Ref. Objective Study design Demographic, participant data PA measure Depression measure Results Epidemiological evidence [10] To examine thebidirectional association between PA and depression/anxietyusing data onphysicalactivityandsymptomsof anxietyanddepressionat three points in time over 8years BritishWhitehallIIprospective cohortstudy Data at baseline (phase 1; 1985), phase 2 (1989-1990), phase 3 (1991-1993). 9,309 participants Baseline: 35-55 yrs. Civil servants. Men 6 374. Self-administered questionnaire. @ phase 1, 2, 3. 30-item GHQ @ phase 1, 2, 3. Depression: 4 or more. Cross-sectional: Inverse association btw PA and depressive sxs at baseline (OR 0.72) Prospective: Reg PA, not irreg PA, α reduced likelihood of depressive sxs at f/u (OR 0.71). Depressive and anxiety sxs at baseline α higher odds of not meeting recommended levels of PA at f/u (OR 1.79) [12] To examine longitudinal change incardiorespiratory fitness, an objective marker of habitual physical activity, andincident depression complaints made to a physician Aerobics Center Longitudinal Study. Subjects were included who did not complain ofdepressionat their first clinic visit in 1971-2003 Cardiorespiratoryfitnessassessed at four clinic visits between 1971 and 2006. Each separated by an average of 2-3 years. 7936 men and 1261 women, aged 20-85 years. Cardiorespiratoryfitness: total time of a symptom-limited maximal treadmill exercise test, using a modified Balke protocol. Depression complaints were obtained from archived physician charts by the medical staff after follow-up to patient responses on a standardized medical history questionnaire Across subsequent visits, there were 446incidentcases in men and 153 cases in women. After adjustment for age, time between visits, BMI at each visit, andfitnessat Visit 1, each 1-minutedeclinein treadmill endurance (i.e., adeclinein cardiorespiratory fitnessof approximately 1 half-MET) between ages 51 and 55 years in men and ages 53 and 56 years in women, increased theoddsof incident depressioncomplaints by approximately 2% and 9.5%, respectively. [15] To compare the effects of higher levels of physical activity on prevalent and incident depression with and without exclusion of disabled subjects. Population-based prospective cohort study. Followed up for 5 yrs 1,947 community-dwelling adults from the Alameda County Study aged 50–94 years at baseline in 1994. PA was measured with an eight-point scale. PA scale based on four questions DSM–12D based on DSM-4. Greater physical activity was protective for both prevalent depression (adjusted odds ratio (OR)=0.90) and incident depression (adjusted OR = 0.83) over 5 years. Exclusion of disabled subjects did not attenuate the incidence results (adjusted OR = 0.79). [18] The objective of thisstudywas to follow individuals over time to examine whether those with higher levels of CRF have lower risk of developing depressive symptoms Prospective cohort study. Average of 12 years of follow-up 11,258menand 3085womenenrolled in the Aerobics Center LongitudinalStudy Participants completed a maximal treadmill exercise test at baseline (1970-1995) and a follow-up health survey in 1990 and/or 1995. CRF was quantified by exercise test duration 20-item CES-D 282womenand 740menreported depressive symptoms. The odds of reportingdepressive symptomswere 31% lower formenwith moderate CRF (OR 0.69) and 51% lower formen with high CRF (OR 0.49), compared tomenwith low CRF. Corresponding ORs forwomenwere 0.56 and 0.46. Clinical trial evidence [53] To determine if a pragmatic aerobic exercise intervention would have antidepressant properties in a group of clinically depressed patient’s. RCT. Single centre, two-armed, parallel-group, observer-blinded randomized clinical superiority trial. Outpatients with major depression (DSM-IV) were allocated to supervised aerobic or stretching exercise groups during a three months period. Mean age in the enrolled group was 41.6 years56 participants were allocated to the aerobic exercise intervention versus 59 participants to the stretching exercise group. 56 participants were allocated to the aerobic exercise intervention versus 59 participants to the stretching exercise group. HAM-D17 Post intervention the mean difference between groups was −0.78 points on the HAM-D17(95% CI −3.2 to 1.6;P=.52). Due to lower recruitment than anticipated, the trial was terminated prior to reaching the pre-defined sample size of 212 participants; therefore the results should be interpreted in that context. [52] To assess the benefit and harm of exercisetrainingin adults withclinicaldepression. Randomized,parallel-group, observer blindedclinicaltrial Criteria for unipolardepression and were aged between 18 and 55 years Patients(N = 165) were allocated to supervised strength,aerobic, or relaxationtrainingduring a 4-month period HAM-D(17) At 4 months, the mean change in HAM-D(17) score was -1.3 (-3.7 to 1.2; p = 0.3) and 0.4 (-2.0 to 2.9; p = 0.3) for thestrengthandaerobicgroupsversustherelaxationgroup. At 12 months, the mean differences in HAM-D(17) score were -0.2 (-2.7 to 2.3; p = 0.8) and 0.6 (-1.9 to 3.1; p = 0.6) for thestrengthandaerobicgroupsversusthe relaxation group. [31] Whether a mind-body exercise, TaiChiChih(TCC), added toescitalopram will augment thetreatmentof geriatricdepressiondesigned to achieve symptomatic remission RCT. 14-week follow-up 112 older adults with major depressionage 60 years and older were recruited and treated withescitalopramfor approx. 