Circulating endocannabinoids and psychological outcomes in women with PTSD.

BACKGROUND: Recent research has attempted to elucidate the relationship between blood-based biomarkers (e.g., endocannabinoids; eCBs: including N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol [2-AG]) and mental health outcomes in psychiatric populations such as posttraumatic stress disorder (PTSD). Prior research suggests that adults with PTSD may have altered circulating eCB tone and a blunted mobilization of eCBs (particularly 2-AG) in response to stress (e.g., aerobic exercise), although our understanding has been limited in part due to heterogenous samples and small sample sizes. METHODS: A subset of data was pooled from five studies in which women with and without PTSD (N = 98) completed questionnaires related to mood states and a blood draw prior to and following a bout of moderate-intensity aerobic exercise in order to determine: 1) whether circulating eCBs differ between groups and whether depressive and PTSD symptom severity are associated with baseline eCBs, 2) whether a bout of aerobic exercise increases circulating eCBs in adult women with PTSD, and 3) whether circulating eCBs are associated with overall mood states and exercise-induced improvements in mood states in women with and without PTSD. RESULTS: PTSD diagnoses were not associated with baseline concentrations of eCBs. Greater depressive symptom severity and PTSD symptom severity within the negative alteration in cognition and mood cluster were associated with lower circulating AEA. Circulating AEA significantly increased following aerobic exercise for both groups, whereas circulating 2-AG only increased in women without PTSD. Greater circulating AEA within the PTSD group was associated with lower depressive mood, confusion, and total mood disturbance. CONCLUSIONS: These findings suggest that greater circulating AEA is associated with better overall mood and lower depressive and PTSD symptom severity, and that an acute bout of moderate-intensity aerobic exercise increases circulating AEA (but not 2-AG) in adult women with PTSD. These findings are consistent with the idea that greater eCB tone (particularly AEA) following pharmacological and/or non-pharmacological manipulations may be beneficial for improving psychological outcomes (e.g., mood, cognition) among PTSD, and possibly other psychiatric populations.

Pain, but not Physical Activity, is Associated with Gray Matter Volume Differences in Gulf War Veterans with Chronic Pain.

Chronic musculoskeletal pain (CMP) is a significant burden for Persian Gulf War Veterans (GWV), yet the causes are poorly understood. Brain structure abnormalities are observed in GWV, however relationships with modifiable lifestyle factors such as physical activity (PA) are unknown. We evaluated gray matter volumes and associations with symptoms, PA, and sedentary time in GWV with and without CMP. Ninety-eight GWV (10 females) with CMP and 56 GWV (7 females) controls completed T1 weighted magnetic resonance imaging, pain and fatigue symptom questionnaires, and PA measurement via actigraphy. Regional gray matter volumes were analyzed using voxel-based morphometry and were compared across groups using analysis of covariance. Separate multiple linear regression models were used to test associations between PA intensities, sedentary time, symptoms, and gray matter volumes. Family-wise cluster error rates were used to control for multiple comparisons (α=0.05). GWV with CMP reported greater pain and fatigue symptoms, worse mood, and engaged in less moderate-to-vigorous PA and more sedentary time than healthy GWV (all p<0.05). GWV with CMP had smaller gray matter volumes in the bilateral insula and larger volumes in the frontal pole (p<0.05adjusted). Gray matter volumes in the left insula were associated with pain symptoms (rpartial=0.26, -0.29; p<0.05adjusted). No significant associations were observed for either PA or sedentary time (p>0.05adjusted). GWV with CMP had smaller gray matter volumes within a critical brain region of the descending pain processing network and larger volumes within brain regions associated with pain sensation and affective processing which may reflect pain chronification.Significance Statement:The pathophysiology of chronic pain in Gulf War Veterans is understudied and not well understood. In a large sample of Gulf War Veterans, we report Veterans with chronic musculoskeletal pain have smaller gray matter volumes in brain regions associated with pain regulation and larger volumes in regions associated with pain sensitivity compared to otherwise healthy Gulf War Veterans. Gray matter volumes in regions of pain regulation were significantly associated with pain symptoms and encompassed the observed group brain volume differences. These results are suggestive of deficient pain modulation that may contribute to pain chronification.

