A link between anxiety and disfunctions of the Hypotalamic-pituitary-adrenal (HPA) axis has been widely reported in both normal and pathological anxiety, but research findings are controversial.

To explore gender differences in the relationships between cortisol and neurosteroids and subthreshold anxiety dimensions.

To investigate the possible correlations between serum cortisol and dehydroepiandrosterone sulphate (DHEA-S) levels, or DHEA-S/cortisol ratio, and the subthreshold panic dimensions in a sample of healthy subjects.

Forty-two Italian civilians, without current or lifetime psychiatry disorders, were recruited and assessed by means of the Structured Clinical Interview for DSM-IV (SCID-I/P) and a specific questionnaire, the so-called Panic Agoraphobic Spectrum-Self Report lifetime version (PAS-SR), for assessing subthreshold panic-agoraphobic dimensions.

The results showed the presence of significant negative correlations between the cortisol levels and the total scores of the PAS-SR and of the following domains: separation sensitivity, panic like symptoms and medication/substance sensitivity. The PAS-SR total and the panic-like symptoms domain scores were related positively to the DHEAS/cortisol ratio. When the sample was distinguished in women and men, it turned out that this correlations were present only in women.

This findings would indicate that cortisol levels are related to subthreshold panic-agoraphobic symptoms, with a gender specificity. Therefore, further studies are needed to investigate those subthreshold conditions in order to indentify possible gender differences that may account for phenotypes at higher risk for psychiatric disorders.