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Ferran Suay. Departament de Psicobiologia. UV




PRINCIPLES OF THE INTERVENTION
ON PHYSICAL AND MENTAL HEALTH
Addressing...


   Physical activity, physical exercise, sport,
    fitness

   Impact on mental health

   Main hypothesis

   Is physical exercise reinforcing?
INTERVENTION ON HEALTH:
Promoting active lifestyles
 Physical activity ≠ physical exercise ≠ sport
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
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
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.
Fitness (physical fitness)


 Muscular strength
 Muscular endurance
 Cardiorespiratory
  endurance
 Flexibility
 Body composition
Muscular endurance

 the ability of a muscle
  or group of muscles to
  sustain repeated
  contractions against a
  resistance for an
  extended period of
  time.
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.
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
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
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
PhA, overweight and obesity

 Obesity
   Health problem:
     Hypertension
     Diabetis (II)
     Cardiovascular diseases
     Osteoartrytis
     Psychological problems
   Echonomic cost
Body Mass Index
(BMI; Quételet Index )



  < 18       lean
  18-25      Normal
  25-30      Overweight
  30-40      Obesity
  >40        Morbid Obesity
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
 Africa & Asia: BMI 22-23 Kg/m2

 USA & Europe: BMI 25-27 Kg/m2
And...what has it to do with mental
                            health?
Background: evolutive resumé
Background: ancient roman already knew it




        MENS SANA IN CORPORE SANO
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”
Acute and chronic exercise

KNOWN EFFECTS
1. Acute exercise and mood states

 Effects observed after 10
  minutes efforts
 Intens effort may:
   Enhance mood (habitual
    exercisers)
   Be aversive (non habituated
    individuals)
Effects more evident
                            For aerobic exercise
                            In fit individuals




• In clinical population

• With worsened mood prior to
 exercise
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)
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)
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.
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
How is it done?
First hypothesis concerning anxiety reduction
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)
How would you prove this hypothesis as
false?
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)
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)
BENEFICIAL EFFECTS




           HARMFUL                        HARMFUL EFFECTS
           EFFECTS




                      PHYSICAL E XE R C I SE
Sedentary lifestyle                        Overtraining
How is it done?
 Main hypothesis concerning antidepressive effects
                              of physical exercise
5HT hypothesis

 Monoamines: Indolamines
 Complex effects on
  behavior: regulation of
   Body temperature
   Sleep
   Mood
   Appetite
   Pain
                   (Carlson 2002)
Serotonin biosynthesis
    TRP HIDROXILASE           5-HTTP DESCARBOXILASE


              5-HIDROXITRYPTOPHAN         SEROTONIN
TRYPTOPHAN
                      5-HTP                 5-HT
   TRP
5HT synthesis &
                                           metabolism




                                            5HT releasing



 The enhanced tryptophan supply is not the cause
for the increased 5HT releasing
studied in relation
to physical exercise

   Pre: 5-HT1A
   Post: 5-HT2
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)
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
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
Summary: PhEx5HT


                       training


                                  5-HT1A sensitivity
Acute PhEx   5-HT activity        5-HT2A sensitivity


              Fatigue, PE
                                     Fatigue, PE
                                   A-D effect
Summary: Chronic PhEx5HT

                Regulation of 5-HT      Malfunction
5-HT activity   neurotransmission       5-HT system




Acute PhEx             training      overtraining
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 )
HPA: variability sources
CIRCADIAN RHYTHMS


               STRESS
 NSQ
                              FEEDBACK
       NPV

         CRH
                                   
                                   -END
HYPOTHALAMUS               POMC

                                  ACTH
               ANTERIOR
               PITUITARY
                                               Glucocorticoids
                                                    (GC)
                                    ADRENAL CORTEX
PhEx ACUTE RESPONSE: HPA & HPG-AXIS

                      -
                 endorphins
 GnRH                                 CRH




LH, FSH                              ACTH



Estradiol
                                    Cortisol
    T


 Tissues
                              EXCITATON
                              INHIBITION
Adaptive mechanism
Protecting muscles (and other tissues) from high GC
concentrations  receptor downregulation (Duclos et al. 2001)




        CRH



                            ACTH


                                                Glucocorticoids
                                                     (GC)
Physical
               exercise



               5-HT



Tª
           ?              HPA/HPG




     EMG
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)
Monoamine related hypothesis about genic expression

                                            BDNF gene
         STRESS
                   Monoamine
               transduction deficit




                           Neurones’ viability
                                ATROPHY
DEPRESSION                      APOPTOSIS

                                HYPOCAMPUS

                                      (modified from Stahl 2002)
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
 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
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)
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
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).
   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).]
The combination of activity and tranylcypromine treatment led to
BDNF mRNA levels significantly elevated above controls in all
hippocampal areas measured.
PhExBDNF

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




           BDNF



   Depression related
      behaviour
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
  neurogenesis and neuronal resilience, neuronal
connectivity and activity-dependent plasticity
Physical
               exercise



               5-HT



Tª
           ?              HPA/HPG
                BDNF




     EMG
PHYSICAL EXERCISE


                                                 GENETIC
  TRAINING
                                                 FACTORS




PSYCHOLOGICAL                          NEUROENDOCRINE REPONSES
   EFFECTS

             Antidepressive        Metabolic
                                   homeostases
             Anxiolytic
IS PHYSICAL EXERCISE
REINFORCING?
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)
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
 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.
Interesting issues
 Positive or negative reinforcer?
 On which characteristics does the reinforcing
  effect rely?
   Aerobic / Anaerobic
   Duration
   Intensity
   Individual / Social
   Interactive
   Others
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.
How could it be studied?

             Experimental design:
             ...
             ...
             ...
             ...
             ...
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/
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.
 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.
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
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
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Physical activity and health

  • 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?
  • 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
  • 34.
  • 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
  • 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:  ...  ...  ...  ...  ...
  • 72.
  • 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