The Feasibility and Effectiveness of a Community-Based Intervention to Reduce Sedentary Behavior in Older Adults.

The purpose of this study was to examine the effectiveness and feasibility of translating a 4-week "Stand Up and Move More" (SUMM) intervention by state aging units to older adults (N = 56, M age = 74 years). A randomized controlled trial assessed sedentary behavior, physical function, and health-related quality of life (HRQoL) before and after the intervention. Participants included healthy community-dwelling, sedentary (sit > 6 hr/day) and aged ≥ 55 years adults. For the primary outcome, the SUMM group (n = 31) significantly (p < .05) reduced total sedentary time post-intervention by 68 min/day on average (Cohen's d = -0.56) compared with no change in the wait-list control group (n = 25, Cohen's d = 0.12). HRQoL and function also improved (p < .05) in the SUMM group post-intervention. Workshop facilitators indicated the intervention was easy to implement, and participants expressed high satisfaction. The SUMM intervention reduced sedentary time, improved physical function and HRQoL, and was feasible to implement in community settings.

Exercise-induced increases in Anandamide and BDNF during extinction consolidation contribute to reduced threat following reinstatement: Preliminary evidence from a randomized controlled trial.

INTRODUCTION: We recently demonstrated that moderate-intensity aerobic exercise delivered during the consolidation of fear extinction learning reduced threat expectancy during a test of extinction recall among women with posttraumatic stress disorder (PTSD). These findings suggest that exercise may be a potential candidate for improving the efficacy of exposure-based therapies, which are hypothesized to work via the mechanisms of fear extinction learning. The purpose of this secondary analysis was to examine whether exercise-induced increases in circulating concentrations of candidate biomarkers: endocannabinoids (anandamide [AEA]; 2-arachidonoylglycerol [2-AG], brain-derived neurotrophic factor (BDNF), and homovanillic acid (HVA), mediate the effects of exercise on extinction recall. METHODS: Participants (N = 35) completed a 3-day fear acquisition (day 1), extinction (day 2), and extinction recall (day 3) protocol, in which participants were randomly assigned to complete either moderate-intensity aerobic exercise (EX) or a light-intensity control (CON) condition following extinction training (day 2). Blood was obtained prior to and following EX or CON. Threat expectancy ratings during tests of extinction recall (i.e., initial fear recall and fear recall following reinstatement) were obtained 24 h following EX or CON. Mediation was tested using linear-mixed effects models and bootstrapping of the indirect effect. RESULTS: Circulating concentrations of AEA and BDNF (but not 2-AG and HVA) were found to mediate the relationship between moderate-intensity aerobic exercise and reduced threat expectancy ratings following reinstatement (AEA 95% CI: -0.623 to -0.005; BDNF 95% CI: -0.941 to -0.005). CONCLUSIONS: Exercise-induced increases in peripheral AEA and BDNF appear to play a role in enhancing consolidation of fear extinction learning, thereby leading to reduced threat expectancies following reinstatement among women with PTSD. Future mechanistic research examining these and other biomarkers (e.g., brain-based biomarkers) is warranted.

Aerobic exercise reduces anxiety and fear ratings to threat and increases circulating endocannabinoids in women with and without PTSD.

Reductions in state anxiety have been reported following an acute bout of aerobic exercise. However, less is known regarding anxiety and fear ratings to specific threatening stimuli following an acute bout of aerobic exercise in women with PTSD. Moreover, the mechanisms responsible for the anxiolytic effects of exercise are not fully understood, although recent studies suggest a role for the endocannabinoid (eCB) system. Thus, this study utilized a randomized, counterbalanced approach to examine anxiety and fear ratings to predictable or unpredictable electric shock administration and circulating concentrations of eCBs and mood states immediately following moderate-intensity aerobic exercise (30 min on treadmill at 70-75% maximum heart rate) and a quiet rest control condition in women with and without a history of trauma, and in women with PTSD (N=42). Results revealed that anxiety and fear ratings to unpredictable and predictable threats were significantly (p<.05) lower following exercise compared to quiet rest, with correlational analyses indicating those with greater increases in circulating eCBs had greater reductions in anxiety and fear ratings to unpredictable and predictable threats following exercise. Also, there were significant (p<.05) reductions in fatigue, confusion, total mood disturbance, and increases in positive affect following exercise for the entire sample. Non-trauma controls and PTSD groups reported significant (p<.05) increases in vigor, with additional mood improvements following exercise for the PTSD group (i.e., decreases in state anxiety, negative affect, tension, anger, and depression). Results from this study suggest that aerobic exercise exerts psychological benefits in women with PTSD, potentially due to exercise-induced increases in circulating concentrations of eCBs.

Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research.

Neuropathic pain is a disease of the somatosensory system that is characterized by tingling, burning, and/or shooting pain. Medication is often the primary treatment, but it can be costly, thus there is an interest in understanding alternative low-cost treatments such as exercise. The following review includes an overview of the preclinical and clinical literature examining the influence of exercise on neuropathic pain. Preclinical studies support the hypothesis that exercise reduces hyperalgesia and allodynia in animal models of neuropathic pain. In human research, observational studies suggest that those who are more physically active have lower risk of developing neuropathic pain compared to those who are less active. Exercise studies suggest aerobic exercise training (e.g., 16 weeks); a combination of aerobic and resistance exercise training (e.g., 10-12 weeks); or high-intensity interval training (e.g., 15 weeks) reduces aspects of neuropathic pain such as worst pain over the past month, pain over the past 24 h, pain scores, or pain interference. However, not all measures of pain improve following exercise training (e.g., current pain, heat pain threshold). Potential mechanisms and future directions are also discussed to aid in the goal of understanding the role of exercise in the management of neuropathic pain. Future research using standardized methods to further understanding of the dose of exercise needed to manage neuropathic pain is warranted.

Psychological and endocannabinoid responses to aerobic exercise in substance use disorder patients.

BACKGROUND: Exercise has been examined as an adjunctive treatment for substance use disorders (SUDs), yet few exercise interventions have been conducted among patients undergoing intensive outpatient (IOP) treatment, who may be the most vulnerable to relapse and for whom exercise could provide the most benefits. This study examined the effects of aerobic exercise, in addition to IOP treatment, on psychological variables and endocannabinoids in individuals with SUDs. Methods: Twenty-one SUD patients (mean age 35 years) were recruited from local IOPs. Participants were randomized to either treatment-as-usual (TAU, at their outpatient clinic) or TAU plus aerobic exercise training (EX). EX participants engaged in supervised, moderate-intensity exercise for 30 min, 3 times/week for 6 weeks. TAU participants came into the laboratory once per week for assessments and a 30-min quiet rest session. Participants provided blood samples and completed questionnaires evaluating substance use, mood states, depression, anxiety, perceived stress, self-efficacy to abstain from substance use, and craving. Data were analyzed with Mann-Whitney U tests or mixed model ANOVAs to determine group differences in outcomes acutely and over 6 weeks. Results: Over 6 weeks, there were reductions in perceived stress (p < 0.01) and craving (p < 0.05) for both groups. There were no group differences in abstinence rates or changes from baseline in self-efficacy, depression, or anxiety (p > 0.05). Acutely, both exercise and quiet rest sessions led to reductions in craving, tension, depression, anger, confusion, and total mood disturbance (all ps < 0.05). In addition, the EX group experienced acute increases in vigor and circulating concentrations of the endocannabinoid, anandamide (p < 0.01). Conclusions: An adjunctive aerobic exercise program during SUD treatment was associated with similar reductions in perceived stress and drug craving as standard care. Thirty minutes of exercise or quiet rest led to acute improvements in mood, but exercise produced the additional benefit of increases in vigor and circulating anandamide.

Translating a "Stand Up and Move More" intervention by state aging units to older adults in underserved communities: Protocol for a randomized controlled trial.

