Neurobiological effects of physical exercise

Source: Wikipedia, the free encyclopedia.

Neurobiological effects of
physical exercise
Exercise therapy – medical intervention
Image of a woman running
A woman engaging in aerobic exercise (jogging)
ICD-9-CM93.19
MeSHD005081
LOINC73986-2
eMedicine324583
]

The neurobiological effects of physical exercise involve possible interrelated effects on brain structure, brain function, and

cognitive function in old age, preventing or treating certain neurological disorders, and improving overall quality of life.[8][9][10][11]

In healthy adults, aerobic exercise has been shown to induce transient effects on cognition after a single exercise session and persistent effects on cognition following consistent exercise over the course of several months.

declarative memory, spatial memory, and information processing speed.[5][7][12][13][14]

Aerobic exercise has both short and long term effects on mood and emotional states by promoting

clinical practice guideline for mild cognitive impairment indicates that clinicians should recommend regular exercise (two times per week) to individuals who have been diagnosed with this condition.[19]

Some

drug addictions.[20][21][22][23]

Reviews of clinical evidence also support the use of exercise as an adjunct therapy for certain

neurodegenerative disorders, particularly Alzheimer's disease and Parkinson's disease.[24][25] Regular exercise may be associated with a lower risk of developing neurodegenerative disorders.[26]

Long-term effects

Neuroplasticity

gray matter volume of the hippocampus, caudate nucleus, and nucleus accumbens.[1]

Structural growth

Reviews of neuroimaging studies indicate that consistent aerobic exercise increases

parietal cortex, cerebellum, and nucleus accumbens.[5][36]

Regular exercise has been shown to counter the shrinking of the hippocampus and memory impairment that naturally occurs in late adulthood.[5] Sedentary adults over age 55 show a 1–2% decline in hippocampal volume annually.[37] A neuroimaging study with a sample of 120 adults revealed that participating in regular aerobic exercise increased the volume of the left hippocampus by 2.12% and the right hippocampus by 1.97% over a one-year period.[37] Subjects in the low intensity stretching group who had higher fitness levels at baseline showed less hippocampal volume loss, providing evidence for exercise being protective against age-related cognitive decline.[37] In general, individuals that exercise more over a given period have greater hippocampal volumes and better memory function.[5] Aerobic exercise has also been shown to induce growth in the white matter tracts in the anterior corpus callosum, which normally shrink with age.[5][35]

The various functions of the brain structures that show exercise-induced increases in gray matter volume include:

Persistent effects on cognition

See also: Executive functions

Concordant with the functional roles of the brain structures that exhibit increased gray matter volumes, regular exercise over a period of several months has been shown to persistently improve numerous executive functions and several forms of memory.

declarative memory,[note 6] and spatial memory.[5][6][7][44] In healthy young and middle-aged adults, the effect sizes of improvements in cognitive function are largest for indices of executive functions and small to moderate for aspects of memory and information processing speed.[1][7] It may be that in older adults, individuals benefit cognitively by taking part in both aerobic and resistance type exercise of at least moderate intensity.[47] Individuals who have a sedentary lifestyle tend to have impaired executive functions relative to other more physically active non-exercisers.[6] A reciprocal relationship between exercise and executive functions has also been noted: improvements in executive control processes, such as attentional control and inhibitory control, increase an individual's tendency to exercise.[6]

