Physical Activity Modulates Common Neuroplasticity Substrates in Major Depressive and Bipolar Disorder
Table 1
Clinical trials of physical activity in persons with mood disorders. To determine the effects of PA on the brain in humans affected by MDs, a computer search of MEDLINE using the terms “mood disorder,” “physical activity,” and “exercise” was used to produce a list of interventional studies. Then, manual searches of key references were performed to identify additional studies. Articles met inclusion criteria if they were peer-reviewed interventional studies in persons diagnosed with MDD or BP. Articles were excluded if they were reviews, case reports, conference abstracts, expert opinions, or clinical studies of adolescents. Duplicate articles and those not available in English language were excluded also. Based on this search and subsequent screening, 37 articles that spanned from 1987 to 2016 were identified. Whereas extensive variations existed in the studies with regard to age, sex, degree of symptoms, phase of disease, and setting, 97% of RCTs (31 out of 32) that measured behavioral outcomes reported positive associations between PA and recovery from depressive symptoms [40, 41, 267, 316, 463–489] by utilizing training ranges of 100–250 min per week for a duration of 2–6 months [40, 41, 316, 463–468, 472–474, 476–485, 487, 488]. One report achieved relief of depressive symptoms following 60 minutes of PA for a duration of 5 weeks [489], whereas another study reported that participants obtained relief following PA 30 min/day for a duration of 1 week [470]. The modalities used in the programs varied, but most of the programs deployed some form of aerobic activity as a core component [40, 41, 96, 464–483, 485–488, 490, 491]. Notably, the one study that failed to find an association between PA and depressive symptoms used a relaxation group as a control [492], a fact that may be problematic given preliminary evidence that stress reduction activities reduce cortisol abnormalities and, in turn, may mitigate depressive symptoms [489]. The remaining studies reported that PA reduced sleep problems [382, 383, 487]; normalized BDNF levels in some studies [267, 268], but failed to do so in others [490]; and reduced cortisol levels [489]. Nevertheless, extant RCTs are still few and leave many questions unresolved.
Aerobic exercise outside during daylight hours (60% max HR) + prompts to take a specific vitamin regimen or control
20 min per session 5 d/wk × 8 wks
Reduced depressive symptoms in both groups, but more so in exercise group; specifically, ↓ depressive symptoms on CES-D in exercise group; ↓ anger and tension on POMS in exercise group; ↑ vitality in exercise group
Add-on aerobic exercise × 10 wks; add-on basic body awareness therapy × 10 wks; or single consult for advice on PA + care as usual
55–60 min session 2 d/wk × 10 wks; group basic body awareness therapy 2 d/wk × 60 min; or advice on PA on one occasion
Reduced depressive symptoms on MADRS in all groups (−10.3 in aerobic PA, −5.8 in body awareness, and −4.6 in advice only group); ↑ cardiovascular fitness gains in aerobic exercise group; ↓ self-rated depression symptoms in PA and basic body awareness groups
Aerobic activity (70–85% max HR); aerobic activity (70–85% max HR) + sertraline; or sertraline only
Supervised 45 min sessions 3 d/wk × 16 wks then follow-up 24 wks after study conclusion
Reduced depressive symptoms on HAM-D; ↑ rate of partial or full recovery from depressive symptoms on HAM-D in exercise group; and ↓ rate of relapse for MDD in exercise group
4 aerobic exercise treatment groups that varied according to intensity: low dose (7.5 kcal/kg/wk for 3 or 5 d/wk × 12 wks); high dose (17.5 kcal/kg/wk for 3 or 5 d/wk × 12 wks); or control
Supervised aerobic activity × 12 wks
Reduced depressive symptoms on HAM-D for high-dose aerobic exercise (17.5 kcal/kg/wk 3–5 d/wk)
20–53 y/o with MDD (), somatization syndrome (), or healthy controls ()
Aerobic exercise or control
30 min/d for 1 wk or reduced PA for 1 wk
Reduced depressive symptoms on BDI 2 following 1 wk of exercise in persons with MDD, but not other groups; ↑ monocytes in healthy controls, but not in persons with MDD or somatization syndrome
18–65 y/o with MDD and sedentary lifestyle and with residual cognitive or attention impairments following tx with SSRIs for 8–12 wks ()
High-dose aerobic exercise (target of either 16 KKW—the equivalent to walking 4 mph × 210 min/wk) or low-dose aerobic control (4 KKW—the equivalent to walking 3.0 mph for 75 min/wk)
Initial supervision during sessions then transition to home-based program × 12 wks
Reduced depressive symptoms in both groups on IDS-C, but greater effect in high-dose exercise group; high dose PA ↑ spatial working memory and both groups ↑ cognitive function (psychomotor speed and executive function)
Supervised aerobic exercises (70–85% of max HR); sertraline; or placebo
45 min session 3 d/wk × 16 wks
Reduced depressive symptoms in both groups on HAM-D and BDI along with higher remission rates compared to placebo; ↔ between groups in verbal memory, verbal fluency, or working memory
Supervised aerobic exercise (70–80% of max HR); home-based exercise; sertraline; or placebo
45 min session 3 d/wk × 16 wks
At 12 mo follow-up, exercisers who reported 180 min/wk exhibited reduced depressive symptoms on HAM-D scores and a ↓ risk for relapse in comparison with persons who reported 0 min of exercise
Structured group exercise (50% max HR) or usual care
45 min session 3 d/wk × 6 wks
Reduced depressive symptoms on MADRS and BDI-2 in both groups, but ↑ response (> 50% decrease of symptoms on MADRS) in exercise group; ↓ diastolic blood pressure in exercise group; ↓ waist circumference in exercise group; ↑ HDL in exercise group; ↑ cardiorespiratory capacity in exercise group
Low-frequency aerobic exercise (within target HR); high-frequency aerobic exercise; or high-frequency aerobic exercise + group team building intervention
1 aerobic activity 30 min session 1 d/wk × 8 wks; 30 min session 3–5 d/wk × 8 wks; 30 min session 3–5 d/wk + group team building × 8 wks
Persons in high-frequency aerobic groups exhibited reduced depressive symptoms on BDI-2, but team-building intervention ↔ depressive symptoms
Aerobics + bright light or aerobics + normal light
Individualized aerobic training 2-3 d/wk × 8 wks
At 8 wks, reduced depressive symptoms on HAM-D and ATYP in both groups, but greater effect in aerobics + bright light group; ↑ in vitality on RAND in both groups, but more so in bright light group
Aerobics + bright light; aerobics + normal light; or stretching in bright light
Supervised sessions 2 d/wk × 8 wks
Reduced depressive symptoms on HAM-D in both aerobic groups; reduced depressive symptoms on SIGH-SAD-SR in aerobic + bright light group; ↔ in serum lipid levels or BMI in any group
Chronotherapeutic intervention (consisting of wake therapy, bright light therapy, sleep phase advance, and sleep time stabilization) or individualized aerobic exercise plan
30 min sessions 5 d/wk × 29 wks
Reduced depressive symptoms on HAM-D in both groups, but even greater response in chronotherapy group—at 9 wks remission rate was 45% for chronotherapy group versus 23% for PA group and at 29 wks remission was 62% for chronotherapy group versus 38% for PA group
60 y/o or greater with osteoarthritis of knee and depressive symptoms ()
Aerobic exercise (50–70% max HR); strength training; or health education
Supervised walking 60 min session 3 d/wk then home-based aerobic activity × 15 mo or supervised progressive strength training 60 min session 3 d/wk × 3 mo + home-based continuation of training × 15 mo
Reduced depressive symptoms on CES-D in aerobic exercise group; ↔ depressive symptoms on CES-D in strength training group; both aerobic and strength training ↓ pain, ↓ self-reported disability, and ↑ walking speed
Reduced depressive symptoms on HAM-D and ↑ quality of life (World Health Organization Quality of Life Assessment Instrument-Brief version (WHOQOL-BREF) during second wk of treatment and at discharge
69–73 y/o with MDD, minor depressive symptoms, or dysthymia ()
Progressive resistance training (3 sets of 8 repetitions of 80% 1 rep max) × 10 wks + unsupervised exercise or health education
Supervised 45 min sessions 3 d/wk × 10 wks followed by unsupervised resistance training 2-3 d/wk × 10 wks
Reduced depressive symptoms in exercise group on BDI at 20 wks and 26 mo follow-up; ↑ morale on measures of aging on the Philadelphia Geriatric Morale Scale
18–55 y/o with MDD who were medicated and unmedicated and received psychotherapy ()
Strength training (2 or 3 trials of 12 reps at 50% max and increasing to 8 reps of 75% max); aerobic exercise (70% max heart rate); or control (stretching and relaxation groups ( for each)
Supervised training 90 min per session 2 d/wk × 16 wks
↔ in depressive symptoms between three groups on HAM-D at 4 mo and 12 mo; ↔ in cognitive symptoms between the three groups at 4 mo and 12 mo
Augmentation of SSRI with 16 kilocalories per kilogram of body weight per wk × 12 wks (equivalent to 150 min per wk at moderate intensity) or 4 kilocalories per kilogram of body weight per wk × 12 wks
Sensor monitored and partially supervised × 12 wks
↓ in hypersomnia on IDS-C, a change that was correlated with ↓ BDNF and ↓ IL-1β; lower baseline levels of IL-1β predicted greater improvements in insomnia
Augmentation of SSRI with 16 kilocalories per kilogram of body weight per wk × 12 wks (equivalent to 150 min per wk at moderate intensity) or 4 kilocalories per kilogram of body weight per wk × 12 wks
Sensor monitored and partially supervised × 12 wks
↓ at-rest levels of copeptin in participants with high exercise compliance
ATYP: Atypical Depression Symptoms Addendum to Hamilton Depression Rating Scale; BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; CES-D: Center for Epidemiologic Studies Depression; GWB: General Well-Being Schedule; GDS: Geriatric Depression Scale; HAM-D: Hamilton Depression Rating Scale; ICD-10-D: International Classification of Diseases-Depression; IDS-SR: Inventory of Depressive Symptomatology-Self Reported; POMS: Profile of Mood States; GCPS: Graded Chronic Pain Scale; CGI: Global Improvement of Depression; MADRS: Montgomery and Asberg Depression Rating Scale; QoL: quality of life; QALY: quality-adjusted life years using EuroQol (EQ-5D); RAND: RAND 36-Item Health Survey; SIGH-SAD-SR: Seasonal Affective Disorders Version Self-Rating Format; STAI: State-Trait Anxiety Inventory; WHOQOL-BREF: World Health Organization Quality of Life Assessment Instrument-Brief version.
