Efects of regular physical activity on mental health. Explaining mechanisms.

1. Ferran Suay. Departament de Psicobiologia. UV
PRINCIPLES OF THE INTERVENTION
ON PHYSICAL AND MENTAL HEALTH

2. Addressing...
 Physical activity, physical exercise, sport,
fitness
 Impact on mental health
 Main hypothesis
 Is physical exercise reinforcing?

3. INTERVENTION ON HEALTH:
Promoting active lifestyles
 Physical activity ≠ physical exercise ≠ sport

4. Physical activity
 Any form of exercise or movement. Physical
activity may include planned activity such as
walking, running, basketball, or other sports.
Physical activity may also include other daily
activities such as household chores, yard
work, walking the dog, etc. ...
Motor activity aimed to immediate
goals

5. Physical exercise
 Physical exercise is any bodily activity that
enhances or maintains physical fitness and
overall health.
 It is performed for various reasons:
strengthening muscles and the cardiovascular
system, honing athletic skills, weight loss or
maintenance and for enjoyment. ...
Systematic activity oriented to
enhance physical fitness

6. sport
 an organized, competitive, and
skillful physical
activity requiring commitment
and fair play, in which a winner
can be defined by objective
means. It is governed by a set
of rules or customs.

7. Fitness (physical fitness)
 Muscular strength
 Muscular endurance
 Cardiorespiratory
endurance
 Flexibility
 Body composition

8. Muscular endurance
 the ability of a muscle
or group of muscles to
sustain repeated
contractions against a
resistance for an
extended period of
time.

9. Muscular strength
 Strength refers to a
muscle's ability to
generate force against
physical objects.
 In the fitness world,
this typically refers to
how much weight you
can lift for different
strength training
exercises.

10. Cardiorespiratory endurance
 the ability of the body to
perform prolonged, large-
muscle, dynamic exercise at
moderate-to-high levels of
intensity.
 Also Known As:
cardiorespiratory fitness,
aerobic fitness, aerobic power

11. Flexibility-Elasticity
 the distance of motion
of a joint, which may be
increased by stretching
 the ability of tissue to
regain its original shape
and size after being
stretched, squeezed, or
otherwise deformed

12. Body composition
 % of fat, bone and muscle in human
bodies.
 Fat % recommendations:
 Men 8 t0 17%
 Women 10 to 21%
 Regulating factors:
 Diet
 Physical Activity
 Metabolism
 Hormones

13. PhA, overweight and obesity
 Obesity
 Health problem:
 Hypertension
 Diabetis (II)
 Cardiovascular diseases
 Osteoartrytis
 Psychological problems
 Echonomic cost

14. Body Mass Index
(BMI; Quételet Index )
< 18 lean
18-25 Normal
25-30 Overweight
30-40 Obesity
>40 Morbid Obesity

15. Weight of a
Category BMI range – kg/m2 BMI Prime 1.8 metres person
with this BMI
Severely
< 16.0 < 0.66 < 53.5 kg
underweight
Underweight 16.0 to 18.5 0.66 to 0.73 53.5 to 59.9 kg
Normal 18.5 to 25 0.74 to 0.99 60 to 80.9 kg
Overweight 25 to 30 1.0 to 1.19 81 to 96.9 kg
Obese Class I 30 to 35 1.2 to 1.39 97 to 112.9 kg
Obese Class II 35 to 40 1.4 to 1.59 113 to 129.9 kg
Obese Class III > 40 > 1.6 > 130 kg

16.  Africa & Asia: BMI 22-23 Kg/m2
 USA & Europe: BMI 25-27 Kg/m2

17. And...what has it to do with mental
health?

18. Background: evolutive resumé

19. Background: ancient roman already knew it
MENS SANA IN CORPORE SANO

20. Background:19th and 20th centuries
“CNS and muscles need exercise, so that its vital
metamorphosis contributes to the normal chemical
composition of the blood that irrigates the brain”
W. James
(1899)
Blumenthal et al.
(1999)
Franz & Hamilton PE efficacy pharmacology
(1905)
“Physical exercise can be effective as an
adjunct in the treatment of major depressive
disorder”

