Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews

Mentis, Alexios‐Fotios A.; Dardiotis, Efthimios; Efthymiou, Vasiliki; Chrousos, George P.

doi:10.1186/s12916-020-01873-7

Cited by 36 publications

(32 citation statements)

References 221 publications

(334 reference statements)

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“…Studies excluded were: a) systematic reviews or meta-analyses other than umbrella reviews, individual studies (including Mendelian randomization studies and randomized controlled trials), clinical cases, conference proceedings, and study protocols; b) umbrella reviews not reporting quantitative data; c) umbrella reviews addressing outcomes other than the onset of an established mental disorder (e.g., those related to clinical outcomes such as relapse, remission or treatment response 15,23 , or biomarkers); d) umbrella reviews employing other classification approaches, such as GRADE 25 , because these mostly apply to interventional effects, not aetiology 26 .…”

Section: Search Strategy and Selection Criteriamentioning

confidence: 99%

“…We present here the first systematic synthesis of umbrella reviews of non‐purely genetic risk and protective factors for mental disorders. This approach has been termed “meta‐umbrella” and offers an overarching field‐wide overview to comprehensively assess a certain topic 23 . Our aims were to provide an evidence‐synthesis comparative atlas of the consistency and magnitude of risk and protective factors for mental disorders beyond genetics, and to formulate recommendations for the next generation of aetiopathological research and preventive psychiatry.…”

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confidence: 99%

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Risk and protective factors for mental disorders beyond genetics: an evidence‐based atlas

et al. 2021

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Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer tain. We conducted a "metaumbrella" systematic synthesis of umbrella reviews, which are systematic reviews of metaanalyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on nonpurely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convinc ing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of metaanalyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 metaanalyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social con tacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For nonorganic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or fourfive (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention deficit/hyperactivity disorder (ADHD), they were maternal prepregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer's disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class IIII risk/protective factors were mostly involved in the early neurodevelopmental period. The evidencebased atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expand ing early intervention and preventive strategies for mental disorders.

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Section: Search Strategy and Selection Criteriamentioning

confidence: 99%

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confidence: 99%

Risk and protective factors for mental disorders beyond genetics: an evidence‐based atlas

et al. 2021

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“…While the T allele is a ”risk allele” for neurodegeneration, it may also be a ”risk allele” for smoking, at least in healthy individuals. Given that smoking increases dementia risk [ 98 ], BDNF rs56164415 polymorphism may have moderating or additive effects, which deserves future studies.…”

Section: Discussionmentioning

confidence: 99%

Moderating Effects of BDNF Genetic Variants and Smoking on Cognition in PTSD Veterans

et al. 2021

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Posttraumatic stress disorder (PTSD) is frequently associated with cognitive disturbances and high prevalence of smoking. This study evaluated cognition in war veterans with PTSD and control subjects, controlled for the effect of smoking and brain derived neurotrophic factor (BDNF) rs6265 and rs56164415 genotypes/alleles. Study included 643 male war veterans with combat related PTSD and 120 healthy controls. Genotyping was done by real time PCR. Cognitive disturbances were evaluated using the Positive and Negative Syndrome Scale (PANSS) cognition subscale and the Rey-Osterrieth Complex Figure (ROCF) test scores. Diagnosis (p < 0.001), BDNF rs56164415 (p = 0.011) and smoking (p = 0.028) were significant predictors of the cognitive decline in subjects with PTSD. BDNF rs56164415 T alleles were more frequently found in subjects with PTSD, smokers and non-smokers, with impaired cognition, i.e., with the higher PANSS cognition subscale scores and with the lower ROCF immediate recall test scores. Presence of one or two BDNF rs56164415 T alleles was related to cognitive decline in PTSD. The T allele carriers with PTSD had advanced cognitive deterioration in smokers and nonsmokers with PTSD, and worse short-term visual memory function. Our findings emphasize the role of the BDNF rs56164415 T allele and smoking in cognitive dysfunction in war veterans with PTSD.

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“…Furthermore, the internalization of UA crystals by leukocytes leads to production of free radicals, release of cathepsin B and activation of inflammasome (37,38). Interestingly, higher SUA levels have been hypothesized to play a protective role in the development of some neurological disorders such as dementia, multiple sclerosis, Alzheimer's disease and Parkinson's disease (39)(40)(41)(42). In a recent metaanalysis involving 5,575 participants, Zhou et al demonstrated a significant inverse association between SUA and Alzheimer's disease or Parkinson's disease (43).…”

Section: Uric Acid As Protective Factormentioning

confidence: 99%

Hyperuricemia in Psoriatic Arthritis: Epidemiology, Pathophysiology, and Clinical Implications

et al. 2021

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Psoriatic arthritis (PsA) represents the articular component of the systemic psoriatic disease and the extra-cutaneous disorder most frequently found in patients with psoriasis. Besides the articular involvement, PsA is associated with several metabolic abnormalities such as insulin resistance, hypertension, diabetes and hyperuricemia. Uric acid is the final product of purine metabolism and the etiological substrate of gout. Accumulating evidence highlights the emerging role of hyperuricemia as a major cardiovascular risk factor. Moreover, different studies evaluated the interplay between hyperuricemia and psoriatic disease, suggesting that individuals affected by psoriasis or PsA might present higher serum levels of uric acid and that hyperuricemia might affect severity of clinical manifestations and degree of inflammation in PsA patients. In this review, we focus on the bidirectional relationship between uric acid and PsA, analyzing how uric acid may be involved in the pathogenesis of psoriasis/PsA and how clinical manifestations of PsA and inflammatory mediators are affected by uric acid concentrations. Finally, the effects of anti-rheumatic drugs on uric acid levels and the potential benefit of urate-lowering therapies on psoriasis and PsA were summarized.

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Non-genetic risk and protective factors and biomarkers for neurological disorders: a meta-umbrella systematic review of umbrella reviews

Cited by 36 publications

References 221 publications

Risk and protective factors for mental disorders beyond genetics: an evidence‐based atlas

Risk and protective factors for mental disorders beyond genetics: an evidence‐based atlas

Moderating Effects of BDNF Genetic Variants and Smoking on Cognition in PTSD Veterans

Hyperuricemia in Psoriatic Arthritis: Epidemiology, Pathophysiology, and Clinical Implications

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