We assessed coping and vegetative reactivity in patients with uveal melanoma (UM) and controls. These aspects are important because they can reveal psychosocial dimensions of disease and because they can potentially be targeted using behavioral approaches. Coping is considered a habitual personality trait that is constant over time and unresponsive to acute stress [
22]. Researchers have previously found that maladaptive coping is associated with faster glaucoma progression [
23] and is more prevalent in patients with HLA-B27-associated acute anterior uveitis [
24] and dry eye disease [
25]. In our investigation, coping was evaluated using an established questionnaire that assesses positive and maladaptive strategies. We found no coping-related differences between UM patients and controls. This was unexpected, because previous studies revealed significant differences in coping between cutaneous melanoma (CM) patients and healthy controls: Trapp et al. showed that patients with CM use negative coping mechanisms more often compared to controls with benign dermatological disease and that the risk for CM with an initial thickness over 1 mm decreases in patients with positive coping strategies [
16]. Furthermore, certain lymphocyte subpopulations showed positive correlations with negative coping strategies in CM patients, but were negatively correlated with healthy controls and their positive coping mechanisms [
14]. Finally, positive coping styles were associated with both good psychosocial adjustment [
13] and better outcomes [
10].
Sufficient heart rate variability (HRV) is a desirable state in healthy individuals because it reflects parasympathetic (vagal) activity. The HRV decreases when the sympathetic system is activated due to stress. As the LF component of HRV is mainly associated with sympathetic activity and the HF component with parasympathetic activity, the LF/HF ratio is a measure of the balance between both systems [
20]. Contrary to HRV, blood pressure variability (BPV) is associated with increased cardiovascular risk [
26,
27]. The LF or LFnu component of BPV is mainly associated with sympathetic activity [
21]. We opted to analyze BPV in addition to HRV, because HRV alone has been critically discussed as a marker for sympathetic activity [
28,
29]. The LF/HF ratio of HRV showed increasing values throughout the measurement sequence in controls (increase of the sympathetic influence during the DT), but decreasing values in the UM group (unexpected decrease of the sympathetic influence during the DT). Similarly, the sympathetic influence on diastolic BPV increased in controls during activation (expressed as an increase of the LFnu component), but decreased in the UM group when mental stress was induced (decrease of the LFnu component). Our data therefore indicate a different pattern of sympathetic activity in UM patients compared to controls. This altered pattern could either be related to cancer pathogenesis (such as in CM) or the result of anxiety related to recent UM diagnosis. Because maladaptive coping (as an indicator of chronic vegetative dysfunction) was not relevant in our patients, we believe that the observed patterns may be interpreted as anxiety related to a life-altering diagnosis, although this is speculative. Heart rate variability has previously been explored in CM research and similar patterns were observed: Compared to healthy controls, patients with atypical cutaneous nevi showed higher questionnaire-based scores for mental tension and higher vegetative arousal after a paper–pencil-based stress test [
15]. Furthermore, CM patients exhibited altered cytokine profiles and higher interleukin‑6 (a cytokine associated with stress) levels compared to healthy controls in response to the Determination Test [
11]. Moreover, HRV is significantly reduced not only in various cancer types compared to healthy controls, but also in patients with metastases compared to non-metastatic patients [
30]. A systematic meta-analysis previously reported that high HRV improves the survival in cancer patients with different etiologies [
31]. Furthermore, it was revealed that patients with prostate and non-small lung cancer with low HRV show higher tumor marker levels compared to patients with high HRV [
32].