Mechanism of effects

Further information: Myokine

BDNF signaling

Further information: Brain-derived neurotrophic factor

One of the most significant effects of exercise on the brain is increased synthesis and expression of BDNF, a neuropeptide and hormone, resulting in increased signaling through its receptor tyrosine kinase, tropomyosin receptor kinase B (TrkB).[4][50][51] Since BDNF is capable of crossing the blood–brain barrier, higher peripheral BDNF synthesis also increases BDNF signaling in the brain.[30] Exercise-induced increases in BDNF signaling are associated with improved cognitive function, improved mood, and improved memory.[29][50] Furthermore, research has provided a great deal of support for the role of BDNF in hippocampal neurogenesis, synaptic plasticity, and neural repair.[5][50] Engaging in moderate-high intensity aerobic exercise such as running, swimming, and cycling increases BDNF biosynthesis through myokine signaling, resulting in up to a threefold increase in blood plasma and BDNF levels;[4][50][51] exercise intensity is positively correlated with the magnitude of increased BDNF biosynthesis and expression.[4][50][51] A meta-analysis of studies involving the effect of exercise on BDNF levels found that consistent exercise modestly increases resting BDNF levels as well.[29] This has important implications for exercise as a mechanism to reduce stress since stress is closely linked with decreased levels of BDNF in the hippocampus. In fact, studies suggest that BDNF contributes to the anxiety-reducing effects of antidepressants. The increase in BDNF levels caused by exercise helps reverse the stress-induced decrease in BDNF which mediates stress in the short term and buffers against stress-related diseases in the long term.[52]

IGF-1 signaling

Further information: Insulin-like growth factor 1

IGF-1 is a

blood–cerebrospinal fluid barrier;[5][50][53][54] consequently, one review noted that IGF-1 is a key mediator of exercise-induced adult neurogenesis, while a second review characterized it as a factor which links "body fitness" with "brain fitness".[53][54] The amount of IGF-1 released into blood plasma during exercise is positively correlated with exercise intensity and duration.[56]

VEGF signaling

Further information: Vascular endothelial growth factor

VEGF is a neurotrophic and

Hypoxia, or inadequate cellular oxygen supply, strongly upregulates VEGF expression and VEGF exerts a neuroprotective effect in hypoxic neurons.[55] Like BDNF and IGF-1, aerobic exercise has been shown to increase VEGF biosynthesis in peripheral tissue which subsequently crosses the blood–brain barrier and promotes neurogenesis and blood vessel formation in the central nervous system.[30][57] Exercise-induced increases in VEGF signaling have been shown to improve cerebral blood volume and contribute to exercise-induced neurogenesis in the hippocampus.[5][57]

Irisin

Further information: FNDC5

A study using FNDC5

irisin levels showed that irisin confers beneficial cognitive effects of physical exercise and that it can serve an exercise mimetic in mice in which it could "improve both the cognitive deficit and neuropathology in Alzheimer's disease mouse models". The mediator and its regulatory system is therefore being investigated for potential interventions to improve – or further improve – cognitive function or alleviate Alzheimer's disease in humans.[58][59][60] Experiments indicate irisin may be linked to regulation of BDNF and neurogenesis in mice.[61]

Short-term effects

Transient effects on cognition

See also: Executive functions

In addition to the persistent effects on cognition that result from several months of daily exercise, acute exercise (i.e., a single bout of exercise) has been shown to transiently improve a number of cognitive functions.[12][62][63] Reviews and meta-analyses of research on the effects of acute exercise on cognition in healthy young and middle-aged adults have concluded that information processing speed and a number of executive functions – including attention, working memory, problem solving, cognitive flexibility, verbal fluency, decision making, and inhibitory control – all improve for a period of up to 2 hours post-exercise.[12][62][63] A systematic review of studies conducted on children also suggested that some of the exercise-induced improvements in executive function are apparent after single bouts of exercise, while other aspects (e.g., attentional control) only improve following consistent exercise on a regular basis.[44] Other research has suggested immediate performative enhancements during exercise, such as exercise-concurrent improvements in processing speed and accuracy during both visual attention and working memory tasks.[64][65]

Exercise-induced euphoria

Main article: Runner's high

Continuous exercise can produce a transient state of

distance running or a "rower's high" in rowing.[66][67][68][69]

Effects on neurochemistry

β-Phenylethylamine

Biosynthetic pathways for catecholamines and trace amines in the human brain[70][71][72]
The image above contains clickable links
In humans, catecholamines and phenethylaminergic trace amines are derived from the amino acid L-phenylalanine.

