We examined whether long QT syndrome (LQTS) mutation carrier status or symptomatic LQTS are associated with depression, and whether there are sex differences in these potential relationships. The sample comprised 782 participants (252 men). Of the 369 genetically defined LQTS mutation carriers, 169 were symptomatic and 200 were asymptomatic. The control group consisted of 413 unaffected relatives. Depression was assessed using the Beck Depression Inventory-II (BDI-II). No association was found for LQTS mutation carrier status with depression. The multinomial logistic regression showed that LQTS mutation carrier men with arrhythmic events scored higher on depression compared with the control group, even when adjusting for age, beta-blockers, antidepressants, and social support (OR = 1.09, 95 % CI [1.02, 1.15], p = .007). The binary logistic regression comparing symptomatic and asymptomatic LQTS mutation carriers showed that symptomatic LQTS was associated with depression in men (OR = 1.10, 95 % CI [1.03, 1.19], p = .009). The results were unchanged when additionally adjusted for education. These findings suggest that symptomatic LQTS is associated with depression in men but not in women. Overall, however, depression is more frequent in women than men. Thus, regular screening for depression in LQTS mutation carriers and their unaffected family members can be important.

Background Depression occurs about twice as often in women as in men, a disparity that remains poorly understood. In a previous publication, Hagen and Rosenstrom predicted and found that grip strength, a highly sexually dimorphic index of physical formidability, mediated much of the effect of sex on depression. Striking results like this are more likely to be published than null results, potentially biasing the scientific record. It is therefore critical to replicate and extend them. Methodology Using new data from the 2013-14 cycle of the National Health and Nutrition Examination Survey, a nationally representative sample of US households (n = 3650), we replicated models of the effect of sex and grip strength on depression reported in Hagen and Rosenstrom, along with additional potential confounds and a new detailed symptom-level exploration. Results Overall, the effects from the original paper were reproduced although with smaller effect sizes. Grip strength mediated 38% of the effect of sex on depression, compared to 63% in Hagen and Rosenstrom. These results were extended with findings that grip strength had a stronger association with some depression symptoms, like suicidality, low interest and low mood than with other symptoms, like appetite changes. Conclusions Grip strength is negatively associated with depression, especially its cognitive-affective symptoms, controlling for numerous possible confounds. Although many factors influence depression, few of these reliably occur cross-culturally in a sex-stratified manner and so are unlikely to explain the well-established, cross-cultural sex difference in depression. The sex difference in upper body strength occurs in all populations and is therefore a candidate evolutionary explanation for some of the sex difference in depression. Lay summary: Why are women at twice the risk of developing depression as men? Depression typically occurs during social conflicts, such as physical or sexual abuse. Physically strong individuals can often single-handedly resolve conflicts in their favor, whereas physically weaker individuals often need help from others. We argue that depression is a credible cry for help. Because men generally have greater strength than women, we argue that men may be more likely to resolve conflicts using physical formidability and women to signal others for help. We find that higher grip strength is associated with lower depression, particularly symptoms like feeling down or thoughts of suicide and that strength accounts for part of the sex difference in rates of depression.