Hypothalamic-pituitary-adrenal depression

Ritchie, JC and Nemeroff, CB (1991) Stress, the hypothalamic-pituitary-adrenal axis and depression. In Stress, Neuropeptides and Systemic Disease (Eds McCubbin, JA, Kaufmann, PG and Nemeroff, CB), Academic Press, London, pp. 181-197. 

Roy, A., Pickar, D., Dejong, J., Karoum, F. Linnoila, M. (1998). Norepinephrine and its metabolites in cerebrospinal fluid, plasma and urine. Relationship to hypothalamic-pituitary-adrenal axis function in depression. Arch. Gen. Psychiatry, 45, 849-57. 

The cortical-hypothalamic-pituitary-adrenal axis has been implicated in major depression 893... 

In depressed patients, cortical-hypothalamic-pituitary-adrenal axis hyperactivity can be explained by the hypersecretion of CRF, and secondary pituitary and adrenal gland hypertrophy. Impaired negative feedback at various CNS sites, including the hippocampus and pituitary are also likely to contribute. Downregulation of hippocampal mineralocorticoid receptors and expression is reported in depressed suicides [50]. In bipolar disorder, hyperactivity of the cortical-hypothalamic-pituitary-adrenal axis has been observed [51]. This increase in cortical-hypothalamic-pituitary-adrenal axis activity has also been observed in mixed mood states, mania and in depression in rapidcycling patients. Partial reversal of HPA overactivity is associated with treatment and recovery from depression. 

Semba J, Wakuta M, Maeda J, Suhara T (2004) Nicotine withdrawal induces subsensitivity of hypothalamic-pituitary-adrenal axis to stress in rats implications for precipitation of depression during smoking cessation. Psychoneuroendociinology 29 215-226... 

Plotsky, P.M., Owens, M.J., and Nemeroff, C.B. (1998) Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis. Psychiatry Clin North Am 21 293-307. 

NPY produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, respiratory depression, and activation of the hypothalamic-pituitary-adrenal axis. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional neuronal actions include inhibition of transmitter release from sympathetic and parasympathetic nerves. Vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. 

Plotsky PM, OwensMJ, Nemeroff CB Psychoneuroendocrinology of depression. Hypothalamic-pituitary-adrenal axis. Psychiatr Clin North Am 1998 21(2) 293. [PMID 9670227]... 

Hypothalamic-pituitary-adrenal axis function in bipolar disorder has been reviewed, but lithium was mentioned only in passing (617). Two studies (n = 25, n = 24), possibly reporting many of the same patients, showed that lithium augmentation of antidepressant-resistant unipolar depression increased hypothalamic-pituitary-adrenal axis activity, measured by the dexamethasone suppression test, either alone or combined with the corticotropin releasing hormone test (618,619). However, the tests did not distinguish between lithium responders and nonresponders. 

Barden N. Implication of the hypothalamic-pituitary-adrenal axis in the physiopathoiogy of depression. J Psychiatry Neurosci. 2004 29 185-193. 

Figure 18.3. Endocrine-immune inter-relationship in depression. In depression, the hypothalamic-pituitary-adrenal (HPA) axis is up-regulated with a down-regulation of its negative feedback controls. Corticotrophin releasing factor (CRF) is hypersecreted from the hypothalamus and induces the release of adrenocortico-trophic hormone (ACTH) from the pituitary. ACTH interacts with receptors on adrenocortical cells and cortisol is released from the adrenal glands adrenal hypertrophy can also occur. Release of cortisol into the circulation has a number of effects, including elevation of blood glucose. The negative feedback of cortisol to the hypothalamus, pituitary and immune system is impaired. This leads to continual activation of the HPA axis and excess cortisol release. Cortisol receptors become desensitized leading to increased activity of the pro-inflammatory immune mediators and disturbances in neurotransmitter transmission.

The past 20 years have witnessed a broad interest in the role of the hypothalamic-pituitary-adrenal axis in the psychobiology of affective disorders. In depressed patients, increases in serum cortisol are frequently reported in addition to disruptions of circadian patterns of cortisol secretion... 

Mental disorders, also called affective disorders, are multi-level, multi-scale and multiple-system diseases (Fig. 7.1). Mental disturbances generally go along with disturbances of autonomous functions. These essentially are (1) sleep disturbances, both sleep duration and sleep pattern, and (2) disturbances of the hypothalamic-pituitary-adrenal (HPA) axis, the so-called stress axis with elevated cortisol levels. It can be expected that disturbances of autonomous control systems as well as mood are caused by neuronal malfunctioning which may concern practically all neuronal levels systemic interactions, neuronal network connections, single neuron dynamics, synaptic transmitters and/or receptors, ion channels, second messengers, and gene expression (Fig. 7.1a). Nevertheless, despite a manifold of data, there are only vague ideas so far about the differences in neuronal dynamics in the brain of a chronically depressed person compared with a person with a sensitive but balanced mood. 

Both GABA and glutamate are important beyond their direct effects as neurotransmitters. They interact with several other neurotransmitter and neuromodulatory systems and have effects on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis, which may contribute to hyperactivity in this circuit in depression. The HPA axis will be discussed later in this article. 

Adrenal steroids chronic corticosteroid therapy with the equivalent of prednisolone 10 mg daily within the previous 3 months suppresses the hypothalamic-pituitary-adrenal system. Without steroid supplementation perioperatively the patient may fail to respond appropriately to the stress of surgery and become hypotensive (see Ch. 34). A single dose of etomidate depresses the hypothalamic-pituitary-adrenal axis for a few hours but this is not associated with an adverse outcome. 

Keywords Alpha-melanocyte stimulating hormone Adre-nocorticotrophic hormone Corticotropin releasing hormone Cytokines Depression Hypothalamic-pituitary-adrenal axis Proenkephalin Proopiomelanocortin Schizophrenia Stress response... 

Maes M, Scharpe S, Meltzer HY, Bosnians E, Suy E, Calabrese J, Cosy ns P (1993) Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res 49 11-27. 

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