21. Acute and chronic exercise
KNOWN EFFECTS

22. 1. Acute exercise and mood states
 Effects observed after 10
minutes efforts
 Intens effort may:
 Enhance mood (habitual
exercisers)
 Be aversive (non habituated
individuals)

23. Effects more evident
 For aerobic exercise
 In fit individuals
• In clinical population
• With worsened mood prior to
exercise

24. 2. Acute exercise and anxiety
 Related to state-anxiety reduction
 Anxiolytic effect independent of
the type of exercise, and time of day
 Moderate to high intensities (>60% VO2max)
 Very high intensities  anxiogenic effect
(Raglin 1997; O’Connor & Davis 1992; Kerr & Sveback 1994; Hale et al. 2002)

25. Animal model
ESTRÉS
•OPEN FIELD BEHAVIOR
•FORCED SWIMMING
HORMONES
•DEPRIVATION
•SHOCKS NEUROTRANSMITERS
•COMBINATION
RECEPTORS
Open field ambulation
Training Defecation (Tharp & Carson 1975)
Independent from fitness enhancements (Dishman et al. 1988)

26. B S Hale, K R Koch, J S Raglin. State anxiety responses to 60 minutes
of cross training. Br J Sports Med 2002;36:105–107
Figure 1. State anxiety responses, measured by the State Trait Anxiety Inventory
(STAI-Y1), over time after cross training sessions. *p<0.05 compared with
baseline.

27. 3. Chronic exercise and anxiety
 Participation in Physical
Exercise programs can reduce trait-
anxiety (Petruzzello et al. 1991)
 Clearest benefits for anxious people
 Effect greater than placebo and
independent from previous expectations
 Efficacy comparable to stress inoculation

28. How is it done?
First hypothesis concerning anxiety reduction

29. TERMOGENIC MODEL
EEG
Physical (8-12 Hz)
Exercise
THAL Motor Cortex estimulation
Tª HPT
motoneuronal activity
SOMATIC
RESPONSES
(vasodilation,...)
WEL-BEING
FEELING MYOTATIC
REFLEX
Von Euler & Soderberg (1957)

30. How would you prove this hypothesis as
false?

31. Complementary mechanism?
Tª changes
Cells (Gisolfi et al. 1980)
Enzims NE
HPT Tª
Reactions
•Catecholamines (Galbo et al. 1979)
•Cortisol (Galbo et al. 1979)
•5-HT (Barchas & Freedman 1962)
-Endorphin (Kelso et al. 19784)

32. 4. Exercise and depression
Background
 Morgan (1969): Less fit psychiatric inmates were the most
depressed ones.
 Consistent relationship between physical activity and mental
health (Salmon 2001)
 Regular exercise reduces stress levels (physiologically as well
as psychologically measured).
 The effects can not be exclusively attributed to an improved
physical condition (Dishman et al. 1988; Salmon 2000)

33. BENEFICIAL EFFECTS
HARMFUL HARMFUL EFFECTS
EFFECTS
PHYSICAL E XE R C I SE
Sedentary lifestyle Overtraining

35. How is it done?
Main hypothesis concerning antidepressive effects
of physical exercise

36. 5HT hypothesis
 Monoamines: Indolamines
 Complex effects on
behavior: regulation of
 Body temperature
 Sleep
 Mood
 Appetite
 Pain
(Carlson 2002)

37. Serotonin biosynthesis
TRP HIDROXILASE 5-HTTP DESCARBOXILASE
5-HIDROXITRYPTOPHAN SEROTONIN
TRYPTOPHAN
5-HTP 5-HT
TRP

38. 5HT synthesis &
metabolism
5HT releasing
 The enhanced tryptophan supply is not the cause
for the increased 5HT releasing

