance of circadian rhythms for brain function20.”

What the sources say

• Not checked yetcites [20] Benca, R. et al. Biological rhythms, higher brain function, and behavior: gaps, opportunities, and challenges. Brain Res. Rev. 62, 57–70 (2009). source

In the paper

“Most people have sleep–wake and activity rhythms that, in the absence of environmental cues, are slightly longer than 24 hours3,4, but the length of this period can be affected by circadian gene variants5.”

What the sources say

• Not checked yetcites [5] Hsu, P. K., Ptacek, L. J. & Fu, Y. H. Genetics of human sleep behavioral phenotypes. Methods Enzymol. 552, 309–324 (2015). source

In the paper

“For example, chronic shift-workers (workers with rotating schedules or consistent night shifts) are vulnerable to various diseases13,14, including psychiatric disorders such as depression15–19.”

What the sources say

• Not checked yetcites [13] Drake, C. L., Roehrs, T., Richardson, G., Walsh, J. K. & Roth, T. Shift work sleep disorder: prevalence and consequences beyond that of symptomatic day workers. Sleep 27, 1453–1462 (2004). source
• Not checked yetcites [14] Ramin, C. et al. Night shift work at specific age ranges and chronic disease risk factors. Occup. Environ. Med. 72, 100–107 (2015). source
• Not checked yetcites [15] Bedrosian, T. A. & Nelson, R. J. Timing of light exposure affects mood and brain circuits. Transl Psychiatry 7, e1017 (2017). source
• Not checked yetcites [16] Bedrosian, T. A. & Nelson, R. J. Influence of the modern light environment on mood. Mol. Psychiatry 18, 751–757 (2013). source
• Not checked yetcites [17] Nakata, A. et al. Association of sickness absence with poor sleep and depressive symptoms in shift workers. Chronobiol. Int. 21, 899–912 (2004). source
• Not checked yetcites [18] Roth, T. Shift work disorder: overview and diagnosis. J. Clin. Psychiatry 73, e09 (2012). source
• Not checked yetcites [19] Wright, K. P. Jr, Bogan, R. K. & Wyatt, J. K. Shift work and the assessment and management of shift work disorder (SWD). Sleep Med. Rev. 17, 41–54 (2012). source

In the paper

“In general, the timing of sleep onset and waking and other biological rhythms (for example, fluctuations in melatonin levels) is earlier relative to adults during early childhood8,9 and shifts later during adolescence, and this shift in timing may be conserved among rodents and non-human primates (NHPs)10.”

What the sources say

• Not checked yetcites [10] Crowley, S. J. et al. A longitudinal assessment of sleep timing, circadian phase, and phase angle of entrainment across human adolescence. PLOS ONE 9, e112199 (2014). source

In the paper

“Sleep loss and consistently shorter sleep durations have been linked to inattentiveness, frustration and hyperactivity in 2–5-year-old children53,54.”

What the sources say

• Not checked yetcites [53] Davis, K. F., Parker, K. P. & Montgomery, G. L. Sleep in infants and young children: part two: common sleep problems. J. Pediatr. Health Care 18, 130–137 (2004). source
• Not checked yetcites [54] Dahl, R. E. Sleep, learning, and the developing brain: early-to-bed as a healthy and wise choice for school aged children. Sleep 28, 1498–1499 (2005).

In the paper

“Regular light–dark schedules also support the maturation of rest–activity, sleep–wake and melatonin rhythms earlier in premature infants71,85.”

What the sources say

• Not checked yetcites [71] Guyer, C. et al. Very preterm infants show earlier emergence of 24-hour sleep-wake rhythms compared to term infants. Early Hum. Dev. 91, 37–42 (2015). source
• Not checked yetcites [85] Rivkees, S. A., Mayes, L., Jacobs, H. & Gross, I. Rest-activity patterns of premature infants are regulated by cycled lighting. Pediatrics 113, 833–839 (2004). source

In the paper

“Gestational circadian disruption also promotes social avoidance and hyperactivity behaviours in pups, even when they are cross-fostered by non-disrupted mothers48, further highlighting the importance of circadian stability during pregnancy on the mother and offspring.”

What the sources say

• Not checked yetcites [48] Smarr, B. L., Grant, A. D., Perez, L., Zucker, I. & Kriegsfeld, L. J. Maternal and early-life circadian disruption have long-lasting negative consequences on offspring development and adult behavior in mice. Sci. Rep. 7, 3326 (2017). source

In the paper

“Other neurodevelopmental disorders, such as PWS and SMS, are linked more directly to dysfunctional circadian rhythm pathways107,108.”

What the sources say

• Not checked yetcites [107] Hoel, E. P., Albantakis, L., Cirelli, C. & Tononi, G. Synaptic refinement during development and its effect on slow-wave activity: a computational study. J. Neurophysiol. 115, 2199–2213 (2016). source
• Not checked yetcites [108] Goldstone, A. et al. The mediating role of cortical thickness and gray matter volume on sleep slow-wave activity during adolescence. Brain Struct. Funct. 223, 669–685 (2017). source

In the paper

“The most consistent related finding in prepubertal children, pubertal adolescents and young adults with ASD is reduced melatonin levels in the evening99–102.”