4 weeks. Seventy-three partial responders toescitalopram continued to receive escitalopramdaily and were randomly assigned to 10 weeks of adjunct use of either 1) TCC for 2 hours per week or 2) health education (HE) for 2 hours per week. TCC. TCC sessions were held for a duration of 2 hours, once a week. Each TCC class was conducted in 120 minutes and also included 10 minutes of warm-up (e.g., stretching and breathing) and 5 minutes of cooldown exercises. HDRS Subjects in theescitalopramand TCC condition were more likely to show greater reduction of depressive symptoms and to achieve adepressionremission as compared with those receivingescitalopramand HE. [56] To assess the effectiveness of an aerobicexerciseprogram compared with standard medication (ie, antidepressants) for treatment of MDD inolderpatients. RCT. 16-weeks One hundred fifty-six men and women with MDD (age, > or = 50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exerciseand medication 16 week aerobic exercise intervention. Subjects attended 3 supervised exercise sessions per week for 16 consecutive weeks. Participants were assigned individual training ranges equivalent to 70% to 85% of heart rate reservecalculated from the maximum heart rate achieved during the treadmill test. Each aerobic session began with a 10-minute warm-up exercise period followed by 30 minutes of continuous walking or jogging at an intensity that would maintain heart rate within the assigned training range. HAM-D, BDI, DSM-IV After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores; adjustment for baseline levels ofdepressionyielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However,patientsreceiving medication alone exhibited the fastest initial response; among patientsreceiving combination therapy, those with less severedepressivesymptoms initially showed a more rapid response than those with initially more severedepressivesymptoms. [57] The purpose of this study was to assess the status of subjects with MDD 6months after completion of a study in which they were randomly assigned to a 4-month course of aerobicexercise, sertraline therapy, or a combination ofexerciseand sertraline. RCT. 156 adult volunteers. 4-month course of aerobic exercise, sertraline therapy, or a combination ofexerciseand sertraline. Three supervised exercise sessions per week for 16 consecutive weeks. Participants were assigned training ranges equivalent to 70% to 85% of heart rate reserve. Each aerobic session began with a 10-minute warm-up period, followed by 30 minutes of continuous cycle ergometry or brisk walking/jogging. HRSD. BDI. Assessments were performed at baseline, after 4months oftreatment, and 6monthsafter treatmentwas concluded At 4months:patients in all three groups exhibited significant improvement; the proportion of remitted participants (i.e, those who no longer met diagnostic criteria for MDD and had an HRSD score <8) was comparable across the threetreatmentconditions. At 10-months: remitted subjects in theexercisegroup had significantly lower relapse rates than subjects in the medication group. Exercising on one's own during the follow-up period was associated with a reduced probability ofdepressiondiagnosis at the end of that period (OR = 0.49). Clinical immunological evidence [65] To examine the extent to which inflammatory markers can be used to predict response to exercise treatment after an incomplete response to an SSRI. To examine how the inflammatory markers change with exercise and if those changes are associated with dose of exercise or changes in symptom severity. Prospective. Randomised. TREAD study. Participants had MDD and were partial responders to an SSRI (i.e. ≥14 HRSD-17 following >6 wks but <6 mnths of treatment). Excluded if regularly engaging in PA Age 18 – 70 yrs 73 participants 12-week Randomized to either 16 or 4 KWW Aerobic EXC (treadmill or cycle ergometers). Combination of supervised and home-based sessions. Clinician: IDS-C30 Self-rated: IDS-SR30 and HRSD17 ELISA of serum at baseline and 12 weeks. IFN-γ, IL-1β, IL-6, TNF-α High baseline TNF-α (>5.493 pg ml) α greater ↓ in depression sxs (IDS-C) over 12 wks Sig pos α between ΔIL-1βand Δdepression sxs. For 16KKW not 4 KKW. NS change in cytokine levels following 12 wks of EXC. NS relationship between EXC dose and change in cytokine levels. High TNF-α may predict better outcomes with EXC vs. SSRI ↓ IL-1βα positive depression treatment outcomes [61] To determine if a long-term exercise intervention among older adults would reduce serum inflammatory cytokines, and if this reduction would be mediated, in part, by improvements in psychosocial factors and/or by β-adrenergic receptor mechanisms. Adults ≥64 yrs. Community-based. Randomised to aerobic or flexibility/strength EXC. 10 months. A subgroup of patients on non-selective Β1Β2-adrenergic antagonists were included. Aerobic (CARDIO) or flexibility/strength EXC (FLEX). 3 d/wk, 45 min/day, 10 months. GDS, PSS, CS, SPS, LOT ELISA of plasma: CRP, IL-6, TNF-α, IL-18 EXC = ↓ depressive symptoms, ↑ optimism (CARDIO = FLEX) CARDIO EXC = ↓ IL-6, IL-18, CRP, TNF-α vs. FLEX FLEX EXC = ↓ TNF-α, no change in IL-6, IL-18, CRP vs. CARDIO. ↓ CRP α ↓ depressive symptoms No effect for non-selective Β1Β2-adrenergic antagonists [67] To evaluate the effects of a behavioral intervention, TCC on circulating markers of inflammation in older adults. 83 healthy older adults (59 – 86 yrs) RCT. 2 arms – TCC, HE. 16 wk intervention + 9 wks follow up TCC and HE. Groups of 7 to 10. TCC 20 mins, 3/wk. BDI PSQI ELISA of plasma for IL-6, CRP, sIL-1ra, sIL-6, sICAM, IL-18 *high IL-6 >2.46 pg/ml High IL-6 at entry: TCC ↓ IL-6 comparable to those in TCC and HE who had low IL-6 at entry. IL-6 in HE remained higher than TCC and HE with low entry IL-6 TCC ns Δcellular markers of inflammation TCC = ↓ depressive sxs α ↓ IL-6