Impact of gender and genetics on emotion processing in Parkinson's disease - A multimodal study

Parkinson's disease (PD) has been suggested to affect males and females differently. Neuropsychiatric symptoms are common and disabling in PD. However, previous studies focusing on emotion recognition in PD have neglected the confounder of gender and lack evidence on the underlying endocrinal and genetic mechanisms. Moreover, while there are many imaging studies on emotion processing in PD, gender-related analyses of neural data are scarce. We therefore aimed at exploring the interplay of the named factors on emotion recognition and processing in PD. 51 non-demented PD patients (26 male) and 44 age- and gender-matched healthy controls (HC; 25 male) were examined clinically and neuropsychologically including an emotion recognition task (Ekman 60faces test). A subsample of 25 patients and 31 HC underwent task-based functional magnetic resonance imaging (fMRI) comprised of videos of emotional facial expressions. To examine the impact of hormones and genetics on emotion processing, blood samples were taken for endocrinal (testosterone, estradiol, progesterone) and genetic testing (5-HTTLPR, Val158Met COMT polymorphisms). No group or gender differences emerged regarding cognitive abilities. Male but not female PD patients exhibited confined impairments in recognizing the emotion anger accompanied by diminished neural response to facial expressions (e.g. in the putamen and insula). Endocrinologically, fear recognition was positively correlated with estrogen levels in female patients, while on the genetic level we found an effect of Val158Met COMT genotype on the recognition of fear in PD patients. Our study provides evidence that impaired emotion processing in PD specifically affects male patients, and that hormones and genetics contribute to emotion recognition performance. Further research on the underlying neural, endocrinological and genetic mechanisms of specific symptoms in PD is of clinical relevance, as it can improve our understanding of the phenomenology and pathobiology of the disease and may allow a more personalized medicine. •Understanding of the phenotypic heterogeneity of Parkinson's disease is needed.•Gender and genetics determine manifestation and progression of Parkinson's disease.•Altered emotion processing in Parkinson's disease is specific to male patients.•This is influenced by endocrinal and genetic factors in both genders.•This finding may impact the diagnosis and treatment of emerging clinical features.