Reproductive depression

Reproductive depression is the depression in women that is related to the hormonal changes of the menstrual cycle, pregnancy and the menopause and is manifested clinically as premenstrual depression, postnatal depression and climacteric depression. These three components occur in the same vulnerable women in that a woman with depression in the menopausal transition will usually have a history of premenstrual syndrome (PMS; premenstrual dysphoric disorder [PMDD]), would have been in a good mood during pregnancy and then develop postnatal depression. When the periods return the depression becomes cyclical as PMS. These three conditions are effectively treated with transdermal estrogens which should be the first-choice therapy rather than antidepressants. Estrogens can be used together with antidepressants. The critical time to prevent long-term mood problems is the correct treatment of postnatal depression. In women with low energy and libido, often a side effect of antidepressants, the addition of transdermal testosterone is useful. These women with reproductive depression are often progesterone/progestogen intolerant and a smaller dose or duration of progestogen is a necessary compromise. Alternatively a Mirena IUS or rarely a hysterectomy is required.     

Neurobiology of depression

Current treatments for depression are inadequate for many individuals, and progress in understanding the neurobiology of depression is slow. Several promising hypotheses of depression and antidepressant action have been formulated recently. These hypotheses are based largely on dysregulation of the hypothalamic-pituitary-adrenal axis and hippocampus and implicate corticotropin-releasing factor, glucocorticoids, brain-derived neurotrophic factor, and CREB. Recent work has looked beyond hippocampus to other brain areas that are also likely involved. For example, nucleus accumbens, amygdala, and certain hypothalamic nuclei are critical in regulating motivation, eating, sleeping, energy level, circadian rhythm, and responses to rewarding and aversive stimuli, which are all abnormal in depressed patients. A neurobiologic understanding of depression also requires identification of the genes that make individuals vulnerable or resistant to the syndrome. These advances will fundamentally improve the treatment and prevention of depression.     

Genetic biomarkers of depression

Depression is a term that has been used to describe a variety of ailments, ranging from minor to incapacitating. Clinically significant depression, termed as major depression, is a serious condition characterized not only by depressed mood but also by a cluster of somatic, cognitive, and motivational symptoms. Significant research efforts are aimed to understand the neurobiological as well as psychiatric disorders, and the evaluation of treatment of these disorders is still based solely on the assessment of symptoms. In order to identify the biological markers for depression, we have focused on gathering information on different factors responsible for depression including stress, genetic variations, neurotransmitters, and cytokines and chemokines previously suggested to be involved in the pathophysiology of depression. The present review illustrates the potential of biomarker profiling for psychiatric disorders, when conducted in large collections. The review highlighted the biomarker signatures for depression, warranting further investigation.     

Steroids and depression.

Patients with endogenous depression (major affective disorder) frequently have high cortisol levels, but the diurnal rhythm is usually maintained and they do not develop the physical signs of Cushing's syndrome. On the other hand, depression is a frequent feature of Cushing's syndrome regardless of etiology, and it is often relieved when the cortisol levels are reduced, by whatever means. The mechanisms of the hypercortisolemia and resistance to dexamethasone suppression commonly found in endogenous depression are poorly understood; contrary to expectations, ACTH levels are not clearly elevated. There is a striking difference in the psychiatric features seen in endogenous hypercorticism compared to those seen after exogenous administration of glucocorticoids or ACTH. This suggests that either there are other stimulating or modifying factors besides ACTH or that the steroids stimulated by ACTH or other peptides differ from those in control subjects, i.e. there may be an alteration in the metabolism of steroids in depression. Little is known about the metabolic changes or the many steroids besides glucocorticoids produced by the hyperactive steroid-producing tissue. Preliminary studies suggest that major depression may be improved by steroid suppression. It is hypothesized that steroids themselves may be important in causing and perpetuating depression.     

Gender differences in depression

Depression is twice as common in women as in men, although some concern has been raised in terms of misdiagnosing depression in men. The incidence of depression in women varies during the life span. The peak incidence during childbearing years appears to be associated with cyclic hormonal changes. Women also present with reproductive -specific mood disorders: pre-menstrual dysphoric disorder (PMDD), depression in pregnancy, postpartal mood disorder (PDD) and perimenopausal depressive disorder. Gender differences were repeatedly observed in response to antidepressant medication. Premenopausal women appear to respond poorly and to show low tolerability to TCAs, but they tend to show greater responsiveness to the SSRIs. In contrast, men and postmenopausal women can respond equally to the TCAs and SSRIs. These differences are contributed to gender differences in pharmacokinetics of antidepressants and to the influence of menstrual cycle. These findings suggest the need for a gender-specific approach to the evaluation and management of depression.