Bianca Lever Van Milligen

The sample consisted of almost 60000 cases without a psychiatric history with a mean age of 49 years. The IDA group had a subsequent increased risk of psychiatric disorders, including depression and anxiety disorders, compared to the non-IDA group after adjustment of sociodemographic and somatic comorbidity during 13 years of follow-up. The sample size could play a role in the different results of our study and this large Taiwanese study, as well as their longitudinal design.

Earlier research was mostly focused on low hemoglobin level in relation to depression and anxiety. In our research, however, we also showed an association between high hemoglobin level and depressive and anxiety disorders. After adjustment for lifestyle and health factors, this relationship became non-significant. Especially smoking seems to be an important factor explaining this association. It has been shown that active smokers have higher hemoglobin levels and that these higher levels are reversible by quitting smoking in persons without somatic diseases [4]. Smoking leads to the production of more red blood cells due to the disastrous effects of carbon monoxide of cigarettes, which hinder oxygen uptake. The increased production of red blood cells compensates these effects and leads to increased hemoglobin level. So, the higher hemoglobin levels in depressed or anxious persons could be largely explained by their higher smoking patterns as compared to healthy controls.

In all, since our conducted study on hemoglobin and depressive and anxiety disorders in 2014, there have been several new initiatives to examine the extent to which low (or high) hemoglobin is linked to depressive and anxiety disorders. In contrast to our results, there are some indications for more anemia among those with depressive or anxiety disorders, which seems independent of lifestyle and sociodemographic covariates. Understanding this association requires further research.

Hand grip strength and lung function

Poorer objective physical function, both hand grip strength and lung function, was found in depressed women compared to healthy women (Chapter 3), which is in line with findings from other studies [5–9]. Following this, depressed and anxious women are more likely to be physically disabled and have higher mortality rates compared to healthy women [10, 11]. These findings of poorer objective physical function in depressed and anxious persons were confirmed in Chapter 4 and 5 describing longitudinal results (see table 8.1). In Chapter 4 we showed that both hand grip strength and lung function predicted the persistence of depressive and/or anxiety disorders after two years of follow-up. In Chapter 5 we showed that during six years of follow-up, physical function remained poorer over time in women with depressive and anxiety disorders compared to healthy control women. However, physical function did not decrease faster over time in current and remitted depressive and anxious women than healthy women. These findings have been found before in the literature on older persons, but our research adds to this knowledge by showing that poorer physical function is already found in younger, middle-aged women. So, impairment of physical function seems to start early in life when persons have affective disorders.

The association between objective physical function and depressive and anxiety disorders in men shows a different pattern than that found in women. Our cross-sectional results show higher lung function in depressed and anxious men compared to healthy men (Chapter 3) while hand grip strength was comparable for both groups. Our longitudinal results show that both hand grip strength and lung function predicted the persistence of depressive and/or anxiety disorders after two years of follow-up in men (Chapter 4) and show that men with depressive and anxiety disorders had higher decline of lung function over time during six years of follow-up compared to healthy men while again no differences were found in hand grip strength (Chapter 5). Consequently, the findings of hand grip strength and lung function are not as consistent in men and were therefore weaker and different compared to the findings in women.

Thus, the association between depression, anxiety and poorer physical function was most consistently present in women, but inconsistent in men. A partial plausible explanation could be a sex-differential pathophysiology of depression and anxiety, potentially partly because of hormonal differences across sex [12]. Indeed, sex hormone differences are quite large, and testosterone is known to have a promoting impact on physical function, such as through direct promotion of muscle growth and strength [13]. As confirmed by our findings, men have higher muscle strength and lung function as compared to women. Maybe at a relative young adult age, the stronger physical function in men prevents a potential impact of mental health conditions to be visible on more objective assessments of physical function.

Although sex-differential hormonal influences may provide an explanation, questions remain about the observed sex differences. Is there truly no relationship between hand grip strength and psychiatric status in men? Are the performance measurements that we used not accurately enough to show differences? Did we perhaps face a ceiling effect in men? Or are there simply no differences in men in objective physical function between those men with and without depressive or anxiety disorders? The