Regulation of 5-HT Receptors and the Hypothalamic-Pituitary-Adrenal Axis

Disturbances in the serotonin (5-HT) system is the neurobiological abnormality most consistently associated with suicide. Hyperactivity of the hypothalmic-pituitary-adrenal (HPA) axis is also described in suicide victims. The HPA axis is the classical neuroendocrine system that responds to stress and whose final product, corticosteroids, targets components of the limbic system, particularly the hippocampus. We will review resulsts from animal studies that point to the possibility that many of the 5-HT receptor changes observed in suicide brains may be a result of, or may be worsened by, the HPA overactivity that may be present in some suicide victims. The results of these studies can be summarized as follows: (1) chronic unpredictable stress produces high corticosteroid levels in rats; (2) chronic stress also results in changes in specific 5-HT receptors (increases in cortical 5-HT2A and decreases in hipocampal 5-HT1A and 5-HT1B); (3) chronic antidepressant administration prevents many of the 5-HT receptor changes observed after stress; and (4) chronic antidepressant administration reverses the overactivity of the HPA axis. If indeed 5-HT receptors have a partial role in controlling affective states, then their modulation by corticosteroids provides a potential mechanism by which these hormones may regulate mood. These data may also provide a biological understanding of how stressful events may increase the risk for suicide in vulnerable individuals and may help us elucidate the neurobiological underpinnings of treatment resistance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73437/1/j.1749-6632.1997.tb52357.x.pd

A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD. © 2021, The Author(s).EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking

Thyrotropin—releasing hormone and amphetamine: A comparison of pharmacological profiles in animals

1. 1. The pharmacological effects of TRH are compared to those produced by d-amphetamine in an attempt to elucidate the mechanisms underlying the activity of this endogenous peptide. 2. 2. Although numerous amphetamine-like actions have been attributed to TRH, several differences have been noted between these compounds and are discussed. 3. 3. At present, it is impossible to propose a single mechanism of action to explain the behavioral effects of TRH

Advances in the treatment of mood and anxiety disorders

Mood and anxiety disorders are prevalent in all countries and cultures, which becomes obvious when standardized diagnostic and evaluation techniques are utilized. It is estimated that ~450 million people worldwide suffer from psychiatric illness. In the United States alone, epidemiologic research has identified that tens of millions of Americans suffer from major depressive disorder (MDD) annually, with many of them being in the prime of their adult lives. In addition to medical, personal, and social costs, depression is also believed to have a significant impact on work productivity. Further epidemiologic research indicates that nearly half of all individuals meeting lifetime criteria for MDD also have met criteria for a comorbid anxiety disorder. With an average age of 16 years for the onset of any lifetime anxiety disorder, anxiety disorders appear to predispose affected individuals to a substantial lifetime risk for MDD. In order to improve outcomes in depression and anxiety disorders, clinicians must enhance the entire process of recognition, diagnosis, and treatment