Not all depression is created equal: sex interacts with disease to precipitate depression

Christina L Nemeth, Constance S Harrell, Kevin D Beck, Gretchen N Neigh

Depression is a common mental disorder that co-occurs in other neurological and somatic diseases. Further, sex differences exist in the prevalence rates of many of these diseases, as well as within non-disease associated depression. In this review, the case is made for needing a better recognition of the source of the symptoms of depression with respect to the sex of the individual; in that, some disease states, which includes the neuroendocrine and immune reactions to the underlying pathophysiology of the disease, may initiate depressive symptoms more often in one sex over the other. The diseases specifically addressed to make this argument are: epilepsy, Alzheimer's disease, cancer, and cardiovascular disease. For each of these conditions, a review of the following are presented: prevalence rates of the conditions within each sex, prevalence rates of depressive symptoms within the conditions, identified relationships to gonadal hormones, and possible interactions between gonadal hormones, adrenal hormones, and immune signaling. Conclusions are drawn suggesting that an evaluation of the root causes for depressive symptoms in patients with these conditions is necessary, as the underlying mechanisms for eliciting the depressive symptoms may be qualitatively different across the four diseases discussed. This review attempts to identify and understand the mechanisms of depression associated with these diseases, in the context of the known sex differences in the disease prevalence and its age of onset. Hence, more extensive, sex-specific model systems are warranted that utilize these disease states to elicit depressive symptoms in order to create more focused, efficient, and sex-specific treatments for patients suffering from these diseases and concurrent depressive symptoms.