39. studied in relation
to physical exercise
 Pre: 5-HT1A
 Post: 5-HT2

40. Animal experiments: rats
Corticosteroids
Stress-induced No-Responses to acute stress
Depression Psychomotor retardation
(animal model)
Anhedonia
 4 weeks of Physical exercise (swimming 30 min/day)
 synthesis & metabolism 5-HT in various brain regions
 Prevention of animal model-induced depression
(Katz 1981)

41. Dey, S. Physical exercise as a novel antidepressant agent: Possible role of serotonin
receptor subtypes . Physiology & Behavior, 55 (2), 1994, 323-329
160 rats housed in group
N=25: swimming 30 min/day; 6 d/week; 4 weeks
Control animals in water (no swimming) = conditions
Open field: pre & + 48 h.
4 groups
•agonists of 5HT1A-5HT2 receptors administration = controls

42. Trained rats results
• Less emotional reactivity
• More exploratory activity
• Responsivity 5HT2 (post-)
• Sensitivity 5HT1A (auto-)
results tricyclic medication (A-D) & ECT in enhancing 5HT2 receptors’ sensitivity
Training  5HT2 + 5HT1A  5HT neurotransmission
Conclusion: 4 weeks of physical exercise prevent stress-
induced depression in 100% of rats

43. Summary: PhEx5HT
training
5-HT1A sensitivity
Acute PhEx 5-HT activity 5-HT2A sensitivity
Fatigue, PE
Fatigue, PE
A-D effect

44. Summary: Chronic PhEx5HT
Regulation of 5-HT Malfunction
5-HT activity neurotransmission 5-HT system
Acute PhEx training overtraining

45. Complementary hypothesis about
antidepressive actions
(Barden et al. 1994)
 A-D would stimulate expression of corticoesteroid
receptors
 responsivity to inhibitory al feedback from
glucocorticoids
 HPA activity ( CRH-neurones expression )

46. HPA: variability sources
CIRCADIAN RHYTHMS
STRESS
NSQ
FEEDBACK
NPV
CRH

-END
HYPOTHALAMUS POMC
ACTH
ANTERIOR
PITUITARY
Glucocorticoids
(GC)
ADRENAL CORTEX

47. PhEx ACUTE RESPONSE: HPA & HPG-AXIS
-
endorphins
GnRH CRH
LH, FSH ACTH
Estradiol
Cortisol
T
Tissues
EXCITATON
INHIBITION

48. Adaptive mechanism
Protecting muscles (and other tissues) from high GC
concentrations  receptor downregulation (Duclos et al. 2001)
CRH
ACTH
Glucocorticoids
(GC)

49. Physical
exercise
5-HT
Tª
? HPA/HPG
EMG

50. Brain-Derived Neurotrophic Factor
(BDNF)
 More abundant neurotrophin in brain
 Stimulates neurogenesis and neuronal
resilience
 “… voluntary exercise can increase levels of
BDNF and other growth factors, stimulate
neurogenesis, increase resistance to brain insult
and improve learning and mental performance”
(Cotman & Berchtold 2002)

51. Monoamine related hypothesis about genic expression
BDNF gene
STRESS
Monoamine
transduction deficit
Neurones’ viability
ATROPHY
DEPRESSION APOPTOSIS
HYPOCAMPUS
(modified from Stahl 2002)

52. Physical activity–antidepressant treatment combination: impact on BDNFand
behavior in an animal model (Russo-Neustadtet al. 2001)
 Tranilcipromine  Tranilcipromine treatment
treatment during 1
week  Voluntary PhEx
No treatment
 Voluntary PhEx + forced swimming
(running on an wheel)
for 1 week
Control group:
• Sedentary
• No treatment
• No forced-swimming