aromatic amino acid decarboxylase (AADC) at approximately the same rate at which dopamine is produced.[77]

In light of this observation, the original paper and both reviews suggest that phenethylamine plays a prominent role in mediating the mood-enhancing euphoric effects of a runner's high, as both phenethylamine and amphetamine are potent euphoriants.[74][75][76]

β-Endorphin

meta-analytic review found that exercise significantly increases the secretion of β-endorphin and that this secretion is correlated with improved mood states.[78] Moderate intensity exercise produces the greatest increase in β-endorphin synthesis, while higher and lower intensity forms of exercise are associated with smaller increases in β-endorphin synthesis.[78] A review on β-endorphin and exercise noted that an individual's mood improves for the remainder of the day following physical exercise and that one's mood is positively correlated with overall daily physical activity level.[78]

However, humans studies showed that pharmacological blockade of endogenous endorphins does not inhibit a runner's high, while blockade of endocannabinoids may have such an effect.[79]

Anandamide

retrograde neurotransmitter that binds to cannabinoid receptors (primarily CB1), in turn producing euphoria.[68][80] It has been shown that aerobic exercise causes an increase in plasma anandamide levels, where the magnitude of this increase is highest at moderate exercise intensity (i.e., exercising at ~⁠70⁠–⁠80⁠% maximum heart rate).[80] Increases in plasma anandamide levels are associated with psychoactive effects because anandamide is able to cross the blood–brain barrier and act within the central nervous system.[80] Thus, because anandamide is a euphoriant and aerobic exercise is associated with euphoric effects, it has been proposed that anandamide partly mediates the short-term mood-lifting effects of exercise (e.g., the euphoria of a runner's high) via exercise-induced increases in its synthesis.[68][80]

Cortisol and the psychological stress response

Diagram of the HPA axis
Diagram of the hypothalamic–pituitary–adrenal axis
See also: Effects of stress on memory

The "stress hormone",

neurotoxic effects in the human brain.[83] For example, chronic psychological stress decreases BDNF expression, which has detrimental effects on hippocampal volume and can lead to depression.[81]

As a physical stressor, aerobic exercise stimulates cortisol secretion in an intensity-dependent manner;[82] however, it does not result in long-term increases in cortisol production since this exercise-induced effect on cortisol is a response to transient negative energy balance.[note 7][82] Aerobic exercise increases physical fitness and lowers neuroendocrine (i.e., HPA axis) reactivity and therefore reduces the biological response to psychological stress in humans (e.g., reduced cortisol release and attenuated heart rate response).[12][84] Exercise also reverses stress-induced decreases in BDNF expression and signaling in the brain, thereby acting as a buffer against stress-related diseases like depression.[81][84]

Glutamate and GABA

excitatory neurotransmitter involved in many aspects of brain function, including learning and memory.[85] Based upon animal models, exercise appears to normalize the excessive levels of glutamate neurotransmission into the nucleus accumbens that occurs in drug addiction.[21] A review of the effects of exercise on neurocardiac function in preclinical models noted that exercise-induced neuroplasticity of the rostral ventrolateral medulla (RVLM) has an inhibitory effect on glutamatergic neurotransmission in this region, in turn reducing sympathetic activity;[86] the review hypothesized that this neuroplasticity in the RVLM is a mechanism by which regular exercise prevents inactivity-related cardiovascular disease.[86]

Exerkines and other circulating compounds

autocrine pathways".[87]

Effects in children

Engaging in active physical pursuits has demonstrated positive effects on the mental health of children and adolescents,[88] enhances their academic performance,[89] boosts cognitive function,[90] and diminishes the likelihood of obesity and cardiovascular diseases among this demographic.[91] Establishing consistent exercise routines with regular frequency and duration is pivotal.[92][93][94] Cultivating beneficial exercise habits and sustaining adequate physical activity may support the overall physical and mental well-being of young individuals. Therefore, identifying factors that either impede or encourage exercise behaviors could be a significant strategy in promoting the development of healthy exercise habits among children and adolescents.