INTRODUCTION: As aging is associated with functional decline, preventing functional limitations and maintaining independence throughout later life has emerged as an important public health goal. Research indicates that sedentary behavior (prolonged sitting) is associated with functional loss and diminished ability to carry out activities of daily living. Despite many efforts to increase physical activity, which can be effective in countering functional loss, only an estimated 8% of older adults meet national physical activity guidelines. Thus, shifting the focus to reducing sitting time is emerging as a potential new intervention strategy but little research has been conducted in this area. With community support and funding, we developed and pilot tested a 4-week "Stand Up and Move More" intervention and found decreases in sedentary behavior, increases in physical activity, and improvements in mobility and vitality in a small sample of older adults. The purpose of this project is to expand upon these pilot results and examine the effectiveness and feasibility of translating a "Stand Up and Move More" intervention by State Aging Units to older adults in underserved communities. Eighty older adults from 4 counties across Wisconsin predominantly made up of rural older adults and older African American adults are randomly assigned to intervention (n = 40) or wait-list control (n = 40) groups. The intervention consists of 4 weekly sessions plus a refresher session at 8 weeks, and is delivered by community partners in each county. The sessions are designed to elicit ideas from older adults regarding how they can reduce their sitting time, help them set practical goals, develop action plans to reach their goals, and refine their plans across sessions to promote behavior change. Sedentary behavior, physical activity levels, functional performance, and health-related quality of life are assessed before and after the intervention to examine the effectiveness of the program. Feasibility of implementing the program by our community partners is assessed via semi-structured interviews. Strengths of this project include strong community collaborations and a high need given that the older adult population is projected to increase substantially in the next 15 years. CONCLUSION: This project will provide an important step in developing effective strategies for maintaining independence in older adults through determining the feasibility and impact of a community-based intervention to break up sitting time.

Serum Endocannabinoid and Mood Changes after Exercise in Major Depressive Disorder.

The endocannabinoid (eCB) system is implicated in the pathophysiology of depression and is responsive to acute exercise in healthy adults. PURPOSE: We aimed to describe acute changes in serum eCB across a prescribed moderate (MOD) and a self-selected/preferred (PREF) intensity exercise session in women with major depressive disorder (MDD) and determine relationships between changes in eCB and mood states. METHODS: Women with MDD (n = 17) exercised in separate sessions for 20 min on a cycle ergometer at both MOD or PREF in a within-subjects design. Blood was drawn before and within 10 min after exercise. Serum concentrations of eCB (anandamide [AEA], 2-arachidonoylglycerol) and related lipids (palmitoylethanolamine, oleoylethanolamine, 2-oleoylglycerol) were quantified using stable isotope-dilution, liquid chromatography/mass spectrometry/mass spectrometry. The profile of mood states and state-trait anxiety inventory (state only) were completed before, 10 min and 30 min postexercise. RESULTS: Significant elevations in AEA (P = 0.013) and oleoylethanolamine (P = 0.024) occurred for MOD (moderate effect sizes: Cohen's d = 0.58 and 0.41, respectively). Significant (P < 0.05) moderate negative associations existed between changes in AEA and mood states for MOD at 10 min (depression, confusion, fatigue, total mood disturbance [TMD] and state anxiety) and 30 min postexercise (confusion, TMD and state anxiety). Significant (P < 0.05) moderate negative associations existed between 2-arachidonoylglycerol and mood states at 10 min (depression and confusion) and 30 min postexercise (confusion and TMD). Changes in eCB or related lipids or eCB-mood relationships were not found for PREF. CONCLUSION: Given the broad, moderate-strength relationships between improvements in mood states and eCB increases after MOD, it is plausible that the eCB system contributes to the mood-enhancing effects of prescribed acute exercise in MDD. Alternative mechanisms are likely involved in the positive mood state effects of preferred exercise.

Loss of exercise- and stress-induced increases in circulating 2-arachidonoylglycerol concentrations in adults with chronic PTSD.

The endocannabinoid (eCB) system is a modulatory system that is both altered by stress and mediates the effects of acute stress, including contributing to restoration of homeostasis. Earlier studies suggest that circulating eCBs are dysregulated in adults with post-traumatic stress disorder (PTSD); however, it is not known whether circulating eCBs remain responsive to stress. The purpose of this study was to examine eCB and psychological responses to physical (exercise) and psychosocial (Trier Social Stress Test) stressors, using a randomized, counterbalanced procedure in adults with PTSD and healthy controls (N = 20, mean age = 24, SD = 7 yrs). Results from mixed-design, repeated measures ANOVAs revealed significant increases (p < .05) in N-arachidonoylethanolamine (AEA) and oleoylethanolamide (OEA) following exercise and psychosocial stress in both groups. However, only the control group exhibited a significant increase (p < .05) in 2-arachidonoylglycerol (2-AG) following exercise and psychosocial stress exposure. These data extend our current understanding of circulating eCB responsiveness in PTSD, and provide preliminary evidence to suggest that the eCB system is hypoactive in PTSD following exposure to physical and psychosocial stressors.