What the sources say

• Not checked yetcites [99] Tordjman, S., Anderson, G. M., Pichard, N., Charbuy, H. & Touitou, Y. Nocturnal excretion of 6-sulphatoxymelatonin in children and adolescents with autistic disorder. Biol. Psychiatry 57, 134–138 (2005). source
• Not checked yetcites [100] Nir, I. et al. Brief report: circadian melatonin, thyroid-stimulating hormone, prolactin, and cortisol levels in serum of young adults with autism. J. Autism Dev. Disord. 25, 641–654 (1995). source
• Not checked yetcites [101] Kulman, G. et al. Evidence of pineal endocrine hypofunction in autistic children. Neuro Endocrinol. Lett. 21, 31–34 (2000).
• Not checked yetcites [102] Melke, J. et al. Abnormal melatonin synthesis in autism spectrum disorders. Mol. Psychiatry 13, 90–98 (2008). source

In the paper

“Most infants, toddlers (2–3-year-olds) and young children (4–11-year-olds) display earlier sleep–wake patterns and a stronger morning preference than do adults, according to the Children’s Chronotype Questionnaire — even when considering the high intra-individual and interindividual variability of sleep onset, mid-points and wake times measured by parental report questionnaires and actigraphy8,9.”

What the sources say

• Not checked yetcites [8] Werner, H., Lebourgeois, M. K., Geiger, A. & Jenni, O. G. Assessment of chronotype in four- to eleven-year-old children: reliability and validity of the Children’s Chronotype Questionnaire (CCTQ). Chronobiol. Int. 26, 992–1014 (2009). source
• Not checked yetcites [9] Simpkin, C. T. et al. Chronotype is associated with the timing of the circadian clock and sleep in toddlers. J. Sleep Res. 23, 397–405 (2014). source

In the paper

“However, rearing premature infants (32 weeks gestational age or older) under regular light–dark schedules in the NICU leads to greater and more rapid weight gain than rearing infants under constant bright light or dim light, effectively shortening their hospital stays76,77.”

What the sources say

• Not checked yetcites [76] Morag, I. & Ohlsson, A. Cycled light in the intensive care unit for preterm and low birth weight infants. Cochrane Database Syst. Rev. 8, CD006982 (2013).
• Not checked yetcites [77] Vasquez-Ruiz, S. et al. A light/dark cycle in the NICU accelerates body weight gain and shortens time to discharge in preterm infants. Early Hum. Dev. 90, 535–540 (2014). source

In the paper

“In adults with ADHD, a loss of circadian gene expression rhythms in the oral mucosa accompanies delays in cortisol rhythm and reduced-amplitude melatonin rhythms89.”

What the sources say

• Not checked yetcites [89] Baird, A. L., Coogan, A. N., Siddiqui, A., Donev, R. M. & Thome, J. Adult attention-deficit hyperactivity disorder is associated with alterations in circadian rhythms at the behavioural, endocrine and molecular levels. Mol. Psychiatry 17, 988–995 (2012). source

In the paper

“Circadian rhythms gradually emerge between birth and the first several months of life.”

What the sources say

• Not checked yetcites [23] Rivkees, S. A. Developing circadian rhythmicity in infants. Pediatr. Endocrinol. Rev. 1, 38–45 (2003).
• Not checked yetcites [52] Kennaway, D. J., Stamp, G. E. & Goble, F. C. Development of melatonin production in infants and the impact of prematurity. J. Clin. Endocrinol. Metab. 75, 367–369 (1992).

In the paper

“Abnormal melatonin rhythms (for example, with phase delays and reduced amplitude) are also reported in children with ADHD87.”

What the sources say

• Not checked yetcites [87] Coogan, A. N. & McGowan, N. M. A systematic review of circadian function, chronotype and chronotherapy in attention deficit hyperactivity disorder. Atten. Defic. Hyperact. Disord. 9, 129–147 (2017). source

In the paper

“Thus, duplication of the 15q11–13 locus and developmental imprinting of SNORD116 and UBE3A may provide a molecular explanation for the circadian rhythm disruptions common to patients with PWS.”

In the paper

“Transitions from weekday to weekend compound the phase delay in the endogenous clock150,151 that is often referred to as ‘social jet-lag’148,152.”

What the sources say

• Not checked yetcites [150] Skeldon, A. C., Phillips, A. J. & Dijk, D. J. The effects of self-selected light–dark cycles and social constraints on human sleep and circadian timing: a modeling approach. Sci. Rep. 7, 45158 (2017). source
• Not checked yetcites [151] Crowley, S. J. & Carskadon, M. A. Modifications to weekend recovery sleep delay circadian phase in older adolescents. Chronobiol. Int. 27, 1469–1492 (2010). source
• Not checked yetcites [148] Touitou, Y. Adolescent sleep misalignment: a chronic jet lag and a matter of public health. J. Physiol. Paris 107, 323–326 (2013). source
• Not checked yetcites [152] Wittmann, M., Dinich, J., Merrow, M. & Roenneberg, T. Social jetlag: misalignment of biological and social time. Chronobiol. Int. 23, 497–509 (2006). source

In the paper

“During adolescence, many developmental changes occur in the frontostriatal reward circuitry, which includes the ventral striatum (VS; including the nucleus accumbens), dorsal striatum (DS) and medial prefrontal cortex (mPFC)169,170.”

What the sources say

• Not checked yetcites [169] Forbes, E. E. et al. Healthy adolescents’ neural response to reward: associations with puberty, positive affect, and depressive symptoms. J. Am. Acad. Child Adolesc. Psychiatry 49, 162–172 (2010).
• Not checked yetcites [170] Padmanabhan, A., Geier, C. F., Ordaz, S. J., Teslovich, T. & Luna, B. Developmental changes in brain function underlying the influence of reward processing on inhibitory control. Dev. Cogn. Neurosci. 1, 517–529 (2011). source

In the paper

“Although the amount of sleep needed per night is variable, the vast majority of US adolescents sleep less than the suggested 8–10 hours of sleep per night, according to the American Academy of Pediatrics146,147.”

