Table 2.

Several factors including social, environmental, lifestyle, habits, and some disorders affecting sleep-including REMS and NA levels. The numbers in parentheses show the cited article in the reference list

	Factors	Symptoms	Changes in NA levels	References
Environmental and Lifestyle changes	Light: Usage of light and electronic appliances/gadgets prior to and during sleep	Affects sleep onset, sleep quality	Increased, in LC and paraventricular hypothalamus	[138, 139, 149]
	Noise: Fragmented sleep because of noisy appliances or noisy environment	Daytime sleepiness, insomnia	Increased, in Serum and Urine	[146, 150, 151]
	Temperature: Extreme temperature disfavors sleep depth	Sleep disruption, especially REM sleep loss	Increased NA level in blood	[20, 147]
	Family/social support: Lack of family emotional support, childhood trauma	Psychological symptoms like anxiety, depression, suicidality, further effects sleep quality	Deficiency in NA and 5-hydroxytryptamine (5-HT)	[159]
	Food habit: Eating heavy food in night may lead to indigestion and affects sleep	Indigestion, frequent awakening, and insomnia	Increased level in plasma	[143–145, 147, 148]
	Shift work: Variable shifts timing in work	Circadian misalignment, insomnia or excessive sleepiness	Increased blood level of NA and cortisol	[149, 160]
Disorders	Cardio-respiratory: Asthma, cough, sputum production	Sleep disturbance, increased insomnia	Increased level	[71, 162–164]
	Stress, anxiety, and depression: Daily work stress, conditional anxiety	Light and brief episodes of sleep, difficult to achieve restful sleep, loss of interest and appetite, apathy, and suicidal thoughts	Extreme level of NA	[23, 71, 161, 165]
	Alzheimer’s: Aging, lifestyle, family history, genetics, and head injuries	loss of interest and appetite, dementia, and sleep/REMS disturbances	Decreased level in many brain areas (difference in depressed and non-depressed AD patients) but Increased level in CSF	[4, 19, 21, 158, 166]
	Parkinson’s: Exposure toxins, environmental factors, and genetic mutation	Impairs motor skills, sleep difficulties, cognitive problems	Loss of LC neurons and decreased level of NA in brain	[156, 157]
Drugs/Chemicals abuse	Caffeine: Consumption during bedtime induces alertness, temporarily blocks adenosine receptor	Maintain alertness, decreases sleep quality	Level of noradrenaline increases in brain	[141, 142, 155]
	Alcohol: Excessive drinking leads to increased awakening, sleep fragmentation	Increase in sleep-onset latency	Decrease in level of NA (however the release of NA is dependent on alcohol dose)	[142, 154]
	Nicotine: Intake (smoking) during sleep time lead to alertness	Maintain alertness, decreases sleep quality	Increases level of noradrenaline, inhibits monoamine oxidase in brain	[142, 152, 153]

LC locus coeruleus, AD Alzheimer’s disease, NA noradrenaline, CSF cerebrospinal fluid