53.  no escape forced swim
 1rst day: 15 min.
 2ond day: 5 min.
 Behaviour assessment:
 Swimming vs. immobility
 in situ BDNF mRNA
hybridization: mRNA levels
in various hippocampal
areas

54. BDNF as an action mechanism for
antidepressant drugs
 A-D drugs  upregulation of BDNF mRNA demonstrated
in Hippocampus and Cortex (Nibuya et al. 1995)
 BDNF infusion recovery of behaviour deficits induced
by animal models of depression (Siuciak et al. 1997)

55. Fig. 1. BDNF is a natural candidate to mediate the benefits of exercise on brain health. (a)
BDNF is transported retrogradely and anterogradely to synapses, where it potentiates
synaptic transmission, participates in gene transcription, modifies synaptic morphology, and
enhances neuronal resilience. BDNF mRNA and protein levels increase in an activity-
dependent manner. (b) Released BDNF binds to its receptor (TrkB) presynaptically to modify
transmitter release and postsynaptically to modify postsynaptic sensitivity, for example, via
interaction with NMDA receptors

56. Fig. 1. Representative autoradiograms from in situ BDNF mRNA hybridization in the rat
hippocampus (coronal plane).
A: Control B: Untreated animal after 2 day forced swim
C: 1 week of physical activity D: combination of running
prior to forced swimming and tranylcypromine
The two-day forced swim procedure led to decreased BDNF mRNA levels
(diminished grain density) (B), which was restored to baseline after prior physical
activity (C). The combination of tranylcypromine and physical activity prior to
forced swim stress led to BDNF mRNA significantly higher than baseline levels (D).

57.  Fig. 2. Effects of exercise on hippocampal BDNF mRNA and protein levels. (a) In
situ hybridization shows that expression of BDNF mRNA in the rat dentate gyrus (DG),
hilus, CA1–CA3 regions and cortex is greater following exercise (seven days of voluntary
wheel-running) than in sedentary animals (b). (c) ELISA quantification of hippocampal
BDNF protein levels in the hippocampus in sedentary (SED) and exercising (EX) animals,
after five days of wheel-running (*P <0.05). (d) Rats and mice acclimate rapidly to the
running wheel and progressively increase their extent of daily running, in some cases up to
a startling 20 kilometers per night. BDNF protein levels correlate with running distance
(average over 14 days running; R2 = 0.771).]

58. The combination of activity and tranylcypromine treatment led to
BDNF mRNA levels significantly elevated above controls in all
hippocampal areas measured.

59. PhExBDNF
 PhEx
 BDNF In HPPC
(Neeper et al. 1995; 1996)
 BDNF mRNA
 upregulation induced by A-D drugs
(Russo-Neustadt et al. 1999)

60. Phisical Antidepressant
exercise drugs
BDNF
Depression related
behaviour

61. results after forced swim
 No-treatment: BDNF mRNA in HPPC
 Differences among groups:
 PhEx & A-D: BDNF mRNA CONTROL
 [PhEx + A-D]:
 mRNA levels > base line (+250%)
 More active (immobility time decrease of 89%)
 Swimming time +& mRNA levels

62.  neurogenesis and neuronal resilience, neuronal
connectivity and activity-dependent plasticity

63. Physical
exercise
5-HT
Tª
? HPA/HPG
BDNF
EMG

64. PHYSICAL EXERCISE
GENETIC
TRAINING
FACTORS
PSYCHOLOGICAL NEUROENDOCRINE REPONSES
EFFECTS
Antidepressive Metabolic
homeostases
Anxiolytic

65. IS PHYSICAL EXERCISE
REINFORCING?

66. Everybody knows that PhEx is healthy
 only around 30% of Western
populations engage in
significant amounts of
exercise weekly
 once initiated, attrition is high
(around 50% of participants
being lost within 3–6 months)
(Brawley & Rodgers, 1993)