A 2003 meta-analysis found a positive effect of exercise in children on perceptual skills, intelligence quotient, achievement, verbal tests, mathematic tests, and academic readiness.[95] The correlation was strongest for the age ranges of 4–7 and 11–13 years.[95]

A 2010 meta-analysis of the effect of activity on children's executive function found that aerobic exercise may briefly aid children's executive function and also influence more lasting improvements to executive function.[96] Other studies suggested that exercise is unrelated to academic performance, perhaps due to the parameters used to determine exactly what academic achievement is.[97] This area of study has been a focus for education boards that make decisions on whether physical education should be implemented in the school curriculum, how much time should be dedicated to physical education, and its impact on other academic subjects.[95]

Another study found that sixth-graders who participated in vigorous physical activity at least three times a week had the highest scores compared to those who participated in moderate or no physical activity at all. Children who participated in vigorous physical activity scored three points higher, on average, on their academic test, which consisted of math, science, English, and world studies.[98]

Neuroimaging studies indicate that exercise may influence changes in brain structure and function.[97] Some investigations have linked low levels of aerobic fitness in children with impaired executive function when older as adults, but lack of selective attention, response inhibition, and interference control may also explain this outcome.[99]

Effects on central nervous system disorders

See also:
Central nervous system disorders

Exercise as prevention and treatment of drug addictions

Clinical and preclinical evidence indicate that consistent aerobic exercise, especially endurance exercise (e.g.,

reinstatement (i.e., relapse) of drug-seeking, and induces opposite effects on striatal dopamine receptor D2 (DRD2) signaling (increased DRD2 density) to those induced by pathological stimulant use (decreased DRD2 density).[21][22] Consequently, consistent aerobic exercise may lead to better treatment outcomes when used as an adjunct treatment for drug addiction.[21][23] As of 2016, more clinical research is still needed to understand the mechanisms and confirm the efficacy of exercise in drug addiction treatment and prevention.[20]

Summary of addiction-related plasticity
Form of neuroplasticity
or behavioral plasticity 		Type of reinforcer Sources
Opiates Psychostimulants High fat or sugar food Sexual intercourse Physical exercise
(aerobic) 		Environmental
enrichment
MSNs
Tooltip medium spiny neurons 		↑ ↑ ↑ ↑ ↑ ↑ [22]
Behavioral plasticity
Escalation of intake Yes Yes Yes [22]
Psychostimulant
cross-sensitization 		Yes Not applicable Yes Yes Attenuated Attenuated [22]
Psychostimulant
self-administration 		↑ ↑ ↓ ↓ ↓ [22]
Psychostimulant
conditioned place preference 		↑ ↑ ↓ ↑ ↓ ↑ [22]
Reinstatement of drug-seeking behavior
 ↑ ↑ ↓ ↓ [22]
Neurochemical plasticity
CREBTooltip cAMP response element-binding protein phosphorylation

in the nucleus accumbens 		↓ ↓ ↓ ↓ ↓ [22]
Sensitized dopamine response
in the nucleus accumbens 		No Yes No Yes [22]
Altered striatal dopamine signaling ↓
DRD3
 ↑
DRD3
 ↑
DRD3
 ↑
DRD2
 ↑
DRD2
 [22]
Altered striatal opioid signaling No change or
↑μ-opioid receptors		 ↑μ-opioid receptors
↑κ-opioid receptors		 ↑μ-opioid receptors ↑μ-opioid receptors No change No change [22]
Changes in striatal opioid peptides ↑dynorphin
No change: enkephalin		 ↑dynorphin ↓enkephalin ↑dynorphin ↑dynorphin [22]
Mesocorticolimbic synaptic plasticity
Number of dendrites in the nucleus accumbens ↓ ↑ ↑ [22]
Dendritic spine density in
the nucleus accumbens 		↓ ↑ ↑ [22]