What the sources say

• Not checked yetcites [146] Paruthi, S. et al. Recommended amount of sleep for pediatric populations: a consensus statement of the American Academy of Sleep Medicine. J. Clin. Sleep Med. 12, 785–786 (2016). source
• Not checked yetcites [147] Basch, C. E., Basch, C. H., Ruggles, K. V. & Rajan, S. Prevalence of sleep duration on an average school night among 4 nationally representative successive samples of American high school students, 2007–2013. Prev. Chron. Dis. 11, E216 (2014).

In the paper

“Environmental factors, such as social pressure from peers and/or decreasing parental involvement in bedtime routines, can also contribute to changes in adolescent sleep timing and duration140.”

What the sources say

• Not checked yetcites [140] Logan, R. W. et al. Impact of sleep and circadian rhythms on addiction vulnerability in adolescents. Biol. Psychiatry 83, 987–996 (2017). source

In the paper

“Attenuating the rise of melatonin during the morning via pharmacological antagonism of β1-adrenergic receptors by acebutolol (as pineal melatonin production is stimulated by sympathetic nervous system activation of β1- and α1-receptors) has been effective for reducing daytime naps, improving concentration and reducing the frequency of tantrums in a sample of ten patients, aged 4–18 years136.”

What the sources say

• Not checked yetcites [136] De Leersnyder, H. et al. β1-adrenergic antagonists improve sleep and behavioural disturbances in a circadian disorder, Smith–Magenis syndrome. J. Med. Genet. 38, 586–590 (2001). source

In the paper

“In mice, paternal deletion of Snord116 increases the expression of several genes specifically during the light phase, including Ube3a, which encodes ubiquitin ligase E3A (UBE3A)116.”

What the sources say

• Not checked yetcites [116] Powell, W. T. et al. A Prader–Willi locus lncRNA cloud modulates diurnal genes and energy expenditure. Hum. Mol. Genet. 22, 4318–4328 (2013). source

In the paper

“Humans, rodents and some NHPs undergo changes in circadian rhythms during adolescence140.”

What the sources say

• Not checked yetcites [140] Logan, R. W. et al. Impact of sleep and circadian rhythms on addiction vulnerability in adolescents. Biol. Psychiatry 83, 987–996 (2017). source

In the paper

“In mice with maternal loss of Ube3a, period lengthening of locomotor rhythms and molecular rhythms in the brain are dependent on core clock factors, including CLOCK and BMAL1 (reF.127).”

What the sources say

• Not checked yetcites [127] Shi, S. Q., Bichell, T. J., Ihrie, R. A. & Johnson, C. H. Ube3a imprinting impairs circadian robustness in Angelman syndrome models. Curr. Biol. 25, 537–545 (2015). source

In the paper

“Early school start times, which are typically more than an hour earlier in US high schools (ages 15–18 years) than in elementary schools (ages 9–10 years) or middle schools (ages 11–13 years), may contribute to these problems of shorter sleep10,148.”

What the sources say

• Not checked yetcites [10] Crowley, S. J. et al. A longitudinal assessment of sleep timing, circadian phase, and phase angle of entrainment across human adolescence. PLOS ONE 9, e112199 (2014). source
• Not checked yetcites [148] Touitou, Y. Adolescent sleep misalignment: a chronic jet lag and a matter of public health. J. Physiol. Paris 107, 323–326 (2013). source

In the paper

“insults during adolescence that affect sleep and circadian stability may contribute to the pathophysiology underlying the vulnerability and progression of these diseases later in life107,108”

What the sources say

• Not checked yetcites [107] Hoel, E. P., Albantakis, L., Cirelli, C. & Tononi, G. Synaptic refinement during development and its effect on slow-wave activity: a computational study. J. Neurophysiol. 115, 2199–2213 (2016). source
• Not checked yetcites [108] Goldstone, A. et al. The mediating role of cortical thickness and gray matter volume on sleep slow-wave activity during adolescence. Brain Struct. Funct. 223, 669–685 (2017). source

In the paper

“Chronic exposure to drugs of abuse can lead to epigenetic changes affecting the molecular clock that may then alter function of the reward circuitry for long periods of time, creating more vulnerability for future drug abuse176.”

What the sources say

• Not checked yetcites [176] Logan, R. W., Williams, W. P. & McClung, C. A. Circadian rhythms and addiction: mechanistic insights and future directions. Behav. Neurosci. 128, 387–412 (2014). source

In the paper

“circadian disruptions can precipitate mood and psychotic episodes in individuals who already have psychiatric disorders189–191”

What the sources say

• Not checked yetcites [189] Frank, E., Swartz, H. A. & Kupfer, D. J. Interpersonal and social rhythm therapy: managing the chaos of bipolar disorder. Biol. Psychiatry 48, 593–604 (2000). source
• Not checked yetcites [190] Malkoff-Schwartz, S. et al. Stressful life events and social rhythm disruption in the onset of manic and depressive bipolar episodes: a preliminary investigation. Arch. Gen. Psychiatry 55, 702–707 (1998). source
• Not checked yetcites [191] Melo, M. C. A., Abreu, R. L. C., Linhares Neto, V. B., de Bruin, P. F. C. & de Bruin, V. M. S. Chronotype and circadian rhythm in bipolar disorder: a systematic review. Sleep Med. Rev. 34, 46–58 (2017). source

In the paper

“5 days of 50% sleep restriction in rats during early adolescence led to alterations in the fractions of projections from the motor cortex to other regions of the brain207”

What the sources say

• Not checked yetcites [207] Billeh, Y. N. et al. Effects of chronic sleep restriction during early adolescence on the adult pattern of connectivity of mouse secondary motor cortex. eNeuro https://doi.org/10.1523/ENEURO.0053-16-2016 (2016). source

In the paper

“suggesting that improving sleep quality alone is not sufficient to prevent relapse”

In the paper

“Treatments to amplify, phase advance or delay circadian rhythms have been developed for potential use in psychiatric disorders in adults.”

