Chad D. Rethorst

The antidepressive effects of exercise: a meta-analysis of randomized trials.

Several meta-analyses examining the effects of exercise on depression have been criticized for including studies of poor methodological integrity. More recent meta-analyses addressed the most common criticism by including only randomized control trials; however, these analyses suffer from incomplete literature searches and lack of moderating variable analyses. Using a more extensive search procedure, the current meta-analysis examines the effects of exercise on depressive symptoms in 58 randomized trials (n = 2982). An overall effect size of −0.80 indicates participants in the exercise treatment had significantly lower depression scores than those receiving the control treatment. This 3/4 SD advantage represents level 1, Grade A evidence for the effects of exercise upon depression. Analysis of moderating variables examined the influence of population characteristics, exercise characteristics and methodological characteristics. Examination of clinical significance in 16 trials with clinically depressed patients found 9 of 16 exercise treatment groups were classified as ‘recovered’ at post-treatment, with another three groups classified as ‘improved’. Analysis showed dropout rates for the exercise treatment were similar to those found in psychotherapeutic and drug interventions.

Pro-Inflammatory Cytokines as Predictors of Antidepressant Effects of Exercise in Major Depressive Disorder

Exercise is an efficacious treatment for major depressive disorder (MDD) and has independently been shown to have anti-inflammatory effects in non-depressed subjects. Patients with MDD have elevated inflammatory cytokines but it is not known if exercise affects inflammation in MDD patients and whether these changes are clinically relevant. In the TReatment with Exercise Augmentation for Depression (TREAD) study, participants who were partial responders to a selective serotonin reuptake inhibitor were randomized to receive one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW), or 4 KKW for 12 weeks. Blood samples were collected before initiation and again at the end of the 12-week exercise intervention. Serum was analyzed using a multiplexed ELISA for interferon-γ (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Higher baseline levels of TNF-α were associated with greater decrease in depression symptoms over the 12-week exercise period (P<0.0001). In addition, a significant positive correlation between change in IL-1β and change in depression symptom scores was observed (P=0.04). There were no significant changes in mean level of any cytokine following the 12-week intervention, and no significant relationship between exercise dose and change in mean cytokine level. Results suggest that high TNF-α may differentially predict better outcomes with exercise treatment as opposed to antidepressant medications for which high TNF-α is linked to poor response. Our results also confirm findings from studies of antidepressant medications that tie decreasing IL-1β to positive depression treatment outcomes.

Evidence-based Recommendations for the Prescription of Exercise for Major Depressive Disorder

Major depressive disorder (MDD) is a source of great disease burden, due in part to the limited accessibility and effectiveness of current treatments. Although current treatments are efficacious in a segment of the population with MDD, there is a clear need for alternative and augmentation treatment strategies. Exercise is one such alternative treatment option. Research has shown exercise to be efficacious as both a stand-alone and an augmentation therapy. As a result, exercise is now included in the American Psychiatric Association’s treatment recommendations. The purpose of this article is to provide clinicians with a knowledge base to prescribe exercise to their patients. The authors describe the evidence supporting the use of exercise in the treatment of MDD, provide evidence-based recommendations for prescribing exercise, and address practical considerations related to prescribing exercise in real-world treatment settings. (Journal of Psychiatric Practice 2013;19:204–212)

Inflammation, obesity, and metabolic syndrome in depression: analysis of the 2009-2010 National Health and Nutrition Examination Survey (NHANES).

OBJECTIVE To describe the rates of elevated inflammation, obesity, and metabolic syndrome (MetS) within a large cohort of individuals with depression and to examine the interrelationships of inflammation and MetS in depressed individuals. METHOD Analyses were conducted on study participants from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) with Patient Health Questionnaire (PHQ-9) depression scores ≥ 10 to (1) examine the relationship of inflammation (C-reactive protein; CRP) with demographic and clinical characteristics and (2) examine the prevalence of MetS criteria within CRP groups. RESULTS 5,579 participants provided PHQ-9 data; of those, 606 had PHQ-9 scores ≥ 10 and were included in further analysis. Of the 606 depressed participants, 585 participants had valid CRP data; 275 participants (47.01%) had CRP levels ≥ 3.0 mg/L, while 170 (29.06%) had CRP levels ≥ 5.0 mg/L. Elevated inflammation was significantly correlated with body weight, waist circumference, body mass index, insulin, 2-hour glucose tolerance, and self-report general health (P values < .05). 112 subjects (41.18%) met American Heart Association/National Heart, Lung, and Blood Institute criteria for MetS. Those with elevated CRP were more likely to meet criteria for MetS (odds ratios of 2.81 for those with CRP levels ≥ 3.0 mg/L and 1.94 for those with CRP levels ≥ 5.0 mg/L). CONCLUSIONS Over 29% of depressed individuals had elevated levels of CRP, and 41% met criteria for MetS. Individuals with elevated inflammation are more likely to be obese and meet criteria for MetS. These results highlight the significant inflammatory and metabolic burden of individuals with depression.

Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

BackgroundThere is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study.Methods/DesignSTRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session.Clinical Trials RegistryClinicalTrials.gov, NCT01141608http://clinicaltrials.gov/ct2/show/NCT01141608?term=Stimulant+Reduction+Intervention+using+Dosed+Exercise&rank=1

Does exercise improve self-reported sleep quality in non-remitted major depressive disorder?

BACKGROUND Sleep disturbances are persistent residual symptoms following remission of major depressive disorder (MDD) and are associated with an increased risk of MDD recurrence. The purpose of the current study was to examine the effect of exercise augmentation on self-reported sleep quality in participants with non-remitted MDD. Method Participants were randomized to receive selective serotonin reuptake inhibitor (SSRI) augmentation with one of two doses of exercise: 16 kilocalories per kilogram of body weight per week (KKW) or 4 KKW for 12 weeks. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). The four sleep-related items on the IDS-C (Sleep Onset Insomnia, Mid-Nocturnal Insomnia, Early Morning Insomnia, and Hypersomnia) were used to assess self-reported sleep quality. RESULTS Significant decreases in total insomnia (p < 0.0001) were observed, along with decreases in sleep onset, mid-nocturnal and early-morning insomnia (ps <0.002). Hypersomnia did not change significantly (p = 0.38). Changes in total, mid-nocturnal and early-morning insomnia were independent of changes in depressive symptoms. Higher baseline hypersomnia predicted a greater decrease in depression severity following exercise treatment (p = 0.0057). No significant moderating effect of any baseline sleep on change in depression severity was observed. There were no significant differences between exercise treatment groups on total insomnia or any individual sleep item. CONCLUSIONS Exercise augmentation resulted in improvements in self-reported sleep quality in patients with non-remitted MDD. Given the prevalence of insomnia as a residual symptom following MDD treatment and the associated risk of MDD recurrence, exercise augmentation may have an important role in the treatment of MDD.

Efficacy of Exercise in Reducing Depressive Symptoms across 5-HTTLPR Genotypes

INTRODUCTION Exercise is effective in the alleviation of depressive symptoms and may have physiological effects similar to those of selective serotonin reuptake inhibitors (SSRI). Recent research has identified the difference in treatment effects across genetic polymorphisms of the serotonin transporter polymorphic region (5-HTTLPR), in which the l allele has been associated with a better response to SSRI compared with the s allele. The purpose of the current research was to examine the antidepressant effects of exercise across 5-HTTLPR genotypes. METHODS Participants, ages 18–23 yr, were randomly assigned to a 5-wk exercise intervention or a no-treatment control group. Participants completed the Beck Depression Inventory before and after the intervention and provided a saliva sample for DNA analysis. RESULTS Exercise resulted in a significant reduction in depressive symptoms compared with the control group. In addition, individuals with at least one l allele demonstrated greater reductions in depressive symptoms compared with ss individuals. CONCLUSIONS The effects of exercise on depressive symptoms appear to be moderated by 5-HTTLPR genotype, suggesting that the mechanisms responsible for the alleviation of depressive symptoms are similar for exercise and SSRI treatment. Furthermore, these findings suggest that 5-HTTLPR genotype should be a factor in determining the proper line of treatment for depression.

Moderating Effects of Moderate-Intensity Physical Activity in the Relationship Between Depressive Symptoms and Interleukin-6 in Primary Care Patients

Objective: To determine whether the relationship between interleukin (IL)-6 and depressive symptoms is moderated by participation in moderate-intensity physical activity in a sample of primary care patients. Elevated inflammation has been associated with a number of poor health outcomes. Depressive symptoms may be related to higher levels of the inflammatory marker IL-6; however, previous findings are inconsistent, possibly due to unidentified moderating factors. Methods: A total of 107 participants, aged ≥40 years, were recruited in Rochester, New York, in 2006 to 2007. Depressive symptoms were measured by the Center for Epidemiologic Studies Depression Scale-Revised, participation in moderate-intensity physical activity was measured using a modified version of the Community Health Activities Model Program for Seniors Activity Questionnaire for Older Adults, and serum IL-6 concentrations were determined using standard enzyme-linked immunosorbent assay protocols and high-sensitivity, anti-cytokine antibody pairs. A hierarchical multiple regression analysis was conducted. Results: The correlation between IL-6 and depressive symptoms was nonsignificant (r = .086, p = .40). The association between IL-6 and depressive symptoms was moderated by participation in moderate-intensity physical activity (p = .02). Among those who did not engage in moderate-intensity physical activity, higher levels of depressive symptoms were significantly associated with higher levels of IL-6 (r = .28, p = .05), whereas this association was not significant among those who did participate in moderate-intensity physical activity (r = −.13, p = .38). Conclusion: Participation in moderate-intensity physical activity may buffer the risk of higher inflammation often associated with higher levels of depressive symptoms. IL = interleukin; CESD-R = Center for Epidemiologic Studies Depression Scale-Revised.

Exercise training – A beneficial intervention in the treatment of alcohol use disorders?

BACKGROUND A growing body of evidence suggests that exercise training may have multiple beneficial effects in individuals with mental health or substance use disorders. Yet, relatively little knowledge exists regarding the benefits of exercise training to augment treatment for alcohol use disorders (AUDs). PURPOSE The purpose of this narrative review is to present a summary of the growing body of published literature supporting exercise training as a treatment strategy for individuals with AUDs. We will provide evidence on the myriad of ways in which exercise may exert a positive effect on AUD outcomes including stress, anxiety, impulsivity, and depression. Further, we will explore how these mechanisms share common neurobiological pathways. The role of exercise in enhancing the social environment and increasing individual self-efficacy to reduce excess and/or inappropriate alcohol consumption will also be discussed. DISCUSSION We will conclude with a description of completed investigations involving exercise training and provide suggestions for next steps in this innovative field of study.

Examining the moderating effect of depressive symptoms on the relation between exercise and self-efficacy during the initiation of regular exercise.

OBJECTIVE People with depressive symptoms report lower levels of exercise self-efficacy and are more likely to discontinue regular exercise than others, but it is unclear how depressive symptoms affect the relation between exercise and self-efficacy. We sought to clarify whether depressive symptoms moderate the relations between exercise and same-day self-efficacy, and between self-efficacy and next-day exercise. METHODS Participants (n = 116) were physically inactive adults (35% reported clinically significant depressive symptoms) who initiated regular exercise and completed daily assessments for 4 weeks. Mixed linear models were used to test whether (a) self-efficacy differed on days when exercise did and did not occur, (b) self-efficacy predicted next-day exercise, and (c) these relations were moderated by depressive symptoms. RESULTS First, self-efficacy was lower on days when no exercise occurred, but this difference was larger for people with high depressive symptoms (p < .001). They had lower self-efficacy than people with low depressive symptoms on days when no exercise occurred (p = .03), but self-efficacy did not differ on days when exercise occurred (p = .34). Second, self-efficacy predicted greater odds of next-day exercise, OR = 1.12, 95% [1.04, 1.21], but depressive symptoms did not moderate this relation, OR = 1.00, 95% CI [.99, 1.01]. CONCLUSIONS During exercise initiation, daily self-efficacy is more strongly related to exercise occurrence for people with high depressive symptoms than those with low depressive symptoms, but self-efficacy predicts next-day exercise regardless of depressive symptoms. The findings specify how depressive symptoms affect the relations between exercise and self-efficacy and underscore the importance of targeting self-efficacy in exercise interventions, particularly among people with depressive symptoms. (PsycINFO Database Record