An implementation evaluation of the physical activity counseling for in-patients with major depressive disorder (PACINPAT) intervention: a randomized controlled trial.

BACKGROUND: The physical activity counseling for in-patients with major depression (PACINPAT) randomized controlled trial was launched to tackle physical inactivity for in-patients with major depressive disorder. Evidence shows that despite potential treatment effects, physical inactivity is prevalent in this population. To contribute to the assessment of how this in-person and remote, theory-based, individually tailored intervention was designed, received and effected behavior, the aim of this study was to evaluate its implementation. METHODS: This implementation evaluation was conducted within a multi-center randomized controlled trial according to the Process Evaluation Framework by the Medical Research Council including the analysis of reach, dose, fidelity and adaptation. Data were collected from the implementers and the participants randomized to the intervention group of the trial. RESULTS: The study sample comprised 95 physically inactive in-patients (mean age: 42 years, 53% women) with diagnosed major depressive disorder. The intervention reached the intended population (N = 95 in-patients enrolled in the study). The intervention dose varied between early dropouts (counseling sessions, M = 1.67) and study completers with some participants receiving a low dose (counseling sessions, M = 10.05) and high dose (counseling sessions, M = 25.37). Differences in the attendance groups were recognizable in the first two counseling sessions (duration of counseling session about 45 min in early dropouts versus 60 min for study completers). Fidelity of the in-person counseling content was partly achieved and adapted, whereas that of the remote counseling content was well achieved. Participants (86% at follow up) reported satisfaction with the implementers of the intervention. Adaptations were made to content, delivery mode and dose. CONCLUSION: The PACINPAT trial was implemented in the intended population, in varying doses and with adaptations made to in-person counseling content and remote counseling dose. These findings are key to understanding outcome analyses within the PACINPAT trial, further developing interventions and contributing to implementation research among in-patients with depressive disorders. TRIAL REGISTRATION: ISRCTN, ISRCTN10469580 , registered on 3rd September 2018.

The angiogenesis inhibitor vasostatin is regulated by neutrophil elastase-dependent cleavage of calreticulin in AML patients.

The calcium-binding protein calreticulin (CRT) regulates protein folding in the endoplasmic reticulum (ER) and is induced in acute myeloid leukemia (AML) cells with activation of the unfolded protein response. Intracellular CRT translocation to the cell surface induces immunogenic cell death, suggesting a role in tumor suppression. In this study, we investigated CRT regulation in the serum of patients with AML. We found that CRT is not only exposed by exocytosis on the outer cell membrane after treatment with anthracyclin but also ultimately released to the serum in vitro and in AML patients during induction therapy. Leukemic cells of 113 AML patients showed increased levels of cell-surface CRT (P < .0001) and N-terminus serum CRT (P < .0001) compared with normal myeloid cells. Neutrophil elastase was identified to cleave an N-terminus CRT peptide, which was characterized as vasostatin and blocked ATRA-triggered differentiation. Levels of serum vasostatin in patients with AML inversely correlated with bone marrow vascularization, suggesting a role in antiangiogenesis. Finally, patients with increased vasostatin levels had longer relapse-free survival (P = .04) and specifically benefited from autologous transplantation (P = .006). Our data indicate that vasostatin is released from cell-surface CRT and impairs differentiation of myeloid cells and vascularization of the bone marrow microenvironment.

Correspondence between the Simple Physical Activity Questionnaire (SIMPAQ) and accelerometer-based physical activity in inpatients treated for major depressive disorders in comparison to non-depressed controls.

Introduction: Major depressive disorders (MDD) are a leading health concern worldwide. While first line medication treatments may fall short of desired therapeutic outcomes, physical activity (PA) interventions appear to be a promising and cost-effective add-on to improve symptoms of depression. This study aimed to address challenges in the assessment of PA in inpatients treated for MDD by examining the correspondence of self-reported and accelerometer-based PA. Methods: In 178 inpatients treated for MDD (mean age: M = 41.11 years, SD = 12.84; 45.5% female) and 97 non-depressed controls (mean age: M = 35.24 years, SD = 13.40; 36.1% female), we assessed self-reported PA via the Simple Physical Activity Questionnaire (SIMPAQ) for one week, followed by a week where PA was monitored using an accelerometer device (Actigraph wGT3x-BT). Additionally, we examined correlations between PA levels assessed with the SIMPAQ and exercise determinants in both groups. Results: Descriptively, inpatients treated for MDD showed lower levels of light PA on accelerometer-based measures, whereas they self-reported increased levels of certain types of PA on the SIMPAQ. More importantly, there was only a small degree of correspondence between self-reported and actigraphy-based PA levels in both in patients (r = 0.15, p < 0.05) and controls (r = 0.03, ns). Only few significant correlations were found for self-reported PA (SIMPAQ subscores) and perceived fitness, whereas self-reported PA and estimated VO2max were unrelated. Furthermore, only weak (and mostly statistically non-significant) correlations were found between exercise determinants and SIMPAQ-based exercise behavior in both populations. Discussion: Our findings emphasize the intricate challenges in the assessment of PA, not only in inpatients treated for MDD, but also in non-depressed controls. Our findings also underline the necessity for a diversified data assessment. Further efforts are needed to refine and improve PA questionnaires for a more accurate data assessment in psychiatric patients and healthy controls.