Attention deficit hyperactivity disorder

Regular physical exercise, particularly aerobic exercise, is an effective

add-on treatment for ADHD in children and adults, particularly when combined with stimulant medication (i.e., amphetamine or methylphenidate), although the best intensity and type of aerobic exercise for improving symptoms are not currently known.[18][100] In particular, the long-term effects of regular aerobic exercise in ADHD individuals include better behavior and motor abilities, improved executive functions (including attention, inhibitory control, and planning, among other cognitive domains), faster information processing speed, and better memory.[18] Parent-teacher ratings of behavioral and socio-emotional outcomes in response to regular aerobic exercise include: better overall function, reduced ADHD symptoms, better self-esteem, reduced levels of anxiety and depression, fewer somatic complaints, better academic and classroom behavior, and improved social behavior.[18] Exercising while on stimulant medication augments the effect of stimulant medication on executive function.[18] It is believed that these short-term effects of exercise are mediated by an increased abundance of synaptic dopamine and norepinephrine in the brain.[18]

Major depressive disorder

A number of medical reviews have indicated that exercise has a marked and persistent

clinical trials supports the efficacy of physical exercise as a treatment for depression over a 2–4 month period.[5] These benefits have also been noted in old age, with a review conducted in 2019 finding that exercise is an effective treatment for clinically diagnosed depression in older adults.[105]

A meta-analysis from July 2016 concluded that physical exercise improves overall quality of life in individuals with depression relative to controls.[9][106]

Cerebrovascular disease

Physical exercise plays a significant role in the prevention and management of

intracerebral haemorrhage.[107][108] Engaging in physical activity before experiencing a stroke has been found to have a positive impact on the severity and outcomes of stroke.[109] Exercise has the potential to increase the expression of VEGF, caveolin, and angiopoietin in the brain. These changes may promote angiogenesis and neovascularization that contribute to improved blood supply to the stroke affected areas of the brain.[110][111][112] Exercise may affect the activation of endothelial nitric oxide synthase (eNOS) and subsequent production of nitric oxide (NO).[113][114][115] The increase in NO production may lead to improved post-stroke cerebral blood flow, ensuring a sufficient oxygen and nutrient supply to the brain. Physical activity has been associated with increased expression and activation of hypoxia-inducible factor 1 alpha (HIF-1α), heat shock proteins, and brain-derived neurotrophic factor (BDNF).[116][117][118] These factors play crucial roles in promoting cellular survival, neuroprotection, and repair processes in the brain following a stroke. Exercise also inhibit glutamate and caspase activities, which are involved in neuronal death pathways.[119][120][121][122] Additionally, it may promote neurogenesis in the brain. These effects collectively contribute to the reduction of brain infarction and edema, leading to potential improvements in neurological and functional outcomes. The neuroprotective properties of physical activity in relation to haemorrhagic strokes are less studied. Pre-stroke physical activity has been associated with improved outcomes after intracerebral haemorrhages.[123] Furthermore, physical activity may reduce the volume of intracerebral haemorrhages.[124][125] Being physically active after stroke also enhance the functional recovery.[126][127][128]

Mild cognitive impairment

The

clinical practice guideline for mild cognitive impairment states that clinicians should recommend regular exercise (two times per week) to individuals who have been diagnosed with this condition.[19] This guidance is based upon a moderate amount of high-quality evidence which supports the efficacy of regular physical exercise (twice weekly over a 6-month period) for improving cognitive symptoms in individuals with mild cognitive impairment.[19]

Neurodegenerative disorders

Alzheimer's disease

Alzheimer's disease is a cortical neurodegenerative disorder and the most prevalent form of dementia, representing approximately 65% of all cases of dementia; it is characterized by impaired cognitive function, behavioral abnormalities, and a reduced capacity to perform basic activities of daily life.[24] Two reviews found evidence for possible positive effects of physical exercise on cognitive function, the rate of cognitive decline, and the ability to perform activities of daily living in individuals with Alzheimer's disease.[24] A subsequent review found higher levels of physical activity may be associated with reduced risk of dementia and cognitive decline.[26]

