Anxious-depressive comorbidity: effects on HPA axis and CNS noradrenergic functions

Psychiatric comorbidity is all too common. An important example is the high comorbidity frequency of depressive and anxiety disorders, 25%-50%, much higher than the 5% or less expected by chance. Possible reasons for this comorbidity include definitional, environmental, and biological factors. Few previous studies have assessed, with proper methodology, potential biological changes associated with this co-occurrence. We assessed both hypothalamic-pituitary-adrenocortical axis (HPA) responses to the Trier Social Stress Test and growth hormone (GH) responses to clonidine, a centrally active alpha-2 adrenoreceptor agonist, in 15 persons with major depression without anxiety, 15 with an anxiety disorder without depression, 18 comorbid for anxiety and depression, and 48 individually matched control subjects. Individuals with depression only were normal on both tests, while those with anxiety only had normal HPA responses but blunted GH responses. Comorbid individuals showed elevated HPA responses and only those comorbid persons with anxiety symptoms predominant also showed blunted GH responses. Controls and anxiety-only subjects showed significant correlations between the results of the two tests. This association was disrupted by the presence of depression with or without comorbidity. Comorbidity is fundamental to understanding the pathophysiologies of depression and anxiety.