Screening for disease and estimating disease risk using biomarkers such as cholesterol or blood pressure have formed a routine part of healthcare for over 50 years 1 . The term mass screening is often used when screening involves the examination of large populations or cohorts. The emotional impact of such screening was largely unquestioned until the publication of a paper presenting evidence of increased absenteeism following the detection of hypertension 2 . Since then there have been numerous reports of the emotional impact of screening upon anxiety, depression, intrusive and troubling thoughts, and, amongst children, absence from school and behavioural disturbance 3 4 .

Screening is a complex event involving those targeted in a range of possible outcomes: awareness of screening; receipt of an invitation; undergoing a screening test; receiving a test result and concern regarding the test result (anxiety over a possible diagnosis as well as potential concern over false positive or false negative results). Awareness of screening appears not to induce emotional distress 5 . Receipt of an invitation for screening may, however, precipitate emotional distress 6 although this is not always the case 7 . More uncertainty and concern exist about the emotional impact of the latter two stages. Individuals can react with concern, anxiety and even depression when informed that they have an elevated risk of developing a disease 8 . While some emotional distress may be helpful, too much can be debilitating 9 . Not only can distress reduce individuals' quality of life, it can also interfere with information processing 10 and hence the ability to be reassured or to make informed choices regarding future treatment options. Emotional distress can also result in people avoiding future surveillance 11 12 13 .

Existing reviews of the emotional impact of screening report few adverse effects on generalised and specific anxiety, depression or quality of life 3 14 15 16 17 . Whilst some studies report an increase in immediate emotional distress, few report distress that is sustained in the longer term. Furthermore, between-group analyses reveal few enduring effects of being identified as having an elevated risk of disease. For example, a meta- analysis assessing standardised differences between those receiving positive compared with negative test results revealed increased anxiety and depression within the first four weeks of receiving test results but no difference after four weeks 3 . These findings stand in contrast to a widespread belief amongst healthcare providers that screening for risk of disease has adverse emotional consequences 18 19 .

The evidence from these reviews is, however, limited in two ways. First, only a minority included randomised controlled trials (RCTs) 3 15 and none restricted inclusion to RCTs, thereby limiting the ability to infer a causal connection between screening and emotional outcomes. Second, the dominant comparisons reported are non-randomised comparisons within screened groups, i.e. between those receiving test results indicating an elevated risk of disease (screen positive) and those receiving test results indicating no elevated risk (screen negative). While such comparisons are important for being able to assess and, where necessary, attempt to prevent excess distress, they do not address the question of interest from a population health perspective, namely, whether screening causes distress in populations invited and participating in screening programmes. Estimating this with precision requires comparisons between those randomised to undergo screening and those randomised not to undergo screening. We report here the first such meta-analytic comparison using data from randomised controlled trials.

The primary aim of this review is to estimate the immediate and longer term emotional impact of undergoing screening or risk assessment for disease. To improve upon existing reviews, we include only randomised controlled trials in which a principal analysis reports emotional outcomes of the randomised groups, i.e. trials where it is possible to compare emotional outcomes in those randomised to undergo screening or risk assessment with those randomised not to undergo such testing. The secondary aim is to estimate the emotional impact of receiving an elevated risk (screen positive) test result, by comparing outcomes of this subgroup with those receiving a non-elevated or average risk test result.

We found no evidence that undergoing screening has an adverse emotional impact when assessed four or more weeks after screening. Too few studies assessed outcomes before four weeks to comment on the shorter term emotional impact of screening. Subgroup comparisons between those receiving positive and those receiving negative test results reveal a small, transient impact of being informed of an elevated risk of disease, discernible on depression.

These findings are consistent with psychological theories of self-regulation which describe the complex ways in which humans maintain emotional equilibrium while managing threats 42 . Managing threats in the current context includes engaging in behaviours to reduce threats to health, as well as using cognitive strategies to minimise the severity or likelihood of the threat. Both of these can reduce emotional distress. Emotional distress is a common and adaptive initial response to risk notification, but, as replicated in the current review, this has usually dissipated by one month 3 . These findings also reflect those from existing, but disparate and methodologically less robust reviews, which have focused on screening for inherited or genetic conditions 14 15 16 43 44 . Only one previous review has assessed the impact of screening for a broader range of conditions 3 .

The strength of our review is that it is the first systematic review with meta- analysis involving comparisons of emotional outcomes assessed in RCTs. The findings are therefore more robust than those from existing reviews. The findings of the review may, however, reflect some bias evident in the conduct of the reviewed studies. This includes bias from sampling as well as from the measures used. Only half of the studies reported outcomes on 80% or more of participants. Consequently, pooled comparisons often contain a small number of studies. Examination of follow-up between randomised arms, however, revealed similar levels of attrition between screened and not-screened groups. Of concern is that those lost to follow-up may have been those who experienced higher levels of distress than those who remained in the studies, for which there is some evidence 12 45 . The studies also varied in the populations sampled in the intervention arm. In some trials, this included attenders and non-attenders 26 27 and in others, only attenders 21 22 25 26 27 28 29 30 33 34 . The measures used to assess emotional outcomes may have been inappropriate or insufficiently sensitive to detect adverse emotional outcomes. All the included studies used standardised measures of generalised emotional functioning. Such measures are not designed to detect subtle changes, such as worry about health, that do not affect general mood states. The claims that can be made from the current review therefore concern general levels of functioning and not more subtle impacts of screening on worries specifically related to health.

The review was also limited by the relatively large heterogeneity of the included studies, as reflected in the I² scores (Figure 2), particularly those above 50%. The studies varied greatly in the demographic characteristics of participants, the diseases for which screening was being undertaken as well as the processes of screening. Pooled comparisons combined studies screening for disparate disease types which may have impacted on the findings. Sensitivity analysis revealed no differences in overall results by disease type with the exception of mental quality of life between screened versus non screened groups. Future reviews might consider the impact of disease specific factors such as prevalence and severity, and test specific factors such as sensitivity and specificity factors on emotional responses. One of the studies included was tailored specifically for smokers 33 , a further two involved multiple screening procedures 31 32 , one of which involved screening for the risk of several diseases 31 . The studies are likely to have varied in the information provided and support offered to participants, but insufficient detail was provided to allow subgroup analysis on this in the current review. Existing evidence suggests this is likely to have affected emotional responses, particularly in the short-term 46 47 48 49 50 .

The results of this review reduce uncertainty about emotional outcomes and suggest that, provided other criteria for screening are met 51 , there are few if any grounds for not screening on the basis that it has adverse longer term emotional outcomes.

("Genetic Screening"[Majr] OR "Mass Screening"[Majr] OR "Risk Assessment"[Majr] OR ((cancer OR diabetes OR heart OR cardiac OR cardioavasc* OR AIDS OR HIV OR osteoporosis OR Huntington*) AND screen*)) AND (emotion* OR anxiety OR distress* OR depression OR mood or anger or GHQ OR K10 OR (quality of life)) NOT (fetal distress OR postpartum depression OR prenatal OR newborn OR maternal) NOT decision aid*[ti] NOT intervention*[ti] AND ((Randomized Controlled Trial[ptyp]).

All authors have completed the Unified Competing Interest form and declare that all authors (REC, LML & TMM) have no financial interests that may be relevant to the submitted work.

TMM has had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Writing the protocol: TMM, REC. Developing the search strategy: LML & TMM. Searching for trials: LML, REC. Selecting trials: TMM, REC. Data entry: REC. Analysis: REC. Interpreting analysis: TMM, REC, LML. Drafting final review: All.