Intervening to reduce sedentary behavior in older adults - pilot results.

Background: Older adults spend most of their day in sedentary behavior (SB) (i.e., prolonged sitting), increasing risk for negative health outcomes, functional loss, and diminished ability for activities of daily living. The purpose of this study was to develop and pilot test an intervention designed to reduce SB in older adults that could be translated to communities. Methods: Two pilot studies implementing a 4-week SB intervention were conducted. SB,physical function, and health-related quality of life were measured via self-report and objective measures. Participants (N=21) completed assessments pre- and post-intervention (studies 1 and 2) and at follow-up (4-weeks post-intervention; study 2). Due to the pilot nature of this research, data were analyzed with Cohen's d effect sizes to examine the magnitude of change in outcomes following the intervention. Results: Results for study 1 indicated moderate (d=0.53) decreases in accelerometry-obtained total SB and increases (d=0.52) in light intensity physical activity post-intervention. In study 2,there was a moderate decrease (d=0.57) in SB evident at follow-up. On average SB decreased by approximately 60 min/d in both studies. Also, there were moderate-to-large improvements in vitality (d=0.74; study 1) and gait speed (d=1.15; study 2) following the intervention. Further,the intervention was found to be feasible for staff to implement in the community. Conclusion: These pilot results informed the design of an ongoing federally funded randomized controlled trial with a larger sample of older adults from underserved communities. Effective,feasible, and readily-accessible interventions have potential to improve the health and function of older adults.

Psychobiological Responses to Aerobic Exercise in Individuals With Posttraumatic Stress Disorder.

Previous reports have shown improvements in mood and increases in endocannabinoids in healthy adults following a session of aerobic exercise, but it is unclear whether adults with posttraumatic stress disorder (PTSD) experience similar responses. The purpose of this study was to examine psychobiological responses (plasma endocannabinoids [eCBs], mood, and pain) to aerobic exercise in a sample of adults with a diagnosis of PTSD (n = 12) and healthy controls (n = 12). Participants engaged in an aerobic exercise session in which they ran on a treadmill for 30 min at a moderate intensity (70 to 75% maximum heart rate [MHR]). Results indicated improvements in mood states and reductions in pain for both groups following exercise, ds = 0.19 to 1.53. Circulating concentrations of N-arachidonylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), and oleoylethanolamide (OEA) significantly increased (ps = .000 to .050) following the aerobic exercise session for both groups. There were no significant time, group, or interaction effects (ps = .062 to .846) for palmitoylethanolamide (PEA) and 2-oleoylglycerol (2-OG). Although eCBs increased significantly for both groups, within-group effect size calculations indicated the healthy controls experienced a greater magnitude of change for AEA when compared with adults with PTSD, d = 1.21 and d = 0.45, respectively; as well as for 2-AG, d = 0.43 and d = 0.21, respectively. The findings from this study indicated that adults with and without PTSD reported significant mood improvements following 30 min of moderate-intensity aerobic exercise. In addition, the endocannabinoid system was activated in adults with and without PTSD, although effect sizes suggest that adults with PTSD may have a blunted endocannabinoid response to exercise.

Endocannabinoid and Opioid System Interactions in Exercise-Induced Hypoalgesia.

Objective: The purpose of this study was to examine the interaction between the endogenous opioid and endocannabinoid (eCB) systems in a pain modulatory process known as exercise-induced hypoalgesia (EIH). Design: Randomized controlled trial. Setting: Clinical research unit in a hospital. Subjects: Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study. Methods: Participants were administered (randomized, double-blind, counterbalanced procedure) an opioid antagonist (i.e., naltrexone) and a placebo prior to performing pain testing and isometric exercise. Results: Results indicated that 2-arachidonoylglycerol (2-AG) and 2-oleoylglycerol (2-OG) increased significantly (P < 0.05) following exercise in both placebo and naltrexone conditions. In comparison, N-arachidonylethanolamine (AEA) and oleoylethanolamine (OEA) increased significantly (P < 0.05) following exercise in the placebo condition but not the naltrexone condition. There were no significant (P > 0.05) differences in palmitolethanolamine (PEA) between the placebo and naltrexone conditions. Conclusions: As reductions in pain (i.e., EIH) were observed following both conditions, these results suggest that the opioid system may not be the primary system involved in exercise-induced hypoalgesia and that 2-AG and 2-OG could contribute to nonopioid exercise-induced hypoalgesia. Moreover, as exercise-induced increases in AEA and OEA were blocked by naltrexone pretreatment, this suggests that the opioid system may be involved in the increase of AEA and OEA following exercise.