Parkinson's disease

gait disturbance, immobility, and frequent falls. Some evidence suggests that physical exercise may lower the risk of Parkinson's disease.[129] A 2017 study found that strength and endurance training in people with Parkinson's disease had positive effects lasting for several weeks.[130] A 2023 Cochrane review on the effects of physical exercise in people with Parkinson's disease indicated that aquatic exercise might reduce severity of motor symptoms and improve quality of life.[131] Furthermore, endurance training, functional training, and multi-domain training (i.e., engaging in several types of exercise) may provide improvements.[131]

See also

Notes

  1. ^ Neurotrophic factors are peptides or other small proteins that promote the growth, survival, and differentiation of neurons by binding to and activating their associated tyrosine kinases.[28]
  2. ^ Adult neurogenesis is the postnatal (after-birth) growth of new neurons, a beneficial form of neuroplasticity.[27]
  3. ^ Attentional control allows an individual to focus their attention on a specific source and ignore other stimuli that compete for one's attention,[32] such as in the cocktail party effect.
  4. ^ Inhibitory control is the process of altering one's learned behavioral responses, sometimes called "prepotent responses", in a way that makes it easier to complete a particular goal.[38][46] Inhibitory control allows individuals to control their impulses and habits when necessary or desired,[38][46] e.g., to overcome procrastination.
  5. ^ Working memory is the form of memory used by an individual at any given moment for active information processing,[32] such as when reading or writing an encyclopedia article. Working memory has a limited capacity and functions as an information buffer, analogous to a computer's data buffer, that permits the manipulation of information for comprehension, decision-making, and guidance of behavior.[38]
  6. ^ Declarative memory, also known as explicit memory, is the form of memory that pertains to facts and events.[39]
  7. ^ In healthy individuals, this energy deficit resolves simply from eating and drinking a sufficient amount of food and beverage after exercising.

