Generalized anxiety disorder is one of the most common psychiatric disorders, affecting a high percentage of human beings around the world. This emotional disorder possesses marked gender differences and occurs more often in women than in men, in a proportion of 2:1. Accompanying the reproductive cycle of women are significant fluctuations in plasma and brain steroid hormone concentrations, including oestradiol, progesterone, and allopregnanolone, among others. These hormonal changes are related to some illnesses and with the development of anxiety and mood swings occurring in the premenstrual and postpartum period, and particularly during the menopause. Menopause is a clinical term used to indicate the cessation of the woman's reproductive ability that occurs naturally, but also may be surgically induced by bilateral oophorectomy, with or without the removal of the Fallopian tubes and uterus. Natural menopause includes specific periods related to the physiological and hormonal changes produced by ovarian failure, it is usually a natural stage that occurs to women in midlife, during their late 40s or early 50s, indicating the end of the reproductive period in the woman. During the menopause transition years, women experience changes in the production of ovarian hormones, which are associated with significant changes in the physiological, emotional, and affective processes. Unfortunately, surgical menopause occurs at an early age, and produces similar physiological and psychiatric disorders, but they are more severe in this instance. In both cases, typical symptoms associated with menopause critically deteriorate the mental health of the women. In this way, the therapeutic management of clinical symptoms of menopause include replacement hormone therapy, the use of anxiolytic and antidepressant drugs, and other natural alternatives based on the use of chemical compounds obtained from plants such as soya. However, a general effective treatment for menopause symptoms does not yet exist. For this reason, experimental studies have proposed ovariectomy in rats as a potential tool to study the effects of a long-term absence of ovarian hormones associated with surgical menopause, which also allowed the study of substances with potential therapeutic application to ameliorate typical symptoms associated with surgical menopause. The aim of this chapter is to review the participation of ovarian hormones in the regulation of emotional and affective disorders in women with natural or surgical menopause; particularly their anatomical pathways, neurotransmission systems, and the resulting behavioural patterns. Finally, preclinical and clinical research suggested that long-term absence of ovarian hormones associated with natural or surgical menopause is the principal cause of physiological and psychiatric disorder in the women; therefore, oestrogenic compounds seem to play an important role in the maintenance of the brain structures that regulate anxiety, mood, memory, and cognitive functions in menopausal women.
Part of the book: A Fresh Look at Anxiety Disorders
Serotonin or 5-hydroxytryptamine (5-HT) is synthesized in both the brain and peripheral system, which exert their actions at a wide family of receptors classified as 5-HT1 to 5-HT7. Pharmacological, behavioral, and clinical studies involve particularly to the 5-HT1A receptors (5-HT1A-R) - auto-receptors (presynaptic) and heteroreceptors (postsynaptic) - in the control of motivated behavior, and consequently in the physiopathology of affective disorders and in the action mechanism of antidepressant drugs. In this way, some research support that 5-HT1A-R participates in the delayed effect of different types of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), and tricyclic drugs, principally. The therapeutic effect of serotonergic drugs as the SSRIs, starting with the binding to auto-receptors, which produces increases of 5-HT in the synaptic cleft as consequence of blockade of serotonin reuptake. While these molecular events occur initially, in the long-term are produced plastic changes at neuronal level, as well as down-regulation of the 5-HT1A-R, which is associated with the therapeutic effects of antidepressant drugs. The purpose of this chapter is to analyze and discuss the current information about of 5-HT1A-R-mediated signaling cascades, the intracellular signaling of 5-HT1A-R, in addition to their expression and pharmacology that are important to treatment of affective disorders symptoms.
Part of the book: Serotonin
Depression is a psychiatric disorder that affects a high percentage of women. Most of the depression disorders turn up during the premenopause and perimenopause stages when the hormonal oscillations make an impact in the brain function principally on the serotonergic system, which is related to neurobiology of depression. 5-HT1A and 5-HT2A receptors change on functionality and density in afferent areas related to emotional modulation and increased serotonin clearance, and the binding potential of serotonin transport has been related to the underlying mechanism of the depression during the climacteric or postmenopausal stage. Some findings have been proven on preclinical studies. These studies on animals have recognized how estrogen treatment activates intracellular signaling pathways as mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK), tyrosine kinase brain-derived neurotrophic factor receptor (TrKB), insulin-like growth factor-1 receptor (IGF-1R), phosphatidylinositol 3-kinase (PI3)/serine/threonine-specific protein kinase (Akt), and metabotropic glutamate receptor 1 (mGluR1) which interact with the serotonergic system to allow establishment of the estradiol effects on mood regulation. Thus, the interaction between the woman’s reproductive status and the serotonin changes could be useful to create prevention strategies, early diagnosis, and medical treatment of climacteric and postmenopausal women with depression, in order to improve their quality of life.
Part of the book: Menopause
Depression and anxiety currently rank as the second and fifth most common causes worldwide of years lived with disability-a reality that has intensified the search for new treatments. There are many studies of herbal extracts and secondary metabolites from plants used in traditional medicine due to their antidepressant and anxiolytic properties. Clinical and preclinical studies about some of the mechanisms of action of metabolites like alkaloids, terpenes, flavonoids, and sterols, among others, have documented effects similar to those produced by clinically effective drugs. These metabolites have shown anxiolytic and antidepressant effects in various experimental models of anxiety by interacting with γ-aminobutyric acid subtype A receptors (GABAA-receptors) and by stimulating the serotonergic, noradrenergic, and dopaminergic neurotransmitter systems. These pharmacological effects can be attributed to plant metabolites that share structural similarities with monoamines, which allow them to bind to receptors. The objective of this chapter is to summarize the various mechanisms of action that have been identified in secondary metabolites with anxiolytic and antidepressant properties. Terpenes, alkaloids, flavonoids, and sterols can interact at different levels of the neurotransmission systems involved in the neurobiology of anxiety and depression, suggesting their potential for treating these mental illnesses.
Part of the book: Behavioral Pharmacology