Marco Solmi

Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: a large‐scale meta‐analysis of 3,211,768 patients and 113,383,368 controls

People with severe mental illness (SMI) – schizophrenia, bipolar disorder and major depressive disorder – appear at risk for cardiovascular disease (CVD), but a comprehensive meta‐analysis is lacking. We conducted a large‐scale meta‐analysis assessing the prevalence and incidence of CVD; coronary heart disease; stroke, transient ischemic attack or cerebrovascular disease; congestive heart failure; peripheral vascular disease; and CVD‐related death in SMI patients (N=3,211,768) versus controls (N=113,383,368) (92 studies). The pooled CVD prevalence in SMI patients (mean age 50 years) was 9.9% (95% CI: 7.4‐13.3). Adjusting for a median of seven confounders, patients had significantly higher odds of CVD versus controls in cross‐sectional studies (odds ratio, OR=1.53, 95% CI: 1.27‐1.83; 11 studies), and higher odds of coronary heart disease (OR=1.51, 95% CI: 1.47‐1.55) and cerebrovascular disease (OR=1.42, 95% CI: 1.21‐1.66). People with major depressive disorder were at increased risk for coronary heart disease, while those with schizophrenia were at increased risk for coronary heart disease, cerebrovascular disease and congestive heart failure. Cumulative CVD incidence in SMI patients was 3.6% (95% CI: 2.7‐5.3) during a median follow‐up of 8.4 years (range 1.8‐30.0). Adjusting for a median of six confounders, SMI patients had significantly higher CVD incidence than controls in longitudinal studies (hazard ratio, HR=1.78, 95% CI: 1.60‐1.98; 31 studies). The incidence was also higher for coronary heart disease (HR=1.54, 95% CI: 1.30‐1.82), cerebrovascular disease (HR=1.64, 95% CI: 1.26‐2.14), congestive heart failure (HR=2.10, 95% CI: 1.64‐2.70), and CVD‐related death (HR=1.85, 95% CI: 1.53‐2.24). People with major depressive disorder, bipolar disorder and schizophrenia were all at increased risk of CVD‐related death versus controls. CVD incidence increased with antipsychotic use (p=0.008), higher body mass index (p=0.008) and higher baseline CVD prevalence (p=0.03) in patients vs. controls. Moreover, CVD prevalence (p=0.007), but not CVD incidence (p=0.21), increased in more recently conducted studies. This large‐scale meta‐analysis confirms that SMI patients have significantly increased risk of CVD and CVD‐related mortality, and that elevated body mass index, antipsychotic use, and CVD screening and management require urgent clinical attention.

Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies

To conduct a systematic review and meta‐analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls (HCs).

Inflammation and frailty in the elderly: A systematic review and meta-analysis

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participants, both 1698 frail (SMD=1.00, 95%CI: 0.40-1.61) and 8568 pre-frail (SMD=0.33, 95%CI: 0.04-0.62) participants had significantly higher levels of C-reactive protein (CRP). Frailty (n=1057; SMD=1.12, 95%CI: 0.27-2.13) and pre-frailty (n=4467; SMD=0.56, 95%CI: 0.00-1.11) were associated with higher serum levels of interleukin-6 compared to people who were robust (n=2392). Frailty and pre-frailty were also significantly associated with elevated white blood cell and fibrinogen levels. In three longitudinal studies, higher serum CRP (OR=1.06, 95%CI: 0.78-1.44,) and IL-6 (OR=1.19, 95%CI: 0.87-1.62) were not associated with frailty. In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed.

Dropout from exercise randomized controlled trials among people with depression: A meta-analysis and meta regression.

OBJECTIVE Exercise has established efficacy in improving depressive symptoms. Dropouts from randomized controlled trials (RCTs) pose a threat to the validity of this evidence base, with dropout rates varying across studies. We conducted a systematic review and meta-analysis to investigate the prevalence and predictors of dropout rates among adults with depression participating in exercise RCTs. METHOD Three authors identified RCTs from a recent Cochrane review and conducted updated searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including major depressive disorder (MDD) and depressive symptoms) that reported dropout rates. A random effects meta-analysis and meta regression were conducted. RESULTS Overall, 40 RCTs were included reporting dropout rates across 52 exercise interventions including 1720 people with depression (49.1 years (range=19-76 years), 72% female (range=0-100)). The trim and fill adjusted prevalence of dropout across all studies was 18.1% (95%CI=15.0-21.8%) and 17.2% (95%CI=13.5-21.7, N=31) in MDD only. In MDD participants, higher baseline depressive symptoms (β=0.0409, 95%CI=0.0809-0.0009, P=0.04) predicted greater dropout, whilst supervised interventions delivered by physiotherapists (β=-1.2029, 95%CI=-2.0967 to -0.3091, p=0.008) and exercise physiologists (β=-1.3396, 95%CI=-2.4478 to -0.2313, p=0.01) predicted lower dropout. A comparative meta-analysis (N=29) established dropout was lower in exercise than control conditions (OR=0.642, 95%CI=0.43-0.95, p=0.02). CONCLUSIONS Exercise is well tolerated by people with depression and drop out in RCTs is lower than control conditions. Thus, exercise is a feasible treatment, in particular when delivered by healthcare professionals with specific training in exercise prescription.