What the sources say

• Not checked yetcites [189] Frank, E., Swartz, H. A. & Kupfer, D. J. Interpersonal and social rhythm therapy: managing the chaos of bipolar disorder. Biol. Psychiatry 48, 593–604 (2000). source
• Not checked yetcites [212] Wirz-Justice, A. & Terman, M. Chronotherapeutics (light and wake therapy) as a class of interventions for affective disorders. Handb. Clin. Neurol. 106, 697–713 (2012). source
• Not checked yetcites [213] Srinivasan, V., De Berardis, D., Shillcutt, S. D. & Brzezinski, A. Role of melatonin in mood disorders and the antidepressant effects of agomelatine. Expert Opin. Investig. Drugs 21, 1503–1522 (2012). source
• Not checked yetcites [214] Wu, J. C. et al. Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol. Psychiatry 66, 298–301 (2009). This study demonstrates, in a cohort of 49 patients with bipolar disorder, the ability of non-invasive circadian therapy (that is, bright light therapy and sleep phase advance) and sleep (that is, acute sleep deprivation) to improve and sustain the therapeutic efficacy of lithium and antidepressants on mood symptoms. source

In the paper

“A major component of many mood, anxiety and psychotic disorders is a disrupted sleep–wake cycle183–188”

What the sources say

• Not checked yetcites [183] Lamont, E. W., Coutu, D. L., Cermakian, N. & Boivin, D. B. Circadian rhythms and clock genes in psychotic disorders. Isr. J. Psychiatry Relat. Sci. 47, 27–35 (2010).
• Not checked yetcites [184] McClung, C. A. How might circadian rhythms control mood? Let me count the ways. Biol. Psychiatry 74, 242–249 (2013). source
• Not checked yetcites [185] Mansour, H. A. et al. Circadian phase variation in bipolar I disorder. Chronobiol. Int. 22, 571–584 (2005). source
• Not checked yetcites [186] McCarthy, M. J. & Welsh, D. K. Cellular circadian clocks in mood disorders. J. Biol. Rhythms 27, 339–352 (2012). source
• Not checked yetcites [187] McClung, C. A. Circadian rhythms and mood regulation: insights from pre-clinical models. Eur. Neuropsychopharmacol. 21, S683–S693 (2011). source
• Not checked yetcites [188] Wulff, K., Dijk, D. J., Middleton, B., Foster, R. G. & Joyce, E. M. Sleep and circadian rhythm disruption in schizophrenia. Br. J. Psychiatry 200, 308–316 (2012). This study reports notable circadian misalignment (phase delays and advances) of sleep–wake cycles and melatonin rhythms in patients with schizophrenia despite other factors, including mood, cognitive status and pharmacological treatments. source

In the paper

“there was no evidence that these interventions improved rates of alcohol abstinence”

What the sources say

• Not checked yetcites [181] Miller, M. B., Donahue, M. L., Carey, K. B. & Scott-Sheldon, L. A. J. Insomnia treatment in the context of alcohol use disorder: a systematic review and meta-analysis. Drug Alcohol Depend. 181, 200–207 (2017). source

In the paper

“this reduction is suggested to result directly from synaptic refinement”

What the sources say

• Not checked yetcites [107] Hoel, E. P., Albantakis, L., Cirelli, C. & Tononi, G. Synaptic refinement during development and its effect on slow-wave activity: a computational study. J. Neurophysiol. 115, 2199–2213 (2016). source
• Not checked yetcites [108] Goldstone, A. et al. The mediating role of cortical thickness and gray matter volume on sleep slow-wave activity during adolescence. Brain Struct. Funct. 223, 669–685 (2017). source

In the paper

“Lower responsivity of the PFC could lead to impaired inhibition of striatal circuits and related behaviours, including impulsivity and risk-taking.”

In the paper

“In fact, larger weekday–weekend advances of sleep onset (for example, similar to the transition from early school start times to weekend schedules) are associated with lower mPFC reactivity to the anticipation and receipt of monetary reward in early adolescents (aged 11–13 years), even after adjusting for puberty, sex and total sleep time149.”

What the sources say

• Not checked yetcites [149] Hasler, B. P. et al. Weekend-weekday advances in sleep timing are associated with altered reward-related brain function in healthy adolescents. Biol. Psychol. 91, 334–341 (2012). source

In the paper

“Mood symptoms can also occur in a seasonal pattern, as in seasonal affective disorder and in many cases of bipolar disorder192,193”

What the sources say

• Not checked yetcites [192] Winthorst, W. H. et al. Seasonal affective disorder and non-seasonal affective disorders: results from the NESDA study. BJPsych Open 3, 196–203 (2017). source
• Not checked yetcites [193] Medici, C. R., Vestergaard, C. H., Hadzi-Pavlovic, D., Munk-Jorgensen, P. & Parker, G. Seasonal variations in hospital admissions for mania: examining for associations with weather variables over time. J. Affect. Disord. 205, 81–86 (2016). source

In the paper

“identifying a common circadian or sleep-related mechanism that is causal for all bipolar disorder or major depression is unlikely”

In the paper

“the majority of adolescents are reported to be sleep deprived208–210”

What the sources say

• Not checked yetcites [208] Carskadon, M. A. Patterns of sleep and sleepiness in adolescents. Pediatrician 17, 5–12 (1990).
• Not checked yetcites [209] Johnson, E. O., Roth, T., Schultz, L. & Breslau, N. Epidemiology of DSM-IV insomnia in adolescence: lifetime prevalence, chronicity, and an emergent gender difference. Pediatrics 117, e247–e256 (2006). source
• Not checked yetcites [210] Sivertsen, B. et al. Delayed sleep phase syndrome in adolescents: prevalence and correlates in a large population based study. BMC Publ. Health 13, 1163 (2013).

