| Familial advanced sleep phase syndrome (FASPS) |
Early sleep and wake times, shortened circadian rhythms [112]. |
Mice expressing human mis-sense mutations in Per2 or CKIδ have advanced phase of activity in a light-dark schedule and a shortened activity rhythm [92],[102]. |
| Delayed sleep phase syndrome (DSPS) |
Extreme evening preference, delayed phase of activity, sleep, core body temperature, and melatonin [113]. |
No model. |
| Seasonal affective disorder (SAD) |
Depressive symptoms occur during shorter winter days [88]–[90]. |
No model. |
| Mood disorders (unipolar depression) and psychoses (schizophrenia, bipolar) |
Depression. Increased sleep latency, impaired sleep continuity, phase advance in endogenous circadian system relative to sleep schedule, phase advances in growth hormone, plasma melatonin, increased plasma cortisol at night. All major affective disorders include circadian phase disturbances in sleep, activity, temperature, and hormone levels (for reviews see [84]–[86]). |
No accurate mouse model. Mutants in serotonergic and dopaminergic systems show disturbances in circadian phase and/or sleep parameters [94]–[97]. Clock mutant has low anxiety, mania, and hyperactivity [42],[43]. Cognitive disturbances in Npas2 mutant [39]. Abnormal sensitisation to drugs of abuse in Clock and Per mutants [50]–[52]. |
| Autism spectrum disorders (ASD) |
Longer sleep latency and greater sleep fragmentation. Abnormalities in circadian rhythm and mean concentration of plasma melatonin [81]. |
Mice expressing a conditional deletion of Pten have a significantly longer free-running period [83]. |
| Down syndrome |
Reduced sleep maintenance, sleep fragmentation, reduction in percent REM sleep, sleep apnea [73]–[75]. |
Ts65Dn mouse mutant shows increased activity in the light phase, a reduction in rhythm amplitude, and a 4-h advance in the phase of activity [76],[77]. |
| Smith-Magenis syndrome |
Inverted rhythm of melatonin secretion [69],[71]. Advanced sleep/wake phase. Nighttime wakening, daytime sleepiness. Reduced total and NREM sleep [70]. |
Heterozygous deletion mutant mice have a hypoactive phenotype and a significantly shorter circadian period [72]. |
| Prader-Willi syndrome |
Sleep apnea, sleep-related and behavioural disturbances including daytime napping and excessive daytime sleepiness [75],[78],[79]. |
Mice deficient for mage-like 2 gene (Magel2) have a reduced circadian activity amplitude with increased daytime activity [80]. |
| Parkinson disease (PD) |
Sleep fragmentation, sleep apnea, REM sleep behaviour disorder, excessive daytime sleepiness [53]. |
No recorded circadian or sleep disturbances in genetic mouse models [114]. |
| Huntington disease (HD) |
Nocturnal awakening and progressive disintegration of daily activity rhythms [55]. |
R6/2 mouse transgenic line has increased daytime and reduced nocturnal activity. Progresses to a complete disintegration of diurnal and circadian activity rhythms [55]. |
| Alzheimer disease (AD) |
Fragmented sleep, increased nocturnal activity, and reduced daytime activity. Delayed phase in peak of daily activity [57]. |
Alterations in sleep regulation and timing in Tg2576 [62] and PDAPP mice [61]. Tg2576 mice also have a significantly longer circadian period [62]. Both TgCRND8 and APP23 mice show changes in daily activity profiles potentially analogous to those seen in AD patients [63],[64]. |
| Aging |
Sleep disturbances due to earlier wake time and reduced sleep consolidation. Partially attributed to age-related reduction in amplitude and advance in phase of circadian rhythms [56],[58]. |
Aging lengthens the period and reduces the amplitude of circadian activity rhythms. The onset of daily activity is significantly delayed and the variability of onset is increased [67]. |
| Prion diseases |
Severe sleep abnormalities, progressive loss of circadian rest-activity, and melatonin rhythms [54],[59],[60]. |
Increased sleep fragmentation and significantly longer circadian period in activity in prion protein null mutants [65]. |