ReviewInflammation and frailty in the elderly: A systematic review and meta-analysis

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participants, both 1698 frail (SMD=1.00, 95%CI: 0.40-1.61) and 8568 pre-frail (SMD=0.33, 95%CI: 0.04-0.62) participants had significantly higher levels of C-reactive protein (CRP). Frailty (n=1057; SMD=1.12, 95%CI: 0.27-2.13) and pre-frailty (n=4467; SMD=0.56, 95%CI: 0.00-1.11) were associated with higher serum levels of interleukin-6 compared to people who were robust (n=2392). Frailty and pre-frailty were also significantly associated with elevated white blood cell and fibrinogen levels. In three longitudinal studies, higher serum CRP (OR=1.06, 95%CI: 0.78-1.44,) and IL-6 (OR=1.19, 95%CI: 0.87-1.62) were not associated with frailty. In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed.

Inflammatory cytokines and anorexia nervosa: A meta-analysis of cross-sectional and longitudinal studies

OBJECTIVE Although inflammation is increasingly implicated in psychiatric disorders, less is known about its role in anorexia nervosa (AN), an illness with low body mass index (BMI). METHODS We performed a systematic PubMed literature search until 12/31/2013 and meta-analyzed cross-sectional and longitudinal studies comparing circulating pro- and anti-inflammatory cytokines between patients with anorexia nervosa (AN) and healthy controls (HCs) (1) before and (2) after weight gain, and (3) within AN patients before and after weight gain. Standardized mean differences (SMDs)± 95% confidence intervals (CIs) for results from ≥ 2 studies were calculated. RESULTS Of 999 initial hits, 22 studies with 924 participants (AN=512, HCs=412) were eligible. Compared to HCs, tumor necrosis factor (TNF)-alpha (SMD=0.35, 95%CI=0.09-0.61, p=0.008), interleukin (IL)1-beta (SMD=0.51, 95%CI=0.18-0.84, p=0.003), IL-6 (SMD=0.43, 95%CI=0.11-0.76, p=0.009), and TNF-receptor-II (SMD=0.42, 95%CI:0.07-0.78, p=0.02) were significantly elevated in AN, while C-reactive protein (SMD=-0.53, 95%CI=-.77, -0.28, p<0.0001) and IL-6 receptor (SMD=-0.85, 95%CI=-1.33, -0.36, p=0.0006) were significantly decreased. No differences were found for TNF-receptor I and TGF-β. Across a subset of eight longitudinal studies (AN=152, HCs=129), significant weight gain (baseline BMI=15.4 ± 1.5, endpoint BMI=18.2 ± 1.6, p<0.0001) was not associated with significant changes in TNF-α, IL-6 and IL1-β. However, after weight gain, IL-6 was not different anymore compared to HCs (SMD=0.06, 95%CI=-0.32, 0.45, p=0.75). In meta-regression, shorter illness duration (p=0.0008), but not younger age (p=0.71) significantly moderated greater IL-6 levels. CONCLUSION Despite abnormally low BMI, AN seems to be associated with increased inflammatory cytokines. Whether specific elevated cytokines represent trait or state markers of AN, and whether they could be treatment targets requires further study.

Inverse relationship between body mass index and mortality in older nursing home residents: A meta-analysis of 19,538 elderly subjects

Body mass index (BMI) and mortality in old adults from the general population have been related in a U‐shaped or J‐shaped curve. However, limited information is available for elderly nursing home populations, particularly about specific cause of death. A systematic PubMed/EMBASE/CINAHL/SCOPUS search until 31 May 2014 without language restrictions was conducted. As no published study reported mortality in standard BMI groups (<18.5, 18.5–24.9, 25–29.9, ≥30 kg/m2), the most adjusted hazard ratios (HRs) according to a pre‐defined list of covariates were obtained from authors and pooled by random‐effect model across each BMI category. Out of 342 hits, 20 studies including 19,538 older nursing home residents with 5,223 deaths during a median of 2 years of follow‐up were meta‐analysed. Compared with normal weight, all‐cause mortality HRs were 1.41 (95% CI = 1.26–1.58) for underweight, 0.85 (95% CI = 0.73–0.99) for overweight and 0.74 (95% CI = 0.57–0.96) for obesity. Underweight was a risk factor for higher mortality caused by infections (HR = 1.65 [95% CI = 1.13–2.40]). RR results corroborated primary HR results, with additionally lower infection‐related mortality in overweight and obese than in normal‐weight individuals. Like in the general population, underweight is a risk factor for mortality in old nursing home residents. However, uniquely, not only overweight but also obesity is protective, which has relevant nutritional goal implications in this population/setting.