In the paper

“The combination of heightened activity in reward-related circuits and underdeveloped cognitive control centres contributes to greater emotionality, impulsivity and reward-seeking behaviour174,175.”

What the sources say

• Not checked yetcites [174] Ernst, M. & Fudge, J. L. A developmental neurobiological model of motivated behavior: anatomy, connectivity and ontogeny of the triadic nodes. Neurosci. Biobehav. Rev. 33, 367–382 (2009). source
• Not checked yetcites [175] Somerville, L. H., Jones, R. M. & Casey, B. J. A time of change: behavioral and neural correlates of adolescent sensitivity to appetitive and aversive environmental cues. Brain Cogn. 72, 124–133 (2010). source

In the paper

“delayed rhythms during adolescence and early adulthood are strongly associated with depression and the severity of mood symptoms195,196”

What the sources say

• Not checked yetcites [195] Raniti, M. B. et al. Sleep duration and sleep quality: associations with depressive symptoms across adolescence. Behav. Sleep Med. 15, 198–215 (2017). source
• Not checked yetcites [196] Lewy, A. J. Depressive disorders may more commonly be related to circadian phase delays rather than advances: time will tell. Sleep Med. 11, 117–118 (2010). source

In the paper

“an estimated 7% of adolescents meet clinical criteria for delayed sleep phase syndrome”

What the sources say

• Not checked yetcites [208] Carskadon, M. A. Patterns of sleep and sleepiness in adolescents. Pediatrician 17, 5–12 (1990).
• Not checked yetcites [209] Johnson, E. O., Roth, T., Schultz, L. & Breslau, N. Epidemiology of DSM-IV insomnia in adolescence: lifetime prevalence, chronicity, and an emergent gender difference. Pediatrics 117, e247–e256 (2006). source
• Not checked yetcites [210] Sivertsen, B. et al. Delayed sleep phase syndrome in adolescents: prevalence and correlates in a large population based study. BMC Publ. Health 13, 1163 (2013).

In the paper

“Circadian and sleep disruptions may amplify these responses by further reducing cortical control and increasing the activity of reward circuitry in human adolescents.”

In the paper

“a single night of total sleep deprivation leads to decreases in mPFC activity and increases in VS activity in response to rewarding stimuli in young adults (aged 18–25 years)180”

What the sources say

• Not checked yetcites [180] Mullin, B. C. et al. Sleep deprivation amplifies striatal activation to monetary reward. Psychol. Med. 43, 2215–2225 (2013). source

In the paper

“symptoms may be related to the amount, duration and intensity of light varying across the seasons (that is, short versus long days)194”

What the sources say

• Not checked yetcites [194] Young, J. W. & Dulcis, D. Investigating the mechanism(s) underlying switching between states in bipolar disorder. Eur. J. Pharmacol. 759, 151–162 (2015). source

In the paper

“The number of vasopressin-expressing cells in the SCN in humans243,244 and rodents245,246 reduces with age, possibly altering SCN output.”

What the sources say

• Not checked yetcites [243] Swaab, D. F., Fliers, E. & Partiman, T. S. The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res. 342, 37–44 (1985). source
• Not checked yetcites [244] Zhou, J. N., Hofman, M. A. & Swaab, D. F. VIP neurons in the human SCN in relation to sex, age, and Alzheimer’s disease. Neurobiol. Aging 16, 571–576 (1995). source
• Not checked yetcites [245] Roozendaal, B., van Gool, W. A., Swaab, D. F., Hoogendijk, J. E. & Mirmiran, M. Changes in vasopressin cells of the rat suprachiasmatic nucleus with aging. Brain Res. 409, 259–264 (1987). source
• Not checked yetcites [246] Tsukahara, S., Tanaka, S., Ishida, K., Hoshi, N. & Kitagawa, H. Age-related change and its sex differences in histoarchitecture of the hypothalamic suprachiasmatic nucleus of F344/N rats. Exp. Gerontol. 40, 147–155 (2005). source

In the paper

“the rapid and lasting antidepressant effects of low-dose ketamine can be predicted based on measures of locomotor activity rhythms before treatment and on how well the treatment strengthens low-amplitude activity rhythms”

What the sources say

• Not checked yetcites [218] Duncan, W. C. Jr et al. Motor-activity markers of circadian timekeeping are related to ketamine’s rapid antidepressant properties. Biol. Psychiatry 82, 361–369 (2017). In a study of 51 patients with major depressive disorder or bipolar disorder, circadian activity patterns prior to and following the administration of ketamine are linked to therapeutic response of mood symptoms. source

In the paper

“Between 20 and 50 years of age, men continue to have greater evening preference on average than women141,220,221”

What the sources say

• Not checked yetcites [141] Roenneberg, T. et al. A marker for the end of adolescence. Curr. Biol. 14, R1038–R1039 (2004). source
• Not checked yetcites [220] Adan, A. & Natale, V. Gender differences in morningness–eveningness preference. Chronobiol. Int. 19, 709–720 (2002). source
• Not checked yetcites [221] Caci, H., Deschaux, O., Adan, A. & Natale, V. Comparing three morningness scales: age and gender effects, structure and cut-off criteria. Sleep Med. 10, 240–245 (2009). source

In the paper

“In humans and rodent models, the amplitude of peripheral oscillatory rhythms dampens with age”

What the sources say

• Not checked yetcites [240] Wang, J. L. et al. Suprachiasmatic neuron numbers and rest–activity circadian rhythms in older humans. Ann. Neurol. 78, 317–322 (2015). source
• Not checked yetcites [241] Chang, H. C. & Guarente, L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153, 1448–1460 (2013). This mouse study reveals that reductions of sirtuin activity in the SCN leads to a gradual age-dependent dampening of SCN activity and locomotor rhythms. source

In the paper

“Taken together, many health problems during adulthood, including sleep problems, depression and anxiety, are linked to circadian disruptions that are caused by shift work or other environmental or genetic disruptions to the sleep–wake cycle.”

