Gonadal hormones and antihormones, serotonin and mood

Gonadal hormones influence activity of several monoaminergic neurotransmitters, and this might be one of the mechanisms by which these hormones are involved in modulation of behavior. Gonadal hormones' levels and mood fluctuate along the normal menstrual cycle; therefore, this might provide a model for the study of the interaction among hormones, mood, and other biochemical variables. The administration of gonadal hormones' antagonists ("antihormones") and the study of their central nervous system (CNS) and behavioral consequences may further elucidate hormonal-neurotransmitter interaction. We have studied several aspects of the serotonergic system along the menstrual cycle. Results show that imipramine receptor-binding in platelets is decreased in women with premenstrual dysphoric changes in the early luteal phase, 5 to 7 days before development of symptoms and shortly after the substantial periovulatory changes in gonadal hormones. The cortisol and prolactin responses to tryptophan were blunted during the late luteal phase compared with the midfollicular phase, and the cortisol, but not prolactin, responses to the serotonergic agonist 1-(m-chlorophenyl) piperazine, (mCPP) was also blunted during that period. An altered postsynaptic serotonergic responsivity might be suggested in these cases. The role of ovulation and gonadal hormones is further demonstrated by the elimination of dysphoric symptoms by the ovulation suppressant danazol.     

Women's mental health in the Muslim world: cultural, religious, and social issues

In Arab communities, several cultural factors, derived mainly from the subordinate position of women, have been shown to affect the prevalence, clinical picture, health seeking behaviour, course and management of psychopathology in women. Women are definitely at a greater risk of developing mental disorders such as depressive, somatoform, anxious or eating disorders, as well as suicidal behaviors. Furthermore, mentally ill women are more stigmatized, have less access to care and suffer from a worse social outcome. This paper describes a series of culture-related risk factors such as education, work, sexuality, marriage, and infertility, which significantly contribute to triggering mental disorders in females, or to worsen their course and outcome. The authors recommend that mental health providers should play a critical role by addressing the cultural as well as psychological conditions that create and maintain threats to women's mental health.     

Clinical variables and hypothalamic-pituitary-adrenal function in depression. The importance of mood reactivity

Forty outpatients with major depressive disorder were studied with the 1 mg DST and the Afternoon Cortisol Test. No relationship was found between hypothalamic-pituitary-adrenal (HPA) axis function and Research Diagnostic Criteria subtypes of depression, with the exception of higher log post-dexamethasone cortisol levels in endogenous depressives. Patients with mood reactivity had lower cortisol values on all assessments. The data suggest that the presence of mood reactivity may be useful as a predictor of normal HPA function in depression.     

The pathophysiologic background for current treatments of premenstrual syndromes

Multiple hypotheses on the etiology of premenstrual syndromes (PMS) that have been proposed during the past 70 years have led to a multitude of treatment modalities. During the past two decades, the following two classes of pharmacologic interventions have emerged: hormonal interventions—mostly suppression of ovulation; and neurotransmitter’s activity stimulation—mostly by specific serotonin reuptake inhibitors. These treatment modalities are based on the hypothesis that the etiology and pathophysiology of PMS are related to ovulation-related luteal activity of gonadal hormones, and their interaction with serotonin and other neurotransmitters. Two other components of the pathophysiology of PMS—the genetic propensity and the dynamically evolving-vulnerability—have not yet been addressed for treatment. Environmental inputs to pathophysiology, which are not discussed here, have been addressed by attempts at changes of lifestyle, coping style, and environment.     

Diurnal cortisol responses to dextroamphetamine in normal subjects

(1) Dextroamphetamine, in doses of 0.1 and 0.15 mg/kg, was administered intravenously morning and evening to normal young men and postmenopausal women, and plasma cortisol responses were assessed. (2) There were no differences in cortisol responses between the young men and older women at either dose. (3) The higher dose elicited a significant and reliable acute cortisol release, while the lower dose did not. (4) In the evening, 0.15 mg/kg amphetamine elicited a larger cortisol increase from baseline than the same dose in the morning. (5) Within morning or evening periods, baseline cortisol values were not significantly correlated with magnitude of cortisol responses, although trends for inverse correlations were observed. (6) It is suggested that these normal diurnal differences in the acute cortisol response to amphetamine may be related to a corresponding rhythm in the responsitivity to amphetamine of neuroendocrine neurotransmitters. (7) The previously reported abnormal cortisol response to amphetamine in a group of endogenous depressives probably is not primarily related to variables of age, sex or baseline cortisol level.     

The cortisol response to desipramine in endogenous depressives and normal controls: preliminary findings

Plasma cortisol levels were monitored for 2 hours after an intramuscular injection of 75 mg desipramine in 13 endogenous depressives and 20 normal controls. Endogenous depressives had a significantly reduced cortisol response in comparison to normal controls, not explained by sex, age, or baseline cortisol differences between groups. A lack of a cortisol rise of 1.5 micrograms/dl above baseline by 45 minutes discriminated best, with 7 of 13 depressives (55%) being identified in contrast to only 1 of 20 normals (5%). The results suggest that this may be a useful biological test with acceptable sensitivity (55%) and excellent specificity (95%). Furthermore, these data suggest that norepinephrine may be stimulatory to cortisol in man.     

The fountain of mental youth. Search for homeostatic and adaptational hormonal processes

Successful mental aging may be defined as maintenance of youthful attitudes, cognitive and adaptational processes despite advanced age. Maintenance of homeostasis and efficient adaptational processes are of utmost importance. It is suggested that multiple hormonal systems and processes are involved in the multidimensional, interdependent, interrelated successful aging process. Changes in their interactions over time probably occur. A complex integrated regulatory homeostatic and normalcy system is proposed. Disruption on this regulating normalization process may cause disorders, as well as accelerated mental aging. Currently not much is known about maintenance of mental normalcy, as well as homeostatic and adaptational underlying mechanisms. Their elucidation would substantially contribute to understanding of well-being, disorders, and successful as well as unsuccessful aging.     

The etiology,biology, and evolving pathology of premenstrual syndromes

Menstrually related symptoms and disorders are multidimensional and affect diverse physiologic systems. Elucidation of the pathophysiologic mechanisms of these disorders should allow for a more precise diagnosis, and provide direction for targeted therapeutic interventions. Several biologic mechanisms that underlie menstrually related symptoms have been proposed. They focus mostly on gonadal hormones, their metabolites and interactions with neurotransmitters and neurohormonal systems, such as serotonin, GABA, cholecystokinin, and the renin-angiotensin-aldosterone system. Altered responses of these systems to gonadal hormone's fluctuations during the menstrual cycle, as well as an increased sensitivity to changes in gonadal hormones may contribute to menstrually related symptoms in vulnerable women. Disrupted homeostasis and deficient adaptation may be core underlying mechanisms. Future directions for clinically-relevant progress include identification of specific subgroups of menstrually-related syndromes, assessment of the genetic vulnerability and changes in vulnerability along the life cycle, the diversified mechanisms by which vulnerability is translated into pathophysiology and symptoms, the normalization process as well as syndromes-based and etiology-based clinical trials.