Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders

Depression is one of the most prevalent and debilitating public health concerns. Although no single cause of depression has been identified, it appears that interaction among genetic, epigenetic, biochemical, environmental, and psychosocial factors may explain its etiology. Further, only a fraction of depressed patients show full remission while using current antidepressants. Therefore, identifying common pathways of the disorder and using that knowledge to develop more effective pharmacological treatments are two primary targets of research in this field. Brain-enriched neurotransmitter CART (cocaine- and amphetamine-regulated transcript) has multiple functions related to emotions. It is a potential neurotrophic factor and is involved in the regulation of hypothalamic-pituitary-adrenal axis and stress response as well as in energy homeostasis. CART is also highly expressed in limbic system, which is considered to have an important role in regulating mood. Notably, adolescents carrying a missense mutation in the CART gene exhibit increased depression and anxiety. Hence, CART peptide may be a novel promising antidepressant agent. In this paper, we summarize recent progress in depression and CART. In particular, we emphasize a new antidepressant function for CART.

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POMC: The Physiological Power of Hormone Processing

Physiological Reviews ◽

10.1152/physrev.00024.2017 ◽

2018 ◽

Vol 98 (4) ◽

pp. 2381-2430 ◽

Cited By ~ 16

Author(s):

Erika Harno ◽

Thanuja Gali Ramamoorthy ◽

Anthony P. Coll ◽

Anne White

Keyword(s):

Energy Homeostasis ◽

Bioactive Peptides ◽

Regulated Secretion ◽

Processing Pathways ◽

Cellular Processing ◽

Pomc Gene ◽

The Individual ◽

The Impact ◽

Pituitary Adrenal Axis

Pro-opiomelanocortin (POMC) is the archetypal polypeptide precursor of hormones and neuropeptides. In this review, we examine the variability in the individual peptides produced in different tissues and the impact of the simultaneous presence of their precursors or fragments. We also discuss the problems inherent in accurately measuring which of the precursors and their derived peptides are present in biological samples. We address how not being able to measure all the combinations of precursors and fragments quantitatively has affected our understanding of the pathophysiology associated with POMC processing. To understand how different ratios of peptides arise, we describe the role of the pro-hormone convertases (PCs) and their tissue specificities and consider the cellular processing pathways which enable regulated secretion of different peptides that play crucial roles in integrating a range of vital physiological functions. In the pituitary, correct processing of POMC peptides is essential to maintain the hypothalamic-pituitary-adrenal axis, and this processing can be disrupted in POMC-expressing tumors. In hypothalamic neurons expressing POMC, abnormalities in processing critically impact on the regulation of appetite, energy homeostasis, and body composition. More work is needed to understand whether expression of the POMC gene in a tissue equates to release of bioactive peptides. We suggest that this comprehensive view of POMC processing, with a focus on gaining a better understanding of the combination of peptides produced and their relative bioactivity, is a necessity for all involved in studying this fascinating physiological regulatory phenomenon.

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The Role of Biomarkers in Research on Caregivers for Cancer Patients: A Scoping Review

Biological Research For Nursing ◽

10.1177/1099800417740970 ◽

2017 ◽

Vol 20 (3) ◽

pp. 300-311 ◽

Cited By ~ 4

Author(s):

Jumin Park ◽

Alyson Ross ◽

Stephen D. Klagholz ◽

Margaret F. Bevans

Keyword(s):

Cancer Patients ◽

Scoping Review ◽

Psychological Health ◽

Predictive Biomarkers ◽

Cell Aging ◽

Future Research ◽

Depression And Anxiety ◽

Caregiver Health ◽

Pituitary Adrenal Axis

Background: Biomarkers can be used as prognostic, predictive, or monitoring indicators of an associated outcome. The purpose of this review was to provide a comprehensive summary of the research examining the use of biomarkers as surrogate end points for clinical outcomes in family caregivers for cancer patients, identify gaps, and make recommendations for future research. Methods: A scoping review, a process of mapping the existing literature, was conducted. Studies comparing biomarkers across caregivers and controls and/or examining relationships between biomarkers and psychological health were reviewed. Results: The studies ( N = 18) of caregivers for cancer patients who were identified used biomarkers to predict outcomes ( n = 13) and to monitor the efficacy of interventions ( n = 6). Biomarkers were divided into two categories based on physiological systems involved: (1) neuroendocrine function (sympathetic–adrenal–medullary axis activity, hypothalamic–pituitary–adrenal axis activity) and (2) immune function. Predictive biomarkers were sensitive to differences between caregivers and controls. The biomarkers were used to evaluate outcomes frequently associated with stress, depression, and anxiety. Cortisol was the biomarker most commonly measured to monitor the efficacy of interventions. Discussion: Biomarkers are most commonly incorporated into caregiver studies to predict group membership and psychological health. Neuroendocrine biomarkers, specifically cortisol, are most frequently assessed. Future research should include biomarkers of other physiologic functions (e.g., cardiovascular function, cognitive dysfunction, and cell aging) and those that serve as multisystem indicators. Expanding the scientific study of biomarkers will contribute to our understanding of the mechanisms through which stress may influence caregiver health.

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