In the paper

“Thus, rhythm alignment and amplification are important therapeutic approaches to helping prevent or treat psychiatric disorders.”

In the paper

“Mutations in clock genes such as CRY1, NFIL3 and RORC have been linked to extreme phase delay (that is, delayed sleep–wake phase disorder) in genetic studies of families224,225.”

What the sources say

• Not checked yetcites [224] Patke, A. et al. Mutation of the human circadian clock gene CRY1 in familial delayed sleep phase disorder. Cell 169, 203–215 (2017). source
• Not checked yetcites [225] Kripke, D. F. et al. Circadian polymorphisms in night owls, in bipolars, and in non-24-hour sleep cycles. Psychiatry Invest. 11, 345–362 (2014). source

In the paper

“This study suggests more severe circadian disruptions are associated with a greater likelihood of developing depression.”

In the paper

“A survey of ~4,000 flight attendants as part of the US National Health and Nutrition Survey (NHANES) found that, compared with the general population, flight attendants are 2–5.7-fold more likely to have sleep disorders, depression, anxiety and/or fatigue230.”

What the sources say

• Not checked yetcites [230] McNeely, E. et al. The self-reported health of U. S. flight attendants compared to the general population. Environ. Health 13, 13 (2014). source

In the paper

“For most people, there is a gradual shift towards an earlier chronotype from adolescence into adulthood141.”

What the sources say

• Not checked yetcites [141] Roenneberg, T. et al. A marker for the end of adolescence. Curr. Biol. 14, R1038–R1039 (2004). source

In the paper

“suggesting that the therapeutic effects are directly related to the strengthening of the circadian system218”

What the sources say

• Not checked yetcites [218] Duncan, W. C. Jr et al. Motor-activity markers of circadian timekeeping are related to ketamine’s rapid antidepressant properties. Biol. Psychiatry 82, 361–369 (2017). In a study of 51 patients with major depressive disorder or bipolar disorder, circadian activity patterns prior to and following the administration of ketamine are linked to therapeutic response of mood symptoms. source

In the paper

“antidepressant and mood-stabilizing medications, such as lithium, valproic acid and selective serotonin reuptake inhibitors (SSRIs), all have dramatic effects on gene expression rhythms that may, at least in part, underlie their therapeutic efficacy215–217”

What the sources say

• Not checked yetcites [215] Li, J., Lu, W. Q., Beesley, S., Loudon, A. S. & Meng, Q. J. Lithium impacts on the amplitude and period of the molecular circadian clockwork. PLOS ONE 7, e33292 (2012).
• Not checked yetcites [216] Johansson, A. S., Brask, J., Owe-Larsson, B., Hetta, J. & Lundkvist, G. B. Valproic acid phase shifts the rhythmic expression of Period2::Luciferase. J. Biol. Rhythms 26, 541–551 (2011). source
• Not checked yetcites [217] Sprouse, J., Braselton, J. & Reynolds, L. Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing. Biol. Psychiatry 60, 896–899 (2006). source

In the paper

“most people who are diagnosed with bipolar disorder have an evening chronotype that persists after adolescence191,226”

What the sources say

• Not checked yetcites [191] Melo, M. C. A., Abreu, R. L. C., Linhares Neto, V. B., de Bruin, P. F. C. & de Bruin, V. M. S. Chronotype and circadian rhythm in bipolar disorder: a systematic review. Sleep Med. Rev. 34, 46–58 (2017). source
• Not checked yetcites [226] Murray, J. M. et al. Prevalence of circadian misalignment and its association with depressive symptoms in delayed sleep phase disorder. Sleep 40, zsw002 (2017).

In the paper

“A large study of 11,450 Canadian nurses found that the strongest relationship between work schedule and depression was in those who work rapidly rotating schedules and undefined rotating schedules (as opposed to slowly rotating schedules)228.”

What the sources say

• Not checked yetcites [228] Hall, A. L., Franche, R. L. & Koehoorn, M. Examining exposure assessment in shift work research: a study on depression among nurses. Ann. Work Expo. Health 62, 182–194 (2018). source

In the paper

“In older adults, less-robust circadian rhythms and more fragmented patterns of activity are risk factors for the development of dementia250.”

What the sources say

• Not checked yetcites [250] Tranah, G. J. et al. Circadian activity rhythms and risk of incident dementia and mild cognitive impairment in older women. Ann. Neurol. 70, 722–732 (2011). source

In the paper

“measures of activity and physiological rhythms in older people can be confounded by health problems, medications and eye problems such as cataracts that can reduce light input to the central clock”

In the paper

“When iron is present in the cytosol (as may occur more frequently with ageing)265,266, dopamine can be oxidized into dopamine quinone (DAQ), which is highly reactive and toxic267,268.”

