6 research outputs found
In Search of HPA Axis Dysregulation in Child and Adolescent Depression
Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative perspective on research investigating the various components of HPA axis functioning among depressed young people. The present narrative review synthesizes evidence from the following five categories of studies conducted with children and adolescents: (1) those examining the HPA system’s response to the dexamethasone suppression test (DST); (2) those assessing basal HPA axis functioning; (3) those administering corticotropin-releasing hormone (CRH) challenge; (4) those incorporating psychological probes of the HPA axis; and (5) those examining HPA axis functioning in children of depressed mothers. Evidence is generally consistent with models of developmental psychopathology that hypothesize that atypical HPA axis functioning precedes the emergence of clinical levels of depression and that the HPA axis becomes increasingly dysregulated from child to adult manifestations of depression. Multidisciplinary approaches and longitudinal research designs that extend across development are needed to more clearly and usefully elucidate the role of the HPA axis in depression
Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia
The mortality of chronic heart failure (CHF) doubles either when
CHF patients are depressed or when their plasma norepinephrine
(NE) level exceeds those of controls by 40%. We hypothesized
that patients with major depression had centrally driven, sustained,
stress-related, and treatment-reversible increases in plasma
NE capable of increasing mortality in CHF patients with depression.
We studied 23 controls and 22 medication-free patients with
melancholic depression. In severely depressed patients before and
after electroconvulsive therapy (ECT), we measured cerebrospinal
fluid (CSF) NE, plasma NE, plasma epinephrine (EPI), and plasma
cortisol hourly for 30 h. In mildly-to-moderately depressed melancholic
patients, we assessed basal and stress-mediated arterial NE
appearance. Severely depressed patients had significant increases
in mean around-the-clock levels of CSF NE (P < 0.02), plasma NE
(P < 0.02), plasma EPI (P < 0.02), and plasma cortisol (P < 0.02). CSF
NE, plasma NE, and cortisol all rose together throughout the night
and peaked in the morning. Each fell to control values after ECT.
Mildly-to-moderately melancholic patients also had increased
basal (P<0.05) and stress-related (P<0.03) arterial NE-appearance
rates. Severely melancholic depressed, medication-free patients
had around-the-clock increases in plasma NE levels capable of
increasing mortality in CHF. Twenty-four-hour indices of central
noradrenergic, adrenomedullary, and adrenocortical secretion
were also elevated. Concurrent diurnal rhythms of these secretions
could potentiate their cardiotoxicity. Even mildly-to-moderately
depressed melancholic patients had clinically relevant increases in
the arterial NE-appearance rate. These findings will not apply to all clinical subtypes of major depression.cerebrospinal fluid epinephrine majo