References

  1. ^
    S2CID 54301951
    .
  2. ^
    PMID 26174783
    .
  3. PMID 24366527
    .
  4. ^
    S2CID 30210091
    .
  5. ^
    PMID 23720292
    .
  6. ^
    PMID 25324754
    .
  7. ^
    PMID 26552574
    .
  8. ^ CDC (1 August 2023). "Benefits of Physical Activity". Centers for Disease Control and Prevention. Retrieved 7 December 2023.
  9. ^
    S2CID 4787287
    .
  10. PMID 27351018
    .
  11. PMID 29755380
    .
  12. ^
    PMID 29765853
    .
  13. ^ "Exercise and mental health". betterhealth.vic.gov.au. Department of Health & Human Services. Retrieved 19 November 2022.
  14. ISBN 9781492595502
    .
  15. ^ "10 great reasons to love aerobic exercise". Mayo Clinic. Retrieved 5 December 2023.
  16. ^
    S2CID 29351791
    .
  17. ^
    S2CID 32304140
    .
  18. ^
    PMID 27400928
    .
  19. ^
    PMID 29282327
    .
  20. ^
    PMID 26903885
    .
  21. ^
    PMID 23806439
    .
  22. ^
    PMID 21459101
    .
  23. ^
    PMID 25397661
    .
  24. ^
    S2CID 24936334
    .
  25. PMID 24018704
    .
  26. ^
    PMID 24885250
    .
  27. ^
    ISBN 9780071481274
    .
  28. ISBN 9780071481274
    .
  29. ^
    PMID 25455510
    .
  30. ^
    PMID 24478719
    .
  31. ^
    S2CID 205895178
    .
  32. ^
    ISBN 9780071481274
    .
  33. PMID 24157077
    .
  34. PMID 24748784
    .
  35. ^
    S2CID 20765865
    .
  36. S2CID 22238883
    .
  37. ^
    PMID 21282661
    .
  38. ^
    ISBN 9780071481274
    .
  39. ^
    ISBN 9780071481274
    .
  40. PMID 25406224
    .
  41. ISBN 9780071481274
    .
  42. PMID 24492077
    .
  43. ISBN 9780071481274
    .
  44. ^
    PMID 25133092
    .
  45. PMID 28825973
    .
  46. ^
    S2CID 15788121
    .
  47. S2CID 13553374
    .
  48. PMID 30197620
    .
  49. S2CID 57765282
    .
  50. ^
    PMID 24999318
    .
  51. ^
    PMID 25362636
    .
  52. PMID 23630504
    .
  53. ^
    S2CID 27947753
    .
  54. ^
    PMID 19955757
    .
  55. ^
    ISBN 9780071481274
    .
  56. S2CID 22974661
    .
  57. ^
    PMID 25327899
    .
  58. ^ "The hormone irisin is found to confer benefits of exercise on cognitive function". medicalxpress.com. Retrieved 21 September 2021.
  59. ^ Reynolds G (25 August 2021). "How Exercise May Help Keep Our Memory Sharp". The New York Times. Retrieved 21 September 2021.
  60. S2CID 237254736
    .
  61. PMID 33493316
    .
  62. ^
    PMID 26581791
    .
  63. ^
    S2CID 8320775
    .
  64. S2CID 52960179
    .
  65. S2CID 236969156
    .
  66. PMID 18604371
    .
  67. PMID 18296435
    . The runner's high describes an euphoric state resulting from long-distance running.
  68. ^
    S2CID 5129200
    .
  69. PMID 19755532
    .
  70. PMID 19948186
    .
  71. PMID 15860375
    .
  72. PMID 24374199
    .
  73. S2CID 207366162
    .
  74. ^
    PMID 11579070
    .
  75. ^
    PMID 15860375
    .
  76. ^
    PMID 18473983
    .
  77. ^
    PMID 19948186
    .
  78. ^
    S2CID 40951545
    .
  79. S2CID 231858251
    .
  80. ^
    S2CID 14531019
    .
  81. ^
    ISBN 9780071481274
    .
  82. ^
    PMID 23415825
    .
  83. ^
    PMID 25657633
    .
  84. ^
    PMID 23412549
    .
  85. ISBN 9780071481274
    .
  86. ^
    PMID 25957223
    .
  87. PMID 35304603
    .
  88. PMID 15973308
    .
  89. doi:10.1037/e303072004-001
    . Retrieved 8 December 2023.
  90. S2CID 6374501
    .
  91. ISBN 9781492596868
    .
  92. S2CID 5659723
    .
  93. ISSN 0091-7435
    .
  94. PMID 9838974
    .
  95. ^
    S2CID 56815489
    .
  96. PMID 21818169
    .
  97. ^
    S2CID 1204039
    .
  98. S2CID 9676116
    .
  99. S2CID 400283
    .
  100. PMID 23972692
    .
  101. ^
    PMID 24813261
    .
  102. ^
    PMID 24026850
    .
  103. PMID 17561174
    .
  104. PMID 25652267
    .
  105. S2CID 209179889
    .
  106. PMID 8410743
    .
  107. S2CID 2753073
    .
  108. S2CID 2332015
    .
  109. PMID 34904691
    .
  110. S2CID 22015361
    .
  111. S2CID 3812671
    .
  112. S2CID 25507984
    .
  113. S2CID 28445967
    .
  114. S2CID 9063866
    .
  115. S2CID 255954922
    .
  116. S2CID 318020
    .
  117. PMID 22204323
    .
  118. PMID 25796156
    .
  119. PMID 19302809
    .
  120. PMID 20714296
    .
  121. PMID 22949807
    .
  122. S2CID 255606303
    .
  123. PMID 36344278
    .
  124. S2CID 258464205
    .
  125. PMID 33840224
    .
  126. S2CID 33967186
    .
  127. PMID 37126346
    .
  128. S2CID 199388335
    .
  129. PMID 30646166
    .
  130. S2CID 29666456
    .
  131. ^
    PMID 36602886
    .
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