Exercise for depression in older adults: a meta-analysis of randomized controlled trials adjusting for publication bias

Objective: To evaluate the antidepressant effects of exercise in older adults, using randomized controlled trial (RCT) data. Methods: We conducted a meta-analysis of exercise in older adults, addressing limitations of previous works. RCTs of exercise interventions in older people with depression (≥ 60 years) comparing exercise vs. control were eligible. A random-effects meta-analysis calculating the standardized mean difference (SMD) (95% confidence interval [95%CI]), meta-regressions, and trim, fill, and fail-safe number analyses were conducted. Results: Eight RCTs were included, representing 138 participants in exercise arms and 129 controls. Exercise had a large and significant effect on depression (SMD = -0.90 [95%CI -0.29 to -1.51]), with a fail-safe number of 71 studies. Significant effects were found for 1) mixed aerobic and anaerobic interventions, 2) at moderate intensity, 3) that were group-based, 4) that utilized mixed supervised and unsupervised formats, and 5) in people without other clinical comorbidities. Conclusion: Adjusting for publication bias increased the beneficial effects of exercise in three subgroup analysis, suggesting that previous meta-analyses have underestimated the benefits of exercise due to publication bias. We advocate that exercise be considered as a routine component of the management of depression in older adults.OBJECTIVE To evaluate the antidepressant effects of exercise in older adults, using randomized controlled trial (RCT) data. METHODS We conducted a meta-analysis of exercise in older adults, addressing limitations of previous works. RCTs of exercise interventions in older people with depression (≥ 60 years) comparing exercise vs. control were eligible. A random-effects meta-analysis calculating the standardized mean difference (SMD) (95% confidence interval [95%CI]), meta-regressions, and trim, fill, and fail-safe number analyses were conducted. RESULTS Eight RCTs were included, representing 138 participants in exercise arms and 129 controls. Exercise had a large and significant effect on depression (SMD = -0.90 [95%CI -0.29 to -1.51]), with a fail-safe number of 71 studies. Significant effects were found for 1) mixed aerobic and anaerobic interventions, 2) at moderate intensity, 3) that were group-based, 4) that utilized mixed supervised and unsupervised formats, and 5) in people without other clinical comorbidities. CONCLUSION Adjusting for publication bias increased the beneficial effects of exercise in three subgroup analysis, suggesting that previous meta-analyses have underestimated the benefits of exercise due to publication bias. We advocate that exercise be considered as a routine component of the management of depression in older adults.

Relationship between depression and frailty in older adults: A systematic review and meta-analysis

AIM Depression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta- analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty. METHODS Two authors searched major electronic databases from inception until November-2016 for cross-sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders. RESULTS From 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07-47.10, I2=94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66-7.35, k=11), also after adjusting for potential confounders (OR=2.64; 95%CI: 1.59-4.37, I2=55%, k=4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00-55.30, I2=97%). People with depression were at increased odds of having frailty (OR=4.07, 95%CI 1.93-8.55, k=8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95-7.08, I2=98%, k=4), whilst in two studies frailty increased the risk of incident depression with an OR=1.90 (95%CI 1.55-2.32, I2=0%). CONCLUSION This meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted.

Inflammation and sarcopenia: A systematic review and meta-analysis

Inflammatory cytokines have been shown to prompt muscle wasting, ultimately stimulating protein catabolism and suppressing muscle synthesis. However, the possible association between inflammatory parameters and sarcopenia is poorly understood. We therefore aimed to summarize the current evidence about this topic with a meta-analysis of studies reporting serum inflammatory parameters in patients with sarcopenia vs. people without sarcopenia (controls). An electronic PubMed and Scopus search through to 09/01/2016 and meta-analysis of cross-sectional studies comparing serum levels of inflammatory cytokines between patients with sarcopenia and controls was made, calculating random-effects standardized mean differences (SMDs) ±95% confidence intervals (CIs) as the effect size. Out of 1370 initial hits, 17 studies with a total of 11249 participants (3072 with sarcopenia and 8177 without) were meta-analyzed. Sarcopenic participants had significantly higher levels of CRP (SMD=0.51; 95%CI 0.26, 0.77; p<0.0001; I2=96%) than controls. Conversely, serum IL6 levels were not significantly different (SMD=0.35; 95%CI: -0.19, 0.89; p=0.21; I2=97%) in people with sarcopenia versus controls. Sarcopenic people did not have higher levels of TNF-α than controls (SMD=0.28; 95%CI -0.26, 0.83; p=0.31; I2=97%). In conclusion, sarcopenia seems to be associated with elevated serum CRP levels; future longitudinal studies are needed to clarify this relationship.