Cerebral white matter structure is disrupted in Gulf War Veterans with chronic musculoskeletal pain.

Chronic musculoskeletal pain (CMP) affects ∼25% of the 700,000 Veterans deployed during the Persian Gulf War (1990-1991). The cause of their pain is unknown, and there are no efficacious treatments. A small body of literature suggests that brain abnormalities exist in Gulf War Veterans (GVs), yet relationships between brain abnormalities and disease symptoms remain largely unexplored. Our purpose was to compare white matter (WM) integrity between GVCMP and matched, healthy Veteran controls (GVCO) and investigate relationships between cerebral WM integrity and symptoms. Thirty GVCMP and 31 controls completed magnetic resonance imaging with diffusion tensor imaging. Tract-based spatial statistics estimated WM fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity over the whole brain (P < 0.05) and were corrected using threshold-free cluster enhancement. GVCMP had greater pain symptoms and mood disturbance and lower quality of life and physical function compared with GVCO (P < 0.05). GVCMP had lower WM integrity across several brain regions implicated in chronic pain (P < 0.05) including the middle and inferior frontal gyrus, corpus callosum, corona radiata, precentral gyrus, external capsule, and posterior thalamic radiation. For GVCMP, WM integrity was associated with pain and mood symptoms in widespread brain areas that were found to be different between groups (P < 0.05). Results indicate widespread WM microstructure disruption across brain regions implicated in pain processing and modulation in chronic pain. The observed relationships between WM microstructure and symptoms encourage the testing of treatments designed to improve the brain health of affected Veterans.

Cognitive Resilience and Psychological Responses across a Collegiate Rowing Season.

INTRODUCTION: Student-athletes face numerous challenges across their competitive season. Although mood states have been previously studied, little is known about adaptations in other psychological responses, specifically cognition. The purpose of this study was to characterize cognitive function, mood, sleep, and stress responses at select time points of a season in collegiate rowers. It was hypothesized that during baseline, typical training, and recovery, athletes would show positive mental health profiles, in contrast to decreases in cognition with increases in negative mood and measurements of stress during peak training. METHODS: Male and female Division I rowers (N = 43) and healthy controls (N = 23) were enrolled and assessed at baseline, typical training, peak training, and recovery. At each time point, measures of cognitive performance (Stroop color-naming task), academic and exercise load, perceived cognitive deficits, mood states, sleep, and stress (via self-report and salivary cortisol) were recorded. RESULTS: Repeated-measures ANOVA revealed significant group-time interactions for perceived exercise load, cognitive deficits, mood states, and perceived stress (P < 0.05). For athletes during peak training, the perception of cognitive deficits was positively correlated with mood disturbance (r = 0.54, P < 0.05) and perceived stress (r = 0.55, P < 0.05) and negatively correlated with response accuracy during incongruent Stroop trials (r = -0.38, P < 0.05). Cognitive performance did not change over the course of the season for either group. Cortisol and sleepiness changed over the course of the season but no significant interactions were observed. CONCLUSION: These results demonstrate that various psychological responses change over the course of a season, but they also highlight adaptation indicative of cognitive resilience among student-athletes.

Endocannabinoid and Mood Responses to Exercise in Adults with Varying Activity Levels.