67. Is exercise enjoyable?
 Animals voluntarily run in  Competitive efforts
activity wheels (up to 20  High intensity or
km/day!) strenouss exercise
 Mood  Non habitual exercisers
 measured before and after
 In regular exercisers
 undertaking strenuous
exercise People don’t do it!!
 at a level with which they
are familiar

68.  Runners’ high
 Compulsory exercisers
 Endorphin hypothesis
 “Most forms of exercise also increase blood -
Endorphin level, especially when exercise intensity
involves reaching the anaerobic threshold and is
associated with the elevation of serum lactate level”.
Hamer M, Karageorghis CI. Psychobiological mechanisms of exercise dependence.
Sports Med. 2007;37(6):477-84.

69. Interesting issues
 Positive or negative reinforcer?
 On which characteristics does the reinforcing
effect rely?
 Aerobic / Anaerobic
 Duration
 Intensity
 Individual / Social
 Interactive
 Others

70. If PhEx is a reinforcer...
 Every body should be able to enjoy it.
 Adherence should be easy to promote.
 Exercise prescription should be one key-
point.

71. How could it be studied?
 Experimental design:
 ...
 ...
 ...
 ...
 ...

73. Guidelines for healthy adults under age 65
Basic recommendations from ACSM and AHA
 Do moderately intense cardio 30 minutes a day, 5 days a week
Or
Do vigorously intense cardio 20 minutes a day, 3 days a week
And
Do eight to 10 strength-training exercises, eight to 12
repetitions of each exercise twice a week.
 Moderate-intensity physical activity means working hard
enough to raise your heart rate and break a sweat, yet still
being able to carry on a conversation.
 It should be noted that to lose weight or maintain weight loss,
60 to 90 minutes of physical activity may be necessary.
 The 30-minute recommendation is for the average healthy
adult to maintain health and reduce the risk for chronic disease.
http://www.acsm.org/

74. Tips for meeting the guidelines
 Do it in short bouts. Moderate-intensity physical
activity can be accumulated throughout the day in 10-
minute bouts, which can be just as effective as exercising
for 30 minutes straight. This can be useful when trying to fit
physical activity into a busy schedule.
 Mix it up. Combinations of moderate- and vigorous-
intensity physical activity can be used to meet the
guidelines. For example, you can walk briskly for 30
minutes twice per week and jog at a higher intensity on two
other days.

75.  Set your schedule. Maybe it’s easier for you to walk during
your lunch hour, or perhaps hitting the pavement right after
dinner is best for you. The key is to set aside specific days and
times for exercise, making it just as much a regular part of
your schedule as everything else.
 The gym isn’t a necessity. It doesn’t take an expensive gym
membership to get the daily recommended amount of
physical activity. A pair of athletic shoes and a little
motivation are all you need to live a more active, healthier
life.
 Make it a family affair. Take your spouse, your children, or a
friend with you during exercise to add some fun to your
routine. This is also a good way to encourage your kids to be
physically active and get them committed early to a lifetime
of health.

76. Figure 1
Perception of pain following aerobic exercise.
KOLTYN, KELLI; GARVIN, ANN; GARDINER, R; NELSON,
TOBEN
Medicine & Science in Sports & Exercise. 28(11):1418-
1421, November 1996.
Figure 1 -Means and standard errors for pain threshold
responses in the exercise and control conditions.
© Williams & Wilkins 1996. All Rights Reserved. Publicado por Lippincott Williams & Wilkins, Inc. 2

77. Figure 2
Perception of pain following aerobic exercise.
KOLTYN, KELLI; GARVIN, ANN; GARDINER, R; NELSON,
TOBEN
Medicine & Science in Sports & Exercise. 28(11):1418-
1421, November 1996.
Figure 2 -Means and standard errors for pain ratings in
the exercise and control conditions.
© Williams & Wilkins 1996. All Rights Reserved. Publicado por Lippincott Williams & Wilkins, Inc. 3