What the sources say

• Not checked yetcites [265] Belaidi, A. A. et al. Marked age-related changes in brain iron homeostasis in amyloid protein precursor knockout mice. Neurotherapeutics https://doi.org/10.1007/s13311-018-0656-x (2018). source
• Not checked yetcites [266] Uranga, R. M. & Salvador, G. A. Unraveling the burden of iron in neurodegeneration: intersections with amyloid beta peptide pathology. Oxid. Med. Cell. Longev. 2018, 2850341 (2018). source
• Not checked yetcites [267] Graham, D. G. Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol. Pharmacol. 14, 633–643 (1978). source
• Not checked yetcites [268] Tse, D. C., McCreery, R. L. & Adams, R. N. Potential oxidative pathways of brain catecholamines. J. Med. Chem. 19, 37–40 (1976). source

In the paper

“even one night of sleep deprivation led to accumulation of amyloid-β (Aβ; one of the proteins that is pathologically accumulated in the brain in AD) in the right hippocampus and thalamus in the human brain284”

What the sources say

• Not checked yetcites [284] Shokri-Kojori, E. et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc. Natl Acad. Sci. USA 115, 4483–4488 (2018). source

In the paper

“environmental and biological disruptions to these systems do seem to worsen progression of these diseases293–295”

What the sources say

• Not checked yetcites [293] Chauhan, R., Chen, K. F., Kent, B. A. & Crowther, D. C. Central and peripheral circadian clocks and their role in Alzheimer’s disease. Dis. Model. Mech. 10, 1187–1199 (2017). source
• Not checked yetcites [294] Homolak, J., Mudrovcic, M., Vukic, B. & Toljan, K. Circadian rhythm and Alzheimer’s disease. Med. Sci. 6, 52 (2018).
• Not checked yetcites [295] Huang, Z. et al. Circadian rhythm dysfunction accelerates disease progression in a mouse model with amyotrophic lateral sclerosis. Front. Neurol. 9, 218 (2018). source

In the paper

“The build-up and expulsion of reactive oxygen species (ROS) also follow a circadian pattern.”

What the sources say

• Not checked yetcites [236] Musiek, E. S. & Holtzman, D. M. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science 354, 1004–1008 (2016). source
• Not checked yetcites [290] McClung, C. A. Mind your rhythms: an important role for circadian genes in neuroprotection. J. Clin. Invest. 123, 4994–4996 (2013). source

In the paper

“in patients with AD, sleep disruptions tend to begin after diagnosis261”

What the sources say

• Not checked yetcites [261] Vitiello, M. V., Prinz, P. N., Williams, D. E., Frommlet, M. S. & Ries, R. K. Sleep disturbances in patients with mild-stage Alzheimer’s disease. J. Gerontol. 45, M131–M138 (1990). source

In the paper

“DAQ has been found in human induced pluripotent stem cell-derived dopaminergic neurons that carry mutations associated with PD269.”

What the sources say

• Not checked yetcites [269] Burbulla, L. F. et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease. Science 357, 1255–1261 (2017). This study demonstrates that mitochondrial stress promotes the accumulation of oxidized dopamine, consequently increasing α-synuclein aggregates in neurons derived from patients with PD, an effect selective to human neurons. source

In the paper

“A recent study in mice revealed that rhythms in the propensity of aggressive behaviours are modulated via a polysynaptic circuit from VIP neurons in the SCN to GABAergic neurons of the subparaventricular zone, which in turn innervate the ventromedial hypothalamus, an area known to regulate aggression283.”

What the sources say

• Not checked yetcites [283] Todd, W. D. et al. A hypothalamic circuit for the circadian control of aggression. Nat. Neurosci. 21, 717–724 (2018). This chemogenetic study in mice reveals a neural circuit involving projections from the SCN to the ventromedial hypothalamus that drives time-of-day-dependent aggressive behaviours. source

In the paper

“SIRT1 binds to CLOCK at the promoter of the gene encoding tyrosine hydroxylase (TH) in dopaminergic neurons to control rhythms in TH expression and, ultimately, dopamine synthesis264”

What the sources say

• Not checked yetcites [264] Logan, R. W. et al. NAD+ cellular redox and SIRT1 regulate the diurnal rhythms of tyrosine hydroxylase and conditioned cocaine reward. Mol. Psychiatry. https://doi.org/10.1038/s41380-018-0061-1 (2018). This study demonstrates mechanistic links between circadian regulation of SIRT1-dependent metabolic signalling and dopaminergic neurotransmission in the mouse ventral tegmental area, which is important for drug reward. source

In the paper

“Thus, deficits in SIRT1 may contribute to toxic levels of DAQ and neurodegeneration.”

In the paper

“more than 80% of people with RBD are later diagnosed with PD or dementia274,275”

What the sources say

• Not checked yetcites [274] Iranzo, A. et al. Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients. PLOS ONE 9, e89741 (2014). source
• Not checked yetcites [275] Schenck, C. H., Boeve, B. F. & Mahowald, M. W. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 14, 744–748 (2013). source

In the paper

“This landmark study suggests that changes in sleep timing and consolidation driven by the circadian system underlie sleep disturbances in elderly individuals.”

What the sources say

• Not checked yetcites [239] Czeisler, C. A. et al. Association of sleep–wake habits in older people with changes in output of circadian pacemaker. Lancet 340, 933–936 (1992). This landmark study suggests that changes in sleep timing and consolidation driven by the circadian system underlie sleep disturbances in elderly individuals. source

In the paper

“Throughout the lifespan, sleep and circadian rhythm disruptions are strongly linked to the pathophysiology of specific psychiatric and neurodegenerative disorders.”

In the paper

“Recent studies have demonstrated that elements of the molecular circadian clock directly regulate cellular metabolism and mitochondrial function in the liver and other tissues316–318.”

