atrial-natriuretic-factor and Depressive-Disorder--Major

Clinical and preclinical studies have gathered substantial evidence that stress response alterations play a major role in the development of major depression, panic disorder and posttraumatic stress disorder. The stress response, the hypothalamic pituitary adrenocortical (HPA) system and its modulation by CRH, corticosteroids and their receptors as well as the role of natriuretic peptides and neuroactive steroids are described. Examplarily, we review the role of the HPA system in major depression, panic disorder and posttraumatic stress disorder as well as its possible relevance for treatment. Impaired glucocorticoid receptor function in major depression is associated with an excessive release of neurohormones, like CRH to which a number of signs and symptoms characteristic of depression can be ascribed. In panic disorder, a role of central CRH in panic attacks has been suggested. Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks. Furthermore, preclinical and clinical data on its anxiolytic activity suggest that non-peptidergic ANP receptor ligands may be of potential use in the treatment of anxiety disorders. Recent data further suggest a role of 3alpha-reduced neuroactive steroids in major depression, panic attacks and panic disorder. Posttraumatic stress disorder is characterized by a peripheral hyporesponsive HPA-system and elevated CRH concentrations in CSF. This dissociation is probably related to an increased risk for this disorder. Antidepressants are effective both in depression and anxiety disorders and have major effects on the HPA-system, especially on glucocorticoid and mineralocorticoid receptors. Normalization of HPA-system abnormalities is a strong predictor of the clinical course, at least in major depression and panic disorder. CRH-R1 or glucorticoid receptor antagonists and ANP receptor agonists are currently being studied and may provide future treatment options more closely related to the pathophysiology of the disorders.

Topics: Adrenal Cortex Hormones; Animals; Antidepressive Agents; Anxiety Disorders; Atrial Natriuretic Factor; Corticotropin-Releasing Hormone; Depressive Disorder, Major; Humans; Hypothalamic Diseases; Hypothalamo-Hypophyseal System; Natriuretic Peptides; Neurotransmitter Agents; Panic Disorder; Pituitary-Adrenal System; Receptors, Atrial Natriuretic Factor; Receptors, Corticotropin-Releasing Hormone; Receptors, Glucocorticoid; Receptors, Mineralocorticoid; Receptors, Steroid; Stress Disorders, Post-Traumatic

Atrial natriuretic peptide (ANP) exerts anxiolytic effects in animals and humans. Patients with anxiety, trauma-associated and depressive disorders exhibit lower ANP plasma levels compared to healthy individuals. However, the role of ANP in patients with major depressive disorder (MDD) with and without concomitant adverse childhood experiences (ACE) and in healthy individuals with and without ACE is not clear. We recruited a total of 93 women: 23 women with MDD and ACE, 24 women with MDD without ACE, 22 women with ACE but no current or lifetime MDD, and 24 healthy women without ACE. ANP plasma levels were measured with a radioimmunoassay. The four groups did not differ in demographic and clinical variables. We found a positive correlation between age and plasma levels of ANP (r = .39; p <  .001). After controlling for age, there was no significant main effect of MDD or ACE on ANP plasma levels, but a significant interaction between MDD and ACE such that ACE was associated with reduced basal ANP levels in the absence of MDD. We assume that low plasma ANP might be a consequence of ACE in the absence of current psychopathology. Therefore, future studies are needed to replicate our findings and to characterize the influencing factors of ACE on ANP more comprehensively, for example by including a comprehensive trauma and comorbidity anamnesis as well as cardiovascular state and risk factors.

Topics: Adult; Adverse Childhood Experiences; Anxiety; Atrial Natriuretic Factor; Comorbidity; Depressive Disorder, Major; Female; Humans; Hypothalamo-Hypophyseal System; Middle Aged; Pituitary-Adrenal System; Surveys and Questionnaires

Increased levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been shown to reduce the hormones in the HPA axis. In this study we addressed the question whether patients with unmedicated major depressive disorder (MDD) might have altered baseline levels of these natriuretic peptides and an altered response to acute exercise.. An incremental exercise test was performed in 18 patients with MDD and in 18 healthy controls. Plasma concentrations of ANP and BNP were determined at rest, during the exercise test and 30 min post exercise using immunoradiometric assays.. During the exercise test the concentrations of ANP and BNP increased significantly in both groups. The MDD group showed significantly lower levels of ANP than the controls at rest, at maximal work rate and post exercise and of BNP at rest and at maximal work rate. The dynamic changes of both ANP and BNP, respectively, from baseline to maximal work rate were significantly lower in the MDD group. A slightly lower (non-significant) maximal work rate was observed in the MDD group compared with the controls.. Group sizes are relatively limited.. Lower concentrations of ANP and BNP during rest and exercise were observed in the MDD patients together with a decreased dynamic response to maximal exercise. Hypothetically, the reduced ANP and BNP concentration contributes to the high hormone levels in the HPA system seen in depressive disorders. Of interest for future research is whether physical training might increase the levels of ANP and BNP and thereby diminish depressive symptoms.

Topics: Adult; Atrial Natriuretic Factor; Case-Control Studies; Depressive Disorder, Major; Exercise; Female; Humans; Male; Natriuretic Peptide, Brain; Rest