Cardiorespiratory fitness, perceived fitness and autonomic function in in-patients with different depression severity compared with healthy controls.

Over 300 million individuals worldwide suffer from major depressive disorder (MDD). Individuals with MDD are less physically active than healthy people which results in lower cardiorespiratory fitness (CRF) and less favorable perceived fitness compared with healthy controls. Additionally, individuals with MDD may show autonomic system dysfunction. The purpose of the present study was to evaluate the CRF, perceived fitness and autonomic function in in-patients with MDD of different severity compared with healthy controls. We used data from 212 in-patients (age: 40.7 ± 12.6 y, 53% female) with MDD and from 141 healthy controls (age: 36.7 ± 12.7 y, 58% female). We assessed CRF with the Åstrand-Rhyming test, self-reported perceived fitness and autonomic function by heart rate variability (HRV). In specific, we used resting heart rate, time- and frequency-based parameters for HRV. In-patients completed the Beck Depression Inventory-II (BDI-II) to self-assess the subjectively rated severity of depression. Based on these scores, participants were grouped into mild, moderate and severe MDD. The main finding was an inverse association between depression severity and CRF as well as perceived fitness compared with healthy controls. Resting heart rate was elevated with increasing depression severity. The time-based but not the frequency-based autonomic function parameters showed an inverse association with depression severity. The pattern of results suggests that among in-patients with major depressive disorder, those with particularly high self-assessed severity scores show a lower CRF, less favorable perceived fitness and partial autonomic dysfunction compared to healthy controls. To counteract these conditions, physical activity interventions may be effective.

Long-term outcomes of physical activity counseling in in-patients with major depressive disorder: results from the PACINPAT randomized controlled trial.

Major depressive disorder (MDD) is an increasingly common psychiatric illness associated with a high risk of insufficient physical activity, which in turn is associated with negative mental and physical health outcomes. Theory-based, individually tailored, in-person and remote physical activity counseling has the potential to increase physical activity levels in various populations. Given this, the present study investigated the effect of such a physical activity intervention on the physical activity behavior of in-patients with MDD. This was a multi-center, two-arm randomized controlled trial including initially insufficiently physically active adult in-patients with MDD from four study sites in Switzerland. The sample consisted of 220 participants (Mage = 41 ± 12.6 years, 52% women), 113 of whom were randomized to the intervention group and 107 to the control group. The main outcome, moderate-to-vigorous physical activity (MVPA), was assessed at three time points via hip-worn accelerometer. According to accelerometer measures, there was no significant difference in minutes spent in MVPA over a 12-month intervention period when comparing the intervention with the control group (ß = -1.02, 95% CI = -10.68 to 8.64). Higher baseline physical activity significantly predicted physical activity at post and follow-up. This study showed that it is feasible to deliver an individually tailored, theory-based physical activity counseling intervention to in-patients with MDD, however yielding no significant effects on accelerometer-based MVPA levels. Further efforts are warranted to identify efficacious approaches.Trial registration: ISRCTN, ISRCTN10469580, registered on 3rd September 2018, https://www.isrctn.com/ISRCTN10469580 .

Cardiorespiratory fitness and cardiovascular risk among in-patients with depression compared to healthy controls.