What the sources say

• Not checked yetcites [316] Neufeld-Cohen, A. et al. Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins. Proc. Natl Acad. Sci. USA 113, E1673–E1682 (2016). source
• Not checked yetcites [317] O’Neill, J. S. & Feeney, K. A. Circadian redox and metabolic oscillations in mammalian systems. Antioxid. Redox Signal. 20, 2966–2981 (2014). source
• Not checked yetcites [318] Marcheva, B. et al. Circadian clocks and metabolism. Handb. Exp. Pharmacol. 217, 127–155 (2013). source

In the paper

“they suggest that targeting rhythms or components of the clock using pharmacological agents might be therapeutically beneficial215,216,331”

What the sources say

• Not checked yetcites [215] Li, J., Lu, W. Q., Beesley, S., Loudon, A. S. & Meng, Q. J. Lithium impacts on the amplitude and period of the molecular circadian clockwork. PLOS ONE 7, e33292 (2012).
• Not checked yetcites [216] Johansson, A. S., Brask, J., Owe-Larsson, B., Hetta, J. & Lundkvist, G. B. Valproic acid phase shifts the rhythmic expression of Period2::Luciferase. J. Biol. Rhythms 26, 541–551 (2011). source
• Not checked yetcites [331] Sprouse, J., Reynolds, L., Braselton, J. & Schmidt, A. Serotonin-induced phase advances of SCN neuronal firing in vitro: a possible role for 5-HT5A receptors? Synapse 54, 111–118 (2004). source

In the paper

“Many of the most effective treatments for brain disorders and other diseases modulate clock function216,326,330,332,333.”

What the sources say

• Not checked yetcites [216] Johansson, A. S., Brask, J., Owe-Larsson, B., Hetta, J. & Lundkvist, G. B. Valproic acid phase shifts the rhythmic expression of Period2::Luciferase. J. Biol. Rhythms 26, 541–551 (2011). source
• Not checked yetcites [326] Ruben, M. D. et al. A database of tissue-specific rhythmically expressed human genes has potential applications in circadian medicine. Sci. Transl Med. 10, eaat8806 (2018). source
• Not checked yetcites [330] McCarthy, M. J. et al. Genetic and clinical factors predict lithium’s effects on PER2 gene expression rhythms in cells from bipolar disorder patients. Transl Psychiatry 3, e318 (2013). source
• Not checked yetcites [332] Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E. & Hogenesch, J. B. A circadian gene expression atlas in mammals: implications for biology and medicine. Proc. Natl Acad. Sci. USA 111, 16219–16224 (2014). source
• Not checked yetcites [333] Dokucu, M. E., Yu, L. & Taghert, P. H. Lithium- and valproate-induced alterations in circadian locomotor behavior in Drosophila. Neuropsychopharmacology 30, 2216–2224 (2005). source

In the paper

“This study demonstrates, in a cohort of 49 patients with bipolar disorder, the ability of non-invasive circadian therapy (that is, bright light therapy and sleep phase advance) and sleep (that is, acute sleep deprivation) to improve and sustain the therapeutic efficacy of lithium and antidepressants on mood symptoms.”

What the sources say

• Not checked yetcites [214] Wu, J. C. et al. Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol. Psychiatry 66, 298–301 (2009). This study demonstrates, in a cohort of 49 patients with bipolar disorder, the ability of non-invasive circadian therapy (that is, bright light therapy and sleep phase advance) and sleep (that is, acute sleep deprivation) to improve and sustain the therapeutic efficacy of lithium and antidepressants on mood symptoms. source

In the paper

“This study reports notable circadian misalignment (phase delays and advances) of sleep–wake cycles and melatonin rhythms in patients with schizophrenia despite other factors, including mood, cognitive status and pharmacological treatments.”

What the sources say

• Not checked yetcites [188] Wulff, K., Dijk, D. J., Middleton, B., Foster, R. G. & Joyce, E. M. Sleep and circadian rhythm disruption in schizophrenia. Br. J. Psychiatry 200, 308–316 (2012). This study reports notable circadian misalignment (phase delays and advances) of sleep–wake cycles and melatonin rhythms in patients with schizophrenia despite other factors, including mood, cognitive status and pharmacological treatments. source

In the paper

“Circadian disruptions may promote vulnerability to or the progression of certain disorders, within a developmental context.”

In the paper

“The evidence for associations between circadian disruptions and brain disorders in humans is mostly epidemiological and correlational.”

In the paper

“Thus, therapies that stabilize circadian and sleep rhythms may at least slow the progression of these disorders.”

In the paper

“Recent genome-wide association studies with more than 100,000 subjects have identified novel loci associated with sleep duration, chronotype and metabolic phenotypes (for example, body mass index)320,321.”

What the sources say

• Not checked yetcites [320] Jones, S. E. et al. Genome-wide association analyses in 128,266 individuals identifies new morningness and sleep duration loci. PLOS Genet. 12, e1006125 (2016). source
• Not checked yetcites [321] Lane, J. M. et al. Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank. Nat. Commun. 7, 10889 (2016).

In the paper

“Using mice, this study demonstrates that light input to the brain reaches neural circuits related to depression and learning through distinct projections from the retina, revealing a potential mechanism by which aberrant light exposure (for example, light at night) affects mood and cognition.”

What the sources say

• Not checked yetcites [324] Fernandez, D. C. et al. Light affects mood and learning through distinct retina-brain pathways. Cell 175, 71–84 (2018). Using mice, this study demonstrates that light input to the brain reaches neural circuits related to depression and learning through distinct projections from the retina, revealing a potential mechanism by which aberrant light exposure (for example, light at night) affects mood and cognition. source