Acute aerobic exercise improves mood and activates the endocannabinoid (eCB) system in physically active individuals; however, both mood and eCB responses to exercise may vary based on habitual levels of physical activity. PURPOSE: This study aimed to examine eCB and mood responses to prescribed and preferred exercises among individuals with low, moderate, and high levels of physical activity. METHODS: Thirty-six healthy adults (21 ± 4 yr) were recruited from low (≤60 min moderate-vigorous physical activity [MVPA] per week), moderate (150-299 min MVPA per week), and high (≥300 MVPA per week) physical activity groups. Participants performed both prescribed (approximately 70%-75% max) and preferred (i.e., self-selected) aerobic exercise on separate days. Mood states and eCB concentrations were assessed before and after exercise conditions. RESULTS: Both preferred and prescribed exercise resulted in significant increases (P < 0.01) in circulating eCB (N-arachidonoylethanolamine [AEA] and 2-arachidonoylglycerol); however, increases in AEA (P < 0.05) were larger in the prescribed condition. Likewise, both preferred and prescribed exercise elicited positive mood improvements compared with preexercise values, but changes in state anxiety, total mood disturbance, and confusion were greater in the preferred condition (P < 0.05). Changes in 2-arachidonoylglycerol concentrations were found to negatively correlate with changes in depression, tension, and total mood disturbance in the preferred condition (P < 0.05), and changes in AEA were positively associated with changes in vigor in the prescribed condition (P < 0.05). There were no significant group differences for mood or eCB outcomes. CONCLUSION: These results indicate that eCB and mood responses to exercise do not differ significantly between samples with varying physical activity levels. This study also demonstrates that in addition to prescribed exercise, preferred exercise activates the eCB system, and this activation may contribute to positive mood outcomes with exercise.

Psychosocial Influences on Exercise-Induced Hypoalgesia.

Objective: The purpose of this study was to examine psychosocial influences on exercise-induced hypoalgesia (EIH). Design: Randomized controlled trial. Setting: Clinical research unit in a hospital. Subjects: Fifty-eight healthy men and women (mean age = 21 ± 3 years) participated in this study. Methods: Participants were first asked to complete a series of baseline demographic and psychological questionnaires including the Pain Catastrophizing Scale, the Fear of Pain Questionnaire, and the Family Environment Scale. Following this, they were familiarized with both temporal summation of heat pain and pressure pain testing protocols. During their next session, participants completed the Profile of Mood States, rated the intensity of heat pulses, and indicated their pressure pain thresholds and ratings before and after three minutes of submaximal, isometric exercise. Situational catastrophizing was assessed at the end of the experimental session. Results: Results indicated that experimental pain sensitivity was significantly reduced after exercise ( P < 0.05). Men and women did not differ on any of the measured psychosocial variables ( P > 0.05). Positive family environments predicted attenuated pain sensitivity and greater EIH, whereas negative and chronic pain-present family environments predicted worse pain and EIH outcomes. Situational catastrophizing and negative mood state also predicted worse pain and EIH outcomes and were additionally associated with increased ratings of perceived exertion and muscle pain during exercise. Conclusions: This study provides preliminary evidence that psychosocial variables, such as the family environment and mood states, can affect both pain sensitivity and the ability to modulate pain through exercise-induced hypoalgesia.

Relationships between serum BDNF and the antidepressant effect of acute exercise in depressed women.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has recently emerged as one potential mechanism with which exercise improves mood in major depressive disorder (MDD). This study examined the relationship between changes in serum total BDNF and mood following acute exercise in MDD. It was hypothesized that acute exercise would increase BDNF in an intensity-dependent manner and that changes in BDNF would be significantly related to improvement in depressed mood post-exercise. METHODS: Twenty-four women (age: 38.6±14.0years) with MDD exercised for 30min on a stationary bicycle at light, moderate and hard exercise intensities and performed a quiet rest session using a within-subjects, randomized and counter-balanced design. Before, 10 and 30min after each session, participants completed the profile of mood states (POMS). Blood was drawn before and within 10min after completion of each session and serum total BDNF (sBDNF) was measured by enzyme-linked immunosorbent assay. Acute exercise-induced changes in POMS Depression and sBDNF were analyzed via 4 session (quiet rest, light, moderate, hard) by 2 measurement (pre, post) ANOVA. Secondary analyses examined the effects of baseline mood and antidepressant usage on sBDNF. RESULTS: Exercise resulted in an acute improvement in depressed mood that was not intensity dependent (p>0.05), resulting in significant acute increases in sBDNF (p=0.006) that were also not intensity-dependent (p>0.05). Acute changes in sBDNF were not significantly correlated to changes in POMS depression at 10m (r=-0.171, p=0.161) or 30m (r=-0.151, p=0.215) post-exercise. The fourteen participants taking antidepressant medications exhibited lower post-exercise sBDNF (p=0.015) than the participants not currently taking antidepressants, although mood responses were similar. CONCLUSION: Acute exercise is an effective mood-enhancing stimulus, although sBDNF does not appear to play a role in this short-term response. Patients who are not currently taking antidepressant medications and those who have greater pre-exercise depression may experience a greater sBDNF response to exercise, but the clinical significance of this is currently unclear. Circulating BDNF levels are unlikely to be altered by steady-state acute exercise in a linear dose-dependent manner. This does not eliminate its potential relevance in the antidepressant response to chronic exercise training, but suggests that other mechanisms are involved in the acute affective response to exercise in depression.

Influence of Exercise Intensity for Improving Depressed Mood in Depression: A Dose-Response Study.

INTRODUCTION: Exercise effectively improves mood in major depressive disorder (MDD), but the optimal exercise stimulus to improve depressed mood is unknown. PURPOSE: To determine the dose-response relationship of acute exercise intensity with depressed mood responses to exercise in MDD. We hypothesized that the acute response to exercise would differ between light, moderate, and hard intensity exercise with higher intensities yielding more beneficial responses. METHODS: Once weekly, 24 women (age: 38.6±14.0) diagnosed with MDD underwent a 30-minute session at one of three steady-state exercise intensities (light, moderate, hard; rating of perceived exertion 11, 13 or 15) or quiet rest on a stationary bicycle. Depressed mood was evaluated with the Profile of Mood States before, 10 and 30 minutes post-exercise. RESULTS: Exercise reduced depressed mood 10 and 30 minutes following exercise, but this effect was not influenced by exercise intensity. Participants not currently taking antidepressants (n=10) had higher baseline depression scores, but did not demonstrate a different antidepressant response to exercise compared to those taking antidepressants. CONCLUSIONS: To acutely improve depressed mood, exercise of any intensity significantly improved feelings of depression with no differential effect following light, moderate, or hard exercise. Pharmacological antidepressant usage did not limit the mood-enhancing effect of acute exercise. Acute exercise should be used as a symptom management tool to improve mood in depression, with even light exercise an effective recommendation. These results need to be replicated and extended to other components of exercise prescription (e.g., duration, frequency, mode) to optimize exercise guidelines for improving depression.

Psychobiological Responses to Preferred and Prescribed Intensity Exercise in Major Depressive Disorder.

Exercise acutely improves mood in major depressive disorder (MDD). However, it is unknown whether benefits differ depending on whether exercise intensity is self-selected or prescribed. PURPOSE: This study aimed to compare psychological and biological responses to preferred and prescribed steady-state exercise intensities to a patient-selected preferred intensity. METHOD: Female adults (N = 24, age = 38.6 ± 14.0 yr) diagnosed with MDD completed four 30-min sessions of cycling exercise at three prescribed intensities (RPE of 11, 13, and 15) and one session with a self-selected intensity (preferred). Order was randomized and counterbalanced. Depressed mood (DM) was evaluated before, 10 min, and 30 min postexercise using the Profile of Mood States. Serum brain-derived neurotrophic factor (BDNF) was measured before and within 10 min postexercise. Changes in BDNF and DM for the preferred session were compared with the following prescribed sessions: 1) performed at the most similar intensity (matched on RPE; closest) and 2) with the greatest improvement in DM (greatest). RESULTS: Compared with the preferred session, improvement in DM was significantly larger after the greatest session (30 min postexercise: -11.8 ± 7.4 vs -3.4 ± 4.8), and the BDNF response was significantly greater after the closest session (5.4 ± 6.9 vs -1.4 ± 9.8 ng·mL). CONCLUSIONS: Permitting patients to select their own exercise intensity did not maximize improvements in mood. Further, preferred intensity exercise was also associated with a smaller BDNF response. Overall, the results suggest that exercise undertaken to improve mood should be prescribed on an individual basis in MDD and not necessarily based on the patient's preferred intensity. Clinicians, psychologists, and other practitioners should consider providing clear exercise intensity recommendations for symptom management in depression rather than allowing patients to self-select their intensity.