Introduction: Compared to the general population, individuals with depression have an increased risk for cardiovascular diseases. Nevertheless, little is known so far whether cardiorespiratory fitness (CRF) moderates this relationship. Therefore, we examined whether common physiological cardiovascular risk factors differ between patients with depression and healthy (non-depressed) controls, whether patients and controls differ in CRF, and whether higher CRF is associated with a lower cardiovascular risk in both patients and healthy controls. Additionally, we examined whether within the patient sample, cardiovascular risk factors differ between patients with mild, moderate and severe depression, and whether the relationship between symptom severity and cardiovascular risk is moderated by patients' CRF levels. Methods: Data from a multi-centric, two-arm randomized controlled trial (RCT) was analyzed, including 210 patients (F32, single episode: n = 72, F33, recurrent major depression: n = 135, F31-II, bipolar type II: n = 3) and 125 healthy controls. Waist circumference, body mass index, body fat, blood pressure, cholesterol levels, triglycerides, and blood glucose were considered as cardiovascular risk markers. CRF was assessed with a submaximal ergometer test. Differences between groups were examined via χ2-tests and (multivariate) analyses of covariance. Results: Compared to healthy controls, patients with depression had a higher cardiovascular risk as evident from about half of the examined indicators. In the total sample, participants with good CRF had more favourable scores across nearly all risk markers than counterparts with poor CRF. For most variables, no interaction occurred between group and fitness, indicating that in patients and controls, similar differences existed between participants with poor and good CRF. Few differences in risk markers were found between patients with mild, moderate and severe depression, and no interaction occurred between depression severity and CRF. Discussion: Patients with depression and healthy controls differ in several cardiovascular risk markers, putting patients at increased risk for CVDs. In contrast, people with good CRF show more favourable cardiovascular risk scores, a relationship which was observed in both healthy controls and patients with depression. Physical health of psychiatric patients should receive the clinical attention that it deserves. Lifestyle interventions targeting healthy diet and/or physical activity are recommended as a physically active and healthy lifestyle contributes equally to patients' mental well-being and cardiovascular health.

Differences in Selective Attention and Inhibitory Control in Patients with Major Depressive Disorder and Healthy Controls Who Do Not Engage in Sufficient Physical Activity.

BACKGROUND: Patients with major depressive disorder (MDD) are characterized by neurocognitive impairments and show deficits in various cognitive performance indicators, including executive function. We examined whether sustained attention and inhibitory control differ between patients with MDD and healthy controls, and whether differences exist between patients with mild, moderate, and severe depression. METHODS: Clinical in-patients (N = 212) aged 18-65 years with a current diagnosis of MDD and 128 healthy controls were recruited. Depression severity was assessed using the Beck Depression Inventory, and sustained attention and inhibitory control were assessed using the oddball and flanker tasks. The use of these tasks promises insights into executive function in depressive patients that are not biased by verbal skills. Group differences were tested via analyses of covariance. RESULTS: Patients with MDD showed slower reaction times in both the oddball and flanker task, independent of the executive demands of the trial types. Younger participants achieved shorter reaction times in both inhibitory control tasks. After correcting for age, education, smoking, BMI, and nationality, only differences in reaction times in the oddball task were statistically significant. In contrast, reaction times were not sensitive to the symptom severity of depression. CONCLUSION: Our results corroborate deficits in basic information processing and specific impairments in higher-order cognitive processes in MDD patients. As difficulties in executive function underlie problems in planning, initiating, and completing goal-directed activities, they may jeopardize in-patient treatment and contribute to the recurrent nature of depression.

Short-term outcomes of physical activity counseling in in-patients with Major Depressive Disorder: Results from the PACINPAT randomized controlled trial.

Introduction: A physical activity counseling intervention based on a motivation-volition model was developed and delivered to in-patients with Major Depressive Disorders with the aim of increasing lifestyle physical activity. The aim of this study is to evaluate the short-term outcomes of this intervention. Methods: A multi-center randomized controlled trial was conducted in four Swiss psychiatric clinics. Adults who were initially insufficiently physically active and were diagnosed with Major Depressive Disorder according to ICD-10 were recruited. The sample consisted of 113 participants in the intervention group (M age = 42 years, 56% women) and 107 in the control group (M age = 40 years, 49% women). Motivation and volition determinants of physical activity were assessed with questionnaires. Implicit attitudes were assessed with an Implicit Association Test. Physical activity was self-reported and measured with hip-worn accelerometers over 7 consecutive days starting on the day following the data collection. Results: According to accelerometer measures, step count decreased on average 1,323 steps less per day (95% CI = -2,215 to -431, p < 0.01) over time in the intervention group compared to the control group. A trend was recognized indicating that moderate-to-vigorous physical activity decreased on average 8.37 min less per day (95% CI = -16.98 to 0.23, p < 0.06) over time in the intervention group compared to the control group. The initial phase of the intervention does not seem to have affected motivational and volitional determinants of and implicit attitudes toward physical activity. Conclusion: Physical activity counseling may be considered an important factor in the transition from in-patient treatment. Methods to optimize the intervention during this period could be further explored to fulfill the potential of this opportunity. Clinical trial registration: https://www.isrctn.com/ISRCTN10469580, identifier ISRCTN10469580.

Psychosocial Health and Physical Activity in People With Major Depression in the Context of COVID-19.

Introduction: Major depression is a psychiatric disease associated with physical inactivity, which in turn affects mental and physical health. A randomized controlled trial is being implemented to facilitate physical activity in people with major depression. In March 2020, Swiss state authorities temporarily legislated a lockdown to contain the Coronavirus disease-19 (COVID-19), which influenced health, behavior and research. The aim of this study was to find out whether data gathered before and during/after the lockdown among in-patients with major depression differ with regard to psychosocial health, physical activity and related attitudes and to establish whether baseline data have been affected by the lockdown. Methods: This is a cross-sectional analysis within a randomized controlled trial. Physically inactive, adult in-patients diagnosed with major depression were recruited from four Swiss psychiatric clinics between January 2019 and December 2020. Psychosocial health was measured with questionnaires pertaining to stress, sleep and health-related quality of life. Physical activity was measured with the Simple Physical Activity Questionnaire. Explicit attitudes were measured with seven questionnaires pertaining to physical activity-related motivation and volition. Implicit attitudes toward physical activity were captured with a single target implicit association test. Results: The sample consisted of 165 participants (n = 119 before lockdown, n = 46 during/after lockdown). No statistically significant differences were found between in-patients with major depression assessed before and during/after the COVID-19 lockdown with regard to psychosocial health (stress, p = 0.51; sleep, p = 0.70; physical component of health-related quality of life, p = 0.55; mental component of health-related quality of life, p = 0.64), self-reported physical activity (p = 0.16) and explicit as well as implicit attitudes toward physical activity (p = 0.94). Hence, the COVID-19-induced lockdown seems not to have led to group differences. Conclusion: Baseline data gathered in in-patients suffering from major depression who are physically inactive upon admission to in-patient treatment in Switzerland seem to be unaffected by the COVID-19-induced lockdown. To assess changes in said population regarding psychosocial health and physical activity patterns over time, longitudinal data are needed.

The impact of lifestyle Physical Activity Counselling in IN-PATients with major depressive disorders on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers: study protocol for a randomized controlled trial.

BACKGROUND: Major depressive disorder (MDD) is a widespread and burdensome psychiatric issue. Physical activity counselling may increase lifestyle physical activity and cardiorespiratory fitness in this specific and particularly vulnerable population, which often suffers from both mental and physical health problems. Therefore, this study will examine the impact of a lifestyle physical activity counselling intervention on physical activity, cardiorespiratory fitness, depression, and cardiovascular health risk markers among in-patients diagnosed with MDD compared to controls. Secondary purposes are to examine the acceptability and perceived usefulness of the intervention among these patients, to find out whether the effectiveness of the intervention is moderated by genetic factors, and to compare baseline values with an age- and gender-matched group of healthy controls. METHODS: The study is designed as a multi-centric two-arm randomized clinical trial including an intervention group and a placebo control group, allocation concealment, single-blinding, and intention-to-treat analysis. Participants (N = 334) will be continuously recruited from four clinics specialized in the treatment of MDD. The intervention builds on a standardized, theory-based, low-cost lifestyle physical activity counselling programme, which was specifically designed for an in-patient rehabilitation setting. The placebo control condition consists of general instructions about health-enhancing physical activity. Data assessments will take place 2-3 weeks after admission to in-patient treatment (baseline), and 6 weeks (post) and 12 months (follow-up) after discharge from in-patient treatment. The primary outcome is objectively assessed physical activity at follow-up. DISCUSSION: Because regular physical activity has proven to be an important predictor of long-term response and remission in patients with major depression, we believe that our planned study may lay important groundwork by showing how individually tailored lifestyle physical activity counselling can be integrated into given clinical structures. Improving physical activity may have important implications for tackling metabolic and cardiovascular disease and increasing mood and cognitive functioning in this at-risk population, hence limiting the future burden of multiple chronic conditions. Increased physical activity may also reduce the likelihood of future depressive episodes. By moving towards the primary prevention of chronic physical conditions, much can be done to enhance the quality and quantity of life of people with MDD. TRIAL REGISTRATION: ISRCTN, ISRCTN10469580 . Registered on 3 September 2018.