GENDER DIFFERENCES IN THE STRESS RESPONSE OF PATIENTS WITH ATOPIC DERMATITIS, ALOPECIA AREATA, AND PREMENSTRUAL DYSPHORIC DISORDER AS OBSERVED BY TRANSLOCATOR PROTEIN 18 KDA (TSPO) 0

Abstract It has been shown that translocator protein 18 kDa (TSPO), which is involved in the production of steroid hormones, is increased under acute stress and decreased under chronic stressful conditions. In our previous studies, expression of TSPO on platelets was significantly correlated with trait anxiety rather than state anxiety in normal human subjects, possibly reflecting an individual’ s sensitivity to stress. Males were more sensitive than females in these stress responses. In clinical studies, association between stress level and severity of symptoms has been reported. The present study was designed to address this issue in dermatology and psychiatry patients based on our previous observation. In atopic dermatitis (AD), 52 patients (30 males, 22 females) and 163 healthy volunteers (89 males, 74 females) participated in this study. State-Trait Anxiety inventory (STAI) scores were significantly higher in patients with AD, especially male patients than in healthy subjects. The expression of platelet TSPO, as determined with a binding assay with [3H]PK11195, was also significantly higher in patients with AD, indicating that AD is a stress-responsive disease. In genomic analysis using lymphocytes, a single nucleotide polymorphism of the human TSPO gene at exon 4 (485G>A), which is presumably associated with an individual’ s stress sensitivity, showed significantly lower frequencies of G/G and higher frequencies of G/A in patients with AD than in healthy subjects. The severity of AD, as determined with the Scoring of Atopic Dermatitis Index, was correlated with TSPO expression in male patients with the G/A phenotype. The results provide new evidence that variation in the TSPO gene affects susceptibility to AD. In contrast, alopecia areata (AA) patients (20 males, 30 females) showed lower TSPO densities, particularly in females, despite higher anxiety scores. But the severity of AA, which was determined as six degrees (S0-S5) by the method of Olsen E et al (1999), was significantly correlated with the density of the TSPO (p<0.01) in AA patients. Psoriasis (42 males, 9 females) was apparently not related to the stress. The results suggest that both AD and AA patients are in a state of stress, whereas the stress responses are impaired in female AA patients with unknown mechanisms. In psychiatry studies, premenstrual dysphoric disorder (PMDD) patients (diagnosed by DSM-Ⅳ) showed significantly higher trait (p<0.001) and state (p<0.05) anxiety scores as compared with normal female control. In addition, despite these high anxiety levels, plasma cortisol was significantly (p<0.05) reduced by nearly 30% and platelet TSPO were reduced to some extent in PMDD patients. It is concluded that stress responses as examined by TSPO do not necessarily reflect anxiety levels in female, rather than in male. These discrepancies between mental and physical responses to stress may be related